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Secondary Aldosteronism

By Ashley B. Grossman, MD, FRCP, FMedSci, Churchill Hospital, University of Oxford

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Secondary aldosteronism is increased adrenal production of aldosterone in response to nonpituitary, extra-adrenal stimuli such as renal hypoperfusion. Symptoms are similar to those of primary aldosteronism. Diagnosis includes measurement of plasma aldosterone levels and plasma renin activity. Treatment involves correcting the cause.

Secondary aldosteronism is caused by reduced renal blood flow, which stimulates the renin-angiotensin mechanism with resultant hypersecretion of aldosterone. Causes of reduced renal blood flow include obstructive renal artery disease (eg, atheroma, stenosis), renal vasoconstriction (as occurs in accelerated hypertension), and edematous disorders (eg, heart failure, cirrhosis with ascites, nephrotic syndrome). Secretion may be normal in heart failure, but hepatic blood flow and aldosterone metabolism are reduced, so circulating levels of the hormone are high.

Symptoms and Signs

Symptoms are similar to those of primary aldosteronism and include hypokalemic alkalosis that causes episodic weakness, paresthesias, transient paralysis, and tetany. In many cases, the only manifestation is hypertension. Peripheral edema may be present.

Diagnosis

  • Serum electrolyte levels

  • Plasma aldosterone

  • Plasma renin activity (PRA)

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, beta-blockers) for 4 to 6 wk before tests are done. Elevated aldosterone and plasma renin activity is indicative of secondary aldosteronism. The principal differences between primary and secondary aldosteronism are shown in Differential Diagnosis of Aldosteronism.

Differential Diagnosis of Aldosteronism

Clinical Finding

Primary Aldosteronism

Secondary Aldosteronism

Adenoma

Hyperplasia

Renovascular or Accelerated Hypertension

Edematous Disorders

BP

↑↑

↑↑↑↑

N or

Edema

Rare

Rare

Rare

Present

Serum Na

N or

N or

N or

N or

Serum K

N or

N or

Plasma renin activity*

↓↓

↓↓

↑↑

Aldosterone

↑↑

*When corrected for age; elderly patients have lower mean plasma renin activity.

↑↑↑↑=very greatly increased; ↑↑= greatly increased; = increased; ↓↓= greatly decreased; = decreased; N = normal.

Treatment

  • Treament of cause

  • Sometimes aldosterone antagonists

Treatment involves correcting the cause. Hypertension can usually be controlled with a selective aldosterone blocker such as spironolactone, starting with 50 mg po once/day and increasing over 1 to 3 mo to a maintenance dose, usually around 100 mg once/day or another potassium-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.

Key Points

  • Diagnosis is suspected in hypertensive patients with hypokalemia.

  • Initial testing includes measurement of plasma aldosterone and plasma renin activity.

  • Unlike primary aldosteronism, plasma renin activity is elevated.

  • Treatment includes correcting the cause. Hypertension may be controlled with aldosterone antagonists.

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* This is the Professional Version. *