What is the role of the aldosterone (aldosterone)/renin ratio in evaluating hyperaldosteronism?

Role of Aldosterone/Renin Ratio in Evaluating Hyperaldosteronism

The aldosterone/renin ratio (ARR) is the preferred initial screening test for primary aldosteronism in patients with hypertension and/or hypokalemia, with a ratio of 20 ng/dL per ng/mL/hr having excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism. 1, 2

Patient Selection for ARR Testing

• ARR testing should be performed in patients with hypertension who have any of the following:
  • Resistant hypertension (BP not controlled on 3 medications including a diuretic) 2
  • Hypokalemia (spontaneous or diuretic-induced) 1, 2
  • Adrenal incidentaloma 1
  • Family history of early-onset hypertension 2
  • Severe hypertension (BP >180/110 mmHg) 2

Proper Test Conditions

• Patients should be potassium-replete before testing, as hypokalemia can suppress aldosterone production 2
• Blood collection should be done in the morning after the patient has been:
  • Out of bed for 2 hours 1, 2
  • Seated for 5-15 minutes immediately before collection 1, 2
• Ideally, interfering medications should be substituted or discontinued when clinically appropriate:
  • Beta-blockers, centrally acting drugs, and diuretics should be stopped when feasible 2
  • Long-acting calcium channel blockers and alpha-receptor antagonists can be used as alternatives as they minimally interfere with ARR 2
  • If medications cannot be stopped, interpret results in the context of specific medications 2, 3

Interpreting ARR Results

• An ARR of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 1
• For a positive ARR test, plasma aldosterone concentration should be at least 10 ng/dL in addition to the elevated ratio 4, 2
• The specificity of the ratio improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 4, 2
• False positives can occur with beta-blockers, which can artificially elevate the ARR 3
• False negatives can occur with certain medications like irbesartan (up to 23.5% false negatives) 3

Confirmatory Testing After Positive ARR

• A positive screening test requires confirmation with additional testing to demonstrate autonomous aldosterone production 2
• Confirmatory tests include:
  • Intravenous saline suppression test 1, 4
  • Oral salt loading with 24-hour urine aldosterone measurement 1, 4
• Testing should be performed with unrestricted salt intake and normal serum potassium levels 4, 2
• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) should be withdrawn at least 4 weeks before testing 4

Subtype Determination

• If primary aldosteronism is confirmed, determine if the source is unilateral or bilateral:
  • Initial imaging using non-contrast CT scan of the adrenal glands 2
  • Adrenal vein sampling is recommended before surgical treatment 1, 2
  • Without adrenal vein sampling, 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 1, 2

Treatment Based on Subtype

• Unilateral disease (aldosterone-producing adenoma):
  • Laparoscopic adrenalectomy is the treatment of choice 2
  • Can provide complete biochemical success in most patients 2
• Bilateral disease (idiopathic hyperaldosteronism):
  • Medical therapy with mineralocorticoid receptor antagonists 2
  • Spironolactone is first-line treatment 1, 2
  • Eplerenone is an alternative when spironolactone side effects occur 1, 2

Common Pitfalls to Avoid

• Not screening high-risk patients - only ~2-4% of eligible patients get screened 2
• Relying solely on hypokalemia as a marker - it's absent in the majority of cases 4, 2
• Dismissing the diagnosis due to normal renin levels - in some cases, primary aldosteronism can present with non-suppressed renin due to renal damage from longstanding hypertension 5
• Not considering medication effects on ARR - different antihypertensive medications can affect the ratio in various ways 3
• Not ensuring adequate potassium levels before testing - hypokalemia can suppress aldosterone production 2

The ARR remains the most useful initial screening tool for primary aldosteronism despite some limitations in diagnostic accuracy 6. When properly performed and interpreted, it can significantly improve detection rates of this common but underdiagnosed cause of secondary hypertension 7.