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

Abstract

ObjectivePrimary 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.DesignA retrospective case‐control study.PatientsConsecutive 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.MeasurementsA 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).ResultsAdrenal 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.ConclusionsVariable expression of steroidogenic enzymes in adrenal adenoma underlies the clinical heterogeneity of PA and is associated with treatment outcomes.

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia

“…A study by Nakamura et al ( 38 ) demonstrated that CYP11B1, a steroidogenic enzyme, which converts deoxycorticosterone to corticosterone, was diffusely detected in the APA, and it could play a pivotal role in the tumor genesis. In another recent study, Ahn et al ( 39 ) showed lower CYP11B1 expression in adrenal adenomas of patients with PA compared with those affected by adrenal Cushing's syndrome. These findings underlined how the variable expression of steroidogenic enzymes in adrenal lesions is associated with the clinical heterogeneity of hormone overproduction.…”

Molecular and Epigenetic Control of Aldosterone Synthase, CYP11B2 and 11-Hydroxylase, CYP11B1

“…Cushing’s syndrome is caused either by excessive medication of cortisol-like compounds or by tumors, such as pituitary and adrenal adenomas, which express high levels of the cortisol synthase gene CYP11B1 and thereby produce a high level of cortisol [ 84 , 85 ]. Previous reports have demonstrated the overexpression of CYP11B1 in adrenal Cushing’s syndrome [ 86 ]. However, the molecular mechanism underlying the CYP11B1 overexpression in adrenal Cushing’s syndrome remains unclear.…”

Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism

“…The IHC examination of CYP11B2 and CYP11B1, key enzymes in aldosterone and cortisol biosynthesis, in adrenal slices is commonly used to identify the source of aberrant secretions of aldosterone and cortisol ( 124 , 125 ). A recent study demonstrated that the immunoreactivity of CYP11B1 was higher in adrenal adenomas of PA patients with concurrent ACS compared to PA patients without ACS ( 126 ). Interestingly, some studies have reported that the immunoreactivity of CYP11B1 was higher in adenomas without KCNJ5 mutations compared with adenomas harboring mutant KCNJ5 ( 92 , 127 ).…”