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Primary Aldosteronism

(Conn Syndrome)

By

Ashley B. Grossman

, MD, University of Oxford; Fellow, Green-Templeton College

Last full review/revision Sep 2020| Content last modified Sep 2020
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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 blood pressure, 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 blood pressure and eliminate other clinical features.

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 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, 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, liver... 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. 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 certain forms of congenital adrenal hyperplasia (in which other mineralocorticoids are elevated) and the dominantly inherited dexamethasone-suppressible hyperaldosteronism. Small adenomas are increasingly recognized as a cause of primary hypertension even when serum potassium levels are normal.

Symptoms and Signs of Primary Aldosteronism

Diagnosis of Primary Aldosteronism

  • Electrolytes

  • Plasma aldosterone

  • Plasma renin activity (PRA)

  • Adrenal imaging

  • Bilateral adrenal vein catheterization (for cortisol and aldosterone levels)

Diagnosis is suspected in patients with hypertension and hypokalemia Hypokalemia Hypokalemia is serum potassium concentration 3.5 mEq/L ( 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common cause is... read more . 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 II receptor blockers [ARBs], beta-blockers) for 4 to 6 weeks 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 Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more Cushing Syndrome , or Liddle syndrome Liddle Syndrome Liddle syndrome is a rare hereditary disorder involving increased activity of the epithelial sodium channel (ENaC), which causes the kidneys to excrete potassium but retain too much sodium and... read more ). High levels of both plasma renin activity and aldosterone suggest secondary hyperaldosteronism Secondary Aldosteronism 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... read more . The principal differences between primary and secondary aldosteronism are shown in table Differential Diagnosis of Aldosteronism Differential Diagnosis of 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 . In children, Bartter syndrome Bartter Syndrome and Gitelman Syndrome Bartter syndrome and Gitelman syndrome are autosomal recessive renal disorders characterized by fluid, electrolyte, urinary, and hormonal abnormalities, including renal potassium, sodium, chloride... read more is distinguished from primary hyperaldosteronism by the absence of hypertension and marked elevation of PRA; there is a similar, milder syndrome in adults with Gitelman syndrome.

Table
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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.

Treatment of Primary Aldosteronism

  • Surgical removal of tumors

  • Spironolactone or eplerenone for hyperplasia

Tumors should be removed laparoscopically. After removal of an adenoma, serum potassium normalizes and blood pressure decreases in all patients; complete normalization of the blood pressure 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 orally once a day and increasing over 1 to 3 months to a maintenance dose, usually around 50 to 100 mg once a day; or by amiloride 5 to 10 mg orally once a day or another potassium-sparing diuretic. 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 can cause 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 Gynecomastia ); it is the drug of choice for long-term treatment in men unless low-dose spironolactone is effective.

Key Points

  • 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.

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