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Google - Insulinoma
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Deficiency of transcription factor Nkx6.1 does not prevent insulin ... - Nature.com
Posted: January 13th, 2023, 8:26am GMT
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Review of Hematology-Oncology Emergencies for Internal Medicine ... - Cureus
Posted: January 10th, 2023, 12:02am GMT
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Brian Garin | The Standard Newspaper - Waukon Standard
Posted: January 2nd, 2023, 12:35am GMT
Brian Garin | The Standard Newspaper Waukon Standard -
The Spontaneous Regression of Primary Gastrointestinal ... - Cureus
Posted: December 26th, 2022, 6:00am GMT
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Messenger RNA in lipid nanoparticles rescues HEK 293 cells from ... - Nature.com
Posted: December 24th, 2022, 6:00am GMT
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Chemical Chaperones to inhibit Endoplasmic reticulum stress | DDDT - Dove Medical Press
Posted: December 23rd, 2022, 6:00am GMT
Chemical Chaperones to inhibit Endoplasmic reticulum stress | DDDT Dove Medical Press -
PLEASE HELP TO SAVE MISTYS LIFE, organized by Selina Mehra - GoFundMe
Posted: December 20th, 2022, 6:00am GMT
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Fuzzy Ferret Rescue Melatonin Implants, organized by Monica ... - GoFundMe
Posted: December 16th, 2022, 6:00am GMT
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What Effect Does Insulin Have on the Body? - EndocrineWeb
Posted: December 15th, 2022, 6:00am GMT
What Effect Does Insulin Have on the Body? EndocrineWeb -
Role of poly(ADP-ribose) polymerase-1 in regulating human islet ... - Nature.com
Posted: December 13th, 2022, 6:00am GMT
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Pancreatic Cancer Symptoms & Treatment in NJ - RWJBarnabas Health
Posted: November 28th, 2022, 8:06pm GMT
Pancreatic Cancer Symptoms & Treatment in NJ RWJBarnabas Health -
In vitro biochemical assessment of mixture effects of two endocrine ... - Nature.com
Posted: November 22nd, 2022, 6:00am GMT
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Minimally Invasive Technique Ablates Pancreatic Insulinoma - Medscape
Posted: November 18th, 2022, 6:00am GMT
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Hunger: Symptoms, Causes, and Treatment - Verywell Health
Posted: November 18th, 2022, 6:00am GMT
Hunger: Symptoms, Causes, and Treatment Verywell Health -
7 Most Expensive Liquids On This Planet You Didn't Know About - Postoast
Posted: November 18th, 2022, 6:00am GMT
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Reactive Hypoglycemia: Causes, How It Feels, Triggers - Verywell Health
Posted: November 16th, 2022, 6:00am GMT
Reactive Hypoglycemia: Causes, How It Feels, Triggers Verywell Health -
Single-cell imaging of α and β cell metabolic response to glucose in ... - Nature.com
Posted: November 12th, 2022, 6:00am GMT
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Insulin Patch Pumps: What Are They? - WebMD
Posted: November 11th, 2022, 6:00am GMT
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Finger Pricks: Tips and Tricks for Reducing Pain - WebMD
Posted: November 7th, 2022, 6:00am GMT
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Adrenalectomy (AAES, 2022) - Medscape Reference
Posted: November 1st, 2022, 5:00am GMT
Adrenalectomy (AAES, 2022) Medscape Reference -
Blood glucose monitoring during surgery in dogs to assess ... - American Veterinary Medical Association
Posted: October 25th, 2022, 5:00am GMT
Blood glucose monitoring during surgery in dogs to assess ... American Veterinary Medical Association -
Case 23-2022: A 49-Year-Old Man with Hypoglycemia | NEJM - nejm.org
Posted: October 20th, 2022, 5:00am GMT
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Adrenal Tumors in 1.4% of Unselected Adults, Hormone Tests Needed - Medscape
Posted: September 12th, 2022, 5:00am GMT
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Hyperinsulinemia: Definition, Symptoms, Treatment, and Diet - Healthgrades
Posted: August 22nd, 2022, 5:00am GMT
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GLP-1-mediated delivery of tesaglitazar improves obesity and ... - Nature.com
Posted: August 22nd, 2022, 5:00am GMT
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FDA makes moves to advance ALS research ahead of upcoming ... - Pharmaceutical Technology
Posted: August 12th, 2022, 5:00am GMT
FDA makes moves to advance ALS research ahead of upcoming ... Pharmaceutical Technology -
14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell ... - Science
Posted: July 22nd, 2022, 5:00am GMT
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Heterogeneous Development of β-Cell Populations in Diabetes ... - Diabetes Journal
Posted: June 30th, 2022, 5:00am GMT
Heterogeneous Development of β-Cell Populations in Diabetes ... Diabetes Journal -
Performance of islets of Langerhans conformally coated via an ... - Science
Posted: June 29th, 2022, 5:00am GMT
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Infographic: Physician Wealth Climbs, With More Worth $5 Million-Plus - Medscape
Posted: June 20th, 2022, 5:00am GMT
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A Mixed Meal Tolerance Test for Clinical Trials - Verywell Health
Posted: May 6th, 2022, 5:00am GMT
A Mixed Meal Tolerance Test for Clinical Trials Verywell Health -
Home diabetes testing 2022: Types, options, and more - Medical News Today
Posted: February 28th, 2022, 6:00am GMT
Home diabetes testing 2022: Types, options, and more Medical News Today -
The smell of insulin - Science
Posted: February 22nd, 2022, 6:00am GMT
The smell of insulin Science -
10 Pancreatic Cancer Symptoms & Signs Not To Ignore - WebMD
Posted: January 20th, 2022, 6:00am GMT
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Insulin Isn't the Only Blood Sugar Regulator - WebMD
Posted: January 4th, 2022, 6:00am GMT
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TEDDY study compares characteristics of children diagnosed with ... - Science Daily
Posted: October 21st, 2021, 5:00am GMT
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The Nature of Neuroendocrine Tumors - OncLive
Posted: September 17th, 2021, 5:00am GMT
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Zegalogue: Uses, Side Effects, Dosages, Precautions - Verywell Health
Posted: May 25th, 2021, 5:00am GMT
Zegalogue: Uses, Side Effects, Dosages, Precautions Verywell Health -
Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any ... - The Oncologist
Posted: December 10th, 2020, 6:00am GMT
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Receptor-Targeted Photodynamic Therapy of Glucagon-Like ... - Journal of Nuclear Medicine
Posted: November 1st, 2020, 5:00am GMT
Receptor-Targeted Photodynamic Therapy of Glucagon-Like ... Journal of Nuclear Medicine -
She Was Healthy and Active. Suddenly She Had a Seizure. - The New York Times
Posted: July 1st, 2020, 5:00am GMT
She Was Healthy and Active. Suddenly She Had a Seizure. The New York Times -
Baqsimi: Dosage, shelf life, side effects, and more - Medical News Today
Posted: May 13th, 2020, 5:00am GMT
Baqsimi: Dosage, shelf life, side effects, and more Medical News Today -
Baqsimi Nasal (Glucagon): Uses, Side Effects, Dosages, Precautions - Verywell Health
Posted: February 15th, 2020, 6:00am GMT
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Hyperinsulinemia: Causes, treatments, and related conditions - Medical News Today
Posted: February 13th, 2020, 6:20pm GMT
Hyperinsulinemia: Causes, treatments, and related conditions Medical News Today -
FDA approves first treatment for severe hypoglycemia that can be ... - FDA.gov
Posted: July 24th, 2019, 5:00am GMT
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Molecular Imaging of Gastroenteropancreatic Neuroendocrine ... - Journal of Nuclear Medicine
Posted: December 1st, 2016, 6:00am GMT
Molecular Imaging of Gastroenteropancreatic Neuroendocrine ... Journal of Nuclear Medicine -
Glucagon-Like Peptide-1 Receptor PET/CT with 68Ga-NOTA ... - Journal of Nuclear Medicine
Posted: May 1st, 2016, 5:00am GMT
Glucagon-Like Peptide-1 Receptor PET/CT with 68Ga-NOTA ... Journal of Nuclear Medicine -
Oral Insulin and Immune Responses in Children at Risk for Diabetes - JAMA Network
Posted: April 21st, 2015, 5:00am GMT
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Somatostatin Receptor Imaging with 68Ga DOTATATE PET/CT ... - RSNA Publications Online
Posted: March 12th, 2015, 5:00am GMT
Somatostatin Receptor Imaging with 68Ga DOTATATE PET/CT ... RSNA Publications Online -
Steve Jobs dead: A layman's guide to islet-cell tumors in the pancreas. - Slate
Posted: October 6th, 2011, 5:00am GMT
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Glucagon-like Peptide 1–Receptor Scans to Localize Occult ... - nejm.org
Posted: August 14th, 2008, 5:00am GMT
PubMed - Insulinoma
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Whipple's triad with high and low insulin levels
Fetched: January 27th, 2023, 5:02am GMT by Thomas Karrasch
Inn Med (Heidelb). 2023 Jan 26. doi: 10.1007/s00108-023-01473-6. Online ahead of print.
ABSTRACT
A 69-year-old female patient and a 70-year-old male patient were admitted to hospital with recurrent, severe hypoglycemic episodes and a typical manifestation of Whipple's triad. In the female, elevated levels of insulin, C‑peptide and pro-insulin together with pathological findings during a fasting test proved the presence of an insulinoma, which could be detected by Ga-68-DOTATOC-PET-CT in the pancreas. There was a very rare co-existence of a neuroendocrine Merkel cell carcinoma. In the male, levels of insulin and C‑peptide were suppressed and a diagnosis of paraneoplastic hypoglycemia by IGF‑2 secretion was made with increased glucose disposal in skeletal muscle proven by 18F‑FDG-PET-CT.
PMID:36703082 | DOI:10.1007/s00108-023-01473-6
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IS THERE A RELATIONSHIP BETWEEN TUBEROUS SCLEROSIS COMPLEX AND INSULINOMA?
Fetched: January 27th, 2023, 5:02am GMT by H Piskinpasa
Acta Endocrinol (Buchar). 2022 Jul-Sep;18(3):350-354. doi: 10.4183/aeb.2022.350.
ABSTRACT
Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disease characterized by multiple hamartomas in multiple organs. However, there is limited evidence about neuroendocrine tumors (NETs) in patients with TSC, and routine screening of NETs is not recommended in the guidelines. Insulinomas are also an extremely rare disease. According to our knowledge, we presented the 10th TSC patient diagnosed with insulinoma in the literature. Thirty-two years old male patient diagnosed with TSC at the age of 27 due to typical skin findings, renal angiomyolipoma, history of infantile seizures, and cranial involvement was referred to our clinic. The main symptoms of the patient were palpitations, diaphoresis, confusion, and symptoms were improved after consuming sugary foods. Seventy-two hours fasting test was performed, and a low glucose level at 41 mg/dl, a high insülin level at 21.65 µIU/mL, and a high C-peptide level at 7.04 ng/mL were found at the 8th hour. In addition, a 12x7 mm lesion in the pancreatic tail was detected in abdominal imaging. Ga-68 PET-CT (gallium-68 positron emission tomography-computed tomography) detected an increased uptake of Ga-68 in the pancreatic tail. The patient underwent distal pancreatectomy, and pathological evaluation was consistent with an insulinoma. The patient's symptoms improved postoperatively. Since in nearly all TSC cases, as in our case, neuropsychiatric abnormalities, such as epilepsy, are one of the main disease manifestations, and these symptoms may be confused with the clinical manifestations of hypoglycemia in insulinoma. Therefore, patients with newly developed neurological symptoms and behavioral defects should be evaluated in terms of insulinoma.
PMID:36699161 | PMC:PMC9867813 | DOI:10.4183/aeb.2022.350
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Difference in the early clinical course between children with type 1 diabetes having a single antibody and those having multiple antibodies against pancreatic β-cells
Fetched: January 26th, 2023, 5:02am GMT by Hiroki Terada
Endocr J. 2023 Jan 24. doi: 10.1507/endocrj.EJ22-0432. Online ahead of print.
ABSTRACT
Islet-cell associated antibodies are predictive and diagnostic markers for type 1 diabetes. We studied the differences in the early clinical course of children with type 1 diabetes with a single antibody and those with multiple antibodies against pancreatic β-cells. Sixty-seven children with type 1 diabetes aged less than 15 years diagnosed between 2010 and 2021 were included in the study and subdivided into two subgroups: children who were single positive for either glutamic acid decarboxylase (GAD) antibodies (n = 16) or insulinoma-associated antigen-2 (IA-2) antibodies (n = 13) and those positive for both antibodies (n = 38) at diagnosis. We compared the patients' clinical characteristics, pancreatic β-cell function, and glycemic control during the 5 years after diagnosis. All clinical characteristics at diagnosis were similar between the two groups. One and two years after diagnosis, children who tested positive for both antibodies showed significantly lower postprandial serum C-peptide (CPR) levels than those who tested positive for either GAD or IA-2 antibodies (p < 0.05). In other periods, there was no significant difference in CPR levels between the two groups. There was a significant improvement in glycosylated hemoglobin (HbA1c) levels after starting insulin treatment in both groups (p < 0.05), but no significant difference in HbA1c levels between the groups. Residual endogenous insulin secretion may be predicted based on the number of positive islet-cell associated antibodies at diagnosis. Although there are differences in serum CPR levels, optimal glycemic control can be achieved by individualized appropriate insulin treatment, even in children with type 1 diabetes.
PMID:36696992 | DOI:10.1507/endocrj.EJ22-0432
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A Novel Somatic Mutation Implicates ATP6V0D1 in Proinsulin Processing
Fetched: January 26th, 2023, 5:02am GMT by Parizad Avari
J Endocr Soc. 2022 Dec 29;7(3):bvac196. doi: 10.1210/jendso/bvac196. eCollection 2023 Jan 6.
ABSTRACT
CONTEXT: Prohormone convertase 1/3 (PC1/3), encoded by protein convertase subtilisin kexin type 1 (PCSK1), converts inactive prohormones into biologically active peptides. Somatic mutations of insulinomas are associated with genetic defects interfering with control of insulin secretion from pancreatic beta cells. However, somatic mutations in proinsulinomas have not been described.
OBJECTIVE: We report a case of a proinsulinoma, with suppressed insulin and C-peptide levels.
METHODS: A 70-year-old woman presented with a 20-year history of "blackouts." During a 72-hour fast, blood glucose level dropped to 1.9 mmol/L with suppressed plasma insulin and C-peptide levels, but proinsulin levels were raised at 37 pmol/L (<10 pmol/L).
RESULTS: Imaging revealed 3 distinct DOTATATE-avid pancreatic lesions. Laparoscopic spleen-preserving distal pancreatomy was performed. In view of discordant insulin, C-peptide, and proinsulin levels, whole exome sequencing analysis was performed on the tumor. In the somatic exome of the tumor, we found mutations in PCSK expression regulators, as well as a novel truncating somatic mutation in ATP6V0D1, a subunit of the ion pump that acidifies the β-cell compartments where the PCSKs act.
CONCLUSION: Appropriately suppressed insulin levels in the context of hypoglycemia do not always indicate the absence of a neuroendocrine islet cell tumor and proinsulin levels may be indicated to solidify the diagnosis. In the context of elevated proinsulin levels, low insulin and C-peptide levels might be explained by somatic mutations that likely implicate proinsulin processing within the tumor. Furthermore, we propose several mechanistic candidates, including ATP6V0D1. Experimental validation using cellular approaches may in future confirm pathomechanisms involved in this rare condition.
PMID:36694809 | PMC:PMC9856271 | DOI:10.1210/jendso/bvac196
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Adult focal β-cell nesidioblastosis: A case report
Fetched: January 24th, 2023, 5:01am GMT by Kui Tu
World J Clin Cases. 2023 Jan 6;11(1):150-156. doi: 10.12998/wjcc.v11.i1.150.
ABSTRACT
BACKGROUND: Nesidioblastosis usually refers to a series of clinical manifestations caused by the proliferation of β-cells in pancreatic islets, and these clinical manifestations are hyperinsulinemia and persistent hypoglycemia. According to the size of the lesion, nesidioblastosis is divided into focal nesidioblastosis, diffuse nesidioblastosis and atypical nesidioblastosis, and its pathogenesis is still unclear. Nesidioblastosis is mainly seen in infants and rarely reported in adults, especially focal nesidioblastosis, which is difficult to distinguish from insulinoma.
CASE SUMMARY: We report a case of adult focal β-cell nesidioblastosis in which the preoperative diagnosis was insulinoma. The patient was a 48-year-old male who suffered from repeated morning and fasting palpitations, sweating, and severe disturbance of consciousness for 5 years. His blood glucose was found to be as low as 1.79 mmol/L during an attack. However, abdominal computed tomography showed no abnormalities. Magnetic resonance imaging and endoscopic ultrasonography demonstrated a nodular mass in the head of the pancreas, combined with hyperinsulinemia and high serum C-peptide. The patient was diagnosed with insulinoma and underwent Beger surgery; however, the postoperative pathological results showed nesidioblastosis.
CONCLUSION: Although surgical resection is the preferred option for nesidioblastosis, some cases can be treated non-surgically. In order to increase clinicians' understanding of nesidioblastosis, it is necessary to review the pathogenesis, diagnosis and treatment of this disease.
PMID:36687197 | PMC:PMC9846974 | DOI:10.12998/wjcc.v11.i1.150
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Islet autoantibody screening in at-risk adolescents to predict type 1 diabetes until young adulthood: a prospective cohort study
Fetched: January 22nd, 2023, 5:02am GMT by Mohamed Ghalwash
Lancet Child Adolesc Health. 2023 Jan 18:S2352-4642(22)00350-9. doi: 10.1016/S2352-4642(22)00350-9. Online ahead of print.
ABSTRACT
BACKGROUND: Screening for islet autoantibodies in children and adolescents identifies individuals who will later develop type 1 diabetes, allowing patient and family education to prevent diabetic ketoacidosis at onset and to enable consideration of preventive therapies. We aimed to assess whether islet autoantibody screening is effective for predicting type 1 diabetes in adolescents aged 10-18 years with an increased risk of developing type 1 diabetes.
METHODS: Data were harmonised from prospective studies from Finland (the Diabetes Prediction and Prevention study), Germany (the BABYDIAB study), and the USA (Diabetes Autoimmunity Study in the Young and the Diabetes Evaluation in Washington study). Autoantibodies against insulin, glutamic acid decarboxylase, and insulinoma-associated protein 2 were measured at each follow-up visit. Children who were lost to follow-up or diagnosed with type 1 diabetes before 10 years of age were excluded. Inverse probability censoring weighting was used to include data from remaining participants. Sensitivity and the positive predictive value of these autoantibodies, tested at one or two ages, to predict type 1 diabetes by the age of 18 years were the main outcomes.
FINDINGS: Of 20 303 children with an increased type 1 diabetes risk, 8682 were included for the analysis with inverse probability censoring weighting. 1890 were followed up to 18 years of age or developed type 1 diabetes between the ages of 10 years and 18 years, and their median follow-up was 18·3 years (IQR 14·5-20·3). 442 (23·4%) of 1890 adolescents were positive for at least one islet autoantibody, and 262 (13·9%) developed type 1 diabetes. Time from seroconversion to diabetes diagnosis increased by 0·64 years (95% CI 0·34-0·95) for each 1-year increment of diagnosis age (Pearson's correlation coefficient 0·88, 95% CI 0·50-0·97, p=0·0020). The median interval between the last prediagnostic sample and diagnosis was 0·3 years (IQR 0·1-1·3) in the 227 participants who were autoantibody positive and 6·8 years (1·6-9·9) for the 35 who were autoantibody negative. Single screening at the age of 10 years was 90% (95% CI 86-95) sensitive, with a positive predictive value of 66% (60-72) for clinical diabetes. Screening at two ages (10 years and 14 years) increased sensitivity to 93% (95% CI 89-97) but lowered the positive predictive value to 55% (49-60).
INTERPRETATION: Screening of adolescents at risk for type 1 diabetes only once at 10 years of age for islet autoantibodies was highly effective to detect type 1 diabetes by the age of 18 years, which in turn could enable prevention of diabetic ketoacidosis and participation in secondary prevention trials.
FUNDING: JDRF International.
PMID:36681087 | DOI:10.1016/S2352-4642(22)00350-9
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Immunohistochemical somatostatin receptor expression in insulinomas
Fetched: January 22nd, 2023, 5:02am GMT by Peltola Elina
APMIS. 2023 Jan 21. doi: 10.1111/apm.13297. Online ahead of print.
ABSTRACT
OBJECTIVE: Insulinomas are rare pancreatic neuroendocrine tumours. Most patients can be cured with surgery, but patients with a metastatic disease show impaired survival. The aim of this study was to evaluate somatostatin receptor (SSTR) 1-5 expression in insulinomas and to correlate the expression profile with clinicopathological variables and with patient outcome.
DESIGN AND METHODS: This retrospective study involved 52 insulinoma patients. After histological re-evaluation, formalin-fixed paraffin-embedded tissue samples were processed into tissue microarrays and stained immunohistochemically with monoclonal SSTR1-5 antibodies.
RESULTS: All the 52 tumours (49 non-metastatic, 3 metastatic) expressed at least one SSTR subtype. SSTR2 was expressed most frequently (71%), followed by SSTR3 (33%), SSTR1 (27%), SSTR5 (6%), and SSTR4 (0%). SSTR3 expression was associated with a larger tumour size (median diameter 19 mm vs. 13 mm, P=0.043), and SSTR3 and SSTR5 expression were associated with impaired overall survival [HR 3.532 (95% CI 1.106-11,277), P=0.033, and HR 6.805 (95% CI 1.364-33.955), P=0.019, respectively].
CONCLUSIONS: Most insulinomas express SSTR2, which may be utilized in diagnostic imaging, and in planning individualized treatment strategies for insulinoma patients. Further studies are needed to clarify the association between SSTR profile and overall survival.
PMID:36680557 | DOI:10.1111/apm.13297
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Imaging of the Glucose-Dependent Insulinotropic Polypeptide Receptor Using a Novel Radiolabeled Peptide Rationally Designed Based on Endogenous GIP and Synthetic Exendin-4 Sequences
Fetched: January 22nd, 2023, 5:02am GMT by Irina Velikyan
Pharmaceuticals (Basel). 2022 Dec 31;16(1):61. doi: 10.3390/ph16010061.
ABSTRACT
Imaging and radiotherapy targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) could potentially benefit the management of neuroendocrine neoplasms (NENs), complementing clinically established radiopharmaceuticals. The aim of this study was to evaluate a GIPR-targeting positron emission tomography (PET) radioligand with receptor-specific binding, fast blood clearance, and low liver background uptake. The peptide DOTA-bioconjugate, C803-GIP, was developed based on the sequence of the endogenous GIP(1-30) and synthetic exendin-4 peptides with selective amino acid mutations to combine their specificity for the GIPR and in vivo stability, respectively. The 68Ga-labeled bioconjugate was evaluated in vitro in terms of binding affinity, specificity, and internalization in HEK293 cells transfected with the human GIPR, GLP1, or GCG receptors and in sections of human insulinoma and NENs. In vivo binding specificity, biodistribution, and tissue background were investigated in mice bearing huGIPR-HEK293 xenografts and in a pig. Ex vivo organ distribution, pharmacokinetics, and dosimetry were studied in normal rats. [68Ga]Ga-C803-GIP was stable and demonstrated a high affinity to the huGIPR-HEK293 cells. Binding specificity was demonstrated in vitro in frozen sections of NENs and huGIPR-HEK293 cells. No specific uptake was observed in the negative controls of huGLP1R and huGCGR cells. A novel rationally designed PET radioligand, [68Ga]Ga-C803-GIP, demonstrated promising binding characteristics and specificity towards the GIPR.
PMID:36678558 | PMC:PMC9864903 | DOI:10.3390/ph16010061
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Atezolizumab induced new-onset type 1 diabetes mellitus
Fetched: January 13th, 2023, 2:07pm GMT by Joaquín de Carlos
J Oncol Pharm Pract. 2023 Jan 12:10781552231151656. doi: 10.1177/10781552231151656. Online ahead of print.
ABSTRACT
INTRODUCTION: Immune checkpoint inhibitors (ICI) are novel therapeutic strategies in cancer treatment, promoting anti-tumor response by boosting cytotoxic T lymphocytes. Despite their high effectiveness, they can trigger the activation of diverse autoimmune diseases in genetically predisposed individuals. New-onset autoimmune diabetes mellitus type 1 (T1D) is an extremely unusual side effect, described in less than 1% of patients.
CASE REPORT: Here we present a 44-year-old male diagnosed with non-surgical hepatocarcinoma, developing programmed death ligand-1 inhibitor-induced autoimmune endocrinopathies, presented as diabetic ketoacidosis and thyroiditis. After two cycles of atezolizumab and bevacizumab, he consulted the emergency department with abdominal pain and diabetes cardinal features (polyuria, polydipsia, vomiting). Blood tests demonstrated hyperglycemia >800 mg/dL, capillary ketonemia >3 mmol/L, metabolic acidosis (pH 7.24 with HCO3 14 mEq/L). Subsequent studies detected a low level of C-peptide, and positive glutamic acid decarboxylase and insulinoma-associated antigen-2 antibodies. Thyroid examination was compatible with thyroiditis, showing a high free thyroxine level (1.91 ng/dL) with low thyrotropin (TSH) (0.08 mIU/L) and negative anti-TSH receptor antibody.
MANAGEMENT & OUTCOME: After reaching metabolic stabilization, treatment with Atezolizumab was restarted, with no further complications showing size stability in the computed tomography control.
DISCUSSION: T1D related to ICI is a rare condition that presents as a life-threatening emergency and should be recognized and treated early. Blood glucose and glycated hemoglobin determinations should be performed at periodic visits for detection. There are genetic factors that predispose susceptible individuals, but there is no evidence of studies to be performed before the onset of ICI or preventive strategies.
PMID:36635950 | DOI:10.1177/10781552231151656
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Insulinoma as a cause of seizure-like activity and spontaneous hypoglycaemia
Fetched: January 11th, 2023, 5:01am GMT by Fahd Fayyaz
BMJ Case Rep. 2023 Jan 10;16(1):e250799. doi: 10.1136/bcr-2022-250799.
ABSTRACT
A woman in her 60s presented to our hospital with recurrent episodes of confusion and double vision with spontaneous recovery to baseline within 10 min. Her initial workup was unremarkable, and she was diagnosed with complex partial seizures and commenced on levetiracetam. The following week, she re-presented with a recurrence of her symptoms, associated with spontaneous hypoglycaemia, with blood glucose levels of 1.9 mmol/L. She was found to have endogenously elevated serum insulin and C peptide levels, which were concomitantly associated with hypoglycaemia. An initial diagnosis of insulinoma was made and she was commenced on diazoxide. MRI and endoscopic ultrasound revealed 16 mm insulinoma in her uncinate process. She underwent surgical resection and remained symptom free at follow-up. This case highlights the importance of blood glucose measurements in patients presenting with neuroglycopenic symptoms and outlines the workup and management of insulinoma.
PMID:36627134 | PMC:PMC9835887 | DOI:10.1136/bcr-2022-250799
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Perfluorooctane sulfonate-induced oxidative stress contributes to pancreatic β-cell apoptosis by inhibiting cyclic adenosine monophosphate pathway: Prevention by pentoxifylline
Fetched: January 10th, 2023, 5:02am GMT by Suma Elumalai
Environ Pollut. 2023 Jan 5;320:120959. doi: 10.1016/j.envpol.2022.120959. Online ahead of print.
ABSTRACT
Endocrine-disrupting chemical perfluorooctane sulfonate (PFOS) acute exposure stimulates insulin secretion from pancreatic β-cells. However, chronic exposure to PFOS on pancreatic β-cells, its role in insulin secretion, and the underlying mechanisms have not been studied. We used rat insulinoma INS-1 and human 1.1b4 islet cells to investigate the chronic effects of PFOS on glucose-stimulated insulin secretion and toxicity implicated in the downregulation of β-cell functionality. Chronic exposure of INS-1 cells or human pancreatic 1.1b4 β-cells to PFOS stimulated the small G-protein RAC1-guanosine triphosphate-dependent nicotinamide adenine dinucleotide phosphate oxidase (NOX2/gp91phox) subunit expression and activation. Upregulated NOX2/gp91phox activation led to elevated reactive oxygen species (ROS) production with a decrease in the cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) pathway in both cell types. Inhibition of cAMP/PKA signaling induces β-cell mitochondrial dysfunction and endoplasmic stress via the loss of PDX1-SERCA2B and glucose-stimulated insulin release. Inhibiting RAC1-NOX2/gp91phox activation or elevating cAMP by pentoxifylline, a Food and Drug Administration-approved phosphodiesterase inhibitor, significantly reduced PFOS-induced ROS production and restored insulin secretory function of pancreatic β-cells. Enhanced secretory function in pentoxifylline-treated cells was associated with increased stability of PDX1-SERCA2B protein levels. Intriguingly, inhibition of cAMP/PKA signaling impaired pentoxifylline-induced insulin secretion caused by the activation of ROS production and mitochondrial dysfunction. Overall, our findings show that PFOS has a new and first-ever direct chronic effect on pancreatic β-cell failure through increased RAC1-NOX2/gp91phox activation and pentoxifylline-induced cAMP/PKA signaling, which inhibits PFOS-mediated mitochondrial dysfunction.
PMID:36621715 | DOI:10.1016/j.envpol.2022.120959
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Insulinoma: Presenting as hypoglycemia in a non-diabetic patient: A rare case report
Fetched: January 10th, 2023, 5:02am GMT by Ranjan Kumar
J Family Med Prim Care. 2022 Oct;11(10):6564-6567. doi: 10.4103/jfmpc.jfmpc_109_22. Epub 2022 Oct 31.
ABSTRACT
PNETs (pancreatic neuroendocrine tumors) are a rare sub-type of pancreatic tumors, with the majority of them being insulinomas. The vast majority of insulinomas (90%) are benign and solitary, with only 10% being malignant. It has a wide range of clinical manifestations and requires a high level of suspicion to diagnose. Surgical excision has long been the gold standard for treating localized PNET and is still the therapy of choice. Recurrent hypoglycemia is usual in diabetic patients, but this is a rare finding in non-diabetic individuals. Here, we are presenting a rare case of insulinoma who was non-diabetic and presented with recurrent hypoglycemic episodes. A 61-year-old non-diabetic male presented with multiple episodes of hypoglycemia in the past. On thorough workup, there was an increased fasting insulin level with the fasting blood glucose level ranging from 60 to 90 mg/dl. His C-peptide and proinsulin were markedly elevated. His abdominal ultrasound failed to pick up any abnormality. His DOTANOC scan revealed a 2 × 2 cm sized lesion in the distal pancreas suggestive of neuroendocrine pathology. He subsequently underwent spleen preserving distal pancreatectomy, following which his blood sugar levels remained normal, and continued to be free of symptoms on follow-up. Our instance emphasizes the need for evaluating insulinoma as a cause of recurrent hypoglycemia in people who are not diabetic. A high index of suspicion in hypoglycemic individuals who do not respond to standard treatment or whose symptom pattern changes will lower the likelihood of insulinoma diagnosis being delayed.
PMID:36618163 | PMC:PMC9810888 | DOI:10.4103/jfmpc.jfmpc_109_22
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Alpha-lipoic acid inhibits sodium arsenite-mediated autophagic death of rat insulinoma cells
Fetched: January 4th, 2023, 5:02am GMT by Yong Cheng
Hum Exp Toxicol. 2023 Jan-Dec;42:9603271221149196. doi: 10.1177/09603271221149196.
ABSTRACT
AIM: To investigate the protective effect of α-lipoic acid on sodium arsenite (NaAsO2) induced INS-1 cells injury and its mechanism.
METHODS: The cell viability was measured by CCK-8 assay. The autophagosomes was observed under transmission electron microscopy. The autophagosomes in cells transfected with green fluorescent protein microtubule-associated protein light chain 3 (GFP-LC3) plasmids were observed under a laser scanning con-focal microscope. The expression of LC3-II, P62, PI3K, and mTOR proteins in INS-1 cells treated with a combination of chloroquine (CQ, autophagy inhibitor) and NaAsO2 were detected by Western blot assay. The expression of LC3-II, P62, PI3K, and mTOR proteins were detected in INS-1 cells treated with a combination of rapamycin (autophagy inducer, mTOR inhibitor) and α-LA.
RESULTS: The cytotoxicity induced by NaAsO2 was reversed by α-LA, and the viability of NaAsO2-treated INS-1 cells increased. α-LA pretreatment decreased the autophagosome accumulation induced by NaAsO2. α-LA also reduced the fluorescence spot aggregation of GFP-LC3 in INS-1 cells exposed to NaAsO2 as observed under a laser scanning con-focal microscope. α-LA inhibited NaAsO2 induced autophagy by up-regulating PI3K and mTOR and down-regulating LC3-II and P62. CQ inhibited NaAsO2 induced autophagy by up-regulating PI3K, mTOR, P62 and down-regulating LC3-II. α-LA inhibited rapamycin-induced autophagy by up-regulating PI3K, mTOR and P62 and down-regulating LC3-II. The results showed that NaAsO2 could induce autophagy activation in INS-1 cells. The α-LA may inhibit autophagy activation by regulating the PI3K/mTOR pathway.
CONCLUSION: The data indicated that α-LA might inhibit the NaAsO2-induced autophagic death of INS-1 cells by regulating the PI3K/mTOR pathway.
PMID:36595328 | DOI:10.1177/09603271221149196
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BYPASS-OMA: Hypoglycemic Hyperinsulinemic Nesidioblastosis after Gastric Bypass Surgery-A Case Report and Review of the Literature
Fetched: January 3rd, 2023, 5:02am GMT by Jessica Cao
Case Rep Endocrinol. 2022 Dec 22;2022:5472304. doi: 10.1155/2022/5472304. eCollection 2022.
ABSTRACT
This rare case vignette describes hypoglycemic, hyperinsulinemic nesidioblastosis in a female patient with prior Roux-en-Y gastric bypass. The patient presented with severe symptomatic hypoglycemia resistant to IV dextrose and diazoxide, requiring surgical resection. Traditional imaging found nonspecific findings, and biochemical analysis was inconsistent with insulinoma. A gallium-68 dotatate PET scan was utilized to successfully localize the tumor in the distal pancreas. She underwent laparoscopic resection of the distal pancreatic lesion with resolution of her symptoms and return to euglycemia. The histological evaluation confirmed the diagnosis of nesidioblastosis. Nesidioblastosis is a rare complication of bariatric surgery that may be more clinically relevant with rising prevalence of obesity. Diagnosis with conventional imaging modalities may be challenging; however, the dotatate PET scan may have high utility in detecting lesions. It is essential for clinicians to consider nesidioblastosis in the differential diagnosis of hyperinsulinemic hypoglycemic conditions and recognize there may be a link with increasing rates of bariatric surgery.
PMID:36588628 | PMC:PMC9800099 | DOI:10.1155/2022/5472304
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A single-center experience on endoscopic ultrasonography-guided ethanol ablation of insulinomas
Fetched: December 29th, 2022, 5:02am GMT by Zhiyu Yan
Pancreatology. 2023 Jan;23(1):98-104. doi: 10.1016/j.pan.2022.12.007. Epub 2022 Dec 13.
ABSTRACT
BACKGROUND/OBJECTIVES: As the most frequent functional pancreatic neuroendocrine tumor, insulinomas may cause a plethora of symptoms and severe impairment in the living of patients by endogenous hyperinsulinemia and subsequent hypoglycemia. Surgery has been regarded as the first choice although a high risk of complications. Ethanol ablation is a promising non-surgical option that could achieve tumor shrinking in a short-term period. But the impact of symptom control and the long-term efficacy lack sufficient and good-quality evidence.
METHODS: A total number of 14 endoscopic ultrasonography-guided ethanol ablations were performed in 9 patients between September 2016 and September 2018 in Peking Union Medical College Hospital. The data were collected and prospectively analyzed.
RESULTS: The follow-up duration ranged from 21 to 1567 days in 9 patients, with a median of 994 days. 4 patients were free from relapse during a median follow-up of 1108 days (range: 994-1567 days). In 5 patients who suffered relapses, the median duration with symptom relief after the first ablation was 128 days (range: 13-393 days). If only repeated ablation was taken into consideration, the median duration with symptom relief was 26 days (range: 1-516 days). No complications happened during the procedures. The severe complication rate after the first ablation was 0.0% (0/9), compared to 7.14% (1/14) if each procedure was counted separately. The only severe complication documented was acute pancreatitis which was completely relieved after symptomatic treatment.
CONCLUSIONS: For patients who are not suitable for surgical resections, endoscopic ultrasonography-guided ethanol ablation of insulinomas could be an effective and safe alternative to relieve symptoms of hypoglycemia.
PMID:36577553 | DOI:10.1016/j.pan.2022.12.007
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Nesidioblastosis: an uncommon complication seen post Roux-en-Y gastric bypass
Fetched: December 27th, 2022, 5:02am GMT by Kiveum Kim
Endocrinol Diabetes Metab Case Rep. 2022 Dec 1;2022:22-0361. doi: 10.1530/EDM-22-0361. Online ahead of print.
ABSTRACT
SUMMARY: Adult-onset nesidioblastosis is a rare complication of Roux-en-Y gastric bypass surgery and may occur months to years after the initial surgical procedure. It is manifested by a hyperinsulinemic, hypoglycemic state. The annual incidence of adult-onset hyperinsulinemic hypoglycemia is believed to be less than 0.1 in 1 000 000 with a mean age of onset of 47 years (1). Here, we describe a patient who presented with worsening hypoglycemic symptoms for 1 year prior to presentation that eventually progressed to hypoglycemic seizures. The onset of this hypoglycemia was 5 years after Roux-en-Y gastric bypass surgery. A full neurological evaluation, which included an EEG, head CT, and MRI, was performed to rule out epilepsy and other seizure-related disorders. After hypoglycemia was confirmed, extensive laboratory studies were obtained to elucidate the cause of the hypoglycemia and differentiate nesidioblastosis from insulinoma. Once the diagnosis of nesidioblastosis was established, a sub-total pancreatectomy was performed, and the patient was discharged and placed on acarbose, a competitive reversible inhibitor of pancreatic α-amylase and intestinal brush border α-glucosidases which slows carbohydrate absorption. The lack of information and understanding of nesidioblastosis due to its rarity makes any knowledge of this rare but important surgical complication essential. As incidence of obesity increases, the number of gastric bypasses being performed increases with it, and understanding this disease process will be essential for the primary care provider. This is the primary reason for the writing of this publication.
LEARNING POINTS: Nesidioblastosis is a persistent hyperinsulinemic, hypoglycemic state, mostly seen after Roux-en-Y gastric bypass surgery, with symptoms occurring postprandially. The incidence is 0.1-0.3% of all post Roux-en-Y gastric bypass patients. The key diagnostic clue to identifying nesidioblastosis is a positive selective arterial calcium stimulation test, showing a diffuse pattern of increased basal hepatic venous insulin concentration, whereas insulinomas would show focal increases. Pathological specimen of pancreas will show diffuse hypertrophy of beta cells. Management includes acarbose and total or subtotal pancreatectomy, which can be curative. With the prevalence of obesity increasing and more patients turning to Roux-en-Y gastric bypass, more patients may be at risk of this potential surgical complication.
PMID:36571473 | DOI:10.1530/EDM-22-0361
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Extraskeletal myxoid chondrosarcoma: a study of 17 cases focusing on the diagnostic utility of INSM1 expression and presenting rare morphological variants associated with non-EWSR1::NR4A3 fusions
Fetched: December 25th, 2022, 5:02am GMT by Jiří Lenz
Hum Pathol. 2022 Dec 20:S0046-8177(22)00283-0. doi: 10.1016/j.humpath.2022.12.005. Online ahead of print.
ABSTRACT
Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain lineage. Insulinoma-associated protein 1 (INSM1) has recently been described as a highly specific and sensitive immunohistochemical marker for EMC. The goal of this study was to evaluate the diagnostic significance of INSM1 immunohistochemistry in EMC. Furthermore, correlations between molecular and morphological findings were performed. Sixteen of 17 EMC cases were stained with the INSM1 antibody. Tumors with at least 5% INSM1-positive cells and any staining intensity were considered positive. Molecular testing was successfully performed in 12/17 cases. The immunohistochemical analysis detected 13 INSM1-positive (81%) and 3 INSM1-negative tumors (19%). The extent of the staining was classified as 1+ in 7 cases (44%), 2+ in 2 cases (13%), 3+ in 2 cases (13%) and 4+ in 2 cases (13%). Intensity of immunostaining was weak in 5 cases (31%), moderate in 2 cases (13%) and strong in 6 cases (38%). Molecular assays revealed 8 EWSR1::NR4A3 positive tumors (67%), 2 TAF15::NR4A3 positive tumors (17%), 1 TCF12::NR4A3 positive tumor (8%) and 1 NR4A3 positive tumor (8%) in which no other gene alteration was identified. Two of them, namely TCF12 positive and one TAF15 positive tumors, were highly cellular and partially associated with pseudopapillary architecture. Our study found that moderate/strong expression of INSM1 in more than 25% of tumor cells was present in only 31% of cases. Thus, the diagnostic utility of INSM1 is rather low. Two morphologically unique cases of non-EWSR1 rearranged EMC with an extremely rare pseudopapillary growth pattern are also reported.
PMID:36563884 | DOI:10.1016/j.humpath.2022.12.005
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177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials
Fetched: December 24th, 2022, 5:02am GMT by Alberto Bongiovanni
Cancers (Basel). 2022 Dec 7;14(24):6022. doi: 10.3390/cancers14246022.
ABSTRACT
INTRODUCTION: Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome.
PATIENTS AND METHODS: A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed.
RESULTS: Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2-63.2) median PFS was 33.0 months (95%CI: 27.1-48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1-94.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2-98.0) vs. 40.0% (95%CI: 6.6-73.4), respectively. A total of 233 adverse events were recorded. Grade 1-2 hematological toxicity was the most frequent.
CONCLUSION: The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS.
PMID:36551507 | PMC:PMC9776442 | DOI:10.3390/cancers14246022
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INSM1 Expression in Mesenchymal Tumors and Its Clinicopathological Significance
Fetched: December 20th, 2022, 5:01am GMT by Qian Zhang
Biomed Res Int. 2022 Dec 7;2022:1580410. doi: 10.1155/2022/1580410. eCollection 2022.
ABSTRACT
BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been identified as a nuclear marker of neuroendocrine tumors. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumor, its expression and clinicopathological significance in mesenchymal tumors remain unclear.
METHODS: We analyzed INSM1 mRNA level in GEO database and conducted immunohistological staining to detect the expression of INSM1 on 576 mesenchymal tumors from pathology department of Tongji Hospital.
RESULTS: At transcription level, INSM1 expression in AITL (angioimmunoblastic T-cell lymphoma) was higher than their adjacent normal tissues as well as Hodgkin's lymphoma. Moreover, INSM1 expression in well-differentiated liposarcoma (WDLPS) was significantly higher than normal fat (P = 0.014) and dedifferentiated liposarcoma (DDLPS) (P = 0.0248). At protein level, the positive rate of INSM1 in AITL was 18/48 (47.4%), while in DDLPS was 9/20 (45%). INSM1 expression in AITL was significantly higher than Hodgkin's lymphoma (P = 0.008). And INSM1 expression in WDLPS was significantly lower than DDLPS (P = 0.015).
CONCLUSION: The combination of GEO data and immunohistochemistry data indicated that the expression level of INSM1 was higher in AITL compared with normal control, suggesting that INSM1 may be involved in pathogenesis of AITL. The abnormal expression of INSM1 was found in WDLPS, and the positive rate of INSM1 was higher in DDLPS than in WDLPS. INSM1 may be involved in the regulation of liposarcoma development. There were significant differences in the expression of INSM1 between AITL and Hodgkin's lymphoma and WDLPS and DDLPS. These findings may assist in the differential diagnosis of these tumors when common markers are difficult to identify, enriching the diagnostic index system of mesenchymal tumors.
PMID:36531655 | PMC:PMC9750778 | DOI:10.1155/2022/1580410
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The cultivation conditions affect the aggregation and functionality of β-cell lines alone and in coculture with mesenchymal stromal/stem cells
Fetched: December 16th, 2022, 5:01am GMT by Florian Petry
Eng Life Sci. 2022 May 20;22(12):769-783. doi: 10.1002/elsc.202100168. eCollection 2022 Dec.
ABSTRACT
The manufacturing of viable and functional β-cell spheroids is required for diabetes cell therapy and drug testing. Mesenchymal stromal/stem cells (MSCs) are known to improve β-cell viability and functionality. We therefore investigated the aggregation behavior of three different β-cell lines (rat insulinoma-1 cell line [INS-1], mouse insulinoma-6 cell line [MIN6], and a cell line formed by the electrofusion of primary human pancreatic islets and PANC-1 cells [1.1B4]), two MSC types, and mixtures of β-cells and MSCs under different conditions. We screened several static systems to produce uniform β-cell and MSC spheroids, finding cell-repellent plates the most suitable. The three different β-cell lines differed in their aggregation behavior, spheroid size, and growth in the same static environment. We found no major differences in spheroid formation between primary MSCs and an immortalized MSC line, although both differed with regard to the aggregation behavior of the β-cell lines. All spheroids showed a reduced viability due to mass transfer limitations under static conditions. We therefore investigated three dynamic systems (shaking multi-well plates, spinner flasks, and shaking flasks). In shaking flasks, there were no β-cell-line-dependent differences in aggregation behavior, resulting in uniform and highly viable spheroids. We found that the aggregation behavior of the β-cell lines changed in a static coculture with MSCs. The β-cell/MSC coculture conditions must be refined to avoid a rapid segregation into distinct populations under dynamic conditions.
PMID:36514533 | PMC:PMC9731603 | DOI:10.1002/elsc.202100168
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Gastroenteropancreatic neuroendocrine tumors : (GEP-NENs)
Fetched: December 16th, 2022, 5:01am GMT by Christian Sebesta
Wien Med Wochenschr. 2022 Dec 13. doi: 10.1007/s10354-022-00979-2. Online ahead of print.
ABSTRACT
The entity of NENs represent a highly heterogenous group of malignancies that require a multidisciplinary approach during the treatment of patients. The following article aims to provide a concise overview of the current state of the art in diagnostics and therapy. One specific feature of G1/G2 NENs is that the indication for surgery is given even in metastatic settings. Specific details regarding the treatment of its various different subgroups need to be gathered from available guidelines or current clinical studies. The field of nuclear medicine offers promising options for diagnostics and therapy which needs further investigation.
PMID:36512264 | DOI:10.1007/s10354-022-00979-2