Adrenocortical Tumor Associated With Pathogenic Variant in KCNJ5 and DNA Methylation of CYP11B2 in Primary Aldosteronism

Abstract

Abstract Primary aldosteronism (PA) is a subtype of secondary hypertension categorized as either unilateral PA (eg, aldosterone-producing adenoma [APA]) or bilateral PA. CYP11B2, an aldosterone synthase, is highly expressed in APA. Recent studies have revealed a high prevalence of pathogenic variants in KCNJ5 and the role of DNA methylation on CYP11B2 in APA. We present a case of unilateral PA with pathogenic variants in KCNJ5 and suppressed CYP11B2 expression. A 55-year-old woman with hypertension was referred to our hospital. A high aldosterone-renin ratio was observed; PA was confirmed using the captopril challenge test and the furosemide upright test. Although computed tomography showed no evident tumors in either adrenal gland, adrenal vein sampling revealed left gland dominance. Postoperatively, the aldosterone-renin ratio decreased and captopril challenge test showed negative findings. Pathogenic variants in the KCNJ5 were detected in the adenoma. Although immunohistochemistry for CYP11B2 was negative in adenoma, an aldosterone-producing cell cluster was confirmed in the adjacent left adrenal gland. Furthermore, DNA methylation analysis of the adenoma indicated hypermethylation in the CYP11B2 promoter region. The pathogenic variant in KCNJ5, specific to APA, induces CYP11B2 overexpression, resulting in excess aldosterone. However, these effects can be suppressed by DNA methylation.