EXPERT ANALYSIS FROM THE ANNUAL INTERNAL MEDICINE PROGRAM
ESTES PARK, COLO. (FRONTLINE MEDICAL NEWS) – Primary aldosteronism, traditionally seen as a rare, stump-the-experts-type disorder, is now accepted as the cause of 5%-10% of all cases of what has been considered essential hypertension.
Primary aldosteronism is a readily treatable disorder, either surgically or medically, depending upon the subtype. So it’s essential to know which hypertensive patients to screen and how to confirm the diagnosis and then to move forward to identify the subtype in play, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.
Primary aldosteronism occurs when the adrenal gland produces excessive aldosterone without being stimulated by renin. Aldosterone causes sodium retention in the kidney in exchange for potassium and hydrogen ions. The result is the triple harms of hypertension, hypokalemia, and metabolic acidosis, explained Dr. McDermott, professor of medicine and clinical pharmacology and director of endocrinology and diabetes practice at University of Colorado Hospital in Aurora.
The two main subtypes of primary aldosteronism are idiopathic hyperaldosteronism (IHA), also known as bilateral adrenal hyperplasia, which accounts for two-thirds of all cases, and unilateral aldosterone-producing adenoma, which accounts for the remaining third.
Which hypertensive patients should be screened for primary aldosteronism? Anyone with resistant hypertension as defined by inadequate blood pressure control while on three or more antihypertensive drugs; those with severe hypertension, meaning readings greater than 160/100 mm Hg; patients with onset of hypertension before age 20; and any hypertensive patient with hypokalemia, which can either be provoked by diuretic therapy or in some cases occurs spontaneously, the endocrinologist continued.
Screening for primary aldosteronism entails getting a morning blood sample to measure plasma aldosterone and plasma renin activity after having the patient sit for 10 minutes. A positive screen requires both a plasma aldosterone level greater than 15 ng/dL and a plasma aldosterone/plasma renin activity ratio greater than 20.
“You can do this screening test in a patient on any medication except spironolactone. They have to stop that drug for at least 2 weeks first,” according to Dr. McDermott.
Confirmation of a positive screening test requires demonstration that the elevated aldosterone can’t be suppressed via volume expansion. This volume expansion can be accomplished in two ways: putting the patient on a high-salt diet for 3 days, which can generally be accomplished simply by eating some potato chips daily on top of a typically high-salt American diet, or by intravenous infusion of 2 L of normal saline over the course of 4 hours.
If a 24-hour urine collection on day 3 of a high-salt diet shows an aldosterone level in excess of 12 mcg, the diagnosis of primary aldosteronism is confirmed.
“If anyone in this room who doesn’t have primary aldosteronism had a high-salt diet for 3 days and we did a 24-hour urine on the third day, your aldosterone would be zero. So a level over 12 mcg is clearly abnormal,” Dr. McDermott emphasized.
Likewise, a plasma aldosterone greater than 10 ng/dL following the IV saline infusion is also confirmatory.
A good clinical clue that primary aldosteronism is due to an aldosterone-producing tumor is severe hypertension and/or severe hypokalemia in a patient under 40 years of age. A plasma aldosterone greater than 25 ng/dL or a urine aldosterone in excess of 30 mcg/24 hours is another useful clue because a tumor produces a lot more aldosterone than does bilateral adrenal hyperplasia.
If, and only if, a patient is willing to undergo surgery in the event further work-up establishes the presence of an aldosterone-producing tumor, the next step is an abdominal CT scan. If it reveals a unilateral hypodense nodule greater than 1 cm in size and the patient is less than 35 years old, referral for unilateral laparoscopic or open adrenalectomy is warranted. Preoperatively the patient should be placed on either spironolactone or eplerenone; these aldosterone antagonists block the effects of aldosterone on the kidney, with resultant normalization of hypertension and hypokalemia.
Bilateral adrenal hyperplasia is much more common than an aldosterone-producing tumor in patients older than age 35, so even when a unilateral nodule is found in such a patient it’s worthwhile to consider adrenal vein sampling. If the sampling lateralizes to one side then adrenalectomy can be offered. If there is no lateralization, however, the patient has IHA and medical management is appropriate. An aldosterone antagonist will normalize the hypokalemia but may not be sufficient to control the elevated blood pressure, in which case a calcium channel blocker, ACE inhibitor, and/or angiotensin receptor blocker can be added.
Dr. McDermott reported having no financial conflicts with regard to his presentation.