Endocrine and hypertensive disorders of potassium regulation: primary aldosteronism

Abstract

The identification of primary aldosteronism as a common cause of resistant hypertension is a significant advance in our ability to care for patients with hypertension. Primary aldosteronism is common, and when unrecognized is associated with an increased incidence of adverse cardiovascular outcomes. Identification of primary aldosteronism is based on use of the plasma aldosterone level, plasma renin activity, and the aldosterone:renin ratio. Differentiation between unilateral and bilateral autonomous adrenal aldosterone production then guides further therapy, with use of mineralocorticoid-receptor blockers for patients with bilateral autonomous adrenal aldosterone production and laparoscopic adrenalectomy for patients with unilateral autonomous aldosterone production. In this review, we discuss in detail the pathogenesis of primary aldosteronism-induced hypertension and potassium disorders, the evaluation of the patient with suspected primary aldosteronism, and the management of primary aldosteronism, both through medications and surgery.

Keywords: Aldosterone; aldosterone-producing adenoma; bilateral adrenal hyperplasia; hypertension; hypokalemia; renin.

Figure 1

Mechanisms through which aldosterone increases blood pressure. Aldosterone production is regulated in large through the renin-angiotensin system, acting through the AT₁ receptor to stimulate adrenal aldosterone production. Aldosterone has multiple effects that regulate blood pressure. These include actions in the CNS, likely mediated through increased sympathetic nervous system tone, direct stimulation of renal NaCl retention, increased arterial vasoconstriction, decreased arterial vasodilatory responses and stimulation of endothelin.

Figure 2

Risk of cardiovascular events in patients with unrecognized primary aldosteronism. Incidence of previous cardiovascular events was determined at time of diagnosis of primary aldosteronism in 54 consecutive patients, and compared with 323 patients matched for age, sex, body mass index and estimated duration of hypertension. Incidence of previous myocardial infarction or reversible ischemia, cerebrovascular accident (CVA) or transient ischemic attack (TIA), sustained cardiac arrhythmia and peripheral arterial disease (PAD) was assessed, and in each case was significantly greater (P<0.05) than in patients with essential hypertension.

Figure 3

Results of randomized controlled trial of spironolactone versus eplerenone in the treatment of primary aldosteronism. Patients with primary aldosteronism were randomized to either spironolactone or eplerenone therapy. Dose was increased at pre-specified time intervals until hypertension control was obtained. At each time point, the likelihood of significantly improved blood pressure control, pre-defined as either a DBP < 90 mmHg or a decrease of at least 10 mmHg was significantly greater in individuals treated with spironolactone. Not shown is that mean improvement in blood pressure at each time point was ~2–2.5-fold greater in patients randomized to spironolactone than in those randomized to eplerenone.

Figure 4

Evaluation and management of suspected primary aldosteronism. See text for details.