What is the screening test for primary aldosteronism?

Screening Test for Primary Aldosteronism

The plasma aldosterone-to-renin ratio (ARR) is the recommended screening test for primary aldosteronism. 1, 2

Who Should Be Screened

Screen the following high-risk hypertensive patients 1, 2:

• Resistant hypertension (blood pressure uncontrolled on 3 medications including a diuretic) 1
• Spontaneous or substantial diuretic-induced hypokalemia 1
• Incidentally discovered adrenal mass on CT or MRI 1
• Family history of early-onset hypertension or stroke at young age (<40 years) 1
• Severe hypertension (BP >180/110 mmHg) 2

Primary aldosteronism affects up to 20% of patients with resistant hypertension, yet only 2-4% of eligible patients are actually screened—a critical gap in diagnosis. 2, 3

How to Perform the ARR Screening Test

Patient Preparation

• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 1, 2
• Encourage unrestricted (liberal) salt intake before testing 2
• Discontinue interfering medications when clinically feasible 1, 2:
  • Stop beta-blockers, centrally acting drugs, and diuretics (these suppress renin and cause false-positives) 2
  • Use long-acting calcium channel blockers or alpha-receptor antagonists as alternatives during testing (minimal ARR interference) 2
  • Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing 1, 2
• If medications cannot be stopped, interpret results in the context of current medications 1, 2

Blood Collection Technique

• Collect blood in the morning (preferably 0800-1000 hours) 2, 4
• Patient should be out of bed for 2 hours prior to collection 1, 2
• Patient seated for 5-15 minutes immediately before blood draw 1, 2
• Draw blood with patient in seated position 1

Interpreting the ARR

Positive Screening Criteria

A positive screening test requires BOTH of the following 1, 2:

• ARR ≥20-30 (when aldosterone measured in ng/dL and renin activity in ng/mL/h) 1, 2
• Plasma aldosterone concentration ≥10-15 ng/dL 1, 2

The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 1, 2

Test Performance Characteristics

The ARR has excellent sensitivity and specificity (>90%) when properly performed with an ARR cutoff of 20 ng/dL per ng/mL/hr. 2 However, real-world studies show the test's sensitivity can be as low as 22% when the recommended cutoff of 91 pmol/mU is used, with specificity of 67-99% depending on medications and population. 2, 5 This variability underscores the importance of proper patient preparation and medication management.

Critical Pitfalls to Avoid

• Do not rely on hypokalemia as a screening trigger—it is absent in approximately 50% of primary aldosteronism cases 1, 2
• Do not proceed with surgery based on CT findings alone—up to 25% of patients might undergo unnecessary adrenalectomy without adrenal vein sampling 2
• Do not skip confirmatory testing—a positive ARR alone is not diagnostic and requires demonstration of autonomous aldosterone secretion 1, 2
• Reproducibility is poor—Bland-Altman analysis shows almost five-fold differences in ARR values taken under identical conditions, emphasizing the need for confirmatory testing 5

Next Steps After Positive Screening

• All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion 1, 2
• Confirmatory test options include 1, 2:
  • Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis) 2
  • Oral sodium loading with 24-hour urine aldosterone measurement 1, 2
  • Fludrocortisone suppression test 2
• Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination (adrenal vein sampling) and treatment planning 1, 2