Endocrine Abstracts

Objective: Clinical and histopathological assessment of a consecutive series of Munich patients operated between 2016 and 2018 for unilateral primary aldosteronism (PA).

Background: Unilateral PA is the most common surgically curable form of hypertension mainly caused by an aldosterone-producing adenomas (APA). Somatic mutations in KCNJ5, CACNA1D, ATP1A1 or ATP2B3drive the aldosterone excess in the majority of APAs. Genetic variants in CLCN2 have been described in a familial form of PA.

Design and method: The study included 60 surgical adrenal specimens from patients diagnosed with unilateral PA at a single referral center over a 3-year period (2016 to 2018). Clinical and biochemical outcomes were determined according to the PASO criteria. Histopathology of all resected adrenal was assessed by hematoxylin and eosin and aldosterone synthase (CYP11B2) staining. Aldosterone-producing adenomas were genotyped for known somatic mutations by CYP11B2-immunohistochemistry-guided Sanger sequencing of formalin-fixed adrenals or exome sequencing of fresh-frozen tissue.

Results: The cohort (29 males and 31 females) displayed a mean age at surgery of 51 ± 13 years and a median duration of hypertension of 103 [39–171] months. Complete biochemical success after surgery was observed in 84% of 54 patients with follow-up and complete clinical success was achieved in 19% (n = 10) with a further 57% (n = 31) displaying significant clinical improvements (partial clinical success). Histopathologic assessment demonstrated an aldosterone-producing adenoma in 78% (47 of 60) with the remaining 13 adrenals showing multiple micronodules or diffuse hyperplasia. In patients with follow-up, complete biochemical success was achieved in 84% of the 43 patients with an aldosterone-producing adenoma compared with 45% of the 11 patients with diffuse hyperplasia or multiple micronodules. Of 40 genotyped aldosterone-producing adenomas, 22 (55%) had a KCNJ5 mutation, 4 carried mutations in ATP1A1 and 4 had CACNA1D mutations. Exome sequencing of an aldosterone-producing adenoma identified a CLCN2 variant (encoding a C244Y mutation).

Conclusions: These findings may contribute to a better understanding of the clinical, histopathologic and genetic correlates of the pathophysiology of unilateral PA.