Local Control of Aldosterone Production and Primary Aldosteronism

Primary aldosteronism (PA) is caused by excessive production of aldosterone by the adrenal cortex and is determined by a benign aldosterone-producing adenoma (APA) in a significant proportion of cases. Local mechanisms, as opposed to circulatory ones, that control aldosterone production in the adrenal cortex are particularly relevant in the physiopathological setting and in the pathogenesis of PA. A breakthrough in our understanding of the pathogenetic mechanisms in APA has been the identification of somatic mutations in genes controlling membrane potential and intracellular calcium concentrations. However, recent data show that the processes of nodule formation and aldosterone hypersecretion can be dissociated in pathological adrenals and suggest a model envisaging different molecular events for the pathogenesis of APA.

TrendsPrimary aldosteronism (PA) is the most common form of endocrine hypertension. Patients with PA exhibit more severe cardiovascular damage than patients with essential hypertension. The most common cause of PA is a benign aldosterone-producing adenoma (APA) of the adrenal cortex.Local mechanisms controlling aldosterone production in the adrenal cortex are particularly relevant in the pathogenesis of PA.In APA, somatic mutations are present that induce increased cytosolic calcium activity and consequent activation of aldosterone production.Recent data show that nodule formation and aldosterone hypersecretion can be dissociated in pathological adrenals and suggest a two-hit model for APA formation.Remarkably, somatic mutations in the same genes that are mutated in APA are also found in cell clusters producing aldosterone in normal adrenal.