Histopathological Classification of Cross-Sectional Image-Negative Hyperaldosteronism.
J Clin Endocrinol Metab. 2017 Apr 01;102(4):1182-1192
Authors: Yamazaki Y, Nakamura Y, Omata K, Ise K, Tezuka Y, Ono Y, Morimoto R, Nozawa Y, Gomez-Sanchez CE, Tomlins SA, Rainey WE, Ito S, Satoh F, Sasano H
Context: Approximately half of patients with primary aldosteronism (PA) have clinically evident disease according to clinical (hypertension) and/or laboratory (aldosterone and renin levels) findings but do not have nodules detectable in routine cross-sectional imaging. However, the detailed histopathologic, steroidogenic, and pathobiological features of cross-sectional image-negative PA are controversial.
Objective: To examine histopathology, steroidogenic enzyme expression, and aldosterone-driver gene somatic mutation status in cross-sectional image-negative hyperaldosteronism.
Methods: Twenty-five cross-sectional image-negative cases were retrospectively reviewed. In situ adrenal aldosterone production capacity was determined using immunohistochemistry (IHC) of steroidogenic enzymes. Aldosterone-driver gene somatic mutation status (ATP1A1, ATP2B3, CACNA1D, and KCNJ5) was determined in the CYP11B2 immunopositive areas [n = 35; micronodule, n = 32; zona glomerulosa (ZG), n = 3] using next-generation sequencing after macrodissection.
Results: Cases were classified as multiple adrenocortical micronodules (MN; n = 13) or diffuse hyperplasia (DH) of ZG (n = 12) based upon histopathological evaluation and CYP11B2 IHC. Aldosterone-driver gene somatic mutations were detected in 21 of 26 (81%) of CYP11B2-positive cortical micronodules in MN; 17 (65%) mutations were in CACNA1D, 2 (8%) in KCNJ5, and 1 each (4% each) in ATP1A1 and ATP2B. One of 6 (17%) of nodules in DH harbored somatic aldosterone-driver gene mutations (CACNA1D); however, no mutations were detected in CYP11B2-positive nonnodular DH areas.
Conclusion: Morphologic evaluation and CYP11B2 IHC enabled the classification of cross-sectional image-negative hyperaldosteronism into MN and DH. Somatic mutations driving aldosterone overproduction are common in micronodules of MN, suggesting a histological entity possibly related to aldosterone-producing cell cluster development.
PMID: 28388725 [PubMed - in process]