The Genetics of Primary Aldosteronism

Abstract

See related article, pp 592–598 For many years it was thought, and taught, that primary aldosteronism was a relatively benign cause of hypertension, rare (<1%) and suspected only in patients with severe hypokalemia. We know now that none of this is the case: primary aldosteronism is relatively common (8% to 13% of unselected hypertensives), with much higher cardiovascular risk factors (stroke, atrial fibrillation, and nonfatal myocardial infarction) than age-, sex-, and blood pressure–matched essential hypertensives and with hypokalemia only in a minority of cases. Not surprisingly given this revisionist climate, much more attention has been focused on screening for, diagnosis of, and management of the condition. Approximately one third of confirmed primary aldosteronism is unilateral, due in the great majority of cases to an aldosterone-producing adenoma (APA), with the remainder bilateral, in the great majority of cases attributed to bilateral adrenal hyperplasia (BAH); together they represent ≈10% of all hypertension. Another ≈20% is so-called resistant hypertension (resistant to ≥3 conventional agents, including a diuretic), a condition in which blood pressure is very substantially lowered (20–30 mm Hg) by the addition of a mineralocorticoid receptor antagonist at a remarkably low dose. As APA is usually a more florid form of primary aldosteronism than BAH–in terms of blood pressure, aldosterone levels, and hypokalemia–it seemed possible that, within the descriptor “low renin hypertension,” there may be a progression from resistant hypertension to BAH and ultimately to the emergence of a dominant module and APA. This perhaps seductive hypothesis has been shown not simply to be the case, at least for a substantial proportion of APA, by the publication by Choi et al,1 largely confirmed and substantially extended by Boulkroun et al,2 in this issue of the journal. In 8 of 22 relatively large APAs, Choi et al1 found 1 of …