When to test for primary hyperaldosteronism (PHA)?

From the Guidelines

Testing for hyperaldosteronism is recommended for patients with resistant hypertension, hypertension with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, or hypertension with family history of early-onset hypertension or cerebrovascular accident at a young age (under 40). According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, screening for primary aldosteronism is recommended in the presence of any of these concurrent conditions. The initial screening test is the aldosterone-to-renin ratio (ARR), which should be performed in the morning after the patient has been upright for at least 2 hours.

Some key points to consider when testing for hyperaldosteronism include:

• Certain medications can affect test results, so ideally, beta-blockers, ACE inhibitors, ARBs, and diuretics should be discontinued 2-4 weeks before testing, with calcium channel blockers and alpha-blockers used as replacement therapy if needed 1.
• Hypokalemia should be corrected before testing as it can suppress aldosterone production and lead to false-negative results 1.
• The diagnosis of primary aldosteronism generally requires a confirmatory test (intravenous saline suppression test or oral salt-loading test) 1.
• If the diagnosis of primary aldosteronism is confirmed, referral to a hypertension specialist or endocrinologist is recommended for further evaluation and treatment 1.

Testing for hyperaldosteronism is important because it is a potentially curable cause of hypertension, and early diagnosis can prevent cardiovascular and renal complications associated with long-standing hypertension and aldosterone excess. The use of the plasma aldosterone: renin activity ratio is recommended when adults are screened for primary aldosteronism 1.

From the Research

When to Test for Hyperaldosteronism

• Patients with low renin resistant hypertension (after treatment with three or more different anti-hypertensive drugs the blood pressure remains above 140/90 mmHg) should be screened for aldosteronism 2
• Individuals with resistant hypertension, as well as those with well-controlled hypertension and a first-degree relative with primary aldosteronism, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, or a family history of an early stroke (i.e., younger than 40 years) should be tested for primary aldosteronism 3
• Screening for primary aldosteronism is recommended for most patients with resistant hypertension, ideally by measurement of 24-hour urinary aldosterone excretion, or by the plasma aldosterone/plasma renin activity ratio 4
• All patients with resistant hypertension should be screened with a plasma aldosterone-renin ratio even if the serum potassium level is normal 5
• The prevalence of primary aldosteronism has ranged from 14%-21% in patients with resistant hypertension, which is considerably higher than in the general hypertensive population 6

Key Factors to Consider

• Resistant hypertension is defined as blood pressure that remains uncontrolled despite using at least three antihypertensive medications in effective doses, ideally including a diuretic 4, 5
• Hyperaldosteronism is now recognized as the most common secondary cause of resistant hypertension 5
• Obstructive sleep apnea is worsened by aldosterone-mediated fluid retention, and treatment with spironolactone may improve OSA severity 6
• Mineralocorticoid receptor antagonists, such as spironolactone or eplerenone, can provide substantial antihypertensive benefit when added to multidrug regimens, even in patients without demonstrable aldosterone excess 4, 6