Primary
aldosteronism (PA) is the most common form and an under-diagnosed cause of secondary arterial
hypertension, accounting for up to 10% of hypertensive cases and associated to increased cardiovascular risk. PA is caused by autonomous overproduction of
aldosterone by the adrenal cortex. It is mainly caused by a unilateral
aldosterone-producing
adenoma (APA) or bilateral adrenal
hyperplasia. Excess
aldosterone leads to arterial
hypertension with suppressed
renin, frequently associated to
hypokalemia. Mutations in genes coding for
ion channels and
ATPases have been identified in APA, explaining the pathophysiology of increased
aldosterone production. Different inherited genetic abnormalities led to the distinction of four forms of
familial hyperaldosteronism (type I to IV) and other genetic defects very likely remain to be identified. Somatic mutations are identified in APA, but also in
aldosterone-producing cell clusters (APCCs) in normal adrenals, in image-negative unilateral
hyperplasia, in transitional lesions and in APCC from adrenals with bilateral adrenal
hyperplasia (BAH). Whether these structures are precursors of APA or whether somatic mutations occur in a proliferative adrenal cortex, is still a matter of debate. This review will summarize our knowledge on the molecular mechanisms responsible for PA and the recent discovery of new genes related to early-onset and familial forms of the disease. We will also address new issues concerning genomic and proteomic changes in adrenals with APA and discuss adrenal pathophysiology in relation to
aldosterone-producing structures in the adrenal cortex.