Diagnostic Approach to Hyperaldosteronism

Initial Screening

The American Heart Association suggests that primary aldosteronism occurs in 5-10% of patients with hypertension and up to 20% of patients with resistant hypertension, making it one of the most common causes of secondary hypertension 1
The European Society of Cardiology recommends screening for primary aldosteronism in patients with resistant hypertension, hypertension with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, early-onset hypertension or history of cerebrovascular accident at a young age, and family history suggesting familial hyperaldosteronism 1, 2, 3, 4

The American College of Cardiology states that an ARR >20 with serum aldosterone >16 ng/dL and plasma renin activity (PRA) <0.6 ng/mL per hour is suggestive of primary aldosteronism, with a high negative predictive value for screening of primary aldosteronism 4
The European Heart Journal suggests that some guidelines recommend an ARR >30 as the diagnostic threshold, although this may vary depending on the laboratory and population being tested 2

The European Society of Hypertension recommends that two approaches exist for ARR testing in patients already on antihypertensive medications: testing without changing medications and interpreting results in context of current medications, or discontinuing interfering medications before testing when feasible 2
The American Heart Association notes that medications that can affect ARR interpretation include mineralocorticoid receptor antagonists, beta-blockers, direct renin inhibitors, ACE inhibitors, ARBs, and diuretics, which can raise or lower aldosterone and renin levels 2, 3, 4, 6

The Endocrine Society recommends that after a positive ARR screening, confirmatory testing is required to diagnose primary aldosteronism, although the specific tests used may vary depending on the clinical context and laboratory capabilities 5

The American College of Cardiology recommends that high-resolution CT or MRI of adrenal glands is indicated only after biochemical confirmation of primary aldosteronism, and that CT/MRI alone is insufficient for subtype differentiation as it may miss aldosterone-producing adenomas or show non-functioning nodules 4, 7
The European Society of Endocrinology states that adrenal vein sampling is currently the most reliable method to differentiate unilateral from bilateral disease, and is essential for patients >40 years with confirmed primary aldosteronism 5

The European Heart Journal notes that false positive ARR results can occur with low-renin states, certain medications, and advanced age, while false negative ARR results can occur with concurrent use of mineralocorticoid receptor antagonists and severe potassium depletion 2, 4
The American Heart Association recommends that interpretation of ARR should consider sodium intake, time in menstrual cycle for females, and laboratory-specific reference ranges and units of measurement 2