What labs are used to diagnose primary hyperaldosteronism (Primary Aldosteronism)?

Diagnostic Labs for Primary Hyperaldosteronism

The most accurate and reliable diagnostic approach for primary hyperaldosteronism begins with measuring the plasma aldosterone concentration to plasma renin activity ratio (ARR), followed by confirmatory testing if the initial screen is positive. 1

Initial Screening Test

• Plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio is the most accurate and reliable screening test for primary aldosteronism 1, 2
• A ratio greater than 30 (when aldosterone is measured in ng/dL and renin in ng/mL/h) is considered positive 1
• For a valid positive test, the plasma aldosterone concentration should be at least 10 ng/dL, as low renin alone can artificially elevate the ratio 1, 2
• Patients should have unrestricted salt intake and normal serum potassium levels when tested 1
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) should be withdrawn at least 4 weeks before testing 1

Testing Conditions and Potential Interferences

• Morning samples (preferably between 8-10 AM) are recommended 3
• Several medications can affect test results 2:
  • Beta-blockers and direct renin inhibitors can lower renin levels
  • Mineralocorticoid receptor antagonists can raise aldosterone levels
  • ACE inhibitors or ARBs elevate renin (if renin remains suppressed while on these medications, it increases the sensitivity of the ratio) 1

Confirmatory Testing

If the ARR is elevated, confirmatory testing is required to definitively diagnose primary aldosteronism 1, 2:

• Intravenous saline suppression test: Normal individuals suppress aldosterone production when given IV saline; failure to suppress indicates primary aldosteronism 1
• Oral salt-loading test: Measuring 24-hour urinary aldosterone while on a high-sodium diet 1, 3
• Captopril challenge test: Another option for confirmatory testing 4

Additional Laboratory Tests

• Basic metabolic panel: To assess for hypokalemia, which may be present (though many patients with primary aldosteronism are normokalemic) 1, 3
• Serum electrolytes: Particularly potassium and sodium levels 1

Subtype Determination (After Confirmation)

Once primary aldosteronism is confirmed, additional testing is needed to determine the subtype 1:

• CT or MRI imaging of adrenal glands: To identify potential adenomas 1
• Adrenal venous sampling: The gold standard to differentiate between unilateral (adenoma) and bilateral (hyperplasia) disease 1, 2
  • Critical before surgical treatment, as CT findings alone can lead to incorrect management in approximately 25% of cases 2

Common Pitfalls to Avoid

• Not testing normokalemic patients: Most patients with primary aldosteronism have normal potassium levels 3, 5
• Relying solely on ARR without confirmatory testing: A high ARR alone is not diagnostic and requires confirmation 1, 3
• Incorrect interpretation of low renin: Low renin can occur in other conditions like low-renin essential hypertension, chronic kidney disease, and excessive sodium intake 2
• Failure to adjust for medications: Certain antihypertensive medications can significantly affect test results 2

Who Should Be Screened

• Patients with resistant hypertension (requiring ≥3 medications) 1, 4
• Hypertension with spontaneous or diuretic-induced hypokalemia 1, 4
• Hypertension with adrenal incidentaloma 1
• Early-onset hypertension or stroke at young age (< 40 years) 4
• First-degree relative with primary aldosteronism 4