Primary aldosteronism is the most common form of secondary hypertension, affecting up to 10% of hypertensive patients. It is responsible for treatment resistance and increased risk of cardiovascular complications.
Over the past 10 years, important discoveries have been made regarding the genetic basis of aldosterone producing adenoma and familial forms of primary aldosteronism. In most cases, genetic abnormalities are found in genes coding for ion channels (KCNJ5, CACNA1D, CACNA1H, CLCN2) as well as ion pumps (ATP1A1, ATP2B3). They occur as somatic mutations in aldosterone producing adenoma and as germline mutations in familial forms of the disease. Mutations in these genes affect intracellular ion homeostasis and/or cell membrane potential, leading to increased intracellular calcium concentrations and activation of calcium signalling, which is the main regulator of aldosterone biosynthesis. In addition, double mutations in CTNNB1 and GNAQ/GNA11 have been identified in aldosterone producing adenoma presenting in puberty, pregnancy and menopause.