Initial Screening for Primary Aldosteronism
Order a simultaneous plasma aldosterone concentration and plasma renin activity (or direct renin concentration) to calculate the aldosterone-to-renin ratio (ARR), which is the recommended initial screening test. 1, 2
Who Should Be Screened
Screen patients with any of the following high-risk features: 1, 2
- Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) - present in up to 20% of these patients 2, 3
- Spontaneous or substantial diuretic-induced hypokalemia 1
- Incidentally discovered adrenal mass on imaging 1, 2
- Family history of early-onset hypertension or stroke at young age (<40 years) 1, 2
- Severe hypertension (BP >180/110 mmHg) 2
- Well-controlled hypertension with first-degree relative with primary aldosteronism, atrial fibrillation, or obstructive sleep apnea 3
Critical pitfall: Do not rely on hypokalemia as a screening trigger—it is absent in 50% of primary aldosteronism cases. 2, 3
Patient Preparation Before Testing
Potassium Repletion
- Ensure serum potassium is normal before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 2
Medication Management
When clinically feasible, adjust interfering medications: 1, 2
- Stop these medications (cause false-positives by suppressing renin): beta-blockers, centrally acting antihypertensives (clonidine), and diuretics 2
- Use these alternatives (minimal ARR interference): long-acting calcium channel blockers and alpha-receptor antagonists 2
- If medications cannot be stopped, interpret results in the context of the specific drugs the patient is taking 2
- Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing 2
Salt Intake
- Patients should have unrestricted salt intake before testing 2
Blood Collection Technique
Follow this specific protocol for accurate results: 2
- Collect blood in the morning 2
- Patient should be out of bed for 2 hours prior to collection 2
- Patient should be seated for 5-15 minutes immediately before blood draw 2
- Draw blood with patient in seated position 2
Interpreting the ARR
Positive Screening Test Criteria
A positive screen requires BOTH of the following: 1, 2
- ARR ≥30 (when aldosterone is in ng/dL and plasma renin activity is in ng/mL/h) 1, 2
- Plasma aldosterone concentration ≥10-15 ng/dL 2
The ARR has excellent sensitivity and specificity (>90%) when using these cutoffs. 2
Additional Interpretation Notes
- The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 2
- Different assay methods (chemiluminescent immunoassay vs radioimmunoassay) are both reliable, with chemiluminescent showing 90% sensitivity and 99% specificity 4
Next Steps After Positive Screening
Confirmatory Testing Required
A positive ARR always requires confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed. 2, 3 Options include: 2, 3
- Oral sodium loading test with 24-hour urine aldosterone measurement
- Intravenous saline suppression test (2L normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms diagnosis) 2
- Captopril challenge test 3
- Fludrocortisone suppression test 3
Referral
Refer all patients with positive screening tests to a hypertension specialist or endocrinologist for confirmatory testing, subtype determination, and treatment planning. 1, 2
Common Diagnostic Pitfalls to Avoid
- Do not proceed to surgery based on CT findings alone—adrenal venous sampling is mandatory to distinguish unilateral from bilateral disease (except in patients <40 years with single adenoma on imaging) 2
- Do not assume normal potassium excludes the diagnosis—hypokalemia is present in only 50% of cases 2, 3
- Do not perform testing while patient is on spironolactone or eplerenone—these must be withdrawn at least 4 weeks prior 2
- Only 2-4% of eligible high-risk patients are actually screened, representing significant underdiagnosis 2, 3