(Conn Syndrome; Conn's Syndrome)
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.
(See also Overview of Adrenal Function.)
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 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 induces secretion of renin. Renin transforms angiotensinogen from the liver to angiotensin I, which is transformed by angiotensin-converting enzyme (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. Sodium retention and water retention resulting from increased aldosterone secretion increase the blood volume and reduce 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 primary aldosteronism 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 due to deficiency of 11 beta-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.
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 plasma renin activity. Ideally, the patient should not take any drugs that affect the renin-angiotensin system (eg, thiazide diuretics, ACE inhibitors, angiotensin II receptor blockers, beta-blockers) for 4 to 6 wk before tests are done. Plasma renin activity 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 plasma renin activity (in ng/mL/h) > 20.
Low levels of both plasma renin activity and aldosterone suggest nonaldosterone mineralocorticoid excess (eg, due to licorice ingestion, Cushing syndrome, or Liddle syndrome). High levels of both plasma renin activity and aldosterone suggest secondary hyperaldosteronism. The principal differences between primary and secondary aldosteronism are shown in Differential Diagnosis of Aldosteronism. In children, Bartter syndrome is distinguished from primary hyperaldosteronism by the absence of hypertension and marked elevation of PRA.
Differential Diagnosis of Aldosteronism
Patients with findings suggesting primary hyperaldosteronism should undergo CT or MRI to determine whether the cause is a tumor or hyperplasia. However, imaging tests 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). It is possible that in the future PET-radionuclide imaging may be more helpful.
Tumors should be removed laparoscopically. After removal of an adenoma, serum potassium 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 50 mg po once/day and increasing over 1 to 3 mo to a maintenance dose, usually around 100 mg once/day; or by amiloride 5 to 10 mg po 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 (which can cause gynecomastia); it is the drug of choice for long-term treatment in men.
About half of patients with hyperplasia need additional antihypertensive treatment.
Diagnosis should be suspected in hypertensive patients with hypokalemia in the absence of Cushing syndrome.
Initial testing includes measurement of plasma aldosterone levels and plasma renin activity.
Adrenal imaging tests are done, but usually bilateral adrenal vein catheterization is needed to distinguish tumor from hyperplasia.
Tumors are removed and patients with adrenal hyperplasia are treated with aldosterone blockers such as spironolactone or eplerenone.
Drug NameSelect Trade