WASHINGTON — When refractory hypertension rears its head, it might be time to look for problems in the renin-aldosterone system, according to one expert who spoke at a meeting sponsored by the National Kidney Foundation.
In patients with hypertension, the prevalence of primary aldosteronism ranges from 5% to 30%, and the rate is especially high among older patients, said J. Howard Pratt, M.D., professor of medicine at Indiana University in Indianapolis.
Aldosterone works on the collecting duct of the distal nephron to increase the activity of the epithelial sodium channels. The resulting increase in the sodium level promotes hypertension.
There are two types of primary aldosteronism: adenoma and bilateral adrenal hyperplasia. “Adrenal hyperplasia is much more common than the adenomas,” Dr. Pratt said. According to many textbooks, adenomas are three times more likely to be the cause of hypertension than hyperplasia. “It's probably the reverse. It's probably much more than three times more common to have hyperplasia than adenoma.”
Classically, this disorder presented with a low serum potassium level. Current thinking is that most of these patients have a normal potassium level because of hyperplasia, he said. Serum sodium is usually greater than 140 μmol/L. Renal cysts are present in about 40% of patients. Left ventricular hypertrophy is also common.
“The work-up for primary aldosteronism is very simple, and I think this is one of the reasons that we see so much of it today,” Dr. Pratt said. The key is to measure plasma renin and aldosterone levels. Patients can be on any kind of medication to treat hypertension when these tests are performed, with the exception of spironolactone, which blocks the action of aldosterone.
For the diagnosis of primary aldosteronism, plasma aldosterone levels should be greater than 15–20 ng/dL with suppressed renin activity. The ratio of aldosterone to renin also should be greater than 20:30. Urine aldosterone excretion also can be measured; a 24-hour level of 12 μg or greater can indicate the disorder.
Once moderately severe primary aldosteronism has been diagnosed through lab tests, it can be useful to get a CT scan or MRI to check for adrenal tumors, Dr. Pratt said.
Adrenal vein catheterization—a technically difficult procedure—should be considered when the adrenal glands appear normal on CT imaging, but there is still a high suspicion of primary aldosteronism—low potassium level and high plasma aldosterone level. “These are the people who typically have adenomas,” he said.
If the patient has a distinct tumor on CT imaging and is older than 40 years, Dr. Pratt performs adrenal vein catheterization because “at that age they could have an incidental adrenal tumor.”
Treatment for an adenoma is laparoscopic removal. Bilateral adrenal hyperplasia is treated medically. “The approach that I take is to use a small dose of spironolactone (25 mg/day) with a small dose of a thiazide diuretic (12.5 mg/day hydrochlorothiazide). This is usually all that is needed for many patients,” Dr. Pratt said.
A calcium channel blocker, ACE inhibitor, or angiotensin II receptor blocker can be added if necessary. “Once you've given spironolactone, you've sort of revved up the renin-angiotensin system, and there's something for these drugs to work on,” he said.
Some patients with refractory hypertension can have low-renin hypertension instead. In this disorder, patients have low renin levels but normal aldosterone levels. These patients are resistant to antihypertensive therapy but do respond to spironolactone (25–50 mg/day) or amiloride (5–10 mg/day), in combination with a diuretic, Dr. Pratt said.