Functional Characteristic and Significance of Aldosterone-Producing Cell Clusters in Primary Aldosteronism and Age-Related Hypertension

Primary aldosteronism (PA) is one of the most frequent curable forms of secondary hypertension. It can be caused by the overproduction of aldosterone in one or both adrenal glands. The most common subtypes of PA are unilateral aldosterone over-production due to aldosterone-producing adenomas (APA) or bilateral aldosterone over-production due to bilateral hyperaldosteronism (BHA). Utilizing the immunohistochemical (IHC) detection of aldosterone synthase (CYP11B2) has allowed the identification of aldosterone-producing cell clusters (APCCs) with unique focal localization positive for CYP11B2 expression in the subcapsular portion of the human adult adrenal cortex. The presence of CYP11B2 supports that synthesis of aldosterone can occur in these cell clusters and therefore might contribute to hyperaldosteronism. However, the significance of the steroidogenic properties of APCCs especially in regards to PA remains unclear. Herein, we review the available evidence on the presence of APCCs in normal adrenals and adrenal tissues adjacent to APAs, their aldosterone-stimulating somatic gene mutations, and their accumulation during the ageing process; raising the possibility that APCCs may play a role in the development of PA and age-related hypertension.