PRIMARY ALDOSTERONISM

Primary aldosteronism (hyperaldosteronism) refers to an inappropriately high aldosterone secretion that does not suppress adequately with sodium loading. Most affected patients have hypertension, although some may be normotensive. Primary aldosteronism is common and is believed to account about 10% of mild hypertension and about 14% of moderate hypertension. It should be suspected with early-onset hypertension or stroke before age 50 years (or both). It may be difficult to distinguish primary aldosteronism from cases of low renin essential hypertension, with which it may overlap. Patients of all ages may be affected, but the peak incidence is between 30-60 years. Excessive aldosterone production increases sodium retention and suppresses plasma renin. It increases renal potassium excretion, which can lead to hypokalemia. Cardiovascular events are more prevalent in patients with aldosteronism.

Primary aldosteronism may be caused by a unilateral aldosterone producing adrenal cortical adenoma (Conn syndrome, 25%) that is more common in women, peaking between ages 30 and 50. However, primary aldoste- ronism is more commonly caused by mostly adrenal cortical hyperplasia that is more common in men mainly between ages 50-60 years. It is important to distinguish the two, since a unilateral aldosteronoma (Conn syndrome) may be cured by surgical resection, whereas patients with bilateral adrenal hyperplasia are treated medically.

SYMPTOMS

Primary aldosteronism is the most common cause of refractory hypertension in youths and middle aged adults. Patients have hypertension that is typically moderate but may be severe. Some patients have only diastolic hypertension, without other symptoms and signs. Edema is rarely seen in primary aldosteronism. Hypokalemia may shows muscle weakness, paresthesias with frank tetany, headache, polyuria, and polydipsia in person.

DIAGNOSIS (LABORATORY FINDINGS AND IMAGING)

Plasma potassium should be determined in hypertensive individuals. However, hypokalemia, once thought to be the hallmark of hyperaldosteronism, is present in only 35% of affected patients: 50% of those with an aldosterone- producing adenoma and 18% of those with adrenal hyperplasia. An elevated serum bicarbonate (HCO,) concentration indicates metabolic alkalosis.

Testing for primary aldosteronism should be done for all hypertensive patients with any of the following:

(A) sustained hypertension above 150/100 mm Hg on 3 different days

(B) hypertension resistant to three conventional anti- hypertensive drugs, including a diuretic;

(C) controlled blood pressure requiring four or more antihypertensive drugs

(D) hypokalemia, whether spontaneous or diuretic induced;

(E) personal or family history of early-onset hyper- tension or cerebrovascular accident at age 40 or younger,

(F) first-degree relative with primary aldosteronism:

(G) presence of an adrenal mass; and

(H) low PRA. For at least 2 weeks prior to testing, patients should have any hypokalemia corrected and then consume a diet high in NaCl and ideally withhold certain medications: all diuretics, ACE inhibitors, ARBS (stimulate PRA); beta-blockers, clonidine, NSAIDs (suppress PRA); oral estrogens and oral contraceptives should also ideally be held.

Medications that are allowed include slow-release verapamil, hydralazine, terazosin, and doxazosin. Plasma potassium, rather than the routine serum potassium, should be measured in cases of unexpected hyperkalemia. Plasma potassium levels must be normal, since hypokalemia suppresses aldosterone.

Some patients with undiagnosed primary aldosteronismare incidentally found to have an adrenal nodule (incidentaloma) during abdominal or chest imaging. All patients with biochemically confirmed primary aldosteronismrequire a thin-section CT scan of the adrenals to screen for a rare adrenal carcinoma. In the absence of a large adrenalcarcinoma, adrenal CT scanning cannot reliably distinguish unilateral from bilateral aldosterone excess, having both a sensitivity and specificity of 78% for unilateral aldosteronism. Therefore, the decision to perform a unilateral adrenalectomy should not be based solely on the adrenal CT scan. Adrenal vein sampling is often required.

Adrenal Vein Sampling

Unfortunately, bilateral selective adrenal vein sampling is invasive, expensive, not widely available, and often unsuccessful. The procedure (and surgery) may not be required for patients whose blood pressure is well controlled with spironolactone or eplerenone and for those with familial hyperaldosteronism. It is indicated only if surgery is contemplated in order to direct the surgeon to the correct adrenal gland Adrenal vein sampling is probably not required in patients who have a classic adrenal adenoma (Conn syndrome), which is characterized by spontaneous hypokalemia and a unilateral adrenal adenoma 10 mm or larger in diameter on CT. However, patients with a persistently suppressed PRA may continue miner alocorticoid blockade. Aldosterone hyper secretion that is lateralized to one adrenal usually indicates that adrenal has a unilateral aldosteronoma or hyperplasia, particularly when aldosterone secretion from the contralateral adrenal is suppressed.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of primary aldosteronism includes other causes of hypokalemia in patients with essential hypertension, especially diuretic therapy: chronic depletion of intravascular volume stimulates renin secretion and secondary hyperaldosteronism. Real (black) licorice (derived from anise) or anise- flavored drinks (sambuca, pastis) contain glycyrrhizinic acid, which has a metabolite that inhibits the enzyme that normally inactivates cortisol in the renal tubule. Oral contraceptives may increase aldosterone secretion in some patients. Renal vascular disease can cause severe hypertension with hypokalemia but PRA is high. Excessive adrenal secretion of other corticosteroids (besides aldosterone), certain congenital adrenal enzyme disorders, and primary cortisol resistance may also cause hypertension with hypokalemia. The differential diagnosis also includes Liddle syndrome, an autosomal dominant cause of hypertension and hypokalemia resulting from excessive sodium absorption from the renal tubule; renin and aldosterone levels are low.

COMPLICATIONS

Cardiovascular complications occur more frequently in primary aldosteronism than in idiopathic hypertension. Following unilateral adrenalectomy for Conn syndrome, suppression of the contralateral adrenal may result in temporary postoperative hypoaldosteronism, characterized by hyperkalemia and hypotension.

TREATMENT

The unilateral adrenal adenoma of Conn syndrome is usually treated by laparoscopic adrenalectomy. During pregnancy, such surgery is best performed during the second trimester. However, long term medical therapy is an option for unilateral hyper aldosteronism, if adequate blood pressure control can be maintained. Bilateral adrenal hyperplasia is best treated with medical therapy. Medical treatment must include a potassium-sparing diuretic, particularly spironolactone, eplerenone, or amiloride. Spironolactone is the most effective drug but also has anti androgen activity and men frequently experience breast tenderness, gynecomastia, or reduced libido. Spironolactone might lead to under virilization of male infants and is contraindicated in pregnancy; reproductive- age women are cautioned to use contraception during therapy. Eplerenone is favored during pregnancy (FDA pregnancy category B) and for men, since it does not have anti androgen effects. Blood pressure must be monitored daily when beginning these anti-mineralocorticoid medications; significant drops in blood pressure have occurred when these drugs are added to other anti hypertensives. Other anti hypertensive drugs may be required, particularly amlodipine, and ACE inhibitors or ARBs. Corticosteroid remediable aldosteronism is very rare, but may respond well to suppression with low dose corticosteroids.

For Informational purpose only. Consult your Physician for advice.