Primary aldosteronism is aldosteronism caused by autonomous production of aldosterone by the adrenal cortex (due to hyperplasia, adenoma, or carcinoma). Symptoms and signs include episodic weakness, elevated BP, and hypokalemia. Diagnosis includes measurement of plasma aldosterone levels and plasma renin activity. Treatment depends on cause. A tumor is removed if possible; in hyperplasia, spironolactone or related drugs may normalize BP and eliminate other clinical features.
Aldosterone is the most potent mineralocorticoid produced by the adrenals. It causes Na retention and K loss. In the kidneys, aldosterone causes transfer of Na from the lumen of the distal tubule into the tubular cells in exchange for K and hydrogen. The same effect occurs in salivary glands, sweat glands, cells of the intestinal mucosa, and in exchanges between ICFs and ECFs.
Aldosterone secretion is regulated by the renin-angiotensin system and, to a lesser extent, by ACTH. Renin, a proteolytic enzyme, is stored in the juxtaglomerular cells of the kidneys. Reduction in blood volume and flow in the afferent renal arterioles induces secretion of renin. Renin transforms angiotensinogen from the liver to angiotensin I, which is transformed by ACE to angiotensin II. Angiotensin II causes secretion of aldosterone and, to a much lesser extent, secretion of cortisol and deoxycorticosterone; it also has pressor activity. Na and water retention resulting from increased aldosterone secretion increases the blood volume and reduces renin secretion.
Primary aldosteronism is caused by an adenoma, usually unilateral, of the glomerulosa cells of the adrenal cortex or, more rarely, by adrenal carcinoma or hyperplasia. Adenomas are extremely rare in children, but the syndrome sometimes occurs in childhood adrenal carcinoma or hyperplasia. In adrenal hyperplasia, which is more common among older men, both adrenals are overactive, and no adenoma is present. The clinical picture can also occur with congenital adrenal hyperplasia from deficiency of 11 β-hydroxylase and the dominantly inherited dexamethasone-suppressible hyperaldosteronism. Hyperplasia as a cause of hyperaldosteronism may be more common than previously recognized but remains an infrequent cause in the presence of hypokalemia.
Symptoms and Signs
Hypernatremia, hypervolemia, and a hypokalemic alkalosis may occur, causing episodic weakness, paresthesias, transient paralysis, and tetany. Diastolic hypertension and hypokalemic nephropathy with polyuria and polydipsia are common. In many cases, the only manifestation is mild to moderate hypertension. Edema is uncommon.
Diagnosis is suspected in patients with hypertension and hypokalemia. Initial laboratory testing consists of plasma aldosterone levels and PRA. Ideally, the patient should not take any drugs that affect the renin-angiotensin system (eg, thiazide diuretics, ACE inhibitors, angiotensin antagonists, β-blockers) for 4 to 6 wk before tests are done. PRA is usually measured in the morning with the patient recumbent. Patients with primary aldosteronism typically have plasma aldosterone > 15 ng/dL (> 0.42 nmol/L) and low levels of PRA, with a ratio of plasma aldosterone (in ng/dL) to PRA (in ng/mL/h) > 20.
Low levels of both PRA and aldosterone suggest nonaldosterone mineralocorticoid excess (eg, due to licorice ingestion, Cushing syndrome, or Liddle syndrome). High levels of both PRA and aldosterone suggest secondary hyperaldosteronism (see Adrenal Disorders: Secondary Aldosteronism). The principal differences between primary and secondary aldosteronism are shown in Table 3: Adrenal Disorders: Differential Diagnosis of Aldosteronism. In children, Bartter syndrome (see Congenital Renal Transport Abnormalities: Bartter Syndrome and Gitelman's Syndrome) is distinguished from primary hyperaldosteronism by the absence of hypertension and marked elevation of PRA.
Patients with findings suggesting primary hyperaldosteronism should undergo CT or MRI to determine whether the cause is a tumor or hyperplasia. Aldosterone levels measured on awakening and 2 to 4 h later while standing also may help make this distinction; in adenoma, levels decline and in hyperplasia, levels increase. However, imaging tests and postural changes on standing are relatively insensitive, and most patients require bilateral catheterization of the adrenal veins to measure cortisol and aldosterone levels to confirm whether the aldosterone excess is unilateral (tumor) or bilateral (hyperplasia).
Tumors should be removed laparoscopically. After removal of an adenoma, serum K normalizes and BP decreases in all patients; complete normalization of the BP without the need for hypotensive therapy occurs in 50 to 70% of patients.
Among patients with adrenal hyperplasia, 70% remain hypertensive after bilateral adrenalectomy; thus, surgery is not recommended. Hyperaldosteronism in these patients can usually be controlled by a selective aldosterone blocker such as spironolactone, starting with 300 mg po once/day and decreasing over 1 mo to a maintenance dose, usually around 100 mg once/day; or by amiloride 5 to 10 mg po once/day or another K-sparing diuretic. The more specific drug eplerenone 50 mg po once/day to 200 mg po bid may be used because, unlike spironolactone, it does not block the androgen receptor; it is the drug of choice for long-term treatment in men. About half of patients with hyperplasia need additional antihypertensive treatment (see Hypertension: General Treatment).
Last full review/revision August 2012 by Ashley B. Grossman, MD, FRCP, FMedSci