What is the indicative aldosterone-to-renin ratio (ARR) value for suspected primary aldosteronism and which hormonal tests are preferred?

Aldosterone-to-Renin Ratio for Suspected Primary Aldosteronism and Preferred Hormonal Tests

An aldosterone-to-renin ratio (ARR) greater than 30 when plasma aldosterone is measured in ng/dL and plasma renin activity in ng/mL/h is indicative of suspected primary aldosteronism, with the plasma aldosterone concentration needing to be at least 10 ng/dL for a valid interpretation. 1, 2

Interpreting the Aldosterone-to-Renin Ratio

• The ARR is the recommended first-line screening test for primary aldosteronism, with high sensitivity and negative predictive value 1
• For a positive ARR test, two conditions must be met:
  • ARR > 30 (when aldosterone is measured in ng/dL and renin activity in ng/mL/h) 1
  • Plasma aldosterone concentration should be at least 10 ng/dL 1, 2
• The specificity of ARR improves when plasma aldosterone is >16 ng/dL and plasma renin activity is <0.6 ng/mL per hour, particularly in patients taking ACE inhibitors or ARBs 1
• Low specificity can occur due to common low-renin states (volume expansion, dietary salt excess) 1, 2

Optimal Testing Conditions

• Patients should have:
  • Unrestricted salt intake 1
  • Normal serum potassium levels 1, 2
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone) withdrawn for at least 4 weeks before testing 1, 2
• Certain medications can affect ARR interpretation:
  • Beta-blockers and direct renin inhibitors can lower renin levels and cause false-positive results 1, 3
  • Mineralocorticoid receptor antagonists can raise aldosterone levels 1
  • ACE inhibitors and ARBs elevate renin activity, which increases the sensitivity of the ratio 1, 3
• Recent research suggests doxazosin and calcium channel blockers like amlodipine have minimal effect on ARR and can be continued during testing 2, 3

Confirmatory Testing

• If ARR screening is positive, confirmatory testing is required to establish the diagnosis 1, 2
• Recommended confirmatory tests include:
  • Intravenous saline suppression test 1, 2
  • Oral salt-loading test 1, 2
• In the setting of hypokalemia, a plasma aldosterone level >20 ng/dL with suppressed renin basically confirms the diagnosis without need for further confirmatory testing 1

Subtype Determination and Management

• After confirmation of primary aldosteronism, adrenal imaging (CT or MRI) should be performed 1
• Adrenal venous sampling is the gold standard for distinguishing between unilateral and bilateral disease, especially in surgical candidates 1, 2
• Treatment options based on subtype:
  • Unilateral aldosterone-producing adenoma: laparoscopic adrenalectomy (improves BP in virtually 100% of patients, with complete cure in about 50%) 1
  • Bilateral adrenal hyperplasia: medical management with mineralocorticoid receptor antagonists (spironolactone or eplerenone) 1, 2

Common Pitfalls to Avoid

• Not all patients with primary aldosteronism present with hypokalemia - it's absent in many cases 2
• Using ARR without considering the absolute aldosterone level can lead to false positives, especially in low-renin states 1, 2
• Failing to account for medication effects on the ARR can lead to misdiagnosis 1, 3
• Recent research suggests current guideline-recommended ARR cutoffs may miss patients with primary aldosteronism who have elevated cardiovascular risk 4

Alternative Testing Methods

• Direct renin concentration (DRC) measurement can be used instead of plasma renin activity (PRA) 5
• The aldosterone-to-direct renin concentration ratio (ADRR) correlates well with ARR and can be used as an alternative screening method 5
• Some studies suggest ARR can be measured without discontinuing all antihypertensive medications, though this approach requires careful interpretation 6, 3