Expression of CYP11B1 and CYP11B2 in adrenal adenoma correlates with clinical characteristics of primary aldosteronism

Abstract Objective Primary aldosteronism (PA) shows histological heterogeneity and clinical variability, including the coexistence of hypercortisolemia. Immunohistochemical analyses of steroidogenic enzymes in adrenal tissues have provided new insights into the pathogenesis of PA. However, a comprehensive analysis of the association between enzyme expression and clinical characteristics of PA has rarely been conducted. We aimed to investigate the correlation between clinical characteristics and steroidogenic enzyme expression in PA. Design A retrospective case‐control study. Patients Consecutive patients who underwent unilateral adrenalectomy for PA ( n = 180). Patients with adrenal Cushing's syndrome (CS) ( n = 29) and nonfunctioning adenoma ( n = 6) as comparator groups. Measurements A tissue microarray of adrenal adenomas was constructed and immunostained for CYP11B1, CYP11B2 and CYP17A1. The expression of the three enzymes was compared between PA and other adrenal diseases and between PA with and without mild autonomous cortisol excess (MACE). Results Adrenal adenomas in PA showed lower CYP11B1, higher CYP11B2 and lower CYP17A1 expression than those in adrenal CS ( p < .001). Nonfunctioning adenomas showed low expression of the three enzymes. PA with MACE showed higher CYP11B1 expression than PA without MACE. CYP11B1 expression was positively correlated with the severity of hypercortisolemia, and CYP11B2 was positively correlated with that of hyperaldosteronism. The expression of CYP11B1 and CYP11B2 had a negative correlation. Patients with absent clinical improvement after adrenalectomy had lower CYP11B2 expression than those with complete success. Conclusions Variable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes.