(See also Overview of Adrenal Function Overview of Adrenal Function The adrenal glands, located on the cephalad portion of each kidney (see figure Adrenal glands), consist of a Cortex Medulla The adrenal cortex and adrenal medulla each have separate endocrine... read more .)
Aldosterone is the most potent mineralocorticoid produced by the adrenals. 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 Primary Aldosteronism 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 Hyponatremia Hyponatremia is decrease in serum sodium concentration < 136 mEq/L (< 136 mmol/L) caused by an excess of water relative to solute. Common causes include diuretic use, diarrhea, heart failure... read more 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 Primary Aldosteronism 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 Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more with ascites, nephrotic syndrome Overview of Nephrotic Syndrome Nephrotic syndrome is urinary excretion of > 3 g of protein/day due to a glomerular disorder plus edema and hypoalbuminemia. It is more common among children and has both primary and secondary... read more )
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 Primary Aldosteronism 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... read more and include hypokalemic alkalosis that causes episodic weakness, paresthesias, transient paralysis, and tetany. In many cases, the only manifestation is hypertension Hypertension Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more . Peripheral edema may be present depending on etiology.
Diagnosis of Secondary Aldosteronism
Serum electrolyte levels
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 drugs 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 and plasma renin activity is indicative of secondary aldosteronism. The principal differences between primary and secondary aldosteronism are shown in the table .
Treatment of Secondary Aldosteronism
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 orally once a day and increasing over 1 to 3 months to a maintenance dose, usually around 100 mg once a day. Another potassium-sparing diuretic can be used instead of spironolactone. The more specific drug eplerenone 50 mg orally once a day to 200 mg orally twice a day may be used because, unlike spironolactone, it does not block the androgen receptor (which may result in gynecomastia Gynecomastia This photo shows enlarged breast tissue in a male patient. Gynecomastia is hypertrophy of breast glandular tissue in males. It must be differentiated from pseudogynecomastia, which is increased... read more and sexual dysfunction); it is the drug of choice for long-term treatment in men if low-dose spironolactone is ineffective.
Diagnosis is suspected in hypertensive patients with 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.