26-24: Primary Aldosteronism

GENERAL CONSIDERATIONS

Primary aldosteronism (hyperaldosteronism) refers to renin-independent, inappropriately high and nonsuppressible aldosterone secretion and is associated with adverse cardiovascular disorders. Although most affected patients have hypertension, some may be normotensive. Primary aldosteronism is prevalent and largely undiagnosed. The prevalence of primary aldosteronism in patients with suppressed PRA is 11% in normotensive individuals, 17% in those with stage 1 untreated hypertension, 25% in those with stage 2 untreated hypertension, and 51% in those with treatment-resistant hypertension. It should be suspected with early-onset hypertension or stroke before age 50 years. It may be difficult to distinguish primary aldosteronism from cases of low renin essential hypertension, with which it may overlap. Patients of all ages may be affected, but the peak incidence is between 30 years and 60 years. Excessive aldosterone production increases sodium retention and suppresses plasma renin. It increases renal potassium excretion, which can lead to hypokalemia. Cardiovascular events are more prevalent in patients with aldosteronism (35%) than in those with essential hypertension (11%).

Primary aldosteronism is most frequently caused by bilateral adrenal cortical hyperplasia (75%) that is more common in men with a 4:1 ratio, peaking between ages 50 and 60. Primary aldosteronism may be also caused by a unilateral aldosterone-producing adrenal cortical adenoma (Conn syndrome, 25%) that is more common in women with a 2:1 ratio, peaking between ages 30 and 50. It is important to distinguish the two, since a unilateral aldosteronoma (Conn syndrome) may be cured by surgical resection, whereas patients with bilateral adrenal hyperplasia are treated medically.

Unilateral aldosterone-producing adrenal adenoma (Conn syndrome) have been found to have somatic mutations in a gene involved with potassium channels (40%). Primary aldosterone has been caused rarely by malignant ovarian tumors. Bilateral aldosteronism may be corticosteroid-suppressible, due to an autosomal-dominant genetic defect allowing ACTH stimulation of aldosterone production.

CLINICAL FINDINGS

A. Symptoms and Signs

Primary aldosteronism is the most common cause of refractory hypertension in youths and middle-aged adults. Patients have hypertension that is typically moderate but may be severe. Some patients have only diastolic hypertension, without other symptoms and signs. Edema is rarely seen in primary aldosteronism. Hypokalemia can produce muscle weakness (at times with paralysis simulating periodic paralysis), paresthesias with tetany, headache, polyuria, and polydipsia.

B. Laboratory Findings

Plasma potassium should be determined in hypertensive individuals. However, hypokalemia, once thought to be the hallmark of hyperaldosteronism, is present in only 37% of affected patients: 50% of those with an aldosterone-producing adenoma and 17% of those with adrenal hyperplasia. An elevated serum bicarbonate (HCO₃) concentration indicates metabolic alkalosis and is commonly present.

Testing for primary ...