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.
(See also Overview of Adrenal Function.)
Aldosterone is the most potent mineralocorticoid produced by the adrenal cortex. It causes sodium retention and potassium loss. In the kidneys, aldosterone causes transfer of sodium from the lumen of the distal tubule into the tubular cells in exchange for potassium and hydrogen. The same effect occurs in salivary glands, sweat glands, cells of the intestinal mucosa, and in exchanges between intracellular fluid (ICF) and extracellular fluid (ECF).
Aldosterone secretion is regulated by the renin-angiotensin system and, to a lesser extent, by adrenocorticotropic hormone (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 or hyponatremia induces secretion of renin. Renin transforms angiotensinogen from the liver to angiotensin I, which is transformed by angiotensin-converting enzyme (ACE) to angiotensin II, which in turn causes secretion of aldosterone; renin also has pressor activity. Sodium retention and water retention resulting from increased aldosterone secretion increase the blood volume and reduce renin secretion.
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)
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 of Secondary Aldosteronism
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 depending on etiology.
Diagnosis of Secondary Aldosteronism
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 plasma renin activity (PRA). Ideally, the patient should not take any medications that affect the renin-angiotensin system (eg, thiazide diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin antagonists, beta-blockers) for 4 to 6 weeks before tests are done. Elevated aldosterone levels and plasma renin activity are indicative of secondary aldosteronism. The principal differences between primary and secondary aldosteronism are shown in the table Distinguishing Primary and Secondary Aldosteronism.
Treatment of Secondary Aldosteronism
Treament of cause
Sometimes aldosterone antagonists
Treatment involves correcting the cause.
spironolactonespironolactone, it does not block the androgen receptor (which may result in gynecomastia and sexual dysfunction); it is the drug of choice for long-term treatment in males if low-dose spironolactone is ineffective.
Key Points
Diagnosis is suspected in patients with hypertension and hypokalemia.
Initial testing includes measurement of plasma aldosterone and plasma renin activity.
Unlike in primary aldosteronism, plasma renin activity is elevated.
Treatment includes correcting the cause.
Hypertension may be controlled with aldosterone antagonists.
