Primary Aldosteronism

Abstract

See related article, p 783–789 Primary aldosteronism (PA) is the most common form of secondary hypertension accounting for ≈10% of patients referred to hypertension clinics and as high as 20% of those with refractory hypertension.1 The most important causes of PA are idiopathic hyperaldosteronism (IHA), also called bilateral zona glomerulosa hyperplasia, responsible for ≈50% to 70% of PA and aldosterone-producing adenomas (APA) in 30% to 50% of PA and less common causes in ≈2% of patients with PA.1 The latter include 3 familial types of PA or hyperaldosteronism. Familial hyperaldosteronism (FHA) I, or glucocorticoid-suppressible aldosteronism, is because of gene duplication by an uneven crossover recombination of the 11β-hydroxylase (CYP11B1) and the aldosterone synthase (CYP11B2) genes, resulting in the expression of an ACTH-regulated chimeric gene in the zona fasciculata, which produces aldosterone. FHA II, the most common, is of yet unknown cause though many cases are in linkage with chromosome 7p22. FHA III is described below.2–4 Until relatively recently, research on PA concentrated in defining ways to diagnose and differentiate between the various types of PA and best way to treating them. Studies of the pathogenesis and the molecular basis of APAs had been limited to searches of aberrant expression of G-protein–coupled receptors and altered expression of genes using microarray technology. Studies of the pathogenesis of IHA had focused on the futile search for unknown aldosterone-stimulating factors in the 1970s and 1980s. In 2011, the use of the whole exome sequencing technique by the Lifton group led to the identification of somatic mutations of the G-protein–activated potassium inward rectifying channel KCNJ5 (Kir3.4 channel) in adenomas of ≈30% of patients with APA2 and initiated the use of this powerful technique to address …