Aldosterone-Producing Cell Clusters Frequently Harbor Somatic Mutations and Accumulate With Age in Normal Adrenals

CONTEXT: Aldosterone synthase (CYP11B2) immunohistochemistry and next-generation sequencing (NGS) have revealed the frequent presence of aldosterone-producing cell clusters (APCCs) harboring somatic mutations in aldosterone-regulating genes in adrenals from Americans without defined hypertension status. OBJECTIVE: Determine the frequency and somatic mutation status of APCCs in a Japanese nonhypertensive cohort. DESIGN SETTING PATIENTS AND INTERVENTIONS: Adrenals from 837 consecutive autopsies at a Japanese institution, Tohoku University Hospital, were screened to select 107 unilateral adrenal glands from nonhypertensive patients. APCC score (APCC number/adrenal cortex area per case) was assessed by CYP11B2 immunohistochemistry. DNA from all APCCs and adjacent adrenal cortex was subjected to NGS using two panels targeting aldosterone-regulating genes. PRIMARY OUTCOME MEASURE: APCC frequency and somatic mutation spectrum. RESULTS: , the most frequently mutated gene in aldosterone-producing adenoma. APCC score was significantly lower than our previous cohort of unilateral computed tomography-negative PA. CONCLUSIONS: ). The role of APCCs in PA pathobiology and non-PA hypertension warrants further investigation.