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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 kidney, 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 kidney. 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 in 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, producing 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

• Electrolytes
• Plasma aldosterone
• Plasma renin activity
• Adrenal imaging
• Bilateral adrenal vein catheterization (for cortisol and aldosterone levels)

Diagnosis is suspected in patients with hypertension and hypokalemia. Initial laboratory testing consists of plasma aldosterone levels and plasma renin activity (PRA). Ideally, tests are done with the patient off of drugs that affect the renin-angiotensin system (eg, thiazide diuretics, ACE inhibitors, angiotensin antagonists, β-blockers) for 4 to 6 wk. 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 nanograms/dL) to PRA (in nanograms/mL/h) > 20.

Low levels of both PRA and aldosterone suggest nonaldosterone mineralocorticoid excess (eg, due to licorice ingestion, Cushing's 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 renin.

Table 3
Differential Diagnosis of Aldosteronism Clinical Finding Primary Aldosteronism Secondary Aldosteronism Adenoma Hyperplasia Renovascular or Accelerated Hypertension Edematous disorders BP ↑↑ ↑ ↑↑↑↑ N, ↑ Edema Rare Rare Rare Present Serum Na N, ↑ N, ↑ N, ↓ N, ↓ Serum K ↓ N, ↓ ↓ N, ↓ Plasma renin activity* ↓↓ ↓↓ ↑↑ ↑ Aldosterone ↑ ↑ ↑↑ ↑ *When corrected for age; elderly patients have lower mean renin activities. ↑↑↑↑ = very greatly increased; ↑↑ = greatly increased; ↑ = increased; ↓↓ = greatly decreased; ↓ = decreased; N = normal.

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. In most cases, bilateral catheterization of the adrenal veins to measure cortisol and aldosterone should be used to confirm whether the aldosterone excess is unilateral (tumor) or bilateral (hyperplasia).

Treatment

• Surgical removal of tumors
• Spironolactone Some Trade Names
  ALDACTONE
  Click for Drug Monograph
  or eplerenone Some Trade Names
  INSPRA
  Click for Drug Monograph
  for hyperplasia

Tumors should be removed laparoscopically. After removal of an adenoma, BP decreases in all patients; complete remission occurs in 50 to 70%.

With adrenal hyperplasia, 70% remain hypertensive after bilateral adrenalectomy; thus surgery is not recommended. Hyperaldosteronism in these patients can usually be controlled by spironolactone Some Trade Names
ALDACTONE
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, 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 Some Trade Names
MIDAMOR
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(5 to 10 mg po once/day) or another K-sparing diuretic. The newer more specific drug eplerenone Some Trade Names
INSPRA
Click for Drug Monograph
may be used because, unlike spironolactone Some Trade Names
ALDACTONE
Click for Drug Monograph
, it does not block the androgen receptor. About ½ of patients with hyperplasia need additional antihypertensive treatment (see Arterial Hypertension: General Treatment).

Last full review/revision November 2007 by Ashley B. Grossman, MD

Content last modified November 2007