Genetic and potential autoimmune triggers of primary aldosteronism.

Abstract

Hypertension is a major life-threatening disease of high morbidity and mortality, which affects between 10% to 40% of the general population in an age-dependent manner. The pathogenesis of essential hypertension is multifactorial, with various underlying contributory mechanisms. Primary aldosteronism (PA) is the leading cause of secondary hypertension that affects 4.3% of patients in the general hypertensive population and 9.5% of patients referred to hypertension units.1 The 2 predominant causes of the constitutive aldosterone secretion that define PA is either aldosterone-producing adenomas (APA) or bilateral adrenal hyperplasia (BAH, also called idiopathic hyperaldosteronism). Exome sequencing has unraveled the pathogenetic basis of around half of APA, but the underlying cause of the aldosterone excess in BAH remains an enigma. The diagnosis of PA is made by a multistep process, recommended by the Endocrine Society guidelines,2 that ends with the invasive protocol of adrenal venous sampling. Once diagnosed, it is imperative to distinguish the surgically correctable forms (APA) from those that should be treated pharmacologically with mineralocorticoid receptor antagonists (BAH). With the application of wider screening for PA, >70% of cases of aldosterone excess have been defined as caused by BAH, with APA making up most of the remainder. APA and BAH are sporadic forms of PA, but 3 rarer familial forms of PA also exist called familial hyperaldosteronism (FH) types I, II, and III, described in more detail below. Three familial forms of PA with distinct clinical characteristics have been described.3,4 FH type I or glucocorticoid remediable aldosteronism is caused by a hybrid gene resulting from the unequal crossing-over between the adjacent genes CYP11B1 and CYP11B2 .5,6 Only few families (≈50) have been identified worldwide. FH type II seems to be inherited as an autosomal dominant trait. A locus has been mapped on chromosome 7p22 …