Primary Aldosteronism: Practical Approach to Diagnosis and Management

Abstract

Primary aldosteronism (PA) is the most common form of secondary hypertension. In many cases, somatic mutations in ion channels and pumps within adrenal cells initiate the pathogenesis of PA, and this mechanism might explain why PA is so common and suggests that milder and evolving forms of PA must exist. Compared with primary hypertension, PA causes more end-organ damage and is associated with excess cardiovascular morbidity, including heart failure, stroke, nonfatal myocardial infarction, and atrial fibrillation. Screening is simple and readily available, and targeted therapy improves blood pressure control and mitigates cardiovascular morbidity. Despite these imperatives, screening rates for PA are low, and mineralocorticoid-receptor antagonists are underused for hypertension treatment. After the evidence for the prevalence of PA and its associated cardiovascular morbidity is summarized, a practical approach to PA screening, referral, and management is described. All physicians who treat hypertension should routinely screen appropriate patients for PA.

Keywords: adrenal cortex; aldosterone; hyperaldosteronism; hypertension; receptors, mineralocorticoid; renin; renin-angiotensin system.

Figure 1

Illustration of the ligand-activated transcription-factor activity of the mineralocorticoid receptor. The liposoluble steroid hormone aldosterone diffuses into cells and binds to and activates the mineralocorticoid receptor. The mineralocorticoid receptor then dimerizes and translocates to the nucleus, where it binds a hormone-response element and regulates the transcription of target genes. This process regulates the abundance of the amiloride-sensitive epithelial-sodium channel on the apical surface of the epithelial cells in the distal-renal tubule and collecting duct, controlling the final 1-5% of sodium reabsorption. MR, mineralocorticoid receptor; MRE, mineralocorticoid response element; SGK1, serum- and glucocorticoid-inducible kinase; GILZ, glucocorticoid-induced leucine zipper; ENaC, amiloride-sensitive epithelial-sodium channel.

Figure 2

Simplified algorithm for PA screening and triaging based primarily on plasma renin and secondarily on serum aldosterone. Aldo, aldosterone; BP, blood pressure; CVA, cerebrovascular accident; DRC, direct renin concentration; FH, family history; MR, mineralocorticoid receptor; PA, primary aldosteronism; PRA, plasma renin activity. Patients with low renin and aldosterone >10 ng/dL are referred for confirmatory testing and subtyping; most patients with aldosterone >20 ng/dL have PA, and those with hypokalemia do not require confirmatory testing.