Screening Test for Hyperaldosteronism
The aldosterone-to-renin ratio (ARR) is the screening test for hyperaldosteronism, measured from morning blood samples taken after the patient has been sitting for at least 15 minutes. 1, 2, 3
How to Perform the Screening Test
Sample Collection Requirements
- Morning samples (more than 2 hours after awakening) 4
- Sitting position after resting for 5-15 minutes 1, 5, 6, 2
- Normal dietary salt intake
- Correct hypokalemia before testing 7
Medication Management Before Testing
Continue most antihypertensives initially, but withhold these specific medications if possible 1, 5, 6, 2:
- Aldosterone antagonists (spironolactone, eplerenone)
- Angiotensin receptor blockers
- Beta-adrenergic blockers
- Clonidine
If withdrawal is unsafe, you can still proceed with testing, but interpret results cautiously. Beta-blockers may cause false positives when aldosterone is 10-15 ng/dL by immunoassay or 7.5-10 ng/dL by LC-MS/MS; above these levels, PA is likely despite beta-blocker use. 3
Interpreting the ARR
Positive Screening Criteria
ARR > 550 pmol/L/ng/mL/h (or 140 pmol/L/ng/L when using direct renin concentration) 1, 5, 6, 2
Critical caveat: Only calculate ARR if aldosterone is > 240 pmol/L (90 pg/mL) to avoid false positives from very low renin values 4. For very low renin values, use a floor value: PRA < 0.2 ng/mL/h should be calculated as 0.2, and direct renin < 5 mIU/L should be calculated as 5 4.
When Confirmatory Testing Can Be Skipped
You can bypass confirmatory testing and proceed directly to treatment in these specific situations 3, 7:
Overt biochemical evidence: PRA < 0.2 ng/mL/h (or direct renin < 2 mU/L) AND aldosterone > 15 ng/dL by LC-MS/MS (or > 20 ng/dL by immunoassay) in patients with resistant hypertension or spontaneous hypokalemia 3
Spontaneous hypokalemia with aldosterone > 20 ng/dL and suppressed renin 7
Familial hyperaldosteronism confirmed by genetic testing 3
When Confirmatory Testing IS Needed
For patients with positive ARR but without the above criteria, proceed with one of these confirmatory tests 1, 5, 6, 2:
- Saline loading test: 2L normal saline over 4 hours; PA confirmed if aldosterone fails to suppress below 280 pmol/L
- Oral sodium loading: 300 mmol/day for 3 days; PA confirmed if aldosterone fails to suppress below 240 pmol/L
- Fludrocortisone suppression test: Oral sodium loading plus fludrocortisone 0.25 mg/day for 2 days; positive if aldosterone ≥ 140 pmol/L
- Captopril suppression test: PA confirmed if aldosterone fails to suppress below 240 pmol/L 2 hours after 25 mg oral captopril
Important pitfall: The first three tests risk inducing hypokalemia, fluid overload, and worsening hypertension 7. The captopril test is safer but may be less sensitive.
Special Populations
Chronic kidney disease: Expect higher false-positive rates because renin decreases with nephron loss and aldosterone can be elevated 3. Consider specialist referral for interpretation 8.
Borderline results: Repeat the initial test or perform a second confirmatory test. Patients negative on both saline infusion and captopril tests are unlikely to have unilateral disease 7.