Aging and Adrenal Aldosterone Production.

Abstract

Aldosterone, the primary mineralocorticoid, is synthesized in the outer zone of the adrenal cortex called the zona glomerulosa (ZG). The production of aldosterone is tightly regulated by angiotensin II (Ang II) and circulating potassium levels.1 Physiologically, aldosterone plays a key role in the maintenance of intravascular volume and blood pressure through sodium retention in the kidney. Excess aldosterone causes hypertension and induces cardiovascular complications.2–5 The autonomous secretion of aldosterone, independent of Ang II and sodium status, is known as primary aldosteronism (PA). PA is the most common cause of endocrine-related hypertension with a prevalence of 5% to 10% in hypertensive population6–10 and ≈20% in resistant hypertension.11–13 Because of the increased risk for cardiovascular complications in patients with PA, early detection of the disease and targeted treatment is recommended.14 The molecular pathogenesis of PA was largely unknown until recently. The development of specific antibodies against aldosterone synthase (CYP11B2), which is required for the final steps of aldosterone production, has allowed the detection of aldosterone-producing cells in resected adrenals.15,16 Using these antibodies, non-neoplastic foci of CYP11B2-expressing cells called aldosterone-producing cell clusters (APCC)15 have been identified in adrenal tissues adjacent to aldosterone-producing adenomas (APA) and in normal human adrenal glands without tumor or hyperplasia.15–20 Studies have shown that APCC are a common occurrence in normal human adrenals.21–23 Because circulating renin and Ang II levels are suppressed in patients with PA, the observation of APCC adjacent to APA suggested that APCC may represent a source of autonomous and renin-independent aldosterone secretion, perhaps even a precursor to APA.24 Over the past 6 years, somatic and germline mutations that cause inappropriate aldosterone production have been identified in patients with PA. Most of the mutations …