Endocrine Abstracts

Arterial hypertension is a major cardiovascular risk factor. Detection of secondary forms of hypertension is key to targeted management and prevention of cardiovascular complications. Primary aldosteronism (PA) is the most common and curable form of secondary arterial hypertension and has an estimated prevalence of ~10% in referred patients and 5% in primary care. PA results from autonomous aldosterone production from the adrenal cortex, caused in the majority of cases by a unilateral aldosterone producing adenoma (APA) or bilateral adrenal hyperplasia (BAH). Whole exome sequencing has allowed identification of recurrent mutations in genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H, CLCN2) and ATPases (ATP1A1 and ATP2B3) in APA and familial forms of PA. Those proteins are responsible for maintaining intracellular ion homeostasis and membrane potential of zona glomerulosa cells. The current pathophysiological model for PA development involves modifications of intracellular ion homeostasis and membrane potential, leading to the activation of calcium signaling, the major trigger for aldosterone production. This presentation will summarize our current knowledge on the genetic basis of PA and discuss the pathogenic mechanisms leading to increased aldosterone production and cell proliferation. Perspectives for clinical management of patients and open questions to be addressed by future research will be discussed.