Genetic mechanisms of primary aldosteronism.

Abstract

Primary aldosteronism (PA) represents the leading cause of secondary hypertension, resulting from autonomous aldosterone production driven in the majority of cases by a lateralized aldosterone-producing adenoma or by bilateral adrenal hyperplasia. Its frequency increases in parallel with hypertension severity, reaching a prevalence of up to 25% of patients with treatment resistant hypertension. Advances in our understanding on the genetic causes of PA have reshaped our understanding of the pathogenesis of the disease, revealing a broad spectrum of somatic and inherited mutations across most aldosterone-producing adenomas as well as familial forms of the disorder. More recently, susceptibility loci shared between unilateral and bilateral PA, and overlapping with known blood-pressure associated variants, have been identified, highlighting genetic susceptibility that extends beyond PA to hypertension in the general population. Associated with clinical and biochemical evidence of a continuum of aldosterone dysregulation in hypertension, these discoveries suggest that common genetic variants may drive aldosterone dysregulation in a large fraction of hypertensive subjects leading, in extreme cases, to overt PA.