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Adrenal Gland Cancer (281 unread)

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Tranexamic Acid During Upper GI Endoscopic Resection Procedures

Posted: January 18th, 2023, 3:00pm GMT

Conditions: Gastric Polyp; Gastric Neoplasm; Duodenal Neoplasms; Esophageal Neoplasms
Interventions: Drug: Tranexamic acid; Drug: Epinephrine injection
Sponsor: Assaf-Harofeh Medical Center
Not yet recruiting

Comparison of Needlescopic vs. Conventional Laparoscopic Adrenalectomy for Tumor Less Than 4 cm

Posted: January 9th, 2023, 3:00pm GMT

Condition: Post Operative Pain, Acute
Interventions: Device: Needlescopic laparoscopic adrenalectomy; Device: conventional laparoscopic adrenalectomy
Sponsor: National Taiwan University Hospital
Not yet recruiting

Adrenal Vein Sampling as a Tool to Identify Biomarkers That Aid the Diagnosis of Adrenocortical Carcinoma

Posted: December 21st, 2022, 3:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention: Other: Blood sampling.
Sponsor: Erasmus Medical Center
Recruiting

Permalink for 'Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma'

Propranolol in Combination With Pembrolizumab and Standard Chemotherapy for the Treatment of Unresectable Locally Advanced or Metastatic Esophageal or Gastroesophageal Junction Adenocarcinoma

Posted: December 15th, 2022, 3:00pm GMT

Conditions: Clinical Stage II Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Esophageal Adenocarcinoma AJCC v8; Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8; Clinical Stage IV Esophageal Adenocarcinoma AJCC v8; Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8; Locally Advanced Esophageal Adenocarcinoma; Locally Advanced Gastroesophageal Junction Adenocarcinoma; Metastatic Esophageal Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Unresectable Esophageal Adenocarcinoma; Unresectable Gastroesophageal Junction Adenocarcinoma
Interventions: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Fluorouracil; Drug: Leucovorin; Drug: Oxaliplatin; Biological: Pembrolizumab; Drug: Propranolol Hydrochloride; Other: Questionnaire Administration
Sponsors: Roswell Park Cancer Institute; United States Department of Defense
Recruiting

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 2:00pm GMT

Conditions: Pediatric Solid Tumor; Osteosarcoma; Rhabdomyosarcoma; Neuroblastoma; Ewing Sarcoma; Wilms Tumor; Adrenocortical Cancer; Desmoplastic Small Round Cell Tumor; Germ Cell Cancer; Rhabdoid Tumor; Clear Cell Sarcoma; Hepatoblastoma; Melanoma; Carcinoma; Malignant Peripheral Nerve Sheath Tumors; Soft Tissue Sarcoma
Interventions: Drug: Fludarabine; Drug: Cyclophosphamide; Drug: MESNA; Drug: B7-H3 CAR T cells
Sponsor: St. Jude Children's Research Hospital
Recruiting

RCT Comparing ESPB Solutions in Breast Surgery

Posted: October 27th, 2020, 2:00pm GMT

Condition: Breast Cancer
Interventions: Drug: Liposomal bupivacaine; Drug: Bupivacaine, epinephrine, dexamethasone, and clonidine
Sponsor: Tufts Medical Center
Recruiting

Neuroendocrine and Adrenal Tumors

Posted: June 16th, 2020, 2:00pm GMT

Conditions: Neuroendocrine Tumors; Adrenal Tumor
Intervention: Other: No intervention
Sponsor: University of Pennsylvania
Not yet recruiting

Permalink for 'Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer'

Testing the Addition of an Anticancer Drug, Olaparib, to the Usual Chemotherapy (Temozolomide) for Advanced Neuroendocrine Cancer

Posted: May 20th, 2020, 2:00pm GMT

Conditions: Advanced Adrenal Gland Pheochromocytoma; Advanced Paraganglioma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Paraganglioma; Unresectable Adrenal Gland Pheochromocytoma; Unresectable Paraganglioma
Interventions: Drug: Olaparib; Other: Quality-of-Life Assessment; Drug: Temozolomide
Sponsor: National Cancer Institute (NCI)
Recruiting

Lu-177-DOTATATE (Lutathera) in Therapy of Inoperable Pheochromocytoma/ Paraganglioma

Posted: July 2nd, 2017, 2:00pm GMT

Conditions: Pheochromocytoma; Paraganglioma; Neuroendocrine Tumors; Neuroendocrine Neoplasms
Interventions: Drug: Lu-177-DOTATATE; Drug: Ga-68-DOTATATE; Drug: F-18-FDG; Drug: Amino Acid solution
Sponsor: National Cancer Institute (NCI)
Recruiting

Permalink for 'FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome'

FLCN-Driven Functional Adrenal Cortical Carcinoma with High Mitotic Tumor Grade: Extending the Endocrine Manifestations of Birt-Hogg-Dubé Syndrome

Fetched: January 27th, 2023, 5:00am GMT by Renee Hofstedter

Endocr Pathol. 2023 Jan 26. doi: 10.1007/s12022-023-09748-2. Online ahead of print.

ABSTRACT

Adrenal cortical carcinoma is an aggressive and rare malignancy of steroidogenic cells of the adrenal gland. Most adult adrenal cortical carcinomas are sporadic, but a small fraction may be associated with inherited tumor syndromes, such as Li-Fraumeni, multiple endocrine neoplasia 1, Lynch syndrome, and Beckwith-Wiedemann syndrome, as well as isolated case reports of non-syndromic manifestations occurring in the context of other pathogenic germline variants. Birt-Hogg-Dubé (BHD) is a rare autosomal dominant syndrome caused by germline pathogenic variants in the FLCN gene. BHD syndrome causes a constellation of symptoms, including cutaneous manifestations, pulmonary cysts and pneumothorax, and risk of renal tumors. With the exception of a single case of adrenal cortical carcinoma, very few reports on the occurrence of adrenal cortical neoplasia in patients with BHD syndrome have been described. However, information on variant allele fraction in the tumor was not available in the index case, which precludes any mechanism supporting loss of heterozygosity. Here we present a case of an adult-onset adrenal cortical carcinoma in a 50-year-old female, found to harbor a germline likely pathogenic variant in the FLCN gene, denoted as c.694C > T (p.Gln232Ter). Genetic testing on the tumor revealed the same FLCN variant at an allele fraction of 83%, suggesting a contributory role to the pathogenesis of the adrenal cortical carcinoma. This case further supports the expansion of the clinical presentation and tumor spectrum of BHD syndrome and the need to consider germline FLCN testing in the clinical genetic workup of patients with adrenal cortical carcinomas.

PMID:36701047 | DOI:10.1007/s12022-023-09748-2

The essentials of acute oncology

Fetched: January 26th, 2023, 5:00am GMT by Kieran Palmer

Clin Med (Lond). 2023 Jan;23(1):45-51. doi: 10.7861/clinmed.2022-0561.

ABSTRACT

The general medical physician will often encounter patients who develop acute complications of their cancer diagnosis or anti-cancer treatment. Here we provide an overview of emergency solid tumour oncology to guide the initial management of these patients.

PMID:36697019 | DOI:10.7861/clinmed.2022-0561

Neoplastic signatures: Comparative proteomics of canine hepatobiliary neuroendocrine tumors to normal niche tissue

Fetched: January 26th, 2023, 5:00am GMT by Tifini L Batts

PLoS One. 2023 Jan 25;18(1):e0280928. doi: 10.1371/journal.pone.0280928. eCollection 2023.

ABSTRACT

Hepatobiliary neuroendocrine neoplasms are rare cancers in humans and dogs. To date, no large-scale primary hepatobiliary neoplasm omics analyses exist in any species. This limits the development of diagnostic biomarkers and targeted therapeutics. Neuroendocrine cancers are a heterogenous group of neoplasms categorized by their tissue-of-origin. Because the anatomic niche of neuroendocrine neoplasms shapes tumor phenotype, we sought to compare the proteomes of 3 canine hepatobiliary neoplasms to normal hepatobiliary tissue and adrenal glands with the objective of identifying unique protein signatures. Protein was extracted from formalin-fixed paraffin-embedded samples and submitted for tandem mass spectroscopy. Thirty-two upregulated and 126 downregulated differentially expressed proteins were identified. Remarkably, 6 (19%) of the upregulated proteins are correlated to non-hepatobiliary neuroendocrine neoplasia and 16 (50%) are functionally annotated within the exosome cellular compartment key to neuroendocrine signaling. Twenty-six (21%) downregulated proteins are enriched in metabolic pathways consistent with alterations in cancer. These results suggests that characteristic neoplastic protein signatures can be gleaned from small data sets using a comparative proteomics approach.

PMID:36696389 | PMC:PMC9876354 | DOI:10.1371/journal.pone.0280928

Steroid profiling characteristics in pediatrc adrenal diseases

Fetched: January 26th, 2023, 5:00am GMT by E A Yanar

Probl Endokrinol (Mosk). 2022 Nov 3;68(6):110-120. doi: 10.14341/probl13166.

ABSTRACT

BACKGROUND: Adrenocortical adenomas are often followed with steroid hormones hyperproduction, and therefore determination of their concentration plays an important role in the differential diagnosis of adrenal diseases. Steroid profiling by tandem mass spectrometry is one of the main diagnostic methods in steroidogenesis characterization. Currently plasma and urinary steroid profiling is of particular interest in differential diagnosis and subtyping patients with adrenocortical adenomas.

AIM: Steroid profiling of pediatric patients with adrenal diseases (incidentalomas, ACTH-secreting pituitary adenoma, ACTH-independent Cushing syndrome, premature adrenarche).

MATERIALS AND METHODS: We conducted a retrospective analysis of steroid profile of 41 pediatric patients with adrenal diseases who were observed between 2005 and 2020 at the Endocrinology Research Centre.

RESULTS: All patients were divided into groups due to diagnosis: with ACTH-secreting pituitary adenoma [n=7], ACTH-independent Cushing syndrome (autonomous cortisol secretion by an adrenal adenoma) [n=4], with incidentaloma [n=7] and premature adrenarche [n=23]. In group of patients with ACTH-independent Cushing syndrome identified statistically significant higher levels of 11-deoxycortisol (р=0, 0035) and significant lower levels of 17-hydroxypregnenolone (р=0, 0026) and DHEA (р=0, 0047) compared to other groups. Statistically significant differences in steroid profiles between other groups were not identified.

CONCLUSION: Results of our study steroid profiling can be used as additional differential diagnosis method in patients with adrenocortical adenomas with or without hormonal hyperproduction (ACTH-independent Cushing syndrome and incidentaloma). Further studies are needed to identify steroid markers for subtyping pediatric adrenal diseases.

PMID:36689716 | DOI:10.14341/probl13166

Survival predictors in patients with ectopic acth syndrome

Fetched: January 26th, 2023, 5:00am GMT by O O Golounina

Probl Endokrinol (Mosk). 2022 Aug 15;68(6):30-42. doi: 10.14341/probl13144.

ABSTRACT

AIM: To determine significant factors affecting the survival of patients with ectopic ACTH syndrome (EAS).

MATERIALS AND METHODS: A multi-center, observational study with a retrospective analysis of patients with EAS. The end point of the study was the fatal outcome of patients from various causes. In order to identify predictors of survival or mortality, univariate and multifactorial Cox regression analyses were carried out. ROC-analysis was used to determine the prognostic threshold values of individual predictors. The survival analysis was carried out using the Kaplan-Mayer method. Statistical data processing was carried out by using IBM SPSS Statistics 23.

RESULTS: The age of patients at the time of diagnosis ranged from 12 to 76 years (Me 40 years [28;54]). The age of the studied population was 55 years [38; 64] for women and 42 years [32; 54] for men. The median period of observation was 50 months [13;91], with a maximum follow-up of 382 months. 92 patients (60,9%) had bronchopulmonary NET, 17 (11,3%) - thymic carcinoid, 8 - pancreatic NET, 5 -pheochromocytoma, 1- cecum NET, 1- appendix carcinoid tumor, 1 - medullary thyroid cancer and 26 (17,2%) patients had an occult NET. The primary tumor was removed in 101 patients (66,9%). Bilateral adrenalectomy was performed in 42 (27,8%) cases. Metastases were revealed in 23,2% (n=35) of patients. Relapse of the disease was observed in 24,4%, long-term remission was preserved in 64 patients (74,4%). Death occurred in 42 patients (28%). The average age of survivors was 47,0±15,2 versus 53,5±15,6 years for the deceased (p=0,022). The average survival time from diagnosis for the deceased was 32 months, Me 16,5 months [7;54]. Multivariate analysis revealed that the following factors have a direct impact on survival: age of diagnosis ≥51 years (OR 4,493; 95% CI 2,056-9,818, p<0,001), bronchopulmonary neuroendocrine tumor (NET) (OR 0,281; 95% CI 0,119-0,665, p=0,004), the presence of distant metastases (OR 2,489; 95% CI 1,141-5,427, p=0,022), late-night salivary cortisol (LNSC) ≥122,2 nmol/L (OR 2,493; 95% CI 1,014-6,128, p=0,047).

CONCLUSION: The prognosis of patients with EAS is influenced by the age of diagnosis, NET localization, distant metastases and level of LNSC. The most common cause of ectopic ACTH syndrome was bronchopulmonary NET which was associated with the best survival rate.

PMID:36689709 | DOI:10.14341/probl13144

Lipid Disorders in People with HIV

Fetched: January 26th, 2023, 5:00am GMT by Sudipa Sarkar

2023 Jan 21. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Hofland J, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Dyslipidemia is highly prevalent in people with HIV (PWH) and contributes to the increased risk of cardiovascular disease seen in this patient population. Factors that contribute to dyslipidemia include HIV infection itself and certain types of antiretroviral therapy (ART). Moreover, the effects of ART on lipids have changed over time as newer therapies have become available. Because some ART medications interact with lipid-lowering therapies, the type of lipid-lowering therapy initiated needs to be considered in this context. Of note, current cardiovascular disease (CVD) risk calculators underestimate CVD risk in PWH because HIV-specific factors also contribute to CVD. HIV-specific variables should be taken into account when calculating atherosclerotic CVD risk in PWH. In addition to statins, other lipid lowering agents, including PCSK9 inhibitors, have been studied in PWH and can be considered in the treatment of dyslipidemia, particularly for low-density lipoprotein (LDL-C) lowering. The ongoing REPRIEVE study will contribute to a better understanding of the use of statins in primary prevention of CV disease in PWH with low CVD risk. Aggressive lipid management in PWH is essential for primary and secondary CVD prevention and optimization of health span and lifespan in this high-risk population. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:33528966 | Bookshelf:NBK567198

Adrenal Androgens and Aging

Fetched: January 26th, 2023, 5:00am GMT by Nektaria Papadopoulou-Marketou

2023 Jan 18. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Hofland J, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Dehydroepiandrosterone (DHEA) and its metabolite DHEA sulfate (DHEAS), are steroid pre-hormones synthesized and secreted primarily by the zona reticularis of the adrenal cortex in response to adrenocorticotropic hormone (ACTH). They are both precursor hormones that may be transformed into weak androgens or estrogens. During the last decades, several epidemiologic and cohort studies have shown the age-related circulating levels of DHEA/DHEAS; these first increase in childhood, a process called “adrenarche”, peak in the 3^rd decade of life, and progressively decrease in midlife, a phenomenon called “adrenopause”. Some authors have linked obesity in childhood with early adrenarche, i.e., increased circulating levels of adrenal androgens; others have associated low levels in late life with increased frailty and all-cause mortality. The potential clinical and therapeutic roles of DHEA/DHEAS have been studied extensively, but the data remain controversial and largely inconclusive. In this chapter, we provide an overview of the physiology and pathophysiology of adrenal androgen synthesis, secretion, and action and present current evidence regarding their efficacy in the management of adrenal insufficiency or aging-related disorders. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905237 | Bookshelf:NBK279006

ACTH-independent production of 11-oxygenated androgens and glucocorticoids in an adrenocortical adenoma

Fetched: January 25th, 2023, 5:00am GMT by Takuya Kitamura

Eur J Endocrinol. 2022 Dec 1;187(6):K39-K45. doi: 10.1530/EJE-22-0508.

ABSTRACT

Due to its rarity, biochemical and histologic characteristics of androgen and glucocorticoid co-secreting adrenocortical adenomas are largely unknown. Herein, we report a case of adrenocortical adenoma that caused marked hyperandrogenemia and mild autonomous cortisol secretion. In this study, we investigated serum steroid profiles using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and histologic characteristics of the resected tumor. LC-MS/MS revealed highly elevated levels of 11-oxygenated androgens which have not been well studied in adrenal tumors. The expression patterns of steroidogenic enzymes determined by immunohistochemistry supported the results of steroid profiling and suggested the capacity of the tumor cells to produce 11-oxygenated androgens. Measurement of 11-oxygenated steroids should facilitate a better understanding of androgen-producing adrenocortical neoplasms.

PMID:36691941 | DOI:10.1530/EJE-22-0508

Corticosteroids for the management of cancer-related fatigue in adults with advanced cancer

Fetched: January 25th, 2023, 5:00am GMT by Amy Sandford

Cochrane Database Syst Rev. 2023 Jan 23;1(1):CD013782. doi: 10.1002/14651858.CD013782.pub2.

ABSTRACT

BACKGROUND: Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review.

OBJECTIVES: To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022. SELECTION CRITERIA: We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments.

DATA COLLECTION AND ANALYSIS: Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear. Comparison 1: corticosteroids compared with placebo Participant-reported fatigue relief The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence). Serious adverse events There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Quality of lIfe One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Comparison 2: corticosteroids compared with active comparator (modafinil) Participant-reported fatigue relief There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence). Serious adverse events There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence). Quality of lIfe One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence).

AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.

PMID:36688471 | PMC:PMC9869433 | DOI:10.1002/14651858.CD013782.pub2

Permalink for 'Dual-energy spectral detector computed tomography differential diagnosis of adrenal adenoma and pheochromocytoma: Changes in the energy level curve, a phenomenon caused by lipid components?'

Dual-energy spectral detector computed tomography differential diagnosis of adrenal adenoma and pheochromocytoma: Changes in the energy level curve, a phenomenon caused by lipid components?

Fetched: January 25th, 2023, 5:00am GMT by Yu-Li Wang

Front Endocrinol (Lausanne). 2023 Jan 6;13:998154. doi: 10.3389/fendo.2022.998154. eCollection 2022.

ABSTRACT

BACKGROUND AND OBJECTIVES: Pheochromocytoma and adrenal adenoma are common space-occupying lesions of the adrenal gland, and incorrect surgery may lead to adrenal crisis. We used a new method, dual-energy spectral detector computed tomography (SDCT), to differentiate between the two.

MATERIALS AND METHODS: We analysed the imaging images of patients with SDCT scans and pathologically confirmed adrenal adenomas (n=70) and pheochromocytomas (n=15). The 40, 70, and 100 KeV virtual monoenergetic images (VMIs) were reconstructed based on the SCDT arterial phase, and the correlation between the arterial/venous phase iodine concentration (AP-IC/VP-IC), the effective atomic number (Z-effect), the slope of the Hounsfield unit attenuation plot (VMI slope) and the pathological results was tested. The Shapiro-Wilk test was used to determine whether the above data conformed to a normal distribution. For parameters with P greater than 0.05, Student's t test was used, and the Mann-Whitney test was used for the remaining parameters. A ROC curve was drawn based on the results.

RESULTS: Student's t test showed that the 40 KeV VMI and the VMI slope were both statistically significant (P<0.01). The Mann-Whitney U test showed that ID-A was statistically significant (P=0.004). ROC curve analysis showed that 40 keV VMI (AUC=0.818), AP-IC (AUC=0.736), difference (AUC=0.817) and VMI-Slope (0.817) could be used to differentiate adrenal adenoma from pheochromocytoma.

CONCLUSION: The effect of lipid components on SDCT parameters can be used to differentiate adrenal adenoma from pheochromocytoma.

PMID:36686431 | PMC:PMC9854128 | DOI:10.3389/fendo.2022.998154

Metastatic Adrenal PEComa: Case Report and Short Review of the Literature

Fetched: January 25th, 2023, 5:00am GMT by Enrico Battistella

Medicina (Kaunas). 2023 Jan 11;59(1):149. doi: 10.3390/medicina59010149.

ABSTRACT

PEComa has become a widely accepted entity, and increased recognition has led to descriptions of this tumor in a wide variety of anatomic sites, including the adrenal gland. PEComa (perivascular epithelioid cell tumor) is a mesenchymal tumor composed of perivascular cells, and the most frequent sites of PEComas are the uterus and retroperitoneum. The incidence is <1 per 1,000,000 people. We report a case of adrenal metastatic PEComa in a 63-year-old man discovered by a spontaneous hematoma of the rectus abdominis. In our case, PEComa of the adrenal gland was a significant diagnostic dilemma as the morphologic and immunophenotypic features of this neoplasm may easily be confused with those of other more commonly encountered lesions.

PMID:36676773 | PMC:PMC9866888 | DOI:10.3390/medicina59010149

Adrenal Gland Primary Neuroblastoma in an Adult Patient: A Case Report and Literature Review

Fetched: January 25th, 2023, 5:00am GMT by Teodora Telecan

Medicina (Kaunas). 2022 Dec 23;59(1):33. doi: 10.3390/medicina59010033.

ABSTRACT

Neuroblastoma (NB) is an undifferentiated malignant tumor of the sympathetic ganglia, occurring in children under 5 years of age. However, it is a rare histology in adult patients, occurring once per every 10 million patients per year. We present the case of a 68-year-old male patient presented to our department for right lumbar pain, asthenia, loss of weight and altered general status. The contrast-enhanced abdominal computer tomography revealed bilateral adrenal tumoral masses of 149 mm and 82 mm on the right and left sides, respectively, with invasion of the surrounding organs. The patient underwent right 3D laparoscopic adrenalectomy and right radical nephrectomy. The pathological result concluded that the excised tumor was a neuroblastoma of the adrenal gland. The patient followed adjuvant oncological treatment; however, due to disease progression, he passed away 22 months after the surgery. To our knowledge, less than 100 cases of adrenal NB in adult patients have been published, the eldest case being diagnosed at 75 years of age; meanwhile, the largest reported tumor measured 200 mm, and was excised through open surgery. Minimally invasive techniques have been limited so far to smaller, organ-confined diseases, thus making the present case the largest adrenal NB removed entirely laparoscopically. Neuroblastoma in the adult population is a rare finding, with worse prognosis compared to pediatric patients. The available literature does not provide enough data for standardized, multimodal management, as the patients are treated following adapted pediatric protocols, thus reinforcing the need for international, multidisciplinary boards for rare tumors.

PMID:36676657 | PMC:PMC9860607 | DOI:10.3390/medicina59010033

Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling

Fetched: January 25th, 2023, 5:00am GMT by Qiqi Lu

Biomolecules. 2023 Jan 4;13(1):104. doi: 10.3390/biom13010104.

ABSTRACT

BACKGROUND: The tumor immune microenvironment (TIME) of adrenocortical carcinoma (ACC) is heterogeneous. However, a classification of ACC based on the TIME remains unexplored.

METHODS: We hierarchically clustered ACC based on the enrichment levels of twenty-three immune signatures to identify its immune-specific subtypes. Furthermore, we comprehensively compared the clinical and molecular profiles between the subtypes.

RESULTS: We identified two immune-specific subtypes of ACC: Immunity-H and Immunity-L, which had high and low immune signature scores, respectively. We demonstrated that this subtyping method was stable and reproducible by analyzing five different ACC cohorts. Compared with Immunity-H, Immunity-L had lower levels of immune cell infiltration, worse overall and disease-free survival prognosis, and higher tumor stemness, genomic instability, proliferation potential, and intratumor heterogeneity. Furthermore, the ACC driver gene CTNNB1 was more frequently mutated in Immunity-L than in Immunity-H. Several proteins, such as mTOR, ERCC1, Akt, ACC1, Cyclin_E1, β-catenin, FASN, and GAPDH, were more highly expressed in Immunity-L than in Immunity-H. In contrast, p53, Syk, Lck, PREX1, and MAPK were more highly expressed in Immunity-H. Pathway and gene ontology analysis showed that the immune, stromal, and apoptosis pathways were highly enriched in Immunity-H, while the cell cycle, steroid biosynthesis, and DNA damage repair pathways were highly enriched in Immunity-L.

CONCLUSIONS: ACC can be classified into two stable immune-related subtypes, which have significantly different antitumor responses, molecular characteristics, and clinical outcomes. This subtyping may provide clinical implications for prognostic and immunotherapeutic stratification of ACC.

PMID:36671489 | PMC:PMC9855412 | DOI:10.3390/biom13010104

Morphological predictors of the efficacy of mitotane therapy in adrenocortical cancer

Fetched: January 24th, 2023, 5:00am GMT by A V Tkachuk

Probl Endokrinol (Mosk). 2023 Jan 8;68(6):76-88. doi: 10.14341/probl13172.

ABSTRACT

BACKGROUND: Adrenocortical cancer (ACC) is an orphan malignant tumor of the adrenal cortex with a predominantly poor prognosis and an aggressive clinical course. Nowadays, mitotane is a non-alternative drug in the treatment of ACC. The search for prognostic parameters that determine the sensitivity of ACC to ongoing treatment is currently an urgent task. Expression levels of the large subunit of ribonucleotide reductase M1 (RRM1), cytochrome P450 2W1 (CYP2W1), and sterol- O-acyltransferase-1 (SOAT1) are considered as potential predictors of response to mitotane therapy.

AIM: To assess the immunohistochemical expression of RRM1, CYP2W1 and SOAT1 in ACC as markers of clinical outcomes and response to the therapy with mitotane.

MATERIALS AND METHODS: The study included 62 patients older than 17 years of age with a diagnosis of ACC confirmed histologically and immunohistochemically. Mitotane therapy was initiated in 29 patients in the postoperative period, 33 patients were under dynamic observation without concomitant drug treatment. Antibodies to RRM1, CYP2W1, SOAT1 were used diluted in accordance with recommendations of firms-manufacturers for immunohistochemical detection.

RESULTS: In the group of patients with low and moderate RRM1, CYP2W1 and SOAT1 immunoreactivity in the tumor and no antitumor therapy, a better DFS was noted (p=0.037, p=0.020 and p=0.001, respectively) compared to the group of patients receiving mitotane therapy at this level of marker expression. With high immunoreactivity of the markers, no statistically significant differences in DFS were found.

CONCLUSION: Consistent with the findings in our study, low expression of RRM1, CYP2W1 and SOAT1 was associated with worse DFS with antitumor therapy. The results of the work indicate the need to assess the levels of immunoreactivity of these markers in patients with ACC before starting treatment with mitotane in order to predict the efficiency of therapy.

PMID:36689714 | DOI:10.14341/probl13172

Permalink for 'Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment'

Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment

Fetched: January 24th, 2023, 5:00am GMT by Keqiang Lu

Front Genet. 2023 Jan 4;13:996180. doi: 10.3389/fgene.2022.996180. eCollection 2022.

ABSTRACT

Background: The only curative option for patients with locally or locally advanced adrenocortical carcinoma is primary tumor curative sexual resection (ACC). However, overall survival remains low, with most deaths occurring within the first 2 years following surgery. The 5-year survival rate after surgery is less than 30%. As a result, more accurate prognosis-related predictive biomarkers must be investigated urgently to detect patients' disease status after surgery. Methods: Data from FerrDb were obtained to identify ferroptosis-related genes, and ACC gene expression profiles were collected from the GEO database to find differentially expressed ACC ferroptosis-related genes using differential expression analysis. The DEFGs were subjected to Gene Ontology gene enrichment analysis and KEGG signaling pathway enrichment analysis. PPI network building and predictive analysis were used to filter core genes. The expression of critical genes in ACC pathological stage and pan-cancer was then investigated. In recent years, immune-related factors, DNA repair genes, and methyltransferase genes have been employed in diagnosing and prognosis of different malignancies. Cancer cells are mutated due to DNA repair genes, and highly expressed DNA repair genes promote cancer. Dysregulation of methyltransferase genes and Immune-related factors, which are shown to be significantly expressed in numerous malignancies, also plays a crucial role in cancer. As a result, we investigated the relationship of AURKA with immunological checkpoints, DNA repair genes, and methyltransferases in pan-cancer. Result: The DEGs found in the GEO database were crossed with ferroptosis-related genes, yielding 42 differentially expressed ferroptosis-related genes. Six of these 42 genes, particularly AURKA, are linked to the prognosis of ACC. AURKA expression was significantly correlated with poor prognosis in patients with multiple cancers, and there was a significant positive correlation with Th2 cells. Furthermore, AURKA expression was positively associated with tumor immune infiltration in Lung adenocarcinoma (LUAD), Liver hepatocellular carcinoma (LIHC), Sarcoma (SARC), Esophageal carcinoma (ESCA), and Stomach adenocarcinoma (STAD), but negatively correlated with the immune score, matrix score, and calculated score in these tumors. Further investigation into the relationship between AURKA expression and immune examination gene expression revealed that AURKA could control the tumor-resistant pattern in most tumors by regulating the expression level of specific immune examination genes. Conclusion: AURKA may be an independent prognostic marker for predicting ACC patient prognosis. AURKA may play an essential role in the tumor microenvironment and tumor immunity, according to a pan-cancer analysis, and it has the potential to be a predictive biomarker for multiple cancers.

PMID:36685952 | PMC:PMC9845395 | DOI:10.3389/fgene.2022.996180

SDHB exon 1 deletion: A recurrent germline mutation in Colombian patients with pheochromocytomas and paragangliomas

Fetched: January 24th, 2023, 5:00am GMT by María Carolina Manotas

Front Genet. 2023 Jan 4;13:999329. doi: 10.3389/fgene.2022.999329. eCollection 2022.

ABSTRACT

Pheochromocytomas (PCCs) and paragangliomas (PGLs) (known as PPGL in combination) are rare neuroendocrine tumors of the adrenal medulla and extra-adrenal ganglia. About 40% of the patients with PPGL have a hereditary predisposition. Here we present a case-series of 19 unrelated Colombian patients with a clinical diagnosis of PPGL tumors that underwent germline genetic testing as part of the Hereditary Cancer Program developed at the Instituto Nacional de Cancerología, Colombia (INC-C), the largest reference cancer center in the country. Ten of 19 patients (52.63%) were identified as carriers of a pathogenic/likely pathogenic (P/LP) germline variant in a known susceptibility gene. The majority of the P/LP variants were in the SDHB gene (9/10): one corresponded to a nonsense variant c.268C>T (p.Arg90*) and eight cases were found to be carriers of a recurrent CNV consisting of a large deletion of one copy of exon 1, explaining 42% (8/19) of all the affected cases. Only one additional case was found to be a carrier of a missense mutation in the VHL gene: c.355T>C (p.Phe119Leu). Our study highlights the major role of SDHB in Colombian patients with a clinical diagnosis of PGL/PCC tumors and supports the recommendation of including the analysis of large deletions/duplications of the SDHB gene as part of the genetic counselling to improve the detection rate of hereditary cases and their clinical care.

PMID:36685941 | PMC:PMC9845289 | DOI:10.3389/fgene.2022.999329

The prognosis difference between elderly and younger patients with adrenocortical carcinoma

Fetched: January 24th, 2023, 5:00am GMT by Shengyin He

Front Genet. 2023 Jan 4;13:1029155. doi: 10.3389/fgene.2022.1029155. eCollection 2022.

ABSTRACT

Background and aim: Adrenocortical carcinoma (ACC) is uncommon in the elderly. This study aimed to compare the surgical prognosis and survival between senior and younger patients. We also explored the factors that were independently related to the survival of elderly patients. Methods: We identified ACC patients between 2010 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database and applied Kaplan-Meier curves to evaluate the overall survival (OS) and cancer-specific survival (CSS) with log-rank tests. We also used Cox regression analysis to estimate the OS and CSS. The Fine and Gray model with the Gray test was used to measure the cumulative incidence function (CIF) of CSS and other mortality causes of patients in a competing-risks setting. Results: Of 876 patients, 44.06% were elderly. A lower proportion of elderly patients underwent surgery, regional lymph node surgery, and chemotherapy than young patients. Elderly patients also had inferior OS and CSS than younger patients. The 1- and 5-year OS of elderly patients who underwent surgery were 68% [95% confidence interval (CI): 62%-74%] and 30% (95% CI: 24%-38%), and the 1- and 5-year CSS were 73% (95% CI: 67%-80%) and 40% (95% CI: 32%-47%). The factors independently related to worsened survival included age ≥60 [Hazard Ratio (HR): 1.47 (1.24-1.75)], metastatic disease [HR: 1.90 (1.49-2.51)], higher grade [HR: 1.94 (1.08-3.46)] and Network for the Study of Adrenal Tumors (ENSAT) stage [HR: 1.99 (1.48-2.66)]. Conclusion: Younger ACC patients had better survival than the elderly. Factors independently related to worsened survival in elderly patients included age ≥60, metastatic disease, higher grade, and European ENSAT stage.

PMID:36685908 | PMC:PMC9845245 | DOI:10.3389/fgene.2022.1029155

Postoperative transverse colon necrosis due to mesenteric injury during laparoscopic surgery for endometrial carcinoma

Fetched: January 24th, 2023, 5:00am GMT by Kentaro Kaji

J Surg Case Rep. 2023 Jan 17;2023(1):rjac636. doi: 10.1093/jscr/rjac636. eCollection 2023 Jan.

ABSTRACT

Hemorrhage and organ injury have been frequently reported as complications associated with trocar puncture in laparoscopic surgery. This report presents a case of delayed intestinal necrosis due to mesenteric injury. A 76-year-old woman who had a history of distal gastrectomy and adrenal insufficiency was diagnosed with stage IA endometrial cancer. We performed laparoscopic total hysterectomy and bilateral salpingo-oophorectomy. The upper abdominal wall and mesentery were adhered, and bleeding from the mesentery was noted during the first trocar puncture of the umbilical region, resulting in ligation and hemostasis. Abdominal pain and fever developed on the third postoperative day, and contrast-enhanced computed tomography demonstrated transverse colon perforation. Emergency laparotomy showed necrosis in the proximal transverse colon and a defect in the marginal artery. Mesenteric injury can lead to delayed intestinal necrosis without intraoperative macroscopic findings. In laparoscopic cases where adhesion is expected, trocar placement should be carefully considered.

PMID:36685120 | PMC:PMC9844956 | DOI:10.1093/jscr/rjac636

Accentuated 123ImIBG uptake by the left lobe of the liver - A clue to nowhere

Fetched: January 24th, 2023, 5:00am GMT by Humayun Bashir

J Pak Med Assoc. 2022 Oct;72(10):2124-2125. doi: 10.47391/JPMA.22-105.

ABSTRACT

A 57-year-old male was imaged with 123I mIBG for left sided suprarenal mass. The planar and SPECT-CT acquisitions revealed features consistent with a left sided pheochromocytoma. There was physiological and high uptake in the hypertrophied left lobe of the liver which was normal at both MRI and non-contrast CT. Asymmetrical increased 123I mIBG uptake in the left lobe of the liver as compared to the right lobe is a known physiological finding with no obvious cause or significance.

PMID:36661015 | DOI:10.47391/JPMA.22-105

Adrenocortical carcinoma metastasis. A long story

Fetched: January 24th, 2023, 5:00am GMT by Federico Mascioli

Ann Ital Chir. 2022 Dec 27;11:S2239253X22038555.

ABSTRACT

INTRODUCTION: Adrenocortical Carcinoma (ACC) is an uncommon adrenal tumor with a predilection for the female population.

CASE REPORT: A 55-year-old woman was referred to our attention to undergo laparoscopic cholecystectomy for symptomatic gallstone disease. She underwent a left adrenalectomy for ACC 5 years before; the follow-up was negative for relapse. During the preoperative study an Ultrasound Scanner study demonstrated a liver lesion in S6 - S7, confirmed by a Magnetic Resonance. A PET identified also a lesion on L1 vertebra. The hepatic US-guided biopsy resulted positive for ACC metastasis. After a muldisciplinary evaluation, the patients underwent a local approach to treat both hepatic and vertebral lesions. Laparoscopic cholecystectomy was performed in order to prevent biliary and pancreatic complications. The minimally invasive technique was adopted in order to reduce surgical trauma in oncological patients, even the previous abdominal surgery and percutaneous hepatic treatment. The patient is alive, with no recurrence after 12 months from local treatments.

CONCLUSION: This is a very unusual case of double ACC metastases, discovered after the end of standard follow-up and locally treated. The patient is recurrence-free 12 months after these procedures. Minimally invasive approach to treat symptomatic cholecystectomy was used in order to avoid pancreato-biliary complications. This study emphasized the necessity to realize tailored protocols for the follow-up of rare neoplasia, as ACC.

KEY WORDS: Adrenocortical carcinoma, Cholecystectomy, Liver metastasis, Thermoablation.

PMID:36655977

Two-institution results of Stereotactic Body Radiation Therapy (SBRT) for treating adrenal gland metastases from liver cancer

Fetched: January 22nd, 2023, 5:00am GMT by Bichun Xu

BMC Cancer. 2023 Jan 21;23(1):73. doi: 10.1186/s12885-023-10519-9.

ABSTRACT

OBJECTIVE: Stereotactic Body Radiation Therapy (SBRT) has been found beneficial for adrenal gland metastases (AGMs) with a high local control rate and low toxicity. The role of SBRT for AGMs in patients with liver cancer has not been well-discussed before. We, therefore, report our two-institution experience to further elaborate on the feasibility and effectiveness of SBRT in the treatment of AGMs from liver cancer.

METHODS: A total of 23 liver cancer patients (19 males, 4 females) with 24 AGMs treated by SBRT from July 2006 to April 2021 were retrospectively included in this study. Toxicity was assessed based on clinical adverse events using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The effectiveness was assessed based on local control (LC), progression-free survival (PFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Univariate analyses were compared by log-rank test. The relevant covariates were evaluated using Cox proportional hazards models.

RESULTS: The median dose was 40 Gy in 5 fractions, with the corresponding median biological effective dose (BED10, α/β = 10 Gy) of 72 Gy. The median overall follow-up time was 15.4 months (range: 4.2-70.6 months). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 25.0%, 20.8%, 33.3%, and 20.8%, respectively. All 6 patients with AGMs accompanying symptoms had varying degrees of alleviation after SBRT. The 0.5-, 1-year and 2-year LC rates were 87.5%, 77.8%, and 77.8%, respectively. The 0.5-, 1-year and 2-year OS rates were 95.5%, 66.8%, and 41.1%, respectively. The treatments were all tolerated with only one patient reporting a grade-3 hepatic injury. The univariate analysis concluded that only gross tumor volume (GTV) < 34.5 ml (p = 0.039) was associated with a favorable LC rate. After multivariate analysis, favorable predictors correlated with OS were GTV < 34.5 ml (p = 0.043), systemic therapy (p = 0.017), and without additional organ metastasis after SBRT (p = 0.009).

CONCLUSION: Our results suggest that SBRT is a safe and effective technique to treat AGM from liver cancer, especially for small GTV (< 34.5ml). Moreover, the small metastatic lesion volume, fewer metastatic lesions, and intervention of systemic therapy are more likely to improve OS.

PMID:36681809 | PMC:PMC9862519 | DOI:10.1186/s12885-023-10519-9

Predictive Biomarkers for Immune-Related Endocrinopathies following Immune Checkpoint Inhibitors Treatment

Fetched: January 22nd, 2023, 5:00am GMT by Almog Shalit

Cancers (Basel). 2023 Jan 6;15(2):375. doi: 10.3390/cancers15020375.

ABSTRACT

In recent years, in the context of the increase in the life expectancy of cancer patients, special attention has been given to immunotherapy and, indeed, to immune checkpoint inhibitors. The use of immune checkpoint inhibitors has increased rapidly, and approximately 40% of cancer patients are eligible for this treatment. Although their impact is valuable on cancer treatment, immune checkpoint inhibitors come with side effects, known as immune-related adverse effects. These can affect many systems, including cutaneous, musculoskeletal, cardiovascular, gastrointestinal, endocrine, neural, and pulmonary systems. In this review, we focus on immune-related endocrinopathies that affect around 10% of all treated patients. Endocrine dysfunctions can manifest as hypophysitis, thyroid dysfunction, hypoparathyroidism, insulin-deficient diabetes mellitus, and primary adrenal insufficiency. Currently, there are multiple ongoing clinical trials that aim to identify possible predictive biomarkers for immune-related adverse effects. The design of those clinical trials relies on collecting a variety of biological specimens (tissue biopsy, blood, plasma, saliva, and stool) at baseline and regular intervals during treatment. In this review, we present the predictive biomarkers (such as antibodies, hormones, cytokines, human leukocyte antigens, and eosinophils) that could potentially be utilized in clinical practice in order to predict adverse effects and manage them appropriately.

PMID:36672324 | PMC:PMC9856539 | DOI:10.3390/cancers15020375

The Role of Glucocorticoids in Breast Cancer Therapy

Fetched: January 21st, 2023, 5:00am GMT by Irma B Mitre-Aguilar

Curr Oncol. 2022 Dec 25;30(1):298-314. doi: 10.3390/curroncol30010024.

ABSTRACT

Glucocorticoids (GCs) are anti-inflammatory and immunosuppressive steroid molecules secreted by the adrenal gland and regulated by the hypothalamic-pituitary-adrenal (HPA) axis. GCs present a circadian release pattern under normal conditions; they increase their release under stress conditions. Their mechanism of action can be via the receptor-independent or receptor-dependent pathway. The receptor-dependent pathway translocates to the nucleus, where the ligand-receptor complex binds to specific sequences in the DNA to modulate the transcription of specific genes. The glucocorticoid receptor (GR) and its endogenous ligand cortisol (CORT) in humans, and corticosterone in rodents or its exogenous ligand, dexamethasone (DEX), have been extensively studied in breast cancer. Its clinical utility in oncology has mainly focused on using DEX as an antiemetic to prevent chemotherapy-induced nausea and vomiting. In this review, we compile the results reported in the literature in recent years, highlighting current trends and unresolved controversies in this field. Specifically, in breast cancer, GR is considered a marker of poor prognosis, and a therapeutic target for the triple-negative breast cancer (TNBC) subtype, and efforts are being made to develop better GR antagonists with fewer side effects. It is necessary to know the type of breast cancer to differentiate the treatment for estrogen receptor (ER)-positive, ER-negative, and TNBC, to implement therapies that include the use of GCs.

PMID:36661673 | PMC:PMC9858160 | DOI:10.3390/curroncol30010024

Favourable prognosis in metastatic adrenal carcinoma: An unexpected outcome

Fetched: January 21st, 2023, 5:00am GMT by Imran Hassan

J Pak Med Assoc. 2022 Oct;72(10):2101-2104. doi: 10.47391/JPMA.3494.

ABSTRACT

The case of a 45-year-old male patient diagnosed with European Network for the Study of Adrenal Tumours (ENSAT) criteria, stage IV adrenocortical carcinoma (ACC) with unexpectedly prolonged survival is being reported. The patient underwent resection of stage IV ACC and despite suboptimal adherence to postoperative mitotane and chemotherapy, had a prolonged survival spanning almost seven years. The possible reasons for such an outcome are discussed. ACC is a rare tumour with stage 4 disease known to be associated with a particularly grim prognosis. A low grade on histology (mitotic index 11-12 per 50 HPF) was likely responsible for the prolonged survival of our patient. Low grade disease may predict extended survival in stage IV ACC.

PMID:36661007 | DOI:10.47391/JPMA.3494

Incidental, Solitary, and Unilateral Adrenal Metastasis as the Initial Manifestation of Lung Adenocarcinoma

Fetched: January 21st, 2023, 5:00am GMT by Hadeel K Al Fares

Cureus. 2022 Dec 17;14(12):e32628. doi: 10.7759/cureus.32628. eCollection 2022 Dec.

ABSTRACT

An adrenal incidentaloma is an adrenal mass ≥ 1 cm in size discovered on imaging performed for indications other than suspected adrenal disease. It has variable etiologies, which can be benign or malignant, including primary or metastatic disease. We present a rare case of metastatic lung adenocarcinoma with isolated unilateral adrenal metastases, presenting as an adrenal incidentaloma in an asymptomatic patient with no known history of malignancy. A 76-year-old man with a past medical history of chronic obstructive pulmonary disease (COPD) and heavy tobacco use was admitted for the evaluation and treatment of pneumonia. He was found to have an incidental 4.6 cm unilateral adrenal mass on his CT chest. He underwent a workup for the mass, including further imaging studies that were indeterminate and a hormonal workup that concluded that the mass was nonfunctional. Due to the patient's comorbidities, it was determined that he was not a surgical candidate. A multidisciplinary team recommended a biopsy, which revealed metastatic lung adenocarcinoma. The primary lung cancer was located using positron emission tomography with 2-deoxy-2-(fluorine-18) fluoro-D-glucose combined with computed tomography (F-FDG-PET/CT). The patient was evaluated by an oncology service and started on chemotherapy. In this case report, we discuss the approach for evaluating adrenal incidentalomas as well as the role the biopsy has in this process based on a literature review. In addition, we draw a comparison between our case and similar cases in the literature while highlighting the differences that make this case unique.

PMID:36660511 | PMC:PMC9845493 | DOI:10.7759/cureus.32628

Intraluminal Small Bowel Metastasis From Primary Lung Cancer

Fetched: January 21st, 2023, 5:00am GMT by Nina D Kosciuszek

World J Oncol. 2022 Dec;13(6):409-416. doi: 10.14740/wjon1532. Epub 2022 Dec 24.

ABSTRACT

Lung cancer is the leading cause of cancer-related death worldwide, with frequent metastases to the brain, liver, adrenal glands, and bone. The incidence of intraluminal small bowel metastases of the lung is extremely rare and poorly documented within the literature. Few case studies have been published since the late 1980s and early 1990s. However, little is known about this rare form of metastasis. Small bowel metastatic disease has atypical symptoms that mimic a variety of other diseases; as a result, signs and symptoms may be overlooked until the disease has progressed to a late stage. Signs of small bowel obstruction, symptomatic anemia, abdominal pain, and peritonitis are commonly reported signs and symptoms. Various modalities can be utilized for the workup of suspected small bowel metastasis, including positron emission tomography, computed tomography, and various forms of endoscopy. The prognosis for lung cancer patients with intestinal metastases is poor, with many only surviving months to a few years after diagnosis. Therefore, it is critical to consider small bowel masses as a differential diagnosis in a patient with primary lung cancer who demonstrates clinical signs consistent with symptomatic anemia secondary to gastrointestinal (GI) bleeding, peritonitis, or small bowel obstruction. We report an unusual case of intraluminal and fungating small bowel masses in a patient who had previously undergone lung resections and chemo-immunotherapy. She was diagnosed with non-small undifferentiated carcinoma with tumor necrosis over 12 years before disease recurrence in the bilateral lungs, right adrenal gland, bone, and small bowel. The discovery of the small bowel metastases occurred while undergoing treatment for advanced-stage disease. At this time, she completed chemo-immunotherapy and remained on maintenance immunotherapy. The patient also underwent a partial right adrenalectomy and radiotherapy to the right adrenal gland. Given that she was experiencing symptomatic anemia and further workup indicated that the GI masses were causing her anemia, she underwent palliative small bowel resection of the masses. The pathology results demonstrated that the masses originated from her primary lung cancer, confirming metastatic disease to the small bowel.

PMID:36660214 | PMC:PMC9822679 | DOI:10.14740/wjon1532

TOP2A Expression in Pheochromocytoma and Abdominal Paraganglioma: a Marker of Poor Clinical Outcome?

Fetched: January 20th, 2023, 5:00am GMT by Karolina Solhusløkk Höse

Endocr Pathol. 2023 Jan 19. doi: 10.1007/s12022-022-09746-w. Online ahead of print.

ABSTRACT

Pheochromocytoma and abdominal paraganglioma (PPGL) are rare neuroendocrine tumors originating from chromaffin cells. Even though only 10-15% of the tumors metastasize, all PPGLs are considered potentially malignant. Topoisomerase 2A (TOP2A) is a protein involved in cell proliferation and has been found to be over-expressed in metastatic PPGL. To provide support whether TOP2A could serve as a prognostic marker, 88 PPGLs (of which 8 metastatic/relapsing) and 10 normal adrenal gland samples were assessed for TOP2A mRNA expression using quantitative real-time PCR (qRT-PCR) and TOP2A immunohistochemistry. Comparisons to clinical parameters connected to metastatic behavior were made, and The Cancer Genome Atlas was used for validation of the results. A significant association between high TOP2A mRNA expression in primary PPGL and subsequent metastatic events (p = 0.008) was found, as well as to specific histological features and clinical parameters connected to metastatic behavior and mutations in SDHB. TOP2A immunoreactivity was calculated as an index of positive nuclei divided by the total amount of nuclei, and this index associated with TOP2A mRNA levels (p = 0.023) as well as the Ki-67 labeling index (p = 0.001). To conclude, TOP2A is a potential prognostic marker as it is frequently elevated in PPGL displaying subsequent metastatic disease, and future studies in larger cohorts are warranted to determine if a TOP2A index as assessed by immunohistochemistry could be a marker of poor outcome. Additionally, elevated levels of TOP2A could indicate a potential actionable event, and future studies with topoisomerase inhibitors would be of interest.

PMID:36656469 | DOI:10.1007/s12022-022-09746-w

Permalink for 'Laparoscopic left nephro-adrenalectomy for renal vein leiomyosarcoma using (ICG) fluorescence and 3D-CT reconstruction: A case report'

Laparoscopic left nephro-adrenalectomy for renal vein leiomyosarcoma using (ICG) fluorescence and 3D-CT reconstruction: A case report

Fetched: January 20th, 2023, 5:00am GMT by Giuseppe Palomba

Ann Ital Chir. 2022 Dec 6;11:S2239253X22038786.

ABSTRACT

INTRODUCTION: Leiomyosarcoma is a rare malignant mesenchymal cancer of smooth muscle and about 50-60 % of cases are from inferior vena cava. Recently, preoperative reconstruction of three-dimensional (3D) images from computed tomography (CT) and intraoperative indocyanine green (ICG) are being developed. We present a case of laparoscopic left nephro-adrenalectomy using ICG fluorescence associated with 3D-CT reconstruction:n.

CASE REPORT: A 72-years-old female patient presented pain in left side from two months. Contrast computed tomography and magnetic resonance imaging showed a solid mass between left-adrenal gland and upper renal pole. After multidisciplinary evaluation, a laparoscopic left nephno-adrenalectomy was performed.

DISCUSSION: The surgery was without intra and postoperative complications. The patient was discharged in the 3rd postoperative day without complications and with oral steroid replacement therapy. Histology confirmed leiomysarcoma of renal vein.

CONCLUSION: In this case, use intraoperative ICG fluorescence associated with preoperative 3D-CT was a valuable support for surgery.

KEY WORDS: Endocrine surgery, Indocyanine green fluorescence, Laparoscopic Nephro-Adrenalectomy, Leiomyosarcoma, Three-dimensional computed tomography reconstruction, Video surgery.

PMID:36655980

Human lung carcinomas synthesize immunoregulatory glucocorticoids

Fetched: January 20th, 2023, 5:00am GMT by Verena M Merk

Genes Immun. 2023 Jan 18. doi: 10.1038/s41435-023-00194-y. Online ahead of print.

ABSTRACT

The need for new options in lung cancer treatment inevitably leads back to basic research. The tumor itself and the tumor environment especially the interaction with the immune system need to be better understood to develop targeted therapies. In the context of lung cancer glucocorticoids (GC) are mainly known as a combination drug to attenuate side-effects of chemotherapies. However, endogenous extra-adrenal GC have been shown to substantially regulate local immune responses within various tissues, including the lung. In this study we investigated whether primary lung tumors have maintained the capacity to synthesize GC and may thereby regulate anti-tumor immune responses. We show that several non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) cell lines express key steroidogenic enzymes and synthesize bioactive GC under steady state conditions. We also show that tumor-derived GC can inhibit splenic T cell activation, thus demonstrating their immunoregulatory potential. Moreover, steroidogenic enzymes were detected by quantitative RT-PCR and immunohistochemistry in tissue sections of different human lung tumors, further strengthening the idea that human lung carcinomas regulate their microenvironment by releasing immunoregulatory GC, which potentially contributes to immune evasion and treatment resistance.

PMID:36653475 | DOI:10.1038/s41435-023-00194-y

Intracardiac paraganglioma with a cough as the first symptom

Fetched: January 20th, 2023, 5:00am GMT by Cao Jingyi

J Cardiothorac Surg. 2023 Jan 17;18(1):30. doi: 10.1186/s13019-022-02087-z.

ABSTRACT

BACKGROUND: Cardiac paragangliomas (PGLs) are clinically rare, with hypertension and metabolic changes as the main symptoms. The tumor is highly related to gene mutation, and surgery is presently the effective treatment. Medical history and clinical manifestations of the patient, routine laboratory examinations and imaging examinations, and pathological examination can help the final diagnosis.

CASE PRESENTATION: The present study presents a 31-year-old male patient with a left atrial mass. The initial symptom was cough. Cardiac enlargement was found during the chest X-ray. The follow-up imaging examination revealed a left atrial occupying lesion, and the possibility of malignant occupying lesions was not ruled out. The patient underwent surgical resection of the mass. The final pathological result revealed paraganglioma. The thoracic computed tomography review two months after the operation revealed that the original occupying lesion disappeared, and no new lesion was found.

CONCLUSIONS: Pheochromocytomas and paragangliomas (PPGLs) are a kind of neuroendocrine tumors. PPGLs can cause secondary hypertension, and lead to a series of clinical syndromes, including myocardial injury, metabolic changes, and so on. The occurrence of PPGIs is related to gene mutation. Biochemical detection, imaging examination, and genetic testing can help diagnose. The tumor should be surgically removed as soon as possible after the diagnosis. As a functional tumor, PPGLs should be fully prepared before surgery to avoid anesthesia and huge fluctuations in blood pressure during and after surgery, or the occurrence of fatal hypertensive crisis and intractable hypotension after tumor resection. Adequate preoperative preparation directly affects the prognosis of patients after surgery. Therefore, multidisciplinary cooperation before, during, and after the operation is extremely important.

PMID:36650563 | PMC:PMC9843092 | DOI:10.1186/s13019-022-02087-z

Evidence for a Founder Effect of SDHB Exon 1 Deletion in Brazilian Patients with Paraganglioma

Fetched: January 19th, 2023, 5:00am GMT by Gustavo F C Fagundes

J Clin Endocrinol Metab. 2023 Jan 18:dgad028. doi: 10.1210/clinem/dgad028. Online ahead of print.

ABSTRACT

BACKGROUND: Limited information is available concerning the genetic spectrum of pheochromocytomas and paragangliomas (PPGL) patients in South America. Germline SDHB large deletions are very rare worldwide, but most of the individuals harboring the SDHB exon 1 deletion were originated from the Iberian Peninsula. Our aim was to investigate the spectrum of SDHB genetic defects in a large cohort of Brazilian patients with PPGLs.

METHODS: The genetic investigation of 155 index PPGL patients was performed by Sanger DNA sequencing, multiplex ligation-dependent probe amplification, and/or target next-generation sequencing panel. Common ancestrality was investigated by microsatellite genotyping with haplotype reconstruction, and analysis of deletion breakpoint.

RESULTS: Among 155 index patients, heterozygous germline SDHB pathogenic or likely pathogenic variants (PV/LPVs) were identified in 22 cases (14.2%). Interestingly, the heterozygous SDHB exon 1 complete deletion was the most frequent genetic defect in SDHB, being identified in 8 out of 22 (36%) of the patients. Haplotype analysis of 5 SDHB flanking microsatellite markers demonstrated a significant difference in haplotype frequencies in a case-control permutation test (p = 0.03). More precisely, 3 closer/informative microsatellites were shared by 6 out of 8 apparently unrelated cases (75%) (SDHB-GATA29A05-D1S2826-D1S2644 | SDHB-186-130-213), which was observed in only 1 chromosome (1/42) without SDHB exon 1 deletion (X2= 29.43; p < 0.001). Moreover, all cases with SDHB exon 1 deletion had the same gene breakpoint pattern of a 15,678 bp deletion previously described in the Iberian Peninsula, indicating a common origin.

CONCLUSION: The germline heterozygous SDHB exon 1 deletion was the most frequent genetic defect in the Brazilian PPGL cohort. Our findings demonstrated a founder effect for the SDHB exon 1 deletion in Brazilian patients with paragangliomas.

PMID:36652439 | DOI:10.1210/clinem/dgad028

Adrenal tumors: diagnostics, perioperative management and surgical treatment

Fetched: January 19th, 2023, 5:00am GMT by Simon Engelmann

Urologie. 2023 Jan 18. doi: 10.1007/s00120-023-02024-5. Online ahead of print.

ABSTRACT

Space-occupying lesions of the adrenal glands are one of the most frequent tumors; however, only a fraction of approximately 20% need further diagnostics and treatment. The diagnostic standard is native computed tomography (CT). For larger tumors and those that cannot be clearly classified as benign, the supplementary radiological modalities magnetic resonance imaging (MRI), contrast CT and ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) should be used. Adrenal gland neoplasms can be hormone-active or hormone-inactive. The most important hormone-active adrenal gland neoplasms are those with autonomous cortisol secretion and autonomous aldosterone secretion as well as pheochromocytomas. Several laboratory tests are available each for the respective hormone activity. The indications for surgery are dependent on the dignity, size and hormone activity. Minimally invasive surgical techniques have become more important due to advantages such as lower blood loss; nevertheless, open surgery is still indispensable for large suspected tumors. Care must be taken preoperatively and postoperatively, particularly in cases of hormone-active tumors.

PMID:36651952 | DOI:10.1007/s00120-023-02024-5

Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma

Fetched: January 19th, 2023, 5:00am GMT by Jack L Williams

Eur J Endocrinol. 2023 Jan 10;188(1):lvac007. doi: 10.1093/ejendo/lvac007.

ABSTRACT

OBJECTIVE: Adrenocortical carcinomas (ACCs) are invasive tumours arising in the adrenal cortex, and steroidogenic tumours are associated with worse prognostic outcomes. Loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1) cause primary adrenal insufficiency and as a key degradative enzyme in the sphingolipid pathway, SGPL1 also influences the balance of pro-proliferative and pro-apoptotic sphingolipids. We, therefore, hypothesized increased SGPL1 may be linked to increased disease severity in ACC.

DESIGN: Analyse SGPL1 expression impact on patient survival and adrenal cancer cell phenotype. We analysed two ACC cohorts with survival and corresponding transcriptomic data, focusing on SGPL1 and sphingolipid pathway genes. In vitro, we generated SGPL1-knockout and overexpressing H295R adrenocortical cells to investigate the role of SGPL1 in cell signalling in ACCs.

RESULTS: We found increased expression of several sphingolipid pathway receptors and enzymes, most notably SGPL1 correlated with reduced patient survival in both cohorts. Overexpression of SGPL1 in the H295R cell line increased proliferation and migration while reducing apoptosis, while SGPL1 knockout had the opposite effect. RNA-seq revealed a global increase in the expression of genes in the electron transport chain in overexpressing cells, correlating with increased aerobic respiration and glycolysis. Furthermore, the opposite phenotype was seen in cells lacking SGPL1. We subsequently found the increased proliferation is linked to metabolic substrate availability and increased capacity to use different fuel sources, but particularly glucose, in overexpressing cells.

CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.

PMID:36651165 | DOI:10.1093/ejendo/lvac007

Volume-outcome relationship in adrenal surgery from 2009-2017 in Germany-a retrospective study

Fetched: January 19th, 2023, 5:00am GMT by Konstantin L Uttinger

Eur J Endocrinol. 2023 Jan 10;188(1):lvac013. doi: 10.1093/ejendo/lvac013.

ABSTRACT

OBJECTIVE: Adrenal resections are rare procedures of a heterogeneous nature. While recent European guidelines advocate a minimum annual caseload for adrenalectomies (6 per surgeon), evidence for a volume-outcome relationship for this surgery remains limited.

DESIGN: A retrospective analysis of all adrenal resections in Germany between 2009 and 2017 using hospital billing data was performed. Hospitals were grouped into three tertiles of approximately equal patient volume.

METHODS: Descriptive, univariate, and multivariate analyses were applied to identify a possible volume-outcome relationship (complications, complication management, and mortality).

RESULTS: Around 17 040 primary adrenal resections were included. Benign adrenal tumors (n = 8,213, 48.2%) and adrenal metastases of extra-adrenal malignancies (n = 3582, 21.0%) were the most common diagnoses. Six hundred and thirty-two low-volume hospitals performed an equal number of resections as 23 high-volume hospitals (median surgeries/hospital/year 3 versus 31, P < .001). Complications were less frequent in high-volume hospitals (23.1% in low-volume hospitals versus 17.3% in high-volume hospitals, P < .001). The most common complication was bleeding in 2027 cases (11.9%) with a mortality of 4.6% (94 patients). Overall in-house mortality was 0.7% (n = 126). Age, malignancy, an accompanying resection, complications, and open surgery were associated with in-house mortality. In univariate analysis, surgery in high-volume hospitals was associated with lower mortality (OR: 0.47, P < .001). In a multivariate model, the tendency remained equal (OR: 0.59, P = .104). Regarding failure to rescue (death in case of complications), there was a trend toward lower mortality in high-volume hospitals.

CONCLUSIONS: The annual caseload of adrenal resections varies considerably among German hospitals. Our findings suggest that surgery in high-volume centers is advantageous for patient outcomes although fatal complications are rare.

PMID:36651160 | DOI:10.1093/ejendo/lvac013

Transfer of Injected Triamcinolone into Human Milk of a Lactating Patient Suffering from Idiopathic Granulomatous Mastitis

Fetched: January 18th, 2023, 5:00am GMT by Casey Rosen-Carole

Breastfeed Med. 2023 Jan;18(1):74-77. doi: 10.1089/bfm.2022.0220.

ABSTRACT

Background: Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory condition of the mammary gland that presents as a painful mass, and it must be distinguished from both infectious mastitis and breast cancer. When diagnosed during lactation, it can result in significant distress and early weaning. Injection of triamcinolone has been used as a successful treatment method, but safety in breastfed infants has not been established. Methods: We present a case of a lactating patient who received a direct injection of triamcinolone (dosage 40 mg) in her breast to treat IGM after failure of oral corticosteroids. Breastmilk samples were expressed by the patient 0, 1, 4, and 24 hours after the procedure, and then daily for 1 week. All the samples were analyzed using liquid chromatography mass spectrometry. The patient was supported by a breastfeeding and lactation medicine clinic. Results: After injection of triamcinolone into the granulomatous mass, breast milk samples were collected and analyzed. No samples were found to contain triamcinolone. A temporary but significant decrease in milk production was noted after injection, though only a slight decrease had been noted with 6 weeks of systemic corticosteroids. With support, the patient rebuilt milk production and continued to breastfeed from both breasts. Conclusion: Triamcinolone was not found in any milk samples (≥0.78 ng/mL) following therapeutic injection of the affected breast. The patient was able to continue breastfeeding from the affected breast with intermittent symptoms.

PMID:36638194 | DOI:10.1089/bfm.2022.0220

New advances in endocrine hypertension: from genes to biomarkers

Fetched: January 17th, 2023, 5:00am GMT by Fabio L Fernandes-Rosa

Kidney Int. 2023 Jan 13:S0085-2538(23)00009-1. doi: 10.1016/j.kint.2022.12.021. Online ahead of print.

ABSTRACT

Hypertension (HT) is a major cardiovascular risk factor that affects 10% to 40% of the general population in an age-dependent manner. Detection of secondary forms of HT is particularly important because it allows the targeted management of the underlying disease. Among hypertensive patients, the prevalence of endocrine HT reaches up to 10%. Adrenal diseases are the most frequent cause of endocrine HT and are associated with excess production of mineralocorticoids (mainly primary aldosteronism), glucocorticoids (Cushing syndrome), and catecholamines (pheochromocytoma). In addition, a few rare diseases directly affecting the action of mineralocorticoids and glucocorticoids in the kidney also lead to endocrine HT. Over the past years, genomic and genetic studies have allowed improving our knowledge on the molecular mechanisms of endocrine HT. Those discoveries have opened new opportunities to transfer knowledge to clinical practice for better diagnosis and specific treatment of affected subjects. In this review, we describe the physiology of adrenal hormone biosynthesis and action, the clinical and biochemical characteristics of different forms of endocrine HT, and their underlying genetic defects. We discuss the impact of these discoveries on diagnosis and management of patients, as well as new perspectives related to the use of new biomarkers for improved patient care.

PMID:36646167 | DOI:10.1016/j.kint.2022.12.021

Composite pheochromocytoma of the adrenal gland-a review of published cases

Fetched: January 17th, 2023, 5:00am GMT by João Costa

Virchows Arch. 2023 Jan 16. doi: 10.1007/s00428-023-03492-y. Online ahead of print.

ABSTRACT

Composite pheochromocytoma (CP) is a rare adrenal tumor, composed of ordinary pheochromocytoma and neuroblastic components. There is a paucity of information in the literature regarding this entity. We report the case of a 56-year-old woman with a CP of the left adrenal gland with a ganglioneuroma component. A review of the published literature found 110 cases of CP. The median age was 51.5 (5.86) years, and 59/110 (53.6%) were female. Association with genetic predisposition syndromes was found in 22/110 (20%), the most common of which was neurofibromatosis type 1, in 15/110 (13.6%). The most common histologic type of the neuroblastic component was ganglioneuroma in 83/110 (75.5%). Twenty-seven cases reported SDHB immunohistochemistry results; none of which was positive. Nine patients (8.2%) presented/developed metastatic disease, and 9 patients (8.2%) died from disease. To our knowledge, this is the largest review describing clinical, histopathological, molecular, and prognostic features of CP.

PMID:36645463 | DOI:10.1007/s00428-023-03492-y

Radical antegrade modular pancreatosplenectomy (RAMPS): does adrenalectomy alter outcomes?

Fetched: January 15th, 2023, 5:00am GMT by Catherine H Davis

HPB (Oxford). 2022 Dec 17:S1365-182X(22)01676-8. doi: 10.1016/j.hpb.2022.12.001. Online ahead of print.

ABSTRACT

BACKGROUND: Radical antegrade modular pancreatosplenectomy (RAMPS) has oncologic superiority compared to a standard distal pancreatectomy (DP). For tumors invading into the adrenal gland, a posterior RAMPS takes the left adrenal gland en bloc with the pancreas specimen. The aim of this analysis is to determine whether addition of adrenalectomy alters the outcomes of DP.

METHODS: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) Procedure-Targeted Pancreatectomy database was accessed from 2014 to 2019. Patients with pancreatic ductal adenocarcinoma (PDAC) undergoing posterior RAMPS were compared to patients having a standard DP. 30-day outcomes were analyzed using multivariable regression.

RESULTS: 3467 PDAC patients underwent DP; 159 (4.6%) also had an adrenalectomy. Posterior RAMPS patients had higher T stage (T3-4 77% vs. 58%, p < 0.01). On multivariable analysis, posterior RAMPS patients had worse perioperative outcomes including more transfusions (OR 2.78, p < 0.01), serious morbidity (OR 1.45, p = 0.04), prolonged hospital stay (OR 1.36, p < 0.05), and less optimal pancreatic surgery (OR 0.61, p < 0.01).

CONCLUSION: Radical antegrade modular pancreatosplenectomy with adrenalectomy (posterior RAMPS) is associated with worse perioperative outcomes compared to a standard distal pancreatectomy. Improved oncologic outcomes must be weighed against higher perioperative morbidity when selecting patients for this more extensive surgical resection.

PMID:36641327 | DOI:10.1016/j.hpb.2022.12.001

Targeting of a new node in lipid metabolism as a potential treatment strategy for ACC

Fetched: January 13th, 2023, 2:06pm GMT by Christopher R LaPensee

Endocrinology. 2023 Jan 13:bqad003. doi: 10.1210/endocr/bqad003. Online ahead of print.

NO ABSTRACT

PMID:36636840 | DOI:10.1210/endocr/bqad003

Permalink for 'Laparoscopic adrenalectomy of pheochromocytoma following management of severe aortic stenosis with transcatheter aortic valve replacement under monitored anesthesia care sedation: a case report'

Laparoscopic adrenalectomy of pheochromocytoma following management of severe aortic stenosis with transcatheter aortic valve replacement under monitored anesthesia care sedation: a case report

Fetched: January 13th, 2023, 2:06pm GMT by Leon Yang

BMC Anesthesiol. 2023 Jan 11;23(1):18. doi: 10.1186/s12871-023-01977-6.

ABSTRACT

BACKGROUND: Management of a patient with an active pheochromocytoma and severe aortic stenosis remains controversial. Adrenalectomy for a pheochromocytoma poses a high risk for stroke, hypertensive emergency, and mortality, compounded by the cardiovascular instability of severe aortic stenosis. In this case report, successful management of an active pheochromocytoma with concomitant severe aortic stenosis was accomplished by performing transcatheter aortic valve replacement under monitored anesthesia care prior to laparoscopic adrenalectomy.

CASE PRESENTATION: An 84-year-old woman with severe aortic stenosis (valve area 0.53 cm²) presented with a symptomatic pheochromocytoma. Transcatheter aortic valve replacement was performed under monitored anesthesia care using a judicious approach of 100 mcg fentanyl total, 4 mg total of midazolam, and a background dexmedetomidine infusion. Alpha-blockade was maintained with 10 mg total of phentolamine mesylate. Laparoscopic adrenalectomy was performed after an uncomplicated postoperative course. The perioperative course for the adrenalectomy was unremarkable and the patient was hemodynamically stable. Postoperative course was uncomplicated and the patient was discharged from the hospital after 5 days.

CONCLUSION: This case report demonstrated the successful approach of managing severe aortic stenosis through a transcatheter aortic valve replacement using monitored anesthesia care sedation prior to laparoscopic adrenalectomy of a symptomatic pheochromocytoma.

PMID:36631749 | PMC:PMC9832737 | DOI:10.1186/s12871-023-01977-6

The Role of Exercise in Diabetes

Fetched: January 13th, 2023, 5:00am GMT by Salwa J. Zahalka

2023 Jan 6. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Exercise is a key component to lifestyle therapy for prevention and treatment of type 2 diabetes (T2D). These recommendations are based on positive associations between physical activity and T2D prevention, treatment, and disease-associated morbidity and mortality. For type 1 diabetes (T1D), we have evidence to support that exercise can reduce diabetes associated complications. However, there are physiological and behavioral barriers to exercise that people with both T2D and T1D must overcome to achieve these benefits. Physiological barriers include diabetes-mediated impairment in functional exercise capacity, increased rates of perceived exertion with lower workloads, and decision making regarding glycemic management. There are additional social and psychological stressors including depression and reduced self-efficacy. Interestingly, there is variability in the response to exercise by sex, genetics, and environment, further complicating the expectations for individual benefit from physical activity. Defining optimal dose, duration, timing, and type of exercise is still uncertain for individual health benefits of physical activity. In this review, we will discuss the preventative value of exercise for T2D development, the therapeutic impact of exercise on diabetes metabolic and cardiovascular outcomes, the barriers to exercise including hypoglycemia, and the impact of sex and gender on cardiorespiratory fitness and adaptive training response in people with and without diabetes. There are still many unknowns regarding the diabetes-mediated impairment in cardiorespiratory fitness, the variability and individual response to exercise training, and the impact of sex and gender. However, there is no debate that exercise provides a health benefit for people with and at risk for diabetes. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:31751111 | Bookshelf:NBK549946

Gynecomastia: Etiology, Diagnosis, and Treatment

Fetched: January 13th, 2023, 5:00am GMT by Ronald S. Swerdloff

ABSTRACT

Gynecomastia is a relatively common disorder. Its causes range from benign physiological processes to rare neoplasms. To diagnose the etiology of the gynecomastia, the clinician must understand the hormonal factors involved in breast development. Parallel to female breast development, estrogen, growth hormone (GH), and IGF-1 are required for breast growth in males. Since a balance exists between estrogen and androgens in males, any disease state or medication that increases circulating estrogens or decreases circulating androgens, causing an elevation in the estrogen to androgen ratio, can induce gynecomastia. Due to the diversity of possible etiologies, including a neoplasm, performing a careful history and physical is imperative. Once gynecomastia has been diagnosed, treatment of the underlying cause is warranted. If no underlying cause is discovered, then close observation is appropriate. If the gynecomastia is severe and of recent onset, medical therapy can be attempted, and if ineffective, glandular tissue can be removed surgically. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905330 | Bookshelf:NBK279105

Utility of Advanced Lipoprotein Testing in Clinical Practice

Fetched: January 13th, 2023, 5:00am GMT by Kenneth R. Feingold

2023 Jan 3. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

A standard lipid panel includes total cholesterol, triglycerides, and HDL-C. LDL-C can then be calculated. While the Friedewald formula is the classical method to calculate LDL-C levels recently developed formulas such as Martin Hopkins formula or Sampson-NIH formula are more accurate when triglycerides are elevated and/or LCL-C levels are low. In some instances, a direct LDL-C assay is employed, particularly when the triglyceride levels are elevated (>400mg/dL). Non-HDL-C can also be calculated (non-HDL-C = total cholesterol – HDL-C). Increasing levels of LDL-C and non-HDL-C are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, numerous studies have demonstrated that the association of non-HDL-C with ASCVD is more robust. It is possible to measure apolipoprotein B and A-I levels, LDL and HDL size, LDL and HDL particle number, and Lp(a). Numerous studies have documented a link between small dense LDL particles and an increased risk of ASCVD; however, the association is markedly reduced or entirely eliminated when the analyses are adjusted for other factors that affect ASCVD risk. Similarly, there is little data demonstrating that HDL subfractions are useful in risk prediction beyond HDL and other traditional risk factors. Apolipoprotein B levels and LDL particle number are more strongly associated with ASCVD than LDL-C, particularly when the levels of LDL-C and apolipoprotein B levels or LDL particle number are discordant. Similarly, while apolipoprotein B levels or LDL particle number are significantly better than non-HDL-C in predicting ASCVD risk when the levels of non-HDL-C and apolipoprotein B levels or LDL particle number are discordant whether this will alter therapy in most patients is debated. The guidelines put forth by a variety of different expert panels and organizations do not require apolipoprotein B or LDL particle number but may use them as risk enhancing factor. It is also the author’s opinion that at this time the routine measurement of apolipoprotein B and/or LDL particle number is not required. Until data demonstrate the superiority of measuring apolipoprotein B or LDL particle number on clinical outcomes it is hard to recommend the routine use of such testing. However, in situations where there is uncertainty measurement of apolipoprotein B and/or LDL particle number can be helpful. Studies have demonstrated an association of Lp(a) with ASCVD. Many experts recommend measuring Lp(a) once in all patients while other experts recommend measuring Lp(a) more selectively in a) patients with unexplained premature CHD, b) patients with a strong family history of premature CHD, c) patients with resistance to LDL lowering with statins, d) patients with rapid unexplained progression of atherosclerosis, and e) patients with familial hypercholesterolemia. Elevations in Lp(a) will stimulate more aggressive lowering of LDL and the consideration of adding drugs that lower Lp(a) such as niacin or PCSK9 inhibitors. While routine use of advanced lipoprotein testing is not routinely recommended it should be recognized that in selected patients the additional information provided can be helpful and result in changes in treatment. As additional drugs to treat lipids are developed and our understanding of lipid and lipoprotein metabolism expands in the future the use of advanced lipoprotein analysis may assume a more important role. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:27099901 | Bookshelf:NBK355893

A Long-Term Survival Case of Paraganglioma Treated with Repeated Surgical Resection

Fetched: January 13th, 2023, 5:00am GMT by Haruka Izumi

Hinyokika Kiyo. 2022 Dec;68(12):385-390. doi: 10.14989/ActaUrolJap_68_12_385.

ABSTRACT

We report a case of long-term survival in paraganglioma treated with repetitive surgery. A 32-year-old man was seen at the hospital because of hypertension and headache. On biochemical tests, elevated serum and urinary levels of noradrenaline were noted. Abdominal computed tomographic (CT) scan revealed a tumor 50 mm in diameter on the dorsal region of the inferior vena cava, superior to the renal artery. Our diagnosis was paraganglioma and we performed open resection of the tumor. Six years later, hypertension and headache appeared and abdominal computed tomography revealed tumors located in right renal hilus and para-aortic regions superior to aortic bifurcation, and ¹²³I-MIBG scintigraphy revealed uptake at the same sites. Therefore, we diagnosed the patient with recurrent pheochromocytoma and performed laparoscopic resection of the tumor. Surgical treatment was repeatedly performed for recurrence, and the symptoms due to hypersecretion of catecholamines could be controlled over a long period.

PMID:36627772 | DOI:10.14989/ActaUrolJap_68_12_385

Permalink for 'Same-day comparative protocol PET/CT-PET/MRI [68 Ga]Ga-DOTA-TOC in paragangliomas and pheochromocytomas: an approach to personalized medicine'

Same-day comparative protocol PET/CT-PET/MRI [68 Ga]Ga-DOTA-TOC in paragangliomas and pheochromocytomas: an approach to personalized medicine

Fetched: January 13th, 2023, 5:00am GMT by Stefan Prado-Wohlwend

Cancer Imaging. 2023 Jan 10;23(1):4. doi: 10.1186/s40644-023-00521-6.

ABSTRACT

BACKGROUND: PET/MRI is an emerging imaging modality which enables the evaluation and quantification of biochemical processes in tissues, complemented with accurate anatomical information and low radiation exposure. In the framework of theragnosis, PET/MRI is of special interest due to its ability to delineate small lesions, adequately quantify them, and therefore to plan targeted therapies. The aim of this study was to validate the diagnostic performance of [⁶⁸ Ga]Ga-DOTA-TOC PET/MRI compared to PET/CT in advanced disease paragangliomas and pheochromocytomas (PGGLs) to assess in which clinical settings, PET/MRI may have a greater diagnostic yield.

METHODS: We performed a same-day protocol with consecutive acquisition of a PET/CT and a PET/MRI after a single [⁶⁸ Ga]Ga-DOTA-TOC injection in 25 patients. Intermodality agreement, Krenning Score (KS), SUVmax (Standard Uptake Value), target-to-liver-ratio (TLR), clinical setting, location, and size were assessed.

RESULTS: The diagnostic accuracy with PET/MRI increased by 14.6% compared to PET/CT especially in bone and liver locations (mean size of new lesions was 3.73 mm). PET/MRI revealed a higher overall lesion uptake than PET/CT (TLR 4.12 vs 2.44) and implied an upward elevation of the KS in up to 60% of patients. The KS changed in 30.4% of the evaluated lesions (mean size 11.89 mm), in 18.4% of the lesions it increased from KS 2 on PET/CT to a KS ≥ 3 on PET/MRI and 24.96% of the lesions per patient with multifocal disease displayed a KS ≥ 3 on PET/MR, that were not detected or showed lower KS on PET/CT. In 12% of patients, PET/MRI modified clinical management.

CONCLUSIONS: PET/MRI showed minor advantages over conventional PET/CT in the detection of new lesions but increased the intensity of SSRs expression in a significant number of them, opening the door to select which patients and clinical settings can benefit from performing PET/MRI.

PMID:36627700 | PMC:PMC9832675 | DOI:10.1186/s40644-023-00521-6

Adrenocortical carcinoma with venous tumor invasion: is there a role for mini-invasive surgery?

Fetched: January 13th, 2023, 5:00am GMT by Alberto Olivero

Langenbecks Arch Surg. 2023 Jan 10;408(1):17. doi: 10.1007/s00423-023-02765-z.

ABSTRACT

OBJECTIVE: This study aims to investigate early oncologic outcomes in patients with adrenocortical carcinoma (ACC) with venous invasion (VI) treated using both open and mini-invasive approaches.

PATIENTS AND MATERIALS: We conducted a retrospective analysis of 4 international referral center databases, including all the patients undergoing adrenalectomy for ACC with VI from January 2007 to March 2020. According to CT scan or MRI, the tumor thrombus was classified into four levels: (1) adrenal vein invasion; (2) renal vein invasion; (3) infra-hepatic Inferior vena cava (IVC); and (4) retro-hepatic IVC. In addition, we divided our patients into patients who had undergone open surgery and mini-invasive surgery.

RESULTS: We identified 20 patients with a median follow-up of 12 months. The median tumor size was 110mm. ENSAT stage was II in 4 patients, III in 13 patients, and IV in 3 patients. Tumor thrombus extended in the adrenal vein (n=5), renal vein (n=1), infra-hepatic IVC (n=9), or into the retro-hepatic IVC (n=5). Ten patients were treated with a mini-invasive approach. The patient treated with an open approach reported a more aggressive disease. The two groups did not differ in surgical margins, surgical time, blood losses, complications, and length of stay. The prognosis resulted worse in the patient undergoing open. Kaplan-Meier analysis indicated a difference in OS for the patients stratified by ENSAT stage (Log-rank p=0.011); we also reported a difference in DFS for patients stratified for thrombus extension (p=0.004) and ENSAT stage (p<0.001).

CONCLUSION: The DFS of patients with VI from ACC is influenced by the staging and the extension of the venous invasion; the staging influences the OS. The mini-invasive approach seems feasible in selected patients; however, further studies investigating the oncological outcomes are needed. A mini-invasive approach for adrenal tumors with venous invasion is an explorable option in very selected patients.

PMID:36625975 | DOI:10.1007/s00423-023-02765-z

Systemic corticosteroids for the treatment of COVID-19

Fetched: January 13th, 2023, 5:00am GMT by Carina Wagner

Emergencias. 2022 Dec;34(6):468-470.

NO ABSTRACT

PMID:36625698

Thromboelastometry-guided surgery in neuroblastoma complicated with disseminated intravascular coagulation

Fetched: January 12th, 2023, 5:00am GMT by M R Pérez-Torres Lobato

Cir Pediatr. 2023 Jan 1;36(1):44-47. doi: 10.54847/cp.2023.01.20.

ABSTRACT

BACKGROUND: Disseminated intravascular coagulation (DIC) is a rare oncological emergency. We report a pediatric neuroblastoma complicated with DIC which required thromboelastometry-guided surgery.

OBSERVATION: A 6-year-old female diagnosed with intermediate risk adrenal neuroblastoma developed tumor-related DIC after chemotherapy first cycle. She remained stable without clinical bleeding and emergent tumor resection guided by intraoperative-thromboelastometry was decided. DIC resolved early after surgery and complete remission was achieved.

CONCLUSION: Treatment of the underlying condition is critical to manage DIC. Thromboelastometry can guide goal-directed therapy, including surgery in pediatric patients. However, larger studies are needed to examine its applicability in different clinical settings, such as cancer related DIC.

PMID:36629349 | DOI:10.54847/cp.2023.01.20

Permalink for 'Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review'

Peritoneal carcinomatosis secondary to metastatic lung cancer complicated with acute suppurative appendicitis: A case report and literature review

Fetched: January 11th, 2023, 5:00am GMT by Ji-Xin Fu

Medicine (Baltimore). 2022 Dec 9;101(49):e31866. doi: 10.1097/MD.0000000000031866.

ABSTRACT

RATIONALE: Lung cancer (LC) is a malignant tumor with the highest morbidity and mortality in the world. The most common metastatic sites of LC are the brain (47%), bone (36%), liver (22%), adrenal glands (15%), thoracic cavity (11%) and distant lymph nodes (10%). Peritoneal carcinomatosis (PC) is a rare clinical event in LC patients. Considering the rarity and nonspecific clinical symptoms of peritoneal metastasis among LC patients, a case of peritoneal metastasis secondary to LC incidentally observed by laparoscopic appendectomy is unusual.

PATIENT CONCERNS: Here, we present a 53-year-old never-smoker woman who presented to the emergency department with a 2-day history of pain in the right abdominal quadrant. Later, laparoscopy revealed acute suppurative appendicitis accompanied by a peritoneal metastatic mass.

DIAGNOSIS: The patient was diagnosed with PC secondary to metastatic LC complicated with acute suppurative appendicitis by immunohistochemistry. Positron emission tomography computed tomography (PET CT) findings further strengthen the evidence of PC from LC.

OUTCOMES: Based on the results of genomic analysis, the patient received targeted therapy with osimertinib 80 mg/d.

LESSONS: Due to the discovery of new targets, the use of molecular therapies improved progression-free survival (PFS) and overall survival (OS), which increases the chance of identifying peritoneal metastasis of LC. For LC patients with abdominal symptoms, clinicians should be aware of the possibility of peritoneal metastasis from LC, especially for patients diagnosed with lung adenocarcinoma or with pleural effusion.

PMID:36626502 | PMC:PMC9750620 | DOI:10.1097/MD.0000000000031866

Permalink for 'Ectopic adrenocorticotrophic hormone syndrome secondary to treatment-related neuroendocrine differentiation of metastatic castrate-resistant prostate cancer'

Ectopic adrenocorticotrophic hormone syndrome secondary to treatment-related neuroendocrine differentiation of metastatic castrate-resistant prostate cancer

Fetched: January 11th, 2023, 5:00am GMT by Chelsea Tan

Endocrinol Diabetes Metab Case Rep. 2023 Jan 1;2023:22-0347. doi: 10.1530/EDM-22-0347. Online ahead of print.

ABSTRACT

SUMMARY: A 64-year-old man with progressive metastatic castrate-resistant prostate adenocarcinoma presented with recurrent fluid overload, severe hypokalaemia with metabolic alkalosis and loss of glycaemic control. Clinical features were facial plethora, skin bruising and proximal myopathy. Plasma adrenocorticotrophic hormone (ACTH), serum cortisol and 24-h urinary cortisol levels were elevated. Low-dose dexamethasone failed to suppress cortisol. Pituitary MRI was normal and 68Gallium-DOTATATE PET-CT scan showed only features of metastatic prostate cancer. He was diagnosed with ectopic ACTH syndrome secondary to treatment-related neuroendocrine prostate cancer differentiation. Medical management was limited by clinical deterioration, accessibility of medications and cancer progression. Ketoconazole and cabergoline were utilised, but cortisol remained uncontrolled. He succumbed 5 months following diagnosis. Treatment-related neuroendocrine differentiation of prostate adenocarcinoma is a rare cause of ectopic ACTH syndrome.

LEARNING POINTS: Neuroendocrine differentiation following prostate adenocarcinoma treatment with androgen deprivation has been described. Ectopic adrenocorticotrophic hormone (ACTH) syndrome should be considered where patients with metastatic prostate cancer develop acute electrolyte disturbance or fluid overload. Ketoconazole interferes with adrenal and gonadal steroidogenesis and can be used in ectopic ACTH syndrome, but the impact may be insufficient. Inhibition of gonadal steroidogenesis is favourable in prostate cancer. More data are required to evaluate the use of cabergoline in ectopic ACTH syndrome. Ectopic ACTH syndrome requires prompt management and is challenging in the face of metastatic cancer.

PMID:36625254 | DOI:10.1530/EDM-22-0347

Huge Hematoma as First Manifestation of Adrenocortical Carcinoma: A Case Report

Fetched: January 11th, 2023, 5:00am GMT by Siavash Świeczkowski-Feiz

Am J Case Rep. 2023 Jan 9;24:e937569. doi: 10.12659/AJCR.937569.

ABSTRACT

BACKGROUND Adrenocortical carcinoma (ACC) is a rare malignancy associated with unfavorable prognosis. It is mainly diagnosed in the fifth or sixth decade of life. Symptoms of ACC are associated with hormonal activity, presence of metastases, and size of the tumor. The treatment and prognosis depend on the stage of the disease assessed with the ENSAT staging system. CASE REPORT A 38-year-old White man was admitted to our department from the city hospital due to a huge hematoma of the right adrenal gland (130×100 mm). On admission, the patient's condition was stable, and no active bleeding or other complications were present. Therefore, initially, conservative treatment was performed. The control CT scan showed reduction of the hematoma (90×80 mm). Due to the unknown character of the tumor and the sudden onset of bleeding, the patient was prepared for elective surgery according to the phaeochromocytoma surgery protocol. Following preparation, the patient underwent right-sided adrenalectomy. In the postoperative histopathological examination, adrenocortical carcinoma was diagnosed, which allowed the patient to receive appropriate oncological treatment. CONCLUSIONS There is currently no clear algorithm for the management of adrenal hemorrhage. A hemodynamically unstable patient requires urgent surgical treatment. Patients in good general condition should be prepared for early elective surgery.

PMID:36617747 | DOI:10.12659/AJCR.937569

Commentary on "Laparoscopic approach of pediatric adrenal tumors"

Fetched: January 11th, 2023, 5:00am GMT by Mario Cuesta Argos

Pediatr Surg Int. 2023 Jan 9;39(1):74. doi: 10.1007/s00383-023-05365-6.

NO ABSTRACT

PMID:36617587 | DOI:10.1007/s00383-023-05365-6

68Ga-DOTAGA-IAC PET/CT for Imaging Metastatic and Recurrent Adrenocortical Carcinoma: A Case Series

Fetched: January 11th, 2023, 5:00am GMT by Somit Pandey

Clin Nucl Med. 2023 Feb 1;48(2):e95-e98. doi: 10.1097/RLU.0000000000004497.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare malignancy with a prevalence of 1 to 2 cases/million/year. The diagnosis depends upon endocrine workup followed by imaging with CT, MRI, and 18F-FDG PET/CT. The treatment includes surgical resection, debulking surgery, chemotherapy, and radiotherapy. However, patients do not respond well to any of the available therapies. We present noninvasive imaging of histopathology-proven ACC patients using 68Ga-DOTAGA-IAC PET/CT, specific for integrin αvβ3. 68Ga-DOTAGA-IAC PET/CT 45 minutes after IV injection showed a decent tumor-to-background ratio and could be used as a promising radiotracer for metastatic and recurrent ACC.

PMID:36607383 | DOI:10.1097/RLU.0000000000004497

Reproductive Health and its Impact on Lipid Management in Adolescent and Young Adult Females

Fetched: January 10th, 2023, 5:00am GMT by Ann Liebeskind

2022 Dec 27. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Lipids disorders are common in youth. Adolescents and young women of childbearing age who have moderate to severe lipid disorders may benefit from treatment with lipid lowering medications (LLM). However, most of these medications are contraindicated in pregnancy. Those who are sexually active should receive counseling on effective methods to prevent unplanned pregnancies. While contraceptives, when appropriate, are typically prescribed by primary care physicians, lipidologists are often asked to address the unique aspects related to use of long-term LLMs, such as statins, in females with hypercholesterolemia. Appropriate counseling and management require not only knowledge of the effects of sexual maturation on lipid and lipoprotein metabolism, but a thorough understanding of current recommendations and potential harms associated with the use of some LLMs, such as statins, should pregnancy occur. In this chapter, we review changes in lipid and lipoprotein metabolism during puberty, current guidelines for use of contraceptive methods in adolescent and young adult females and laws that pertain to this unique population. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:36622930 | Bookshelf:NBK588296

Immune Checkpoint Inhibitors and Endocrine Disorders: A Position Statement from the Korean Endocrine Society

Fetched: January 10th, 2023, 5:00am GMT by Hyemi Kwon

Endocrinol Metab (Seoul). 2022 Dec;37(6):839-850. doi: 10.3803/EnM.2022.1627. Epub 2022 Dec 26.

ABSTRACT

Immune checkpoint inhibitors (ICIs) including an anti-cytotoxic T-lymphocyte-associated antigen 4 inhibitor, anti-programmed cell death protein 1 (PD-1) inhibitors, and anti-PD-ligand 1 inhibitors are representative therapeutics for various malignancies. In oncology, the application of ICIs is currently expanding to a wider range of malignancies due to their remarkable clinical outcomes. ICIs target immune checkpoints which suppress the activity of T-cells that are specific for tumor antigens, thereby allowing tumor cells to escape the immune response. However, immune checkpoints also play a crucial role in preventing autoimmune reactions. Therefore, ICIs targeting immune checkpoints can trigger various immune-related adverse events (irAEs), especially in endocrine organs. Considering the endocrine organs that are frequently involved, irAEs associated endocrinopathies are frequently life-threatening and have unfavorable clinical implications for patients. However, there are very limited data from large clinical trials that would inform the development of clinical guidelines for patients with irAEs associated endocrinopathies. Considering the current clinical situation, in which the scope and scale of the application of ICIs are increasing, position statements from clinical specialists play an essential role in providing the appropriate recommendations based on both medical evidence and clinical experience. As endocrinologists, we would like to present precautions and recommendations for the management of immune-related endocrine disorders, especially those involving the adrenal, thyroid, and pituitary glands caused by ICIs.

PMID:36604955 | PMC:PMC9816514 | DOI:10.3803/EnM.2022.1627

Retroperitoneal laparoscopic partial adrenalectomy (RLPA) for 20-40 mm nonfunctional adrenal tumors in the day surgery mode

Fetched: January 10th, 2023, 5:00am GMT by Xuwen Li

Front Endocrinol (Lausanne). 2022 Dec 20;13:1099818. doi: 10.3389/fendo.2022.1099818. eCollection 2022.

ABSTRACT

OBJECTIVES: To investigate the outcome and safety of retroperitoneal laparoscopic partial adrenalectomy in the treatment of nonfunctional unilateral adrenal tumors in the day surgery mode.

METHODS: Nineteen patients bearing nonfunctional unilateral 20-40 mm adrenal tumors were prospectively enrolled and underwent retroperitoneal laparoscopic partial adrenalectomy in the day surgery unit of our hospital between June 2021 and March 2022. All patients were diagnosed with non-functional adrenal tumors as outpatients before being admitted to the day surgery unit with their consent. Patient demographics and perioperative data were prospectively documented. The patients were followed up by telephone on day 1, 3 and 7 after discharge and followed up for 6 months.

RESULTS: The patient's age was 50.5 ± 11.9 yr (range from 19.0 - 69.0). Seven patients were female. Twelve patients underwent surgery on the left side. The maximal diameter of tumor was 28.3 ± 5.7 mm (20.0 - 40.0 mm). Operation time was 72.1 ± 14.9 min (58.0 - 120.0 min). Mean blood loss was 64.7 ± 50.4 ml (30.0 - 200.0 ml). The gastrointestinal function recovery time was 9.7 ± 2.6 h (6.0 - 16.0 h). Retroperitoneal drainage was removed 24.8 ± 13.3 h (range 18.0 - 72.0) after surgery. Four patients were transferred to the general ward for postoperative management, while others were discharged within 24 hours after surgery. Length of hospital stay was 48.8 ± 13.1 h (38.0 - 85.0h). Hospitalization expense was 24168.4 ± 2910.3 RMB¥ (20844.3 - 34369.8 RMB¥). Postoperative pathology revealed 17 cortical adenoma, 1 pheochromocytoma and 1 lymphatic duct tumor.

CONCLUSION: Retroperitoneal laparoscopic partial adrenalectomy for nonfunctional unilateral adrenal tumors in the day surgery mode is safe when strict selection criteria and perioperative management protocol are followed, which has the potential to shorten length of hospital stay and reduce lower hospitalization costs.

PMID:36605942 | PMC:PMC9807863 | DOI:10.3389/fendo.2022.1099818

Stereotactic MR-Guided Radiotherapy for Adrenal Gland Metastases: First Clinical Results

Fetched: January 9th, 2023, 5:00am GMT by Morgan Michalet

J Clin Med. 2022 Dec 30;12(1):291. doi: 10.3390/jcm12010291.

ABSTRACT

Stereotactic MR-guided Radiotherapy (MRgRT) is an interesting treatment option for adrenal gland metastases (AGM). We reviewed data from 12 consecutive patients treated with MRgRT for an AGM in our center between 14 November 2019 and 17 August 2021. Endpoints were tolerance assessment, the impact of adaptive treatment on target volume coverage and organs at risk (OAR) sparing, local control (LC), and overall survival (OS). The majority of patients were oligometastatic (58.3%), with 6 right AGM, 5 left AGM and 1 left and right AGM. The prescribed dose was 35 to 50 Gy in 3 to 5 fractions. The median PTV V95% on the initial plan was 95.74%. The median V95% of the PTVoptimized (PTVopt) on the initial plan was 95.26%. Thirty-eight (69%) fractions were adapted. The PTV coverage was significantly improved for adapted plans compared to predicted plans (median PTV V95% increased from 89.85% to 91.17%, p = 0.0478). The plan adaptation also significantly reduced Dmax for the stomach and small intestine. The treatment was well tolerated with no grade > 2 toxicities. With a median follow-up of 15.5 months, the 1-year LC and OS rate were 100% and 91.7%. Six patients (50%) presented a metastatic progression, and one patient (8.3%) died of metastatic evolution during the follow-up. Adaptation of the treatment plan improved the overall dosimetric quality of MRI-guided radiotherapy. A longer follow-up is required to assess late toxicities and clinical results.

PMID:36615093 | PMC:PMC9821305 | DOI:10.3390/jcm12010291

Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis

Fetched: January 9th, 2023, 5:00am GMT by Hans K Ghayee

Int J Mol Sci. 2022 Dec 29;24(1):584. doi: 10.3390/ijms24010584.

ABSTRACT

The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient's macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.

PMID:36614027 | PMC:PMC9820690 | DOI:10.3390/ijms24010584

Osteoporosis: Prevention and Treatment

Fetched: January 7th, 2023, 5:00am GMT by Sarah Zaheer

ABSTRACT

Despite the health consequences of osteoporosis and the availability of effective treatments, it is under-diagnosed and under-treated. For example, although 90% of patients with hip fractures have osteoporosis, in 2007 only 20% of patients with fragility fractures were evaluated and treated. In a retrospective study of patients with hip fractures, less than 15% of subjects were diagnosed and less than 13% were treated with medications for osteoporosis, including calcium and vitamin D. Fracture patients require evaluation of secondary causes and treatment of osteoporosis to help prevent subsequent fractures. The preceding chapters summarize the pathogenesis and the clinical evaluation of osteoporosis. This chapter will review established therapeutic options and new approaches for the prevention and treatment of osteoporosis. Strategies include both lifestyle and medical approaches to enhance bone strength. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905299 | Bookshelf:NBK279073

Lung Tumor Skin Metastasis: Case Report of a Solitary Cutaneous Ulcerated Lesion as Initial Manifestation of Lung Carcinoma

Fetched: January 7th, 2023, 5:00am GMT by Francesco Falbo

Case Rep Oncol. 2022 Nov 10;15(3):1034-1038. doi: 10.1159/000527077. eCollection 2022 Sep-Dec.

ABSTRACT

Lung cancer has the highest cancer incidence, and it is the most common cause of cancer death worldwide. Cutaneous metastases are infrequent compared to hilar nodes, adrenal glands, liver, brain, and bones. However, unusual skin lesions in patients at high risk of lung cancer should be regarded carefully to rule out a metastatic manifestation of an occult primary site tumor. Surgical excision, or incisional biopsy when the former is deemed unfeasible, should be performed to allow histopathological examination in case of occult primary site. In patients affected by advanced lung tumors, surgical excision could be beneficial in terms of pain control and improvement of the quality of life. We report a case of a solitary large skin lesion as an early manifestation of a lung adenocarcinoma.

PMID:36605228 | PMC:PMC9808127 | DOI:10.1159/000527077

Coincidence of primary adrenocortical carcinoma and melanoma: three CASE reports

Fetched: January 6th, 2023, 5:00am GMT by Ye Lynn Ko

BMC Endocr Disord. 2023 Jan 6;23(1):4. doi: 10.1186/s12902-022-01253-7.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous prognosis, while adrenal metastasis from other primary cancers, including melanoma, may occur more frequently. ACC may rarely occur as part of familial cancer syndromes, but even in sporadic cases, a significant proportion of patients had other malignancies before or after diagnosis of ACC. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma.

CASE DESCRIPTION: Patient 1 - A 37-yr-old man with a superficial spreading BRAF-positive melanoma was found to harbour a progressively growing left adrenal mass. Initially, he was suspected of having adrenal metastasis, but the histology after adrenalectomy confirmed ACC. Patient 2 - A 68-year-old man with a history of recurrent BRAF-positive melanoma was diagnosed with disseminated metastatic melanoma recurrence, including a rapidly enlarging left adrenal mass. Consequently, he underwent left adrenalectomy, and histology again confirmed ACC. Patient 3 - A 50-yr-old man was referred with histological diagnosis of metastatic ACC. He had a background history of pT1 melanoma. We undertook targeted sequencing of ACC tissue samples in all cases. Somatic variants were observed in the known driver genes CTNNB1 (Patient 1), APC and KMT2D (Patient 2), and APC and TP53 (Patient 3). Germline TP53 variants (Li-Fraumeni syndrome) were excluded in all cases. Retrospective review of our patient cohort in the last 21 years revealed a frequency of 0.5% of histologically diagnosed melanoma metastasis among patients referred for adrenal masses. On the other hand, 1.6% of patients with histologically confirmed ACC had a previous history of melanoma.

CONCLUSION: Sporadic ACC can occur in the background of melanoma, even if adrenal metastasis might appear to be the most likely diagnosis. Coexistent primary adrenal malignancy should be considered and investigated for in all patients with a history of melanoma with suspicious adrenal lesions.

PMID:36604647 | PMC:PMC9817389 | DOI:10.1186/s12902-022-01253-7

Childhood pheochromocytoma crisis complicated with brain stem infarction: A case report

Fetched: January 6th, 2023, 5:00am GMT by Fujing Xie

Medicine (Baltimore). 2022 Dec 23;101(51):e32479. doi: 10.1097/MD.0000000000032479.

ABSTRACT

RATIONALE: Pheochromocytoma crises are very rarely seen in children. In this report, we present a case of the death related to occult pheochromocytoma crisis combined cerebral infarction.

PATIENT CONCERNS: A 5-year-old boy has a 1-month history of polydipsia, polyuria, sweating, and weight loss of 2.5 kg. He was admitted to our hospital because of 1 week of anorexia, 2 days of vomiting, and 12 hours of convulsions and confusion. Magnetic resonance imaging of the brain and cervical spinal cord showed abnormal signals in the left parie-occipital lobe, medulla oblongata till C7 cervical vertebrae.

DIAGNOSES: Based on patient's complaints and clinical appearance, provisional diagnosis of pheochromocytoma crisis complicated brainstem infarction was considered.

INTERVENTIONS: Tracheal intubation, volume expansion, continuous infusion of dobutamine, and sedation reduce intracranial pressure. Chest compression was performed when the child suddenly developed sobbing respiration.

OUTCOMES: The patient was dead. Congenital metabolic defects screening suggested mild ketonuria. Trio whole exon sequencing revealed a synonymous mutation of von Hippel-Lindau syndrome c.414 A > G in the decedent. Autopsy revealed pheochromocytoma, acute myocarditis, liquefaction necrosis of the medulla oblongata cerebral edema, and congestion.

LESSONS: Early clinical symptoms of pheochromocytoma in children are not typical. It may induce serious complications and develop into a pheochromocytoma crisis and cause death without proper treatment.

PMID:36595857 | PMC:PMC9794225 | DOI:10.1097/MD.0000000000032479

Permalink for 'Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models'

Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models

Fetched: January 5th, 2023, 5:00am GMT by Martin Ullrich

Theranostics. 2023 Jan 1;13(1):278-294. doi: 10.7150/thno.77918. eCollection 2023.

ABSTRACT

Pheochromocytomas and paragangliomas (PCCs/PGLs) are catecholamine-producing tumors. In inoperable and metastatic cases, somatostatin type 2 receptor (SSTR2) expression allows for peptide receptor radionuclide therapy with [¹⁷⁷Lu]Lu-DOTA-TATE. Insufficient receptor levels, however, limit treatment efficacy. This study evaluates whether the epigenetic drugs valproic acid (VPA) and 5-Aza-2'-deoxycytidine (DAC) modulate SSTR2 levels and sensitivity to [¹⁷⁷Lu]Lu-DOTA-TATE in two mouse PCC models (MPC and MTT). Methods: Drug-effects on Sstr2/SSTR2 were investigated in terms of promoter methylation, mRNA and protein levels, and radiotracer binding. Radiotracer uptake was measured in subcutaneous allografts in mice using PET and SPECT imaging. Tumor growth and gene expression (RNAseq) were characterized after drug treatments. Results: DAC alone and in combination with VPA increased SSTR2 levels along with radiotracer uptake in vitro in MPC (high-SSTR2) and MTT cells (low-SSTR2). MTT but not MPC allografts responded to DAC and VPA combination with significantly elevated radiotracer uptake, although activity concentrations remained far below those in MPC tumors. In both models, combination of DAC, VPA and [¹⁷⁷Lu]Lu-DOTA-TATE was associated with additive effects on tumor growth delay and specific transcriptional responses in gene sets involved in cancer and treatment resistance. Effects of epigenetic drugs were unrelated to CpG island methylation of the Sstr2 promoter. Conclusion: This study demonstrates that SSTR2 induction in mouse pheochromocytoma models has some therapeutic benefit that occurs via yet unknown mechanisms. Transcriptional changes in tumor allografts associated with epigenetic treatment and [¹⁷⁷Lu]Lu-DOTA-TATE provide first insights into genetic responses of PCCs/PGLs, potentially useful for developing additional strategies to prevent tumor recurrence.

PMID:36593963 | PMC:PMC9800739 | DOI:10.7150/thno.77918

Antidepressant Drug Interaction in the Diagnosis of an Adrenal Tumor

Fetched: January 4th, 2023, 5:00am GMT by Aldo Stoppa

Prim Care Companion CNS Disord. 2022 Dec 27;24(6):22cr03259. doi: 10.4088/PCC.22cr03259.

NO ABSTRACT

PMID:36584362 | DOI:10.4088/PCC.22cr03259

Clinical characteristics and pre-surgery diagnostic criteria of aldosterone-producing adrenocortical carcinoma

Fetched: January 4th, 2023, 5:00am GMT by Xinyi Zhang

Chin Med J (Engl). 2022 Oct 20;135(20):2512-2514. doi: 10.1097/CM9.0000000000002415.

NO ABSTRACT

PMID:36583872 | DOI:10.1097/CM9.0000000000002415

Rare case of pancreatic adenocarcinoma with spermatic cord and testicular metastasis

Fetched: January 4th, 2023, 5:00am GMT by Chung-Hao Yu

BMJ Case Rep. 2022 Dec 7;15(12):e250289. doi: 10.1136/bcr-2022-250289.

ABSTRACT

Male gonadal metastases from pancreatic carcinomas are extremely rare, with fewer than 20 cases documented in the literature. Herein, we report a man in his 50s who presented at the genitourinary outpatient department with an enlarged scrotum (right side) that had developed progressively over several weeks. He also reported mild upper abdominal discomfort. Scrotal sonography revealed a hydrocele on the right side without testicular lesions. A mass pancreatic tail lesion with invasion of the spleen and left adrenal gland was identified through abdominal CT and MRI. Endoscopic ultrasound fine needle biopsy and right radical orchiectomy were performed. Moderately differentiated adenocarcinoma of the pancreatic tail with hematogenous metastasis to the right testis, epididymis and spermatic cord was verified on the basis of the pathology report. Disease progression occurred despite the patient receiving palliative chemoradiation therapy.

PMID:36593606 | PMC:PMC9730350 | DOI:10.1136/bcr-2022-250289

Effective treatment with mitotane for a canine case of presumed ectopic Cushing's syndrome-related pheochromocytoma

Fetched: January 4th, 2023, 5:00am GMT by Konatsu Miura

Open Vet J. 2022 Sep-Oct;12(5):762-767. doi: 10.5455/OVJ.2022.v12.i5.22. Epub 2022 Oct 10.

ABSTRACT

BACKGROUND: In humans, ectopic Cushing's syndrome (ECS) is characterized by hypercortisolemia, which is caused by small lung carcinoma, bronchial carcinoids, and pheochromocytoma. In dogs, only a few cases of ECS associated with pheochromocytoma have been reported to date.

CASE DESCRIPTION: Herein, we describe a canine case of malignant pheochromocytoma that is presumed to be the cause of ECS. An 11-year-old, castrated, male Toy Poodle with hypercortisolemia was diagnosed with an adrenal tumor (AT) and treated with mitotane. Although repeated adrenocorticotropic hormone stimulation tests revealed improvement in the dog's condition by mitotane treatment, its condition started declining 197 days post-diagnosis, and he died on day 280. The necropsy revealed the AT was a pheochromocytoma, not an adrenocortical tumor. However, because of no pathological change in the pituitary gland and the other adrenal gland, pheochromocytoma was presumed to be the cause of ECS.

CONCLUSION: This is the first report that describes the effectiveness of mitotane against presumed ECS-related pheochromocytoma.

PMID:36589399 | PMC:PMC9789766 | DOI:10.5455/OVJ.2022.v12.i5.22

Clinical identification of expressed proteins in adrenal medullary hyperplasia detected with hypertension

Fetched: January 3rd, 2023, 5:00am GMT by He Ma

Front Endocrinol (Lausanne). 2022 Dec 13;13:1014366. doi: 10.3389/fendo.2022.1014366. eCollection 2022.

ABSTRACT

BACKGROUND: Hypertension remains a challenging public health problem worldwide, and adrenal gland-related diseases are one class of the major causes for secondary hypertension. Among them, one relatively rare pattern is adrenal hyperplastic hypertension caused by adrenal medullary hyperplasia (AMH), leading to excessive secretion of autonomic catecholamine. Given that the pathological changes of adrenal medulla are not well correlated to the onset and even severity of secondary hypertension, the molecular basis why some AMH patients are accompanied with hypertension remains unclear and is worth exploring.

AIMS: For this reason, this study aims at investigating differentially expressed proteins in clinical AMH tissue, with special focus on the potential contribution of these differentially expressed proteins to AMH development, in order to have a better understanding of mechanisms how AMH leads to secondary hypertension to some extent.

METHODS AND RESULTS: To this end, AMH specimens were successfully obtained and verified through computed tomography (CT) and haematoxylin-eosin (HE) staining. Proteomic analyses of AMH and control tissues revealed 782 kinds of differentially expressed proteins. Compared with the control tissue, there were 357 types of upregulated proteins and 425 types of downregulated proteins detected in AMH tissue. Of interest, these differentially expressed proteins were significantly enriched in 60 gene ontology terms (P < 0.05), including 28 biological process terms, 14 molecular function terms, and 18 cellular component terms. Pathway analysis further indicated that 306 proteins exert their functions in at least one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Western blotting showed enhanced expression of phenylethanolamine N- methyltransferase (PNMT), myelin protein zero (MPZ), and Ras-related protein Rab-3C (RAB3C), and reduced expression of cluster of differentiation 36 (CD36) observed in AMH tissue in comparison with controls.

CONCLUSIONS: Clinical AMH specimens display a different proteomic profile compared to control tissue. Of note, PNMT, MPZ, RAB3C, and CD36 are found to differentially expressed and can be potential targets for AMH, providing a theoretical basis for mechanistic exploration of AMH along with hypertension.

PMID:36583008 | PMC:PMC9792999 | DOI:10.3389/fendo.2022.1014366

Heterogeneous circulating miRNA profiles of PBMAH

Fetched: January 3rd, 2023, 5:00am GMT by Kazunari Hara

Front Endocrinol (Lausanne). 2022 Dec 13;13:1073328. doi: 10.3389/fendo.2022.1073328. eCollection 2022.

ABSTRACT

OBJECTIVE: Primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing syndrome, is often diagnosed as a bilateral adrenal incidentaloma with subclinical cortisol production. Circulating microRNAs (miRNAs) are a characteristic of adrenocortical adenomas, but miRNA expression in PBMAH has not been investigated. We aimed to evaluate the circulating miRNA expression in patients with PBMAH and compare them with those in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA).

METHODS: miRNA profiling of plasma samples from four, five, and five patients with NFA, CPA, and PBMAH, respectively, was performed. Selected miRNA expressions were validated using quantitative RT-PCR.

RESULTS: PBMAH samples showed distinct miRNA expression signatures on hierarchical clustering while NFA and CPA samples were separately clustered. PBMAH was distinguished from the adenoma group of NFA and CPA by 135 differentially expressed miRNAs. Hsa-miR-1180-3p, hsa-miR-4732-5p, and hsa-let-7b-5p were differentially expressed between PBMAH and adenoma (P = 0.019, 0.006, and 0.003, respectively). Furthermore, PBMAH could be classified into two subtypes based on miRNA profiling: subtype 1 with a similar profile to those of adenoma and subtype 2 with a distinct profile. Hsa-miR-631, hsa-miR-513b-5p, hsa-miR-6805-5p, and hsa-miR-548av-5p/548k were differentially expressed between PBMAH subtype 2 and adenoma (P = 0.027, 0.027, 0.027, and 1.53E-04, respectively), but not between PBMAH, as a whole, and adenoma.

CONCLUSION: Circulating miRNA signature was identified specific for PBMAH. The existence of subtype-based miRNA profiles may be associated with the pathophysiological heterogeneity of PBMAH.

PMID:36583003 | PMC:PMC9792611 | DOI:10.3389/fendo.2022.1073328

$Permalink for 'Repeated vertebral compression fractures in young adult may imply functional adrenal tumor'$

Repeated vertebral compression fractures in young adult may imply functional adrenal tumor

Fetched: January 2nd, 2023, 5:00am GMT

Neuro Endocrinol Lett. 2022 Dec 29;43(6). Online ahead of print.

ABSTRACT

Wernicke encephalopathy (WE) is an acute or subacute neurologic disorder resulting from thiamine deficiency. A Magnetic Resonance Imaging (MRI) test is useful in addition to the clinical manifestation, which is the main basis for the diagnosis. Typical MRI findings include areas surrounding the aqueduct and third ventricle, as well as those in the medial thalamus, dorsal medulla, tectal plate, and mamillary bodies. We reported a case of WE with extensive cortical lesions. The beneficial effects of thiamine supplementation and low dosage of glucocorticoid did not sustain after discharge. Eventually, we found that the condition he had was brought on by gastric diffuse large B-cell lymphoma. Thiamine supplements combined with glucocorticoids may be a good administration regimen. The etiology of WE is frequently disregarded. In individuals with WE, it is essential to take the underlying illness into account. Malignancy, especially gastrointestinal tract cancer, should be considered. A good administration regimen may include glucocorticoids and thiamine supplements.

PMID:36586126

A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma

Fetched: December 31st, 2022, 5:00am GMT by Yuanyuan Deng

Front Genet. 2022 Dec 13;13:796681. doi: 10.3389/fgene.2022.796681. eCollection 2022.

ABSTRACT

Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor derived from the adrenal cortex. Because of its highly aggressive nature, the prognosis of patients with adrenocortical carcinoma is not impressive. Hypoxia exists in the vast majority of solid tumors and contributes to invasion, metastasis, and drug resistance. This study aimed to reveal the role of hypoxia in Adrenocortical carcinoma and develop a hypoxia risk score (HRS) for Adrenocortical carcinoma prognostic prediction. Methods: Hypoxia-related genes were obtained from the Molecular Signatures Database. The training cohorts of patients with adrenocortical carcinoma were downloaded from The Cancer Genome Atlas, while another three validation cohorts with comprehensive survival data were collected from the Gene Expression Omnibus. In addition, we constructed a hypoxia classifier using a random survival forest model. Moreover, we explored the relationship between the hypoxia risk score and immunophenotype in adrenocortical carcinoma to evaluate the efficacy of immune check inhibitors (ICI) therapy and prognosis of patients. Results: HRS and tumor stage were identified as independent prognostic factors. HRS was negatively correlated with immune cycle activity, immune cell infiltration, and the T cell inflammatory score. Therefore, we considered the low hypoxia risk score group as the inflammatory immunophenotype, whereas the high HRS group was a non-inflammatory immunophenotype. In addition, the HRS was negatively related to the expression of common immune checkpoint molecules such as PD-L1, CD200, CTLA-4, and TIGIT, suggesting that patients with a lower hypoxia risk score respond better to immunotherapy. Conclusion: We developed and validated a novel hypoxia risk score to predict the immunophenotype and response of patients with adrenocortical carcinoma to immune check inhibitors therapy. These findings not only provide fresh prognostic indicators for adrenocortical carcinoma but also offer several promising treatment targets for this disease.

PMID:36583015 | PMC:PMC9792869 | DOI:10.3389/fgene.2022.796681

Permalink for 'Adrenocortical Carcinoma With Cushing's Syndrome and Extensive Tumor Thrombosis of the Inferior Vena Cava in a 30-Year-Old Filipino Female'

Adrenocortical Carcinoma With Cushing's Syndrome and Extensive Tumor Thrombosis of the Inferior Vena Cava in a 30-Year-Old Filipino Female

Fetched: December 31st, 2022, 5:00am GMT by Kristine Abas

J ASEAN Fed Endocr Soc. 2022;37(2):95-100. doi: 10.15605/jafes.037.02.10. Epub 2022 Aug 7.

ABSTRACT

Adrenocortical carcinoma (ACC) is a rare and aggressive neoplasm with poor prognosis. We report a case of a 30-year-old female who presented with profound classic features of an adrenocorticotrophic hormone (ACTH)-independent Cushing's syndrome (CS) and a large adrenal mass with massive venous tumor thrombosis of the entire inferior vena cava (IVC), left renal and adrenal veins confirmed by imaging. Adrenal biopsy histopathology and immunohistochemistry confirmed ACC. Systemic palliative chemotherapy was administered. This rare case presents a unique and atypical presentation of an extensive tumor thrombosis of IVC. With the advanced stage at diagnosis, aggressive nature and poor prognosis of the disease, there is still a need to determine viable therapeutic options for metastatic ACC associated with venous invasion.

PMID:36578899 | PMC:PMC9758552 | DOI:10.15605/jafes.037.02.10

Endocrine Testing for the Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)

Fetched: December 30th, 2022, 5:00am GMT by Rainer U. Pliquett

2022 Dec 22. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The diagnosis of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) relies on an adequate assessment of a hyponatremic state (that is a serum sodium level <136 mmol/l) and on the exclusion of other causative conditions leading to an appropriate secretion of antidiuretic hormone (ADH). The understanding of mechanisms involved in pathological ADH secretion is essential for diagnosis and therapy. Although some forms are due to dysregulation in central nervous system regulation, other forms are dependent on diseases in peripheral organs and structures including ADH-producing/secreting neuroendocrine tumors, while others are induced by drugs. ADH regulation is closely linked to other systems such as the sympathetic nervous system via and baroreflex regulation. Patients with hyponatremia should be assessed carefully whether or not neurological symptoms exist. Further, assessment of volume status is needed. Based on symptoms and volume status, the need for intensive-care monitoring is determined. In parallel, laboratory findings of blood and urine must be analyzed appropriately. It is important to demonstrate true hyponatremia, which is paralleled by a decrease in serum osmolality. Mandatory laboratory diagnostic steps comprise the determination of blood and urine electrolytes and serum and urine osmolality, analysis of thyroid, adrenocortical, and kidney function as well as uric acid. Different test results such as a high fractional uric acid excretion may hint to an existing SIADH. Assessment of urine osmolality and urine sodium concentration and intravascular volume level may allow for further discrimination and may be indicative for a specific underlying disorder, causing SIADH. Brain volume changes (“hydrocephalus ex vacuo”) may depend on age rendering the elderly more tolerant to acute or chronic serum sodium changes. The course of incident hyponatremia, if documented, may affect therapy. A serum sodium drop within less than 48 hours is considered acute hyponatremia. A rapid bolus of 100 to 150 ml of intravenous 3% hypertonic saline is appropriate to avoid catastrophic outcomes in severe cases of acute symptomatic hyponatremia. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905283 | Bookshelf:NBK279055

Ovarian Reserve Testing

Fetched: December 30th, 2022, 5:00am GMT by Amanda Deadmond

2022 Dec 21. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

The ovaries affect far more than reproductive health. Estrogen affects cardiovascular, skeletal, mental health, and numerous other aspects of wellness. Additionally, ovarian dysfunction can reflect disequilibrium relating to multiple conditions. Efficient and effective ovarian testing can give women valuable answers about their fertility, time to menopause, and other conditions and symptoms they may face. Though no test is perfect, antral follicle count (AFC) and anti- Müllerian hormone (AMH) provide more sensitive and specific results that allow for the continuum of ovarian function, and have advantages over classic tests such as follicle stimulating hormone (FSH), estradiol, the clomiphene citrate challenge test (CCCT), and others. This chapter explores these and additional ovarian assays, their underlying mechanisms, and limitations that may favor one test over another depending on circumstances. Particular emphasis is given to evaluating perimenopausal status, procreation, and etiologies for amenorrhea. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905286 | Bookshelf:NBK279058

Adrenal steroids and resistance to hormonal blockade of prostate and breast cancer

Fetched: December 30th, 2022, 5:00am GMT by Patrick Michael

Endocrinology. 2023 Jan 9;164(3):bqac218. doi: 10.1210/endocr/bqac218.

ABSTRACT

Prostate cancer and breast cancer are sex-steroid-dependent diseases that are driven in major part by gonadal sex steroids. Testosterone (T) is converted to 5α-dihydrotestosterone, both of which stimulate the androgen receptor (AR) and prostate cancer progression. Estradiol is the major stimulus for estrogen receptor-α (ERα) and proliferation of ERα-expressing breast cancer. However, the human adrenal provides an alternative source for sex steroids. A number of different androgens are produced by the adrenals, the most abundant of which is dehydroepiandrosterone (DHEA) and DHEA sulfate. These precursor steroids are subject to metabolism by peripherally expressed enzymes that are responsible for the synthesis of potent androgens and estrogens. In the case of prostate cancer, the regulation of one of these enzymatic steps occurs at least in part by way of a germline-encoded missense in 3β-hydroxysteroid dehydrogenase-1 (3βHSD1), which regulates potent androgen biosynthesis and clinical outcomes in men with advanced prostate cancer treated with gonadal T deprivation. The sex steroids that drive prostate cancer and breast cancer require a common set of enzymes for their generation. However, the pathways diverge once 3-keto, Δ4-androgens are generated and these steroids are either turned into potent androgens by steroid-5α-reductase, or into estrogens by aromatase. Alternative steroid receptors have also emerged as disease- and treatment-resistance modifiers, including a role for AR in breast cancer and glucocorticoid receptor both in breast and prostate cancer. In this review, we integrate the commonalities of adrenal steroid physiology that regulate both prostate and breast cancer while recognizing the clear distinctions between these diseases.

PMID:36580423 | DOI:10.1210/endocr/bqac218

A Rare Case of Aggressive Atypical Cervical Cancer With Multi-Organ Involvement

Fetched: December 30th, 2022, 5:00am GMT by Carina Hernandez

Cureus. 2022 Dec 26;14(12):e32968. doi: 10.7759/cureus.32968. eCollection 2022 Dec.

ABSTRACT

Squamous cell carcinoma (SCC) of cervical origin with metastasis to the brain is rare. Our patient was a 30-year-old Caucasian female with squamous cell carcinoma, initially with unknown primary, with metastases to the brain, kidney, cervix, lung, adrenal glands, vulva, pelvic wall, and scalp. She initially presented to her outpatient gynecologist for a vulvar mass. A biopsy of the vulvar mass was consistent with SCC. The patient continued to have fatigue along with thoracic rib pain. An initial work-up was performed, including imaging which showed diffuse metastatic disease involving the lungs, kidneys and adrenal glands, as well as a pathological compression fracture of the seventh thoracic vertebra with cord compression. Brain magnetic resonance imaging (MRI) showed multiple metastatic lesions and she underwent craniotomy for brain lesion resection. Given the aggressive nature of the patient's disease and her symptomatic burden, she was started on chemotherapy in the hospital with Carboplatin, Paclitaxel, and Pembrolizumab.

PMID:36578845 | PMC:PMC9792719 | DOI:10.7759/cureus.32968

HIV-related bilateral inflammatory myofibroblastic tumors of the adrenal gland: a case report and literature review

Fetched: December 28th, 2022, 5:00am GMT by Mengmeng Zhang

AIDS Res Ther. 2022 Dec 24;19(1):66. doi: 10.1186/s12981-022-00492-x.

ABSTRACT

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare disease that mostly occurs in younger people and is located in the lungs in the general population. We report a rare case of adrenal IMT in a patient with HIV infection, which is believed to be the first of its kind worldwide.

CASE PRESENTATION: We present a rare case of a 44-year-old man with HIV infection who was diagnosed with adrenal IMT. The patient refused regular highly active antiretroviral therapy 13 years ago until he was admitted to hospital after an adrenal mass was found. The patient underwent successful computed-tomography-guided needle biopsy, and pathological analysis showed fibroblastic-myofibroblastic proliferation with inflammatory infiltration, which confirmed a diagnosis of IMT. We failed to perform complete resection of the tumor because of its diffuse invasion. The patient was complicated with severe multiple pulmonary infections postoperatively because of immunodeficiency, which eventually caused his death 2 months later.

CONCLUSION: Differential diagnosis of IMT is difficult, and tumor biopsy is an essential means of diagnosis. Surgical resection is preferred for both adrenal and HIV-related IMTs. Conservative treatment should be considered when there are technical difficulties with complete resection, and most patients have achieved good outcomes. However, more cases and longer follow-up are warranted to confirm long-term outcomes of HIV-related IMT.

PMID:36566196 | PMC:PMC9789583 | DOI:10.1186/s12981-022-00492-x

Permalink for 'Risk prediction model establishment with tri-phasic CT image features for differential diagnosis of adrenal pheochromocytomas and lipid-poor adenomas: Grouping method'

Risk prediction model establishment with tri-phasic CT image features for differential diagnosis of adrenal pheochromocytomas and lipid-poor adenomas: Grouping method

Fetched: December 28th, 2022, 5:00am GMT by Zhongfeng Niu

Front Endocrinol (Lausanne). 2022 Dec 8;13:925577. doi: 10.3389/fendo.2022.925577. eCollection 2022.

ABSTRACT

OBJECTIVES: The purpose of this study was to establish a risk prediction model for differential diagnosis of pheochromocytomas (PCCs) from lipid-poor adenomas (LPAs) using a grouping method based on tri-phasic CT image features.

METHODS: In this retrospective study, we enrolled patients that were assigned to a training set (136 PCCs and 183 LPAs) from two medical centers, along with an external independent validation set (30 PCCs and 54 LPAs) from another center. According to the attenuation values in unenhanced CT (CTu), the lesions were divided into three groups: group 1, 10 HU < CTu ≤ 25 HU; group 2, 25 HU < CTu ≤ 40 HU; and group 3, CTu > 40 HU. Quantitative and qualitative CT imaging features were calculated and evaluated. Univariate, ROC, and binary logistic regression analyses were applied to compare these features.

RESULTS: Cystic degeneration, CTu, and the peak value of enhancement in the arterial and venous phase (DEpeak) were independent risk factors for differential diagnosis of adrenal PCCs from LPAs. In all subjects (groups 1, 2, and 3), the model formula for the differentiation of PCCs was as follows: Y = -7.709 + 3.617*(cystic degeneration) + 0.175*(CTu ≥ 35.55 HU) + 0.068*(DEpeak ≥ 51.35 HU). ROC curves were drawn with an AUC of 0.95 (95% CI: 0.927-0.973) in the training set and 0.91 (95% CI: 0.860-0.929) in the external validation set.

CONCLUSION: A reliable and practical prediction model for differential diagnosis of adrenal PCCs and LPAs was established using a grouping method.

PMID:36568104 | PMC:PMC9772429 | DOI:10.3389/fendo.2022.925577

Bladder paraganglioma treated with open partial cystectomy: a case report

Fetched: December 28th, 2022, 5:00am GMT by Tugay Aksakallı

J Med Case Rep. 2022 Dec 25;16(1):479. doi: 10.1186/s13256-022-03715-x.

ABSTRACT

BACKGROUND: Bladder paraganglioma is a neuroendocrine tumor that accounts for less than 0.1% of all bladder tumors. Symptoms caused by catecholamine release such as hypertension, palpitation, syncope, and macroscopic hematuria are the most common findings. Treatment modalities include transurethral resection, and partial or total cystectomy.

CASE PRESENTATION: A 38-year-old Turkish female patient was examined for hematuria that had been persisting for 6 months. Among the clinical findings, only hematuria was present. Absence of adrenergic symptoms such as hypertension, palpitations, and syncope at the first presentation made it difficult to consider bladder paraganglioma in the differential diagnosis. Therefore, cystoscopy and transurethral resection were performed with the thought of urothelial cancer. Findings such as hypertension and bradycardia that developed during diagnostic transurethral resection suggested that it might be bladder paraganglioma. After the radiological evaluation and endocrinological preparation, the patient underwent partial cystectomy.

CONCLUSION: The rarity of cases having been reported in the literature leads to uncertainties in the management of bladder paraganglioma. Adrenergic symptoms developing during transurethral resection should suggest paraganglioma in the differential diagnosis. A multidisciplinary approach and medical treatment are mandatory to prevent life-threatening complications such as hypertensive crisis, vascular collapse, and multiple-organ system failure. We aimed to report the clinical presentation that includes only macroscopic hematuria mimicking urothelial cancer and to emphasize the multidisciplinary approach in the treatment.

PMID:36566235 | PMC:PMC9790119 | DOI:10.1186/s13256-022-03715-x

Minimally invasive techniques in benign and malignant adrenal tumors

Fetched: December 27th, 2022, 5:00am GMT by Ahmet Bulent Dogrul

World J Clin Cases. 2022 Dec 16;10(35):12812-12821. doi: 10.12998/wjcc.v10.i35.12812.

ABSTRACT

Minimally invasive adrenalectomy has become the main treatment modality for most adrenal lesions. Both laparoscopic transabdominal and retroperitoneoscopic approaches are safe and feasible options, each with respective advantages, including better surgical outcomes, fewer complications, and faster recovery over open adrenalectomy. While open surgery remains a valid modality in treatment of adrenocortical cancer in the presence of some findings such as invasion, robotic platforms, and minimally invasive surgery have gained popularity as technology continues to evolve. Organ preservation during adrenalectomy is feasible in some conditions to prevent adrenal insufficiency. Ablative technologies are increasingly utilized in benign and malignant tumors, including the adrenal gland, with various outcomes. A multidisciplinary team, an experienced surgeon, and a high-volume center are recommended for any surgical approaches and management of adrenal lesions. This review article evaluated recent findings and current evidence on minimally invasive adrenalectomy.

PMID:36569018 | PMC:PMC9782958 | DOI:10.12998/wjcc.v10.i35.12812

Comparative Analysis of Laparoscopic and Robotic Transperitoneal Adrenalectomy Performed at a Single Institution

Fetched: December 27th, 2022, 5:00am GMT by Yun Suk Choi

Medicina (Kaunas). 2022 Nov 29;58(12):1747. doi: 10.3390/medicina58121747.

ABSTRACT

Background and Objectives: Laparoscopic adrenalectomy (LA) is the standard surgical approach for adrenalectomy. At present, robotic adrenalectomy (RA) has been introduced at various hospitals. This study evaluated our initial experience with robotic adrenalectomy compared with conventional laparoscopic adrenalectomy. Materials and&nbsp;Methods: From October 2018 to March 2022, 56 adrenalectomies were performed by a single endocrine surgeon. Thirty-two patients underwent LA (LA group), and twenty-four patients underwent RA (RA group). Results: Patients in the RA group were significantly younger than those in the LA group (48.6 ± 9.7 years vs. 55.1 ± 11.4 years, p = 0.013). The RA group had a shorter operation time than the LA group (76.1 ± 28.2 min vs. 118.0 ± 54.3 min, p < 0.001). The length of hospital stay and postoperative pain level between the two groups were similar. There were no complications in the RA group. There was no significant difference in the pathologic diagnosis between the two groups. The cost of surgery was significantly higher in the RA group than in the LA group (5288.5 US dollars vs. 441.5 ± 136.8 US dollars, p < 0.001). Conclusions: In our initial experience, RA showed a shorter operation time than LA and no complications. RA could be a viable alternative surgical option for adrenalectomy, notwithstanding its higher cost.

PMID:36556949 | PMC:PMC9786224 | DOI:10.3390/medicina58121747

Bioinformatics analysis: relationship between adrenocortical carcinoma and KIFs

Fetched: December 27th, 2022, 5:00am GMT by Xiao Li

Biotechnol Genet Eng Rev. 2022 Dec 26:1-11. doi: 10.1080/02648725.2022.2160560. Online ahead of print.

ABSTRACT

Adrenal cortical cancer has a relatively low incidence, but a dismal 5-year survival rate. Surgical intervention is the gold standard of care today. In spite of this progress, patients continue to have a dismal outlook. The results of this study demonstrate that kinin superfamily (KIF) has strong ties to many different types of cancers. However, their prognostic and immune cell infiltration of adrenocortical carcinoma (ACC) remain unclear. Multiple databases were searched for information on the transcription level of KIFs, its correlation with clinical data of ACC patients, patients' overall survival (OS), first progression survival (FPS), and progression free interval (PFI). Its role and association with immune cells were also investigated. We observed an increase in the expression of KIF4A, KIF11, KIF20A, and KIF22. There was a strong correlation between them and the advancedness of ACC tumors. Parallel to this, KIFs are connected to the concepts of operating systems, distributed file systems, and partitioned file systems. Similarly, we found five key genes, PRC1, PLK1, KIF23, KIFC1, and KIF5A, through data analysis, all of which participate in multiple cellular pathways. Both KIF4A and KIF11 expression levels were marginally positively correlated with immune infiltration. Because KIF4A, KIF11, KIF20A, and KIF22 are involved in multiple ACC processes and can influence the onset and progression of ACC, they provide a mechanistically grounded framework for diagnosing and managing the disease.

PMID:36572958 | DOI:10.1080/02648725.2022.2160560

Permalink for 'Corrigendum to "Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up": [Annals of Oncology volume 31 (2020) 1476-1490]'

Corrigendum to "Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up": [Annals of Oncology volume 31 (2020) 1476-1490]

Fetched: December 25th, 2022, 5:00am GMT by M Fassnacht

Ann Oncol. 2022 Dec 21:S0923-7534(22)04775-5. doi: 10.1016/j.annonc.2022.12.006. Online ahead of print.

NO ABSTRACT

PMID:36564283 | DOI:10.1016/j.annonc.2022.12.006

Congenital adrenal hyperplasia is a very rare cause of adrenal incidentalomas in Sweden

Fetched: December 24th, 2022, 5:00am GMT by Fredrik Sahlander

Front Endocrinol (Lausanne). 2022 Dec 5;13:1017303. doi: 10.3389/fendo.2022.1017303. eCollection 2022.

ABSTRACT

BACKGROUND: Undiagnosed congenital adrenal hyperplasia (CAH) can cause adrenal incidentalomas, but the frequency is unclear.

OBJECTIVES: This study aimed to investigate the prevalence of CAH in a population with adrenal incidentalomas and report the clinical characterization.

MATERIAL AND METHODS: This was a prospective study performed at a regional hospital from 2016 to 2021. Patients with adrenal incidentalomas were investigated with an adrenocorticotropic hormone (ACTH)-stimulation test in addition to hormonal workup. Serum cortisol and 17-hydroxyprogesterone (17OHP) were analyzed. Individuals with a basal or stimulated 17OHP ≥30 nmol/L were classified as suspicious non-classic CAH, and a CYP21A2-gene analysis was performed in these subjects.

RESULTS: In total, 320 individuals with adrenal incidentalomas were referred to the center, and of these individuals, an ACTH-stimulation test was performed in 222 (median age, 67 (24-87) years; 58.6% women; and 11.7% with bilateral lesions). None of the individuals presented a basal 17OHP ≥30 nmol/L, but there were 8 (3.6%) who did after ACTH stimulation. Four of these subjects (50%) presented bilateral lesions, and the tumor size was larger compared to that of the individuals with a stimulated 17OHP <30 nmol/L (median, 38 (19-66) vs. 19 (11-85) mm, p=0.001). A CYP21A2 variation (p.Val282Leu) was detected in one of the eight subjects with a stimulated 17OHP ≥30 nmol/L, i.e., the patient was a heterozygotic carrier. None of the eight subjects presented with cortisol insufficiency or clinical signs of hyperandrogenism.

CONCLUSIONS: The prevalence of non-classic CAH in an adrenal incidentaloma cohort was 3.6% based on stimulated 17OHP and 0% based on gene analysis. CAH should be considered in AI management in selected cases and confirmed by genetic analysis.

PMID:36545328 | PMC:PMC9760763 | DOI:10.3389/fendo.2022.1017303

Anti-PD-1 antibodies, a novel treatment option for advanced chemoresistant pulmonary lymphoepithelioma carcinoma

Fetched: December 24th, 2022, 5:00am GMT by Na Zhou

Front Immunol. 2022 Dec 6;13:1001414. doi: 10.3389/fimmu.2022.1001414. eCollection 2022.

ABSTRACT

BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (LELC) exhibits a unique immune microenvironment, including high PD-L1 expression and abundant infiltrating-immune cells. However, the availability of PD-1/PD-L1 inhibitors in patients with LELC is still not determined.

METHODS: A total of 36 cases of pulmonary LELC treated with PD-1/PD-L1 inhibitors were reviewed, including 10 cases from our institute and 26 cases included from the literature. The Kaplan-Meier method and log-rank test were utilized to analyze the survival outcomes of LELC patients receiving immunotherapy, and the factors related to immunotherapy response were further examined.

RESULTS: Of the 10 patients from our institute, the median age was 53.5 years, adrenal glands and distant lymph nodes were the most common metastatic sites, and 4 of 8 (50%) patients had a PD-L1 TPS ≥50%. The median progression-free survival and overall survival in patients from our institute and from the literature were 11.6 and 27.3 months, 17.2 months and not reached, respectively. In all 36 patients, the objective response rate was as high as 57.6%. Patients with higher PD-L1 expression were more likely to have a tumor response, but the association of PD-L1 expression with survival time remains to be determined.

CONCLUSIONS: PD-1/PD-L1 inhibitors in patients with pulmonary LELC demonstrated a promising efficacy in retrospective cohorts, and deserve further validation in prospective studies administrating in front-line setting.

PMID:36561745 | PMC:PMC9763302 | DOI:10.3389/fimmu.2022.1001414

Permalink for 'A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome'

A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome

Fetched: December 24th, 2022, 5:00am GMT by Ravina Rai

Front Cell Infect Microbiol. 2022 Dec 6;12:1042663. doi: 10.3389/fcimb.2022.1042663. eCollection 2022.

ABSTRACT

Cervical cancer is a dreaded form of cancer in women, the fourth most common cancer, with around 0.3 million females suffering from this disease worldwide. Over the past several decades, global researches have focused on the mitigation of cervical lesions and cancers and have explored the impact of physiological and psychological stress and insomnia on cervical pathogenesis. Furthermore, disruption of the cervicovaginal microbiome profiles is identified as an added high-risk factor for the occurrence of cervical cancer. The physiological regulation of stress has an underlying mechanism controlled via hypothalamic pituitary adrenal (HPA) and sympatho-adrenal medullary (SAM) axes. Disruptions in these axes have been identified as the factors responsible for maintaining the homeostasis balance. Recent studies on microbiomes have offered novel ways to combat cervical cancer and cervix infection by exploring the interplay of the cervicovaginal microbiome. Moreover, the integration of various immune cells and microbiome diversity is known to act as an effective strategy to decipher the cervix biological activity. Cytokine profiling and the related immune competence, and physiological stress and insomnia impart to the regulatory networks underlying the mechanism which may be helpful in designing mitigation strategies. This review addressed the current progress in the research on cervical cancer, HPV infection, immune cell interaction, and physiological stress and insomnia with the cervicovaginal microbiome to decipher the disease occurrence and therapeutic management.

PMID:36560927 | PMC:PMC9763463 | DOI:10.3389/fcimb.2022.1042663

Adverse Events of PD-1 or PD-L1 Inhibitors in Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis

Fetched: December 24th, 2022, 5:00am GMT by Yixi Zhang

Life (Basel). 2022 Nov 28;12(12):1990. doi: 10.3390/life12121990.

ABSTRACT

(1) Background: This study aimed to develop a comprehensive understanding of the treatment-related adverse events when using PD-1 or PD-L1 inhibitors in triple-negative breast cancer (TNBC). (2) Methods: We conducted a meta-analysis of Phase II/III randomized clinical trials. Studies were searched for using PubMed, Embase, and Cochrane Library from 1 March 1980 till 30 June 2022. Data on adverse events were mainly extracted from ClinicalTrials.gov and published articles. A generalized linear mixed model with the logit transformation was employed to obtain the overall incidence of adverse events across all studies. For serious adverse events with low incidences, the Peto method was used to calculate the odds ratio (OR) and 95% confidence interval (95%CI) in the PD-1 or PD-L1 inhibitors groups compared to the control groups. (3) Results: Nine studies were included in the meta-analysis, including a total of 2941 TNBC patients treated with PD-1 or PD-L1 inhibitors (including atezolizumab, pembrolizumab and durvalumab) and 2339 patients in the control groups. Chemotherapy alone was the control group in all studies. The average incidences of all serious immune-related adverse events of interest (hypothyroidism, hyperthyroidism, pneumonitis, pruritus, rash) were less than 1%, except for adrenal insufficiency (1.70%, 95%CI: 0.50-5.61%) in the PD-1 or PD-L1 groups. PD-1 or PD-L1 inhibitors significantly increased the risk of serious pneumonitis (OR = 2.52, 95%CI: 1.02-6.26), hypothyroidism (OR = 5.92, 95%CI: 1.22-28.86), alanine aminotransferase (ALT) elevation (OR = 1.66, 95%CI: 1.12-2.45), and adrenal insufficiency (OR = 18.81, 95%CI: 3.42-103.40). For non-serious adverse events, the patients treated with PD-1 or PD-L1 inhibitors had higher risk of aspartate aminotransferase (AST) elevation (OR =1.26, 95%CI: 1.02-1.57), hypothyroidism (OR = 3.63, 95%CI: 2.92-4.51), pruritus (OR = 1.84, 95%CI: 1.30-2.59), rash (OR = 1.29, 95%CI: 1.08-1.55), and fever (OR = 1.77, 95%CI: 1.13-2.77), compared with chemotherapy alone. (4) Conclusions: The incidence of serious immune-related adverse events in PD-1 or PD-L1 inhibitors groups is low but significantly higher than in chemotherapy groups. When using PD-1 or PD-L1 inhibitors for the treatment of TNBC, serious pneumonitis, hypothyroidism, ALT elevation, and adrenal insufficiency should be considered. Non-serious adverse events, such as AST elevation, rash, and fever, should also be taken into consideration.

PMID:36556355 | PMC:PMC9787874 | DOI:10.3390/life12121990

The Role of Apoptosis and Autophagy in the Hypothalamic-Pituitary-Adrenal (HPA) Axis after Traumatic Brain Injury (TBI)

Fetched: December 24th, 2022, 5:00am GMT by Serpil Taheri

Int J Mol Sci. 2022 Dec 10;23(24):15699. doi: 10.3390/ijms232415699.

ABSTRACT

Traumatic brain injury (TBI) is a major health problem affecting millions of people worldwide and leading to death or permanent damage. TBI affects the hypothalamic-pituitary-adrenal (HPA) axis either by primary injury to the hypothalamic-hypophyseal region or by secondary vascular damage, brain, and/or pituitary edema, vasospasm, and inflammation. Neuroendocrine dysfunctions after TBI have been clinically described in all hypothalamic-pituitary axes. We established a mild TBI (mTBI) in rats by using the controlled cortical impact (CCI) model. The hypothalamus, pituitary, and adrenals were collected in the acute (24 h) and chronic (30 days) groups after TBI, and we investigated transcripts and protein-related autophagy (Lc3, Bcln1, P150, Ulk, and Atg5) and apoptosis (pro-caspase-3, cleaved caspase-3). Transcripts related to autophagy were reduced in the hypothalamus, pituitary, and adrenals after TBI, however, this was not reflected in autophagy-related protein levels. In contrast, protein markers related to apoptosis increased in the adrenals during the acute phase and in the pituitary during the chronic phase. TBI stresses induce a variation of autophagy-related transcripts without modifying the levels of their proteins in the HPA axis. In contrast, protein markers related to apoptosis are increased in the acute phase in the adrenals, which could lead to impaired communication via the hypothalamus, pituitary, and adrenals. This may then explain the permanent pituitary damage with increased apoptosis and inflammation in the chronic phase. These results contribute to the elucidation of the mechanisms underlying endocrine dysfunctions such as pituitary and adrenal insufficiency that occur after TBI. Although the adrenals are not directly affected by TBI, we suggest that the role of the adrenals along with the hypothalamus and pituitary should not be ignored in the acute phase after TBI.

PMID:36555341 | PMC:PMC9778890 | DOI:10.3390/ijms232415699

Genotype-Phenotype Correlations and Clinical Outcomes in 155 Cases of Pheochromocytoma and Paraganglioma

Fetched: December 23rd, 2022, 5:00am GMT by Hogan Wang

World J Surg. 2022 Dec 22. doi: 10.1007/s00268-022-06862-w. Online ahead of print.

ABSTRACT

BACKGROUND: Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumours, often associated with germline mutations that influence the disease biology and clinical course. We aimed to describe the genotypic and phenotypic characteristics of a consecutive series of PPGL patients and correlate mutation status with clinical outcomes.

METHODS: We performed a retrospective cohort study of all PPGL patients who presented to a tertiary referral centre between March 2005 and February 2022. Genotypic, phenotypic and follow-up data were analysed.

RESULTS: A total of 140 patients were included. Of these, 94 (67%) patients underwent genetic testing and a mutation was detected in 36 (38%) patients. Mutation presence was associated with younger age, smaller tumour size and bilateral adrenal tumours. Disease recurrence occurred at a median time of 5.4 (IQR 2.8-11.0) years after treatment in 21 (15%) patients, of which 14 (67%) had a mutation in a susceptibility gene. Recurrence pattern was influenced by mutation type; higher local recurrence risk for SDHA, SDHB, and MEN2B disease, and higher metastatic risk for SDHB, VHL and MEN2A disease. Recurrence occurred in three (3%) patients with mutation absence. Multivariate analysis revealed that age ≤40 years and mutation presence were associated with increased risk of disease recurrence.

CONCLUSIONS: Genotypic characteristics strongly influence disease presentation and recurrence risk, which may occur more than 5 years after initial treatment. Routine genetic testing of PPGL patients is warranted given the high prevalence of mutations, allowing for prognostication and tailored follow-up. In the presence of germline mutations, follow-up should be life-long.

PMID:36550325 | DOI:10.1007/s00268-022-06862-w

$Permalink for 'Effectiveness of Low-Dose Ketamine Infusion in Opioid Refractory Cancer Pain: A Case Report'$

Effectiveness of Low-Dose Ketamine Infusion in Opioid Refractory Cancer Pain: A Case Report

Fetched: December 23rd, 2022, 5:00am GMT by Tuheen S Nath

Cureus. 2022 Nov 18;14(11):e31662. doi: 10.7759/cureus.31662. eCollection 2022 Nov.

ABSTRACT

Most patients with advanced cancer experience debilitating pain, which significantly affects their quality of life and has both physical and psychological implications. Opioids have been the mainstay of treatment for chronic cancer pain, but some people develop serious adverse effects or may become refractory to opioid use. There is always a need and search for alternative non-opioid analgesics with an acceptable safety profile, and one such drug is ketamine. In this era of evolving analgesic therapeutics, ketamine has been noted to have favourable results. Ketamine, a phencyclidine analogue, is an N-methyl-D-aspartate antagonist (NMDA), and it has been shown to have an analgesic effect at sub-anaesthetic doses by blocking NMDA-induced pain sensitization and enhancing opioid receptor sensitization. This is a case report of a 46-year-old Indian female with recurrent metastatic adenocarcinoma endometrium (International Federation of Obstetrics and Gynecology (FIGO) Grade II) involving the vaginal vault, rectum, and adrenal glands, along with para-rectal, bilateral iliac, and retroperitoneal nodal metastases, in which ketamine infusion was used successfully to alleviate the pain that was initially not controlled with an incremental dose of opioids. The patient presented with progressive pain in the peri-anal region, rated 8/10 on the Numerical Pain Rating Scale (NRS), following which she was treated with escalating doses of intravenous (IV) fentanyl, but with little to no relief. In view of the patient's opioid-resistant pain, she was started on a low-dose ketamine IV infusion (50 mg in 50 ml of 0.9% NS) as "burst therapy," at infusion rates of 0.02 mg/kg/hr-0.08 mg/kg/hr, with adequate pain relief occurring at 0.08 mg/kg/hr. Literature suggests weight-based dosing of ketamine ranging from 0.06 mg/kg/hr to 0.8 mg/kg/hr was previously used to achieve satisfactory results. In this patient, even lower doses were effectively used to achieve optimum long-term analgesia, cause an upliftment in the patient's overall mood and quality of life, and cause a significant reduction in opioid usage. However, further research is required to assess the efficacy of ketamine at such doses and its effect on opioid consumption. This case report will promote further study regarding optimum IV ketamine dosing and administration in the management of opioid-refractory pain in cancer patients, especially in the Indian population.

PMID:36545179 | PMC:PMC9762523 | DOI:10.7759/cureus.31662

In Situ Metabolomics of Cortisol-Producing Adenomas

Fetched: December 23rd, 2022, 5:00am GMT by Masanori Murakami

Clin Chem. 2022 Dec 21:hvac191. doi: 10.1093/clinchem/hvac191. Online ahead of print.

ABSTRACT

BACKGROUND: Recent advances in omics techniques have allowed detailed genetic characterization of cortisol-producing adrenal adenoma (CPA). In contrast, the pathophysiology of CPAs has not been elucidated in detail on the level of tumor metabolic alterations.

METHODS: The current study conducted a comprehensive mass spectrometry imaging (MSI) map of CPAs in relation to clinical phenotypes and immunohistochemical profiles of steroidogenic enzymes. The study cohort comprised 46 patients with adrenal tumors including CPAs (n = 35) and nonfunctional adenomas (n = 11).

RESULTS: Severity of cortisol hypersecretion was significantly correlated with 29 metabolites (adjusted P < 0.05). Adrenal androgens derived from the classic androgen pathway were inversely correlated with both cortisol secretion (rs = -0.41, adjusted P = 0.035) and CYP11B1 expression (rs = -0.77, adjusted P = 2.00E-08). The extent of cortisol excess and tumor CYP11B1 expression further correlated with serotonin (rs = 0.48 and 0.62, adjusted P = 0.008 and 2.41E-05). Tumor size was found to be correlated with abundance of 13 fatty acids (adjusted P < 0.05) and negatively associated with 9 polyunsaturated fatty acids including phosphatidic acid 38:8 (rs = -0.56, adjusted P = 0.009).

CONCLUSIONS: MSI reveals novel metabolic links between endocrine function and tumorigenesis, which will further support the understanding of CPA pathophysiology.

PMID:36544353 | DOI:10.1093/clinchem/hvac191

Androgens and Cardiovascular Disease in Men

Fetched: December 22nd, 2022, 5:00am GMT by Bu B. Yeap

2022 Dec 14. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Testosterone is the principal male sex hormone or androgen, which regulates sexual characteristics and body composition. Testosterone is converted to bioactive metabolites dihydrotestosterone and estradiol. Circulating testosterone peaks in early adulthood and declines gradually across middle and older age: older men exhibit lower testosterone and dihydrotestosterone concentrations compared to younger men. In older men, lower testosterone concentrations are associated with higher incidence of cardiovascular events. Lower testosterone and dihydrotestosterone concentrations have also been associated with higher cardiovascular mortality in older men. However, causation is unproven as a randomized placebo-controlled trial of testosterone treatment sufficiently powered to examine outcomes of cardiovascular events or mortality has yet to be reported. Potential mechanisms by which testosterone could exert beneficial actions in the vasculature include reduction in cholesterol accumulation and modulation of inflammation. Smaller randomized trials of testosterone therapy have shown improvements in surrogate endpoints related to cardiovascular risk. However, other trials of testosterone have not shown improvements in carotid atherosclerosis, as assessed by carotid intima-media thickness. One study reported an increase in coronary atheroma assessed using coronary computed tomography angiography in older men receiving testosterone therapy over 12 months. Although one randomized trial of testosterone therapy in older men with mobility limitations reported an excess of adverse events in the treatment arm, larger recent trials in middle-aged to older men did not find any excess of cardiovascular adverse events with testosterone treatment. Meta-analyses of testosterone trials generally have not shown an increase in cardiovascular adverse events. Retrospective case-control studies of health insurance databases have major methodological limitations. The results from such studies are inconsistent, associating testosterone prescriptions with either increased or decreased risk of cardiovascular events, and with lower mortality. While androgen deprivation in men with prostate cancer results in adverse metabolic effects, abuse of high dosages of androgenic steroids is associated with harm. Thus, while some epidemiological studies associate higher circulating concentrations (but within the normal range) of endogenous androgens with lower risk of cardiovascular events and mortality, the effects of exogenous androgens in the form of testosterone therapy seeking to maintain physiological circulating androgen concentrations on the cardiovascular system remain uncertain. This evidence gap has to be accommodated in the current clinical management of hypogonadal men and should be addressed by further randomized interventional studies to clarify whether testosterone treatment has beneficial, neutral or adverse effects on the cardiovascular system. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905374 | Bookshelf:NBK279151

Cryptorchidism and Hypospadias

Fetched: December 22nd, 2022, 5:00am GMT by John M. Hutson

ABSTRACT

Undescended testis (UDT) is a common abnormality, affecting about 1/20 males at birth. Half of these have delayed testicular descent, with the testis in the scrotum by 10-12 weeks after term. Beyond this spontaneous descent is rare. Current treatment recommendations are that UDT beyond 3 months of age need surgery before 12 months of age. Some children have scrotal testes in infancy but develop UDT later in childhood because the spermatic cord does not elongate with age, leaving the testes behind as the scrotum moves further from the groin with growth of the pelvis. This is now known as ascending/acquired cryptorchidism, and orchidopexy is controversial. Many authors recommend surgery once the testes no longer reside spontaneously in the scrotum, but some groups recommend conservative treatment. The fetal testis descends in 2 separate hormonal and anatomical steps, with the first step occurring between 8-15 weeks’ gestation. Insulin-like hormone 3 (INSL3) from developing Leydig cells stimulates the genito-inquinal ligament, or gubernaculum, to swell where it ends in the inguinal area of the abdominal wall. This holds the testis near the future inguinal canal as the fetal abdomen enlarges. By contrast, in female fetuses, lack of INSL3 allows the gubernaculum to elongate into a round ligament and lets the ovary move away from the groin. The second or inguinoscrotal phase is controlled by androgen and occurs between 25-35 weeks’ gestation, where the gubernaculum and testis migrate together to the scrotum. Androgens guide this complex process, both directly and indirectly via a neurotransmitter, calcitonin gene-related peptide (CGRP), released from the genitofemoral nerve. After migration is complete the proximal processus vaginalis closes (preventing inguinal hernia) and then the fibrous remnant disappears completely, allowing the spermatic cord to elongate with age, to keep the testis scrotal. The transabdominal phase is a simple mechanical process, and abnormalities are uncommon, with intra-abdominal testes found in 5-10% of boys with UDT. Anomalies of the complex inguinoscrotal phase account for most UDT seen clinically. The undescended testis suffers heat stress when not at the lower scrotal temperature (33 degrees Celsius), interfering with testicular physiology and development of germ cells into spermatogonia. UDT interrupts transformation of neonatal gonocytes into type-A spermatogonia, the putative spermatogenic stem cells at 3-9 months of age. Recent evidence suggests orchidopexy between 6-12 months improves germ cell development, with early reports of improved fertility, but little evidence yet for changes in malignancy prognosis. Hypospadias is also a common abnormality in newborn males, affecting about 1/150 boys. Androgens control masculinization of the genital tubercle into penis between 8-12 weeks’ gestation, with tubularization of the urethra from the perineum to the tip of the glans. If this process is disrupted hypospadias occurs, with a variable proximal urethral meatus, failed ventral preputial development producing a dorsal hood, and discrepancy in the ventral versus dorsal penile length, causing a ventral bend in the penis, known as chordee. Surgery to correct hypospadias is recommended between 6-18 months, as technical advances now allow operation to be done before the infant acquires long-term memory of the surgery. Severe hypospadias overlaps with disorders of sex development (DSD), so that babies without a fused scrotum containing 2 testes and who present with ‘hypospadias’ need full DSD investigations at birth. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905331 | Bookshelf:NBK279106

Male Contraception

Fetched: December 22nd, 2022, 5:00am GMT by David J. Handelsman

2022 Dec 8. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.

ABSTRACT

Men continue to have a strong interest and commitment to effective family planning. Traditional methods of male contraception have long included periodic abstinence, non-vaginal ejaculation, condoms, and vasectomy, the latter two representing physical methods to prevent sperm from reaching the site of fertilization. However, for male contraception the reversible methods are not reliable, and the only reliable method, vasectomy, is not intended as reversible. During the 20^th century, a wide array of reversible and highly reliable female hormonal contraceptive methods was marketed; however, no new methods for male fertility regulation have been introduced for centuries. For men to share more equally the burdens as well as the benefits of family planning, more effective reversible male contraceptive methods need to be available. Most studies into male contraception have been conducted with hormonal methods, analogous to well-known female hormonal contraceptives, making them the closest to introducing a reliable, reversible male contraceptive method. The most promising hormonal approach is the combination of an androgen (usually testosterone) with a progestin and multiple studies have shown such combinations of depot steroids displays high contraceptive efficacy, based on reliable and reversible suppression of sperm output, with few side effects. While research into novel methods for male fertility regulation has continued in the public sector, private sector research into male contraception, essential for effective commercial product development, has stalled in recent decades. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.

PMID:25905319 | Bookshelf:NBK279094

High expression of GMNN predicts malignant progression and poor prognosis in ACC

Fetched: December 21st, 2022, 5:00am GMT by Xinzhao Zhao

Eur J Med Res. 2022 Dec 20;27(1):301. doi: 10.1186/s40001-022-00950-2.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare endocrine neoplasm, which is characterized by poor prognosis and high recurrence rate. Novel and reliable prognostic and metastatic biomarkers are lacking for ACC patients. This study aims at screening potential prognostic biomarkers and therapeutic targets of ACC through bioinformatic methods and immunohistochemical (IHC) analysis.

METHODS: In the present study, by using the Gene Expression Omnibus (GEO) database we identified differentially expressed genes (DEGs) in ACC and validated these DEGs in The Cancer Genome Atlas (TCGA) ACC cohort. A DEGs-based signature was additionally constructed and we assessed its prognosis and prescient worth for ACC by survival analysis and nomogram. Immunohistochemistry (IHC) was used to verify the relationship between hub gene-GMNN expressions and clinicopathologic outcomes in ACC patients.

RESULTS: A total of 24 DEGs correlated with the prognosis of ACC were screened from the TCGA and GEO databases. Five DEGs were subsequently selected in a signature which was closely related to the survival rates of ACC patients and GMNN was identified as the core gene in this signature. Univariate and multivariate Cox regression showed that the GMNN was an independent prognostic factor for ACC patients (P < 0.05). Meanwhile, GMNN was closely related to the OS and PFI of ACC patients treated with mitotane (P < 0.001). IHC confirmed that GMNN protein was overexpressed in ACC tissues compared with normal adrenal tissues and significantly correlated with stage (P = 0.011), metastasis (P = 0.028) and Ki-67 index (P = 0.014).

CONCLUSIONS: GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.

PMID:36539849 | PMC:PMC9764478 | DOI:10.1186/s40001-022-00950-2

Low number of neurosecretory vesicles in neuroblastoma impairs massive catecholamine release and prevents hypertension

Fetched: December 21st, 2022, 5:00am GMT by Annick Mühlethaler-Mottet

Front Endocrinol (Lausanne). 2022 Dec 1;13:1027856. doi: 10.3389/fendo.2022.1027856. eCollection 2022.

ABSTRACT

INTRODUCTION: Neuroblastoma (NB) is a pediatric cancer of the developing sympathetic nervous system. It produces and releases metanephrines, which are used as biomarkers for diagnosis in plasma and urine. However, plasma catecholamine concentrations remain generally normal in children with NB. Thus, unlike pheochromocytoma and paraganglioma (PHEO/PGL), two other non-epithelial neuroendocrine tumors, hypertension is not part of the usual clinical picture of patients with NB. This suggests that the mode of production and secretion of catecholamines and metanephrines in NB is different from that in PHEO/PGL, but little is known about these discrepancies. Here we aim to provide a detailed comparison of the biosynthesis, metabolism and storage of catecholamines and metanephrines between patients with NB and PHEO.

METHOD: Catecholamines and metanephrines were quantified in NB and PHEO/PGL patients from plasma and tumor tissues by ultra-high pressure liquid chromatography tandem mass spectrometry. Electron microscopy was used to quantify neurosecretory vesicles within cells derived from PHEO tumor biopsies, NB-PDX and NB cell lines. Chromaffin markers were detected by qPCR, IHC and/or immunoblotting.

RESULTS: Plasma levels of metanephrines were comparable between NB and PHEO patients, while catecholamines were 3.5-fold lower in NB vs PHEO affected individuals. However, we observed that intratumoral concentrations of metanephrines and catecholamines measured in NB were several orders of magnitude lower than in PHEO. Cellular and molecular analyses revealed that NB cell lines, primary cells dissociated from human tumor biopsies as well as cells from patient-derived xenograft tumors (NB-PDX) stored a very low amount of intracellular catecholamines, and contained only rare neurosecretory vesicles relative to PHEO cells. In addition, primary NB expressed reduced levels of numerous chromaffin markers, as compared to PHEO/PGL, except catechol O-methyltransferase and monoamine oxidase A. Furthermore, functional assays through induction of chromaffin differentiation of the IMR32 NB cell line with Bt2cAMP led to an increase of neurosecretory vesicles able to secrete catecholamines after KCl or nicotine stimulation.

CONCLUSION: The low amount of neurosecretory vesicles in NB cytoplasm prevents catecholamine storage and lead to their rapid transformation by catechol O-methyltransferase into metanephrines that diffuse in blood. Hence, in contrast to PHEO/PGL, catecholamines are not secreted massively in the blood, which explains why systemic hypertension is not observed in most patients with NB.

PMID:36531507 | PMC:PMC9751011 | DOI:10.3389/fendo.2022.1027856

Individualized medical treatment options in Cushing disease

Fetched: December 21st, 2022, 5:00am GMT by Aleksandra Gilis-Januszewska

Front Endocrinol (Lausanne). 2022 Dec 2;13:1060884. doi: 10.3389/fendo.2022.1060884. eCollection 2022.

ABSTRACT

Cushing disease (CD) is caused by a pituitary tumor which oversecretes adrenocorticotropic hormone (ACTH). It is a serious endocrine disease associated with increased mortality and impaired quality of life. The management of CD remains challenging. Although transsphenoidal surgery is the treatment of choice in most cases, in approximately half of CD patients, second or third-line treatment options are needed. Currently, new medical therapies are available which target adrenal steroidogenesis, pituitary somatostatin and dopamine receptors, and glucocorticoid receptors. Selection of which medication to use should be individualized and is determined by many factors including severity of the disease, possible side effects, patients preferences and local availability. The aim of this article is to describe currently available medical therapy to help clinicians individualize the treatment options in the context of recently updated Pituitary Society recommendations.

PMID:36531477 | PMC:PMC9755355 | DOI:10.3389/fendo.2022.1060884

Permalink for 'Rectal leiomyosarcoma as the initial phenotypic manifestation of Li-Fraumeni-like syndrome: a case report and review of the literature'

Rectal leiomyosarcoma as the initial phenotypic manifestation of Li-Fraumeni-like syndrome: a case report and review of the literature

Fetched: December 21st, 2022, 5:00am GMT by Natalia Parisi Severino

J Med Case Rep. 2022 Dec 19;16(1):468. doi: 10.1186/s13256-022-03671-6.

ABSTRACT

BACKGROUND: Leiomyosarcoma is a rare malignant tumor of smooth muscle origin and represents 10-20% of all soft tissue sarcomas. Primary colon and rectal sarcomas constitute < 0.1% of all large bowel malignancies. In Li-Fraumeni syndrome, sarcomas are the second most frequent cancer (25%). Li-Fraumeni syndrome is a genetic disease with a familial predisposition to multiple malignant neoplasms. This syndrome has an autosomal dominant pattern of inheritance and high penetrance characterized by germline TP53 mutations. Patients with a history of cancer who do not meet all the "classic" criteria for Li-Fraumeni syndrome are considered to have Li-Fraumeni-like syndrome. To the best of our knowledge, this article is the first report of a patient with rectal leiomyosarcoma as the initial phenotypic manifestation of Li-Fraumeni-like syndrome. The authors also present a literature review.

CASE PRESENTATION: A 67-year-old Brazilian woman underwent anterior rectosigmoidectomy and panhysterectomy secondary to rectal leiomyosarcoma. She subsequently developed carcinomatosis and died 2 years after the operation. Her family medical history consisted of a daughter who died at 32 years of age from breast cancer, a granddaughter diagnosed with adrenocortical carcinoma at 6 years of age and two siblings who died from prostate cancer. A genetic study was carried out to identify a pathogenic variant of Li-Fraumeni syndrome. In the DNA extracted from the peripheral blood leukocyte, restriction fragment length polymorphism was analyzed to search for mutations in the TP53 gene. The DNA sequencing identified the germline pathogenic variant p. R337H heterozygous in exon 10 of TP53. The patient was classified as having Li-Fraumeni-like syndrome.

CONCLUSION: In patients with rectal leiomyosarcoma, it is advisable to investigate the family history of cancer and perform genetic studies to screen for Li-Fraumeni syndrome.

PMID:36529791 | PMC:PMC9761972 | DOI:10.1186/s13256-022-03671-6

Adrenocortical carcinoma presenting with upper intestinal bleeding in a patient with risk factors for gastric ulcer

Fetched: December 21st, 2022, 5:00am GMT by Karla Mariaca

Endocrinol Diabetes Nutr (Engl Ed). 2022 Dec;69(10):910-911. doi: 10.1016/j.endien.2021.12.008.

NO ABSTRACT

PMID:36526356 | DOI:10.1016/j.endien.2021.12.008

Adrenal nodules for the non-specialist: What to look out for and when to refer

Fetched: December 21st, 2022, 5:00am GMT by Alex J Graveling

J R Coll Physicians Edinb. 2022 Dec;52(4):350-356. doi: 10.1177/14782715221138467. Epub 2022 Nov 30.

NO ABSTRACT

PMID:36451593 | DOI:10.1177/14782715221138467

Adrenal Vein Sampling as a Tool to Identify Biomarkers That Aid the Diagnosis of Adrenocortical Carcinoma

Posted: December 21st, 2022, 3:00pm GMT

Condition: Adrenocortical Carcinoma
Intervention: Other: Blood sampling.
Sponsor: Erasmus Medical Center
Recruiting

B7-H3-Specific Chimeric Antigen Receptor Autologous T-Cell Therapy for Pediatric Patients With Solid Tumors (3CAR)

Posted: May 21st, 2021, 2:00pm GMT

ONCOCYTIC ADRENOCORTICAL CARCINOMA IN A YOUNG PATIENT

Fetched: January 27th, 2023, 5:00am GMT by Y Singh

Acta Endocrinol (Buchar). 2022 Jul-Sep;18(3):383-386. doi: 10.4183/aeb.2022.383.

ABSTRACT

CONTEXT: Adrenocortical carcinoma (ACC) is a rare neoplasm with an aggressive course and poor prognosis. The worldwide incidence is about 0.5 to 2 cases per million population per year. Oncocytic adrenocortical carcinoma is a rare histopathological variant of ACC with only a few reported cases in the literature.

CASE REPORT: We report a case of an oncocytic variant of adrenocortical carcinoma in a 21-year-old male patient who presented with a left adrenal mass. Imaging studies confirmed a large left adrenal mass with involvement of the left renal vein and inferior vena cava. Endocrine workup showed mildly elevated serum cortisol levels.

DISCUSSION: Oncocytic AAC is a rare histopathological variant of ACC, as well as a rare subgroup of oncocytic adrenal neoplasms Hormonally active or functioning adrenocortical carcinomas most commonly secrete cortisol whereas co-secretion of multiple steroid hormones is a rare phenomenon.

CONCLUSIONS: Surgery remains the mainstay of treatment, but most of the patients present late with large masses and eventually become unsuitable for curative resection.

PMID:36699174 | PMC:PMC9867804 | DOI:10.4183/aeb.2022.383

Morphological predictors of the efficacy of mitotane therapy in adrenocortical cancer

Fetched: January 26th, 2023, 5:00am GMT by A V Tkachuk

Probl Endokrinol (Mosk). 2023 Jan 8;68(6):76-88. doi: 10.14341/probl13172.

ABSTRACT

AIM: To assess the immunohistochemical expression of RRM1, CYP2W1 and SOAT1 in ACC as markers of clinical outcomes and response to the therapy with mitotane.

PMID:36689714 | DOI:10.14341/probl13172

Rare Cancers of Childhood Treatment (PDQ®): Patient Version

Fetched: January 25th, 2023, 5:00am GMT by PDQ Pediatric Treatment Editorial Board

2023 Jan 19. In: PDQ Cancer Information Summaries [Internet]. Bethesda (MD): National Cancer Institute (US); 2002–.

ABSTRACT

This PDQ cancer information summary has current information about the treatment of rare cancers of childhood. It is meant to inform and help patients, families, and caregivers. It does not give formal guidelines or recommendations for making decisions about health care.

Editorial Boards write the PDQ cancer information summaries and keep them up to date. These Boards are made up of experts in cancer treatment and other specialties related to cancer. The summaries are reviewed regularly and changes are made when there is new information. The date on each summary ("Date Last Modified") is the date of the most recent change. The information in this patient summary was taken from the health professional version, which is reviewed regularly and updated as needed, by the PDQ Pediatric Treatment Editorial Board.

PMID:26389276 | Bookshelf:NBK65835

Permalink for 'Fluoro-2-Deoxyglucose-Positron Emission Tomography/Computed Tomography in the Diagnosis and Management of Adrenocortical Carcinoma: A 10-Year Experience from a Tertiary Care Institute'

Fluoro-2-Deoxyglucose-Positron Emission Tomography/Computed Tomography in the Diagnosis and Management of Adrenocortical Carcinoma: A 10-Year Experience from a Tertiary Care Institute

Fetched: January 24th, 2023, 5:00am GMT by Venkata Subramanian Krishnaraju

Indian J Nucl Med. 2022 Jul-Sep;37(3):227-235. doi: 10.4103/ijnm.ijnm_4_22. Epub 2022 Nov 2.

ABSTRACT

PURPOSE: Adrenocortical carcinoma (ACC) is a rare primary malignancy of the adrenal gland. The present study was aimed to compare the performance of fluoro-2-deoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) compared to contrast-enhanced computed tomography (CECT) in diagnosis and management of ACC.

MATERIALS AND METHODS: A retrospective analysis of the PET-CT studies from January 2010 to October 2020 was performed. Patients with adrenal lesions suspicious of ACC and diagnosed cases of ACC who underwent PET-CT for staging, restaging, and surveillance were reanalyzed. The PET-CT parameters were compared with the clinical, biochemical, histopathological, and CECT parameters.

RESULTS: The study included 96 scans performed in 77 patients (36 males, aged 40.4 ± 17.9 years). Of these, 55 scans were performed to diagnose and stage suspected ACC (30 of them diagnosed as ACC), 31 for restaging, and 10 scans for surveillance of ACC. PET/CT revealed metastases from an extra-adrenal primary in 5/55 patients. FDG-PET-CT had a sensitivity and specificity of 100% and 70% to diagnose ACC. Standardized uptake value-peak more than 5.4 had a sensitivity of 90.9% and specificity of 91.7% for differentiating ACC from non-ACC lesions, while tumor-to-liver ratio peak (TLRpeak) of 3.3 was most specific. PET-CT changed the staging in 23.3% of the patients with an accuracy of 100%. PET-CT changed the management plan in 25.8% of the patients during restaging with a sensitivity and specificity of 95.6% and 100%, respectively. For surveillance, CECT was as sensitive as PET-CT; however, PET-CT was more specific (100% vs. 97.9%).

CONCLUSION: FDG-PET-CT performs better than CECT in the diagnosis, staging, restaging, and surveillance of ACC.

PMID:36686301 | PMC:PMC9855239 | DOI:10.4103/ijnm.ijnm_4_22

Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment

Fetched: January 24th, 2023, 5:00am GMT by Keqiang Lu

Front Genet. 2023 Jan 4;13:996180. doi: 10.3389/fgene.2022.996180. eCollection 2022.

ABSTRACT

PMID:36685952 | PMC:PMC9845395 | DOI:10.3389/fgene.2022.996180

The prognosis difference between elderly and younger patients with adrenocortical carcinoma

Fetched: January 24th, 2023, 5:00am GMT by Shengyin He

Front Genet. 2023 Jan 4;13:1029155. doi: 10.3389/fgene.2022.1029155. eCollection 2022.

ABSTRACT

PMID:36685908 | PMC:PMC9845245 | DOI:10.3389/fgene.2022.1029155

Establishment of prognostic models of adrenocortical carcinoma using machine learning and big data

Fetched: January 24th, 2023, 5:00am GMT by Jun Tang

Front Surg. 2023 Jan 6;9:966307. doi: 10.3389/fsurg.2022.966307. eCollection 2022.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant tumor with a short life expectancy. It is important to identify patients at high risk so that doctors can adopt more aggressive regimens to treat their condition. Machine learning has the advantage of processing complicated data. To date, there is no research that tries to use machine learning algorithms and big data to construct prognostic models for ACC patients.

METHODS: Clinical data of patients with ACC were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. These records were screened according to preset inclusion and exclusion criteria. The remaining data were applied to univariate survival analysis to select meaningful outcome-related candidates. Backpropagation artificial neural network (BP-ANN), random forest (RF), support vector machine (SVM), and naive Bayes classifier (NBC) were chosen as alternative algorithms. The acquired cases were grouped into a training set and a test set at a ratio of 8:2, and a 10-fold cross-validation method repeated 10 times was performed. Area under the receiver operating characteristic (AUROC) curves were used as indices of efficiency.

RESULTS: The calculated 1-, 3-, 5-, and 10-year overall survival rates were 62.3%, 42.0%, 34.9%, and 26.1%, respectively. A total of 825 patients were included in the study. In the training set, the AUCs of BP-ANN, RF, SVM, and NBC for predicting 1-year survival status were 0.921, 0.885, 0.865, and 0.854; those for predicting 3-year survival status were 0.859, 0.865, 0.837, and 0.831; and those for 5-year survival status were 0.888, 0.872, 0.852, and 0.841, respectively. In the test set, AUCs of these four models for 1-year survival status were 0.899, 0.875, 0.886, and 0.862; those for 3-year survival status were 0.871, 0.858, 0.853, and 0.869; and those for 5-year survival status were 0.841, 0.783, 0.836, and 0.867, respectively. The consequences of the 10-fold cross-validation method repeated 10 times indicated that the mean values of 1-, 3-, and 5-year AUROCs of BP-ANN were 0.890, 0.847, and 0.854, respectively, which were better than those of other classifiers (P < 0.008).

CONCLUSION: The model combined with BP-ANN and big data can precisely predict the survival status of ACC patients and has the potential for clinical application.

PMID:36684185 | PMC:PMC9857757 | DOI:10.3389/fsurg.2022.966307

In Silico Pan-Cancer Analysis Reveals Prognostic Role of the Erythroferrone (ERFE) Gene in Human Malignancies

Fetched: January 22nd, 2023, 5:00am GMT by Qingyu Xu

Int J Mol Sci. 2023 Jan 15;24(2):1725. doi: 10.3390/ijms24021725.

ABSTRACT

The erythroferrone gene (ERFE), also termed CTRP15, belongs to the C1q tumor necrosis factor-related protein (CTRP) family. Despite multiple reports about the involvement of CTRPs in cancer, the role of ERFE in cancer progression is largely unknown. We previously found that ERFE was upregulated in erythroid progenitors in myelodysplastic syndromes and strongly predicted overall survival. To understand the potential molecular interactions and identify cues for further functional investigation and the prognostic impact of ERFE in other malignancies, we performed a pan-cancer in silico analysis utilizing the Cancer Genome Atlas datasets. Our analysis shows that the ERFE mRNA is significantly overexpressed in 22 tumors and affects the prognosis in 11 cancer types. In certain tumors such as breast cancer and adrenocortical carcinoma, ERFE overexpression has been associated with the presence of oncogenic mutations and a higher tumor mutational burden. The expression of ERFE is co-regulated with the factors and pathways involved in cancer progression and metastasis, including activated pathways of the cell cycle, extracellular matrix/tumor microenvironment, G protein-coupled receptor, NOTCH, WNT, and PI3 kinase-AKT. Moreover, ERFE expression influences intratumoral immune cell infiltration. Conclusively, ERFE is aberrantly expressed in pan-cancer and can potentially function as a prognostic biomarker based on its putative functions during tumorigenesis and tumor development.

PMID:36675239 | PMC:PMC9864255 | DOI:10.3390/ijms24021725

Emerging Perspectives on the Antiparasitic Mebendazole as a Repurposed Drug for the Treatment of Brain Cancers

Fetched: January 22nd, 2023, 5:00am GMT by Daniela Meco

Int J Mol Sci. 2023 Jan 10;24(2):1334. doi: 10.3390/ijms24021334.

ABSTRACT

Repurposing approved non-antitumor drugs is a promising and affordable strategy in drug discovery to identify new therapeutic uses different from the original medical indication that may help increase the number of possible, effective anticancer drugs. The use of drugs in ways other than their original FDA-approved indications could offer novel avenues such as bypassing the chemoresistance and recurrence seen with conventional therapy and treatment; moreover, it can offer a safe and economic strategy for combination therapy. Recent works have demonstrated the anticancer properties of the FDA-approved drug Mebendazole. This synthetic benzimidazole proved effective against a broad spectrum of intestinal Helminthiasis. Mebendazole can penetrate the blood-brain barrier and has been shown to inhibit the malignant progression of glioma by targeting signaling pathways related to cell proliferation, apoptosis, or invasion/migration, or by increasing the sensitivity of glioma cells to conventional chemotherapy or radiotherapy. Moreover, several preclinical models and ongoing clinical trials explore the efficacy of Mebendazole in multiple cancers, including acute myeloid leukemia, brain cancer, oropharyngeal squamous cell carcinoma, breast cancer, gastrointestinal cancer, lung carcinoma, adrenocortical carcinoma, prostate cancer, and head and neck cancer. The present review summarizes central literature regarding the anticancer effects of MBZ in cancer cell lines, animal tumor models, and clinical trials to suggest possible strategies for safe and economical combinations of anticancer therapies in brain cancer. Mebendazole might be an excellent candidate for the treatment of brain tumors because of its efficacy both when used as monotherapy and in combination as an enhancement to standard chemotherapeutics and radiotherapy, due to its effectiveness on tumor angiogenesis inhibition, cell cycle arrest, apoptosis induction, and targeting of critical pathways involved in cancer such as Hedgehog signaling. Therefore, attention to MBZ repurposing has recently increased because of its potential therapeutic versatility and significant clinical implications, such as reducing medical care costs and optimizing existing therapies. Using new treatments is essential, particularly when current therapeutics for patients with brain cancer fail.

PMID:36674870 | PMC:PMC9862092 | DOI:10.3390/ijms24021334

Identifying Immune-Specific Subtypes of Adrenocortical Carcinoma Based on Immunogenomic Profiling

Fetched: January 22nd, 2023, 5:00am GMT by Qiqi Lu

Biomolecules. 2023 Jan 4;13(1):104. doi: 10.3390/biom13010104.

ABSTRACT

BACKGROUND: The tumor immune microenvironment (TIME) of adrenocortical carcinoma (ACC) is heterogeneous. However, a classification of ACC based on the TIME remains unexplored.

PMID:36671489 | PMC:PMC9855412 | DOI:10.3390/biom13010104

Favourable prognosis in metastatic adrenal carcinoma: An unexpected outcome

Fetched: January 21st, 2023, 5:00am GMT by Imran Hassan

J Pak Med Assoc. 2022 Oct;72(10):2101-2104. doi: 10.47391/JPMA.3494.

ABSTRACT

PMID:36661007 | DOI:10.47391/JPMA.3494

Dyskeratosis Congenita and Related Telomere Biology Disorders

Fetched: January 20th, 2023, 5:00am GMT by Sharon A Savage

2009 Nov 12 [updated 2023 Jan 19]. In: Adam MP, Everman DB, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023.

ABSTRACT

CLINICAL CHARACTERISTICS: Dyskeratosis congenita and related telomere biology disorders (DC/TBD) are caused by impaired telomere maintenance resulting in short or very short telomeres. The phenotypic spectrum of telomere biology disorders is broad and includes individuals with classic dyskeratosis congenita (DC) as well as those with very short telomeres and an isolated physical finding. Classic DC is characterized by a triad of dysplastic nails, lacy reticular pigmentation of the upper chest and/or neck, and oral leukoplakia, although this may not be present in all individuals. People with DC/TBD are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome or acute myelogenous leukemia, solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), taurodontism, liver disease, gastrointestinal telangiectasias, and avascular necrosis of the hips or shoulders. Although most persons with DC/TBD have normal psychomotor development and normal neurologic function, significant developmental delay is present in both forms; additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome and Coats plus syndrome). Onset and progression of manifestations of DC/TBD vary: at the mild end of the spectrum are those who have only minimal physical findings with normal bone marrow function, and at the severe end are those who have the diagnostic triad and early-onset BMF.

DIAGNOSIS/TESTING: A majority of individuals with DC/TBD have abnormally short telomeres for their age, as determined by multicolor flow cytometry fluorescence in situ hybridization (flow-FISH) on lymphocyte subsets. To date, ACD, CTC1, DKC1, NAF1, NHP2, NOP10, PARN, POT1, RPA1, RTEL1, STN1, TERC, TERT, TINF2, WRAP53, and ZCCHC8 are the genes in which pathogenic variants are known to cause DC/TBD and to result in very short telomeres. Pathogenic variants in one of these 16 genes have been identified in approximately 80% of individuals who meet clinical diagnostic criteria for DC/TBD.

MANAGEMENT: Treatment of manifestations: Treatment is tailored to the individual. Hematopoietic cell transplantation (HCT) is the only curative treatment for BMF and leukemia, but long-term outcome has historically been poor due to treatment toxicity; if a suitable donor is not available, androgen therapy may be considered for BMF. Treatment of other cancers is tailored to the type of cancer. Of note, cancer therapy may pose an increased risk for prolonged cytopenias as well as pulmonary and hepatic toxicity. Treatment of pulmonary fibrosis is primarily supportive, although lung transplantation may be considered.

Surveillance: For BMF: complete blood count (CBC) annually if normal and more often if abnormal; annual bone marrow aspirate and biopsy. For those on androgen therapy: routine monitoring of CBC, liver function, liver ultrasound, and endocrinology evaluation. For cancer risk: monthly self-examination for oral, head, and neck cancer; annual cancer screening by an otolaryngologist and dermatologist; annual gynecologic examination. For pulmonary fibrosis: annual pulmonary function tests starting either at diagnosis or when the individual can perform the test (often age ~8 years); bubble echocardiogram to look for pulmonary arteriovenous malformations if suspected based on clinical symptoms. Routine dental screening every six months and good oral hygiene are recommended.

Agents/circumstances to avoid: Blood donation by family members if HCT is being considered; non-leukodepleted and non-irradiated blood products; the combination of androgens and granulocyte colony-stimulating factor in treatment of BMF (has been associated with splenic rupture); toxic agents implicated in tumorigenesis (e.g., smoking, excessive sun exposure).

Evaluation of relatives at risk: If a relative has signs or symptoms suggestive of DC/TBD or is being evaluated as a potential HCT donor, telomere length testing – or, if the pathogenic variant(s) in the family are known, molecular genetic testing – is warranted.

GENETIC COUNSELING: The mode of inheritance of DC/TBD varies by gene:

X-linked: DKC1
Autosomal dominant: NAF1, RPA1, TERC, TINF2, and ZCCHC8
Autosomal dominant or autosomal recessive: ACD, PARN, RTEL1, and TERT
Autosomal recessive: CTC1, NHP2, NOP10, POT1, STN1, and WRAP53

Genetic counseling regarding risk to family members depends on accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing. Once the DC/TBD-related pathogenic variant(s) have been identified in an affected family member, prenatal and preimplantation genetic testing are possible.

PMID:20301779 | Bookshelf:NBK22301

Adrenocortical carcinoma metastasis. A long story

Fetched: January 20th, 2023, 5:00am GMT by Federico Mascioli

Ann Ital Chir. 2022 Dec 27;11:S2239253X22038555.

ABSTRACT

INTRODUCTION: Adrenocortical Carcinoma (ACC) is an uncommon adrenal tumor with a predilection for the female population.

KEY WORDS: Adrenocortical carcinoma, Cholecystectomy, Liver metastasis, Thermoablation.

PMID:36655977

Permalink for 'The management of post-operative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients'

The management of post-operative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients

Fetched: January 20th, 2023, 5:00am GMT by Anna Calabrese

Eur J Endocrinol. 2023 Jan 10;188(1):lvad002. doi: 10.1093/ejendo/lvad002.

ABSTRACT

OBJECTIVE: The management of adrenocortical carcinoma (ACC) recurrences remains controversial, and we present herein our experience with postoperative ACC recurrences.

DESIGN AND METHODS: Retrospective analysis in a single reference center of 106 patients with ACC recurrence.

RESULTS: The median follow-up was 45 months, the median recurrence-free survival (RFS) 12 months (IQR 6-23), and the median overall survival (OS) 45 months (IQR 29-75). ACC recurrences occurred as a unique lesion (group A) in 35.8%, multiple lesions in a single organ (group B) in 20.8%, and affecting multiple organs (group C) in 43.4% of patients. Baseline characteristics of patients stratified by the type of recurrence did not differ between them, except RFS, which was significantly longer in group A. Locoregional treatments were used in 100% of patients of group A, 68.2% in group B, and 26.1% in group C. After treatment of recurrence, 60.4% of patients became free of disease attaining a second RFS of 15 months (IQR 6-64). Margin status RX and R1, percent increase in Ki67, and recurrence in multiple organs were associated with an increased risk of mortality, while adjuvant mitotane treatment and longer time to first recurrence were associated with reduced risk. Recurrence in multiple organs and systemic treatment of recurrence had a negative impact on survival from the treatment of recurrence.

CONCLUSIONS: This study shows that patients with ACC have a better prognosis when the disease recurs as a single lesion and supports the use of locoregional treatments to treat disease recurrence.

PMID:36655273 | DOI:10.1093/ejendo/lvad002

The Etiological Profile of Adrenal Incidentalomas

Fetched: January 20th, 2023, 5:00am GMT by Fatima-Zahra Lahmamssi

Cureus. 2022 Dec 15;14(12):e32564. doi: 10.7759/cureus.32564. eCollection 2022 Dec.

ABSTRACT

Introduction An adrenal incidentaloma (AI) is an unsuspected tumor in one or both adrenal glands, which is discovered incidentally on an imaging exam not prompted by adrenal exploration. The etiologies can be multiple; they condition therapeutic management. The objective of our study is to describe the etiological and therapeutic profiles of AI in our department. Materials and methods A retrospective study was carried out in the Endocrinology, Diabetology, and Nutrition Department of the Hassan II University Hospital of Fez on patients managed for AI from September 2009 until March 2022. We included all the patients who were followed and/or hospitalized for adrenal incidentalomas. Results There were 86, predominantly female, patients (67.85%). The mean age was 58.91+/-14.40 years. The clinical findings were a unilateral adrenal mass in 73.25% of patients, localized on the left in 39.53%, on the right in 33.72%, and a bilateral one in 26.75%. Its size varied from 12 to 196 mm, with an average of 35.5 mm. The most common etiologies found in our series were a non-functional adrenal adenoma in 54.56%, a subclinical cortisolic adenoma in 19.76%, an adrenocortical carcinoma in 5.81%, and a pheochromocytoma in 5.81%. Adrenalectomy was indicated in 19.76% of our patients, 17.44% were monitored closely, 20.94% were monitored for comorbidities, and 41.86% had been advised to abstain from treatment. Conclusion An adrenal incidentaloma has become more and more frequent. It constitutes an entity with various etiologies, which can be serious. The main etiology in our series was non-functioning adrenal adenoma, for which therapeutic abstention was indicated in 48% of cases.

PMID:36654569 | PMC:PMC9840518 | DOI:10.7759/cureus.32564

Elevated sphingosine-1-phosphate lyase leads to increased metabolism and reduced survival in adrenocortical carcinoma

Fetched: January 19th, 2023, 5:00am GMT by Jack L Williams

Eur J Endocrinol. 2023 Jan 10;188(1):lvac007. doi: 10.1093/ejendo/lvac007.

ABSTRACT

CONCLUSIONS: We, therefore, propose that SGPL1-overexpressing ACC tumours reduce patient survival by increasing fuel usage for anabolism and energy production to facilitate growth and invasion.

PMID:36651165 | DOI:10.1093/ejendo/lvac007

Permalink for 'Carbonic anhydrases III and IX are new players in the crosstalk between adrenocortical carcinoma and its altered adipose microenvironment'

Carbonic anhydrases III and IX are new players in the crosstalk between adrenocortical carcinoma and its altered adipose microenvironment

Fetched: January 17th, 2023, 5:00am GMT by L Fei

J Endocrinol Invest. 2023 Jan 16. doi: 10.1007/s40618-023-02008-4. Online ahead of print.

ABSTRACT

PURPOSE: Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC.

RESULTS/METHODS: CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (n = 14) (fold increase FI = 7.4 ± 0.1, P < 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06, P < 0.001), compared with lower stages (n = 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11, P < 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1, P < 0.01, respectively).

CONCLUSION: Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.

PMID:36646964 | DOI:10.1007/s40618-023-02008-4

The role of multimodal salvage therapy in the management of recurrent adrenocortical carcinoma

Fetched: January 12th, 2023, 5:00am GMT by Toshiki Kijima

Jpn J Clin Oncol. 2023 Jan 10:hyac207. doi: 10.1093/jjco/hyac207. Online ahead of print.

ABSTRACT

BACKGROUND: Adrenocortical carcinoma is an aggressive tumor which often recurs despite apparent complete resection. This study assessed the long-term outcomes for patients with recurrent adrenocortical carcinoma after multimodal salvage therapy with chemotherapy, chemoradiotherapy and surgery.

METHODS: We retrospectively reviewed medical records of patients who had a pathological diagnosis of adrenocortical carcinoma between 1996 and 2017. Kaplan-Meier curves were used to assess progression-free and cancer-specific survivals among all patients and cancer-specific survival among patients with tumor recurrence. Log-rank test was used to compare patient survivals by modality of salvage therapy (chemotherapy, chemoradiotherapy and chemotherapy/chemoradiotherapy plus surgery).

RESULTS: Of 20 patients who underwent initial surgery, recurrence occurred in 14 (70%) with a median interval of 7.5 (range 1.0-12.6) months. Salvage therapy provided was chemotherapy only (n = 7), chemoradiotherapy (n = 2) and chemotherapy/chemoradiotherapy plus surgery (n = 5). Of the five patients who received salvage surgery, three underwent repeated resections. The potential benefit of multimodal salvage therapy was suggested in five patients (4 with chemotherapy/chemoradiotherapy plus surgery and 1 with chemoradiotherapy) who achieved durable disease control (cancer-specific survival from initial recurrence, 22-258 months). With a median follow-up of 25 months from recurrence, the 5-year cancer-specific survival rate was 58%. cancer-specific survival after recurrence was prolonged in patients with ≤ stage 3 disease, positive response to chemotherapy/chemoradiotherapy and salvage surgery.

CONCLUSIONS: Long-term disease control and survival could be achieved in highly selected patients with recurrent adrenocortical carcinoma using a multidisciplinary approach. Patients who had relatively limited recurrent sites and responded well to chemotherapy/chemoradiotherapy may be considered for salvage surgery on a case-by-case basis.

PMID:36629278 | DOI:10.1093/jjco/hyac207

SARS-CoV-2-correlated ASGR1 is a novel potential marker for the treatment and identification of multiple human cancers

Fetched: January 12th, 2023, 5:00am GMT by Tao Huang

Am J Transl Res. 2022 Dec 15;14(12):8862-8878. eCollection 2022.

ABSTRACT

OBJECTIVES: Cancer patients are reported to be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the COVID-19 (the Corona Virus Disease 2019) patients with cancer suffer from certain serious complications. ASGR1 has been recently identified as a novel receptor of SARS-CoV-2 in human cells; however, there are limited studies on ASGR1 in various human cancers.

METHODS: This study utilized a comprehensive analysis of COVID-19-related ASGR1 in multiple human cancers based on 18,589 multi-center samples. Using Wilcoxon rank-sum analysis, a difference in ASGR1 expression between cancer and control tissues was detected. Cox regression analysis, Kaplan-Meier curves, and receiver operating characteristic curves were utilized to determine the correlation between ASGR1 expression and the clinical parameters of cancer patients. The immune relevance and potential mechanisms of ASGR1 in various cancers were also investigated.

RESULTS: Abnormal ASGR1 mRNA expression was observed in 16 of 20 different cancers (e.g., it was upregulated in colon adenocarcinoma but downregulated in cholangiocarcinoma; P < 0.05). ASGR1 was related to prognosis, e.g., overall survival, in 14 cancers (P < 0.05), such as adrenocortical carcinoma. The gene was also found to be a potential marker that can be utilized to distinguish eleven cancers from controls with moderate to high accuracy (e.g., the area under the curve for cholangiocarcinoma = 1.000). ASGR1 expression was related to DNA methyltransferases, mismatch repair genes, immune checkpoints, levels of tumor mutational burden, microsatellite instability, neoantigen count, and immune infiltration levels in certain cancers (P < 0.05). The gene plays a role in multiple cancers by affecting four signaling pathways, such as cytokine-cytokine receptor interaction. Cancer patients with high ASGR1 expression are sensitive to 25 drugs, including ulixertinib.

CONCLUSIONS: SARS-CoV-2-correlated ASGR1 is a novel marker that can be used for treating and identifying multiple human cancers.

PMID:36628237 | PMC:PMC9827325

Adrenocortical carcinoma with venous tumor invasion: is there a role for mini-invasive surgery?

Fetched: January 11th, 2023, 5:00am GMT by Alberto Olivero

Langenbecks Arch Surg. 2023 Jan 10;408(1):17. doi: 10.1007/s00423-023-02765-z.

ABSTRACT

OBJECTIVE: This study aims to investigate early oncologic outcomes in patients with adrenocortical carcinoma (ACC) with venous invasion (VI) treated using both open and mini-invasive approaches.

PMID:36625975 | DOI:10.1007/s00423-023-02765-z

Precocious puberty in a child: A rare cause and review of literature

Fetched: January 10th, 2023, 5:00am GMT by Thulasiraj Saminathan

J Family Med Prim Care. 2022 Oct;11(10):6523-6525. doi: 10.4103/jfmpc.jfmpc_376_22. Epub 2022 Oct 31.

ABSTRACT

Precocious puberty (PP) in pediatric office practice is challenging as the cause varies from benign to malignant conditions. Adrenocortical tumors are rare in childhood and pseudo-precocious puberty is the most common clinical presentation in children. We report a case of a 5-year-old boy who presented with features of abdominal distention and virilization, and his abdominal magnetic resonance imaging (MRI) revealed an adrenal tumor which was confirmed as adrenocortical carcinoma by biopsy. This case report highlights the importance of the awareness among general practioners and pediatricians to rule out adrenocortical tumors while evaluating a child with PP.

PMID:36618181 | PMC:PMC9810850 | DOI:10.4103/jfmpc.jfmpc_376_22

Huge Hematoma as First Manifestation of Adrenocortical Carcinoma: A Case Report

Fetched: January 10th, 2023, 5:00am GMT by Siavash Świeczkowski-Feiz

Am J Case Rep. 2023 Jan 9;24:e937569. doi: 10.12659/AJCR.937569.

ABSTRACT

PMID:36617747 | DOI:10.12659/AJCR.937569

Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis

Fetched: January 9th, 2023, 5:00am GMT by Hans K Ghayee

Int J Mol Sci. 2022 Dec 29;24(1):584. doi: 10.3390/ijms24010584.

ABSTRACT

PMID:36614027 | PMC:PMC9820690 | DOI:10.3390/ijms24010584

Permalink for 'Outcome for Pediatric Adreno-Cortical Tumors Is Best Predicted by the COG Stage and Five-Item Microscopic Score-Report from the German MET Studies'

Outcome for Pediatric Adreno-Cortical Tumors Is Best Predicted by the COG Stage and Five-Item Microscopic Score-Report from the German MET Studies

Fetched: January 9th, 2023, 5:00am GMT by Michaela Kuhlen

Cancers (Basel). 2022 Dec 30;15(1):225. doi: 10.3390/cancers15010225.

ABSTRACT

BACKGROUND: Adrenocortical tumors (ACTs) encompassing the adrenocortical adenoma (ACA), carcinoma (ACC), and tumors of undetermined malignant potential (ACx) are rare endocrine neoplasms with a poor prognosis. We report on pediatric ACT patients registered with the Malignant Endocrine Tumor studies and explore the EXPeRT recommendations for management.

PATIENTS: Data from the ACT patients (<18 years) were analyzed. For the risk prediction, the patients were retrospectively assigned to the COG stages and the five-item score.

RESULTS: By December 2021, 161 patients with ACT (ACA n = 51, ACx n = 19, and ACC n = 91) had been reported (the median age at the diagnosis was 4.3 years with a range of 0.1-17.8), with lymph node and distant metastases in 10.7% and 18.9% of the patients with ACC/ACx. The mean follow-up was 4.5 years (with a range of 0-16.7). The three-year overall (OS) and event-free survival (EFS) rates were 65.5% and 50.6%. In the univariate analyses, the OS was impaired for patients aged ≥ 4 years (p = 0.001) with the initial biopsy (p = 0.016), tumor spillage (p = 0.028), incomplete tumor resection (p < 0.001), unfavorable histology (p = 0.047), and COG stages III/IV (p = 0.002). Multivariate analysis revealed COG stages III/IV and an unfavorable five-item score as independent negative prognostic factors for the EFS and OS.

CONCLUSIONS: Age defines the clinical presentation and prognosis in pediatric ACTs. The outcome is best predicted by the COG stage and five-item score.

PMID:36612221 | PMC:PMC9818514 | DOI:10.3390/cancers15010225

68Ga-DOTAGA-IAC PET/CT for Imaging Metastatic and Recurrent Adrenocortical Carcinoma: A Case Series

Fetched: January 7th, 2023, 5:00am GMT by Somit Pandey

Clin Nucl Med. 2023 Feb 1;48(2):e95-e98. doi: 10.1097/RLU.0000000000004497.

ABSTRACT

PMID:36607383 | DOI:10.1097/RLU.0000000000004497

Coincidence of primary adrenocortical carcinoma and melanoma: three CASE reports

Fetched: January 6th, 2023, 5:00am GMT by Ye Lynn Ko

BMC Endocr Disord. 2023 Jan 6;23(1):4. doi: 10.1186/s12902-022-01253-7.

ABSTRACT

PMID:36604647 | PMC:PMC9817389 | DOI:10.1186/s12902-022-01253-7

In silico drug screen reveals potential competitive MTHFR inhibitors for clinical repurposing

Fetched: January 5th, 2023, 5:00am GMT by Nazlıgül Keske

J Biomol Struct Dyn. 2023 Jan 4:1-14. doi: 10.1080/07391102.2022.2163697. Online ahead of print.

ABSTRACT

MTHFR (Methylenetetrahydrofolate reductase) is a pivotal enzyme involved in one-carbon metabolism, which is critical for the proliferation of cancer cells. In line with this, published literature showed that MTHFR knockdown caused impaired growth of multiple types of cancer cells. Moreover, higher MTHFR expression levels were linked to shorter overall survival in hepatocellular carcinoma, adrenocortical carcinoma, and low-grade glioma, bringing the need to design MTHFR inhibitors as a possible treatment option. No competitive inhibitors of MTHFR have been reported as of today. This study aimed to identify potential competitive MTHFR inhibitor candidates using an in silico drug screen. A total of 30470 molecules containing biogenic compounds, FDA-approved drugs, and those in clinical trials were screened against the catalytic pocket of MTHFR in the presence and absence of cofactors. Binding energy and ADMET analysis revealed that Vilanterol (β2-adrenergic agonist), Selexipag (prostacyclin receptor agonist), and Ramipril Diketopiperazine (ACE inhibitor) are potential competitive inhibitors of MTHFR. Molecular dynamics analyses and MM-PBSA calculations with these compounds particularly revealed the amino acids between 285-290 for ligand binding and highlighted Vilanterol as the strongest candidate for MTHFR inhibition. Our results could guide the development of novel MTHFR inhibitor compounds, which could be inspired by the drugs brought into the spotlight here. More importantly, these potential candidates could be quhickly tested as a repurposing strategy in pre-clinical and clinical studies of the cancers mentioned above.Communicated by Ramaswamy H. Sarma.

PMID:36597898 | DOI:10.1080/07391102.2022.2163697

A pan-cancer analysis of the oncogenic role of polypyrimidine tract binding protein 1 (PTBP1) in human tumors

Fetched: January 4th, 2023, 5:00am GMT by Qing Huang

Medicine (Baltimore). 2022 Dec 30;101(52):e32428. doi: 10.1097/MD.0000000000032428.

ABSTRACT

BACKGROUND: Polypyrimidine tract-binding protein 1 (PTBP1) is an RNA-binding protein that regulates several posttranscriptional events and is closely related to the development of multiple tumors. However, little is known about PTBP1. Thus, we carried out a systematic pan-cancer analysis to explore the relationship between PTBP1 and cancer.

METHODS: We used The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas datasets, as well as several bioinformatics tools, to explore the role of PTBP1 in 33 tumor types.

RESULTS: The expression of PTBP1 in most tumor tissues was higher than that in normal tissues. Survival analysis indicated that overexpression of PTBP1 generally predicted poor overall survival in patients with tumors such as adrenocortical carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, and skin cutaneous melanoma. In addition, we compared the phosphorylation and immune infiltration of PTBP1 in cancer-associated fibroblasts between normal and primary tumor tissues and explored the putative functional mechanism of tumorigenesis mediated by PTBP1.

CONCLUSION: These results provide clues to better understand PTBP1 from the perspective of bioinformatics and highlight its importance in various human cancers.

PMID:36595978 | PMC:PMC9803410 | DOI:10.1097/MD.0000000000032428

Effective treatment with mitotane for a canine case of presumed ectopic Cushing's syndrome-related pheochromocytoma

Fetched: January 3rd, 2023, 5:00am GMT by Konatsu Miura

Open Vet J. 2022 Sep-Oct;12(5):762-767. doi: 10.5455/OVJ.2022.v12.i5.22. Epub 2022 Oct 10.

ABSTRACT

CONCLUSION: This is the first report that describes the effectiveness of mitotane against presumed ECS-related pheochromocytoma.

PMID:36589399 | PMC:PMC9789766 | DOI:10.5455/OVJ.2022.v12.i5.22

Clinical characteristics and pre-surgery diagnostic criteria of aldosterone-producing adrenocortical carcinoma

Fetched: December 31st, 2022, 5:00am GMT by Xinyi Zhang

Chin Med J (Engl). 2022 Oct 20;135(20):2512-2514. doi: 10.1097/CM9.0000000000002415.

NO ABSTRACT

PMID:36583872 | DOI:10.1097/CM9.0000000000002415

A hypoxia risk score for prognosis prediction and tumor microenvironment in adrenocortical carcinoma

Fetched: December 31st, 2022, 5:00am GMT by Yuanyuan Deng

Front Genet. 2022 Dec 13;13:796681. doi: 10.3389/fgene.2022.796681. eCollection 2022.

ABSTRACT

PMID:36583015 | PMC:PMC9792869 | DOI:10.3389/fgene.2022.796681

Permalink for 'Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumors in dogs and identifies CYP26B1 as a potential new therapeutic target'

Transcriptome sequencing reveals two subtypes of cortisol-secreting adrenocortical tumors in dogs and identifies CYP26B1 as a potential new therapeutic target

Fetched: December 31st, 2022, 5:00am GMT by Karin Sanders

Vet Comp Oncol. 2022 Dec 29. doi: 10.1111/vco.12871. Online ahead of print.

ABSTRACT

Cushing's syndrome (CS) is a serious endocrine disorder that is relatively common in dogs, but rare in humans. In ~15%-20% of cases, CS is caused by a cortisol-secreting adrenocortical tumour (csACT). To identify differentially expressed genes that can improve prognostic predictions after surgery and represent novel treatment targets, we performed RNA sequencing on csACTs (n = 48) and normal adrenal cortices (NACs; n = 10) of dogs. A gene was declared differentially expressed when the adjusted p-value was <.05 and the log2 fold change was >2 or < -2. Between NACs and csACTs, 98 genes were differentially expressed. Based on the principal component analysis (PCA) the csACTs were separated in two groups, of which Group 1 had significantly better survival after adrenalectomy (p = .002) than Group 2. Between csACT Group G1 and Group 2, 77 genes were differentially expressed. One of these, cytochrome P450 26B1 (CYP26B1), was significantly associated with survival in both our canine csACTs and in a publicly available data set of 33 human cortisol-secreting adrenocortical carcinomas. In the validation cohort, CYP26B1 was also expressed significantly higher (p = .012) in canine csACTs compared with NACs. In future studies it would be interesting to determine whether CYP26B1 inhibitors could inhibit csACT growth in both dogs and humans.

PMID:36582114 | DOI:10.1111/vco.12871

Adrenocortical Carcinoma With Cushing's Syndrome and Extensive Tumor Thrombosis of the Inferior Vena Cava in a 30-Year-Old Filipino Female

Fetched: December 30th, 2022, 5:00am GMT by Kristine Abas

J ASEAN Fed Endocr Soc. 2022;37(2):95-100. doi: 10.15605/jafes.037.02.10. Epub 2022 Aug 7.

ABSTRACT

PMID:36578899 | PMC:PMC9758552 | DOI:10.15605/jafes.037.02.10

Bioinformatics analysis: relationship between adrenocortical carcinoma and KIFs

Fetched: December 27th, 2022, 5:00am GMT by Xiao Li

Biotechnol Genet Eng Rev. 2022 Dec 26:1-11. doi: 10.1080/02648725.2022.2160560. Online ahead of print.

ABSTRACT

PMID:36572958 | DOI:10.1080/02648725.2022.2160560

Permalink for 'Impact of multimodal therapy on margin status on overall survival for patients undergoing adrenalectomy for localized adrenocortical carcinoma'

Impact of multimodal therapy on margin status on overall survival for patients undergoing adrenalectomy for localized adrenocortical carcinoma

Fetched: December 27th, 2022, 5:00am GMT by Kyle Hickey

Indian J Urol. 2022 Oct-Dec;38(4):276-281. doi: 10.4103/iju.iju_77_22. Epub 2022 Oct 1.

ABSTRACT

INTRODUCTION: Adrenocortical carcinoma is a rare malignancy that typically presents with advanced features and carries a poor prognosis. Complete surgical resection offers patients the best survival outcomes, but this is not always achievable and many require additional therapy for advanced features. Some literature has explored the role of chemotherapy and radiation, but little has been conducted to explore the effects of multimodal therapy.

METHODS: We retrospectively reviewed the National Cancer Database for adults with primary nonmetastatic adrenocortical carcinoma (ACC) who underwent either partial or radical adrenalectomy. Excluded patients included those with metastatic disease and those with primary tumor >30 cm. Patients were categorized based on adjuvant treatment; chemotherapy, radiation therapy (RT), RT + chemotherapy, or no adjuvant therapy. Overall survival (OS) was compared using survival curves, log rank tests, and multivariate survival analysis.

RESULTS: We identified 1644 patients with localized ACC treated with adrenalectomy. The median tumor size was 10.6 cm. A total of 278 patients had positive margin status (R1), and 416 patients had nodal (pN+) disease. Out of all patients, a minority (39.4%) received adjuvant therapy, which was most commonly given as chemotherapy only. Statistically significant increase in OS was noted with the use of RT + chemotherapy in the node-negative, margins-positive (pN0/pNx; R1) subgroup versus patients who did not receive adjuvant therapy (5-year OS 60.5% and 28.2%, respectively [P = 0.002]). This held true on multivariate analysis with significant improvement in OS in the pN0/pNx; R1 population with RT + chemotherapy compared to those who received no treatment (hazard ratio: 0.40 [95% confidence interval: 0.2-0.9], P = 0.02).

CONCLUSIONS: Our findings support the use of adjuvant chemotherapy plus RT in patients with positive surgical margins and no nodal disease. Additional studies are required to confirm these findings, clarify the objective benefit of multimodal therapy, and to determine the optimal chemotherapy/RT combination.

PMID:36568465 | PMC:PMC9787443 | DOI:10.4103/iju.iju_77_22

Effects of o,p'-DDE, a Mitotane Metabolite, in an Adrenocortical Carcinoma Cell Line

Fetched: December 24th, 2022, 5:00am GMT by Camila Bach

Pharmaceuticals (Basel). 2022 Nov 29;15(12):1486. doi: 10.3390/ph15121486.

ABSTRACT

In South Brazil, the incidence of pediatric adrenocortical carcinoma (ACC) is higher than in other regions and countries worldwide. The ACC treatment includes therapy with mitotane, the only adrenolytic drug approved by the FDA. The mitotane metabolism occurs via two main reactions: the β-hydroxylation, which yields the final product o,p'-DDA, and the α-hydroxylation, which will give the final product o,p'-DDE. It is speculated that o,p'-DDE may be an active metabolite since it has a cytotoxic effect on adrenocortical carcinoma cells (H295R). No further studies have been conducted to confirm this hypothesis; however, it was found that mitotane and its metabolites are present at significantly different concentrations in the plasma of the patients. Our study aimed to assess the in vitro effects of o,p'-DDE and o,p'-DDD in cell death pathways, oxidative parameters, and interaction with adrenal CYP's involved in the steroidogenic process in the H295R cell line. It was found that o,p'-DDE had a different effect than the o,p'-DDD on apoptosis, inhibiting this cell death pathway, but it promotes cell necrosis at higher concentrations. In contrast to o,p'-DDD, the o,p'-DDE did not have effects on the different oxidative parameters evaluated, but exhibited stimulatory interactions with steroidogenic CYP's, at intermediate concentrations. Therefore, we demonstrated important cell effects of o,p'-DDE; its plasma levels during mitotane therapy should be monitored as an important therapeutic parameter.

PMID:36558937 | PMC:PMC9784234 | DOI:10.3390/ph15121486

A Pan-Cancer Landscape of ABCG2 across Human Cancers: Friend or Foe?

Fetched: December 24th, 2022, 5:00am GMT by Chen Lyu

Int J Mol Sci. 2022 Dec 15;23(24):15955. doi: 10.3390/ijms232415955.

ABSTRACT

Emerging evidence from research or clinical studies reported that ABCG2 (ATP-binding cassette sub-family G member 2) interrelates with multidrug resistance (MDR) development in cancers. However, no comprehensive pan-cancer analysis is available at present. Therefore, we explore multiple databases, such as TCGA to investigate the potential therapeutic roles of ABCG2 across 33 different tumors. ABCG2 is expressed on a lower level in most cancers and shows a protective effect. For example, a lower expression level of ABCG2 was detrimental to the survival of adrenocortical carcinoma (TCGA-ACC), glioblastoma multiforme (GBM), and kidney renal clear cell carcinoma (KIRC) patients. Distinct associations exist between ABCG2 expression and stemness scores, microenvironmental scores, microsatellite instability (MSI), and tumor mutational burden (TMB) of tumor patients. We observed a significant positive correlation between the ABCG2 mutation site and prognosis in uterine corpus endometrial carcinoma (UCEC) patients. Moreover, transmembrane transporter activity and hormone biosynthetic-associated functions were found to be involved in the functionality of ABCG2 and its related genes. The cDNAs of cancer cell lines were collected to detect exon mutation sequences and to analyze ABCG2 mRNA expression. The mRNA expression level of ABCG2 showed a significant difference among spheres and drug-resistant cancer cell lines compared with their corresponding adherent cancer cell lines in six types of cancer. This pan-cancer study provides, for the first time, a comprehensive understanding of the multifunctionality of ABCG2 and unveils further details of the potential therapeutic role of ABCG2 in pan-cancer.

PMID:36555598 | PMC:PMC9784838 | DOI:10.3390/ijms232415955

Non-Functioning Adrenocortical Carcinoma Presenting as Retroperitoneal Hemorrhage With Early Metastasis

Fetched: December 23rd, 2022, 5:00am GMT by Zabih Ullah Khan

Cureus. 2022 Nov 19;14(11):e31665. doi: 10.7759/cureus.31665. eCollection 2022 Nov.

ABSTRACT

Adrenocortical cancer is a rare neoplasm with varied clinical presentation and overall poor outcome. This should be managed with timely intervention at highly specialized centers. Our aim is to report this rare case presentation of large non-functional adrenocortical cancer, complicated by spontaneous rupture while awaiting workup leading to life-threatening hemorrhage. Despite successful emergency radical surgical management and achieving negative margins, the patient developed early recurrence as intra-abdominal metastasis within two months. This can likely be attributed to the aggressive nature of the tumor as indicated by the high Ki-67 index or spillage of the tumor cells following spontaneous rupture. We recommend managing these non-functioning adrenocortical cancers as early as possible at highly specialized centers with reference to published standard guidelines.

PMID:36545164 | PMC:PMC9761335 | DOI:10.7759/cureus.31665

High expression of GMNN predicts malignant progression and poor prognosis in ACC

Fetched: December 21st, 2022, 5:00am GMT by Xinzhao Zhao

Eur J Med Res. 2022 Dec 20;27(1):301. doi: 10.1186/s40001-022-00950-2.

ABSTRACT

CONCLUSIONS: GMNN is a novel tumor marker for predicting the malignant progression, metastasis and prognosis of ACC, and may be a potential therapeutic target for ACC.

PMID:36539849 | PMC:PMC9764478 | DOI:10.1186/s40001-022-00950-2

Rectal leiomyosarcoma as the initial phenotypic manifestation of Li-Fraumeni-like syndrome: a case report and review of the literature

Fetched: December 19th, 2022, 5:00am GMT by Natalia Parisi Severino

J Med Case Rep. 2022 Dec 19;16(1):468. doi: 10.1186/s13256-022-03671-6.

ABSTRACT

CONCLUSION: In patients with rectal leiomyosarcoma, it is advisable to investigate the family history of cancer and perform genetic studies to screen for Li-Fraumeni syndrome.

PMID:36529791 | PMC:PMC9761972 | DOI:10.1186/s13256-022-03671-6

Ferroptosis Biomarkers for Predicting Prognosis and Immunotherapy Efficacy in Adrenocortical Carcinoma

Fetched: December 18th, 2022, 5:00am GMT by Chengquan Shen

Arch Med Res. 2023 Jan;54(1):45-55. doi: 10.1016/j.arcmed.2022.12.003. Epub 2022 Dec 15.

ABSTRACT

BACKGROUND: Numerous studies have suggested that ferroptosis plays an important regulatory role in cancer cell death. Nonetheless, the potential effects of ferroptosis regulators on the prognosis, the expression of immunomodulatory factors in the tumor microenvironment and on the efficacy of immunotherapy in adrenocortical carcinoma (ACC) remain largely unknown.

METHODS: Public ACC datasets were used to investigate the relationship between ferroptosis regulators and prognosis and clinical features. A ferroptosis scoring system was established for individual cases of ACC using principal component analysis algorithms. Hub ferroptosis-related genes involved in immunoregulation and immunotherapy efficacy in ACC were further identified.

RESULTS: Twenty ferroptosis regulators were differentially expressed in ACC and 17 ferroptosis regulators were closely related to prognosis in ACC. A ferroptosis scoring system was developed based on ACSL4, FANCD2, and SLC7A1 expression, and the ferroptosis regulators could serve as an independent prognostic factor for ACC. Further analyses indicated that the ferroptosis score integrated with the tumor mutation burden (TMB), and immune-checkpoint gene expression could predict prognosis in ACC. RNA isolation and reverse transcription‑quantitative polymerase chain reaction (RT-qPCR) demonstrated significant differences in the expression levels of ACSL4, FANCD2, and SLC7A1 between ACC and normal tissues. Furthermore, FANCD2 was significantly related to immunotherapy efficacy and prognosis in ACC.

CONCLUSION: Our study demonstrated that ferroptosis was significantly associated with prognosis, clinical characteristics, immune-checkpoint gene expression, and tumor microenvironment immune cell infiltration in ACC. The current study provides comprehensive evidence for further research on ferroptosis regulators in ACC and provides new insight into the epigenetic regulation of the antitumor immune response.

PMID:36528469 | DOI:10.1016/j.arcmed.2022.12.003

Adrenocortical carcinoma presenting with upper intestinal bleeding in a patient with risk factors for gastric ulcer

Fetched: December 18th, 2022, 5:00am GMT by Karla Mariaca

Endocrinol Diabetes Nutr (Engl Ed). 2022 Dec;69(10):910-911. doi: 10.1016/j.endien.2021.12.008.

NO ABSTRACT

PMID:36526356 | DOI:10.1016/j.endien.2021.12.008

Huge adrenal schwannoma: a rare type of adrenal tumor, misconceived as adrenocortical carcinoma

Fetched: December 16th, 2022, 5:00am GMT by Jeong Hee Han

J Surg Case Rep. 2022 Dec 7;2022(12):rjac562. doi: 10.1093/jscr/rjac562. eCollection 2022 Dec.

ABSTRACT

Schwannoma is a benign and uncommon neoplasm arising from the neural crest cells. The most common tumor sites are the skin and subcutaneous tissue of the head and neck. Retroperitoneal schwannomas account for 1-3% of all schwannomas and are predominantly female. In particular, adrenal schwannoma is very rare, and due to its large size at the time of diagnosis, adrenal schwannoma is frequently misdiagnosed as adrenocortical carcinoma or pheochromocytoma. Adrenal schwannoma is difficult to distinguish it from other adrenal diseases based on imaging findings alone. In this report, we introduce the case of a huge left adrenal schwannoma.

PMID:36518652 | PMC:PMC9731616 | DOI:10.1093/jscr/rjac562

Hepatic Adrenal Rest Tumors Mimicking Hepatocellular Carcinoma: A Case Report and Review of the Literature

Fetched: December 16th, 2022, 5:00am GMT by Ahmad Al-Taee

Cureus. 2022 Nov 10;14(11):e31343. doi: 10.7759/cureus.31343. eCollection 2022 Nov.

ABSTRACT

Adrenal rest tumors are rare collections of aberrantly located adrenocortical tissue. They are most commonly found in the kidneys, and hepatic involvement is rare with few published case reports. When located in the liver, imaging findings are frequently indistinguishable from hepatocellular carcinoma (HCC), but when resected, histologic examination shows adrenocortical tissue. Here, we present a patient with a history of nonalcoholic steatohepatitis with advanced fibrosis who was identified as having HCC by cross-sectional imaging but was found to have a hepatic adrenal rest tumor (HART) after resection. HARTs can share imaging characteristics with HCC, and this alternative diagnosis should be considered, especially for hepatic segment VII lesions.

PMID:36514652 | PMC:PMC9741547 | DOI:10.7759/cureus.31343

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