Laboratory Testing for Primary Aldosteronism
The plasma aldosterone-to-renin ratio (ARR) is the recommended screening test for primary aldosteronism. 1
Initial Screening Test
Measure the aldosterone-to-renin ratio (ARR) as the primary screening test for primary aldosteronism. 1
- ARR cutoff value: A ratio >30 (when plasma aldosterone is in ng/dL and plasma renin activity in ng/mL/h) is considered positive for screening. 1
- Aldosterone threshold: The plasma aldosterone concentration should be at least 10 ng/dL to interpret a positive ARR as meaningful, since very low renin levels alone can falsely elevate the ratio. 1
Additional Basic Laboratory Tests
Check serum potassium levels, though hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value. 1
Obtain a basic metabolic profile including serum sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, and creatinine. 1
Perform urinalysis as part of the initial evaluation. 1
Critical Pre-Test Conditions
Ensure proper testing conditions to maximize ARR accuracy:
- Normalize serum potassium before testing, as hypokalemia lowers aldosterone levels and can cause false-negative results. 1
- Unrestricted salt intake should be maintained, as sodium restriction raises aldosterone and can cause false-negatives. 1
- Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before testing. 1
- Avoid beta-blockers during screening when possible, as they suppress renin and can cause false-positive ARR results. 1, 2
- ACE inhibitors and ARBs actually increase the sensitivity of the test by elevating renin; if renin remains suppressed despite these medications, it strengthens the diagnosis. 1, 2
Confirmatory Testing
If the ARR is positive, confirmatory testing is generally required before proceeding to lateralization studies:
- Intravenous saline suppression test (plasma aldosterone measured at 4 hours of infusion). 1
- Oral sodium loading test (with 24-hour urine aldosterone collection). 1
- Captopril challenge test. 3
- Fludrocortisone suppression test. 3
Common Pitfalls
False-positive ARR results occur commonly (up to 30% in essential hypertension) due to low-renin states from volume expansion or dietary salt excess. 1, 2 Using both an elevated ARR AND an aldosterone level >150 pg/mL (or >10 ng/dL) reduces false-positives to approximately 3%. 2
Medication interference is a major source of diagnostic error. Beta-blockers suppress renin and increase false-positive rates, while mineralocorticoid receptor antagonists raise aldosterone levels and cause false-negatives. 1, 2
Hypokalemia alone is inadequate for screening, as 61% of primary aldosteronism patients are normokalemic. 1
When to Screen
Screen patients with hypertension who have any of the following:
- Resistant hypertension (uncontrolled on 3+ medications). 1
- Spontaneous or substantial diuretic-induced hypokalemia. 1
- Incidentally discovered adrenal mass. 1
- Family history of early-onset hypertension or stroke at young age (<40 years). 1
- Obstructive sleep apnea with hypertension. 1, 3
- Type 2 diabetes with hypertension. 3