What lab work is needed to test for primary aldosteronism?

Laboratory Testing for Primary Aldosteronism

The aldosterone-to-renin ratio (ARR) is the recommended screening test for primary aldosteronism, with a positive result defined as ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) AND plasma aldosterone concentration ≥10 ng/dL. 1

Initial Screening Test

Core Laboratory Tests

• Plasma aldosterone concentration (measured in ng/dL) 1
• Plasma renin activity (measured in ng/mL/h) 1
• Serum potassium (to ensure normal levels before testing and assess for hypokalemia) 1
• Serum sodium (as part of electrolyte assessment) 1

ARR Interpretation Criteria

• ARR cutoff: ≥30 when using standard units (ng/dL per ng/mL/h) 1
• Minimum aldosterone requirement: Plasma aldosterone must be ≥10 ng/dL even if the ratio is elevated, as very low renin levels can create falsely elevated ratios 1, 2
• Alternative cutoff: Some centers use ARR >20 with excellent sensitivity and specificity (>90%) 2

Critical Pre-Test Preparation

Patient Preparation Requirements

• Potassium repletion: Patients must be potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 2, 3
• Salt intake: Unrestricted salt intake is required before testing 1, 2
• Medication withdrawal timeline: Mineralocorticoid receptor antagonists (spironolactone, eplerenone) must be withdrawn for at least 4 weeks before testing 1, 2

Medication Management

Medications to discontinue when feasible: 2

• Beta-blockers (can suppress renin and cause false positives)
• Diuretics (affect both aldosterone and renin)
• Centrally acting drugs

Acceptable alternatives during testing: 2

• Long-acting calcium channel blockers (minimal ARR interference)
• Alpha-receptor antagonists (minimal ARR interference)

Important caveat: If medications cannot be safely stopped, testing can proceed with careful interpretation in the context of current medications, though this may reduce test accuracy 2, 3, 4

Blood Collection Technique

• Timing: Collect blood in the morning after patient has been out of bed for 2 hours 2
• Position: Patient should be seated for 5-15 minutes immediately before collection 2
• Posture: Blood must be drawn with patient in seated position 2

Confirmatory Testing (Required After Positive Screening)

A positive ARR screening test always requires confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed. 1, 2

Confirmatory Test Options

1. Intravenous saline suppression test: Administer 2L of 0.9% saline over 4 hours with aldosterone measurement before and after 1, 3
2. Oral sodium loading test: High sodium diet with 24-hour urine collection for aldosterone measurement 1, 3
3. Fludrocortisone suppression test: Failure to reduce plasma aldosterone below threshold confirms diagnosis 3

Additional Laboratory Tests for Confirmatory Phase

• 24-hour urine aldosterone (when using oral salt loading method) 1, 2
• 24-hour urine sodium (to confirm adequate salt loading) 3
• Repeat serum potassium (to ensure normal levels during confirmatory testing) 2, 3

Common Pitfalls to Avoid

False-Positive Results

• Very low renin states: Can create elevated ARR even without true aldosterone excess; this is why the minimum aldosterone threshold of ≥10 ng/dL is critical 1, 2
• Interfering medications: Beta-blockers, ACE inhibitors, and ARBs can significantly lower the ARR and cause false negatives 5

False-Negative Results

• Hypokalemia: Suppresses aldosterone production, leading to falsely normal results 2, 3
• Inadequate salt intake: Can affect ARR interpretation 3
• Failure to withdraw mineralocorticoid antagonists: These directly interfere with testing 1

Test Reproducibility Issues

• Studies show almost five-fold variation in ARR values taken under identical conditions, emphasizing the need for confirmatory testing rather than relying on a single ARR measurement 5
• The sensitivity of ARR using the recommended cutoff of 30 can be as low as 22% in some studies, though specificity remains high at 98.7% 5

Clinical Context for Testing

Who Should Be Screened

Screen patients with hypertension who have any of the following: 1

• Resistant hypertension (uncontrolled on 3+ medications including a diuretic)
• Spontaneous or substantial diuretic-induced hypokalemia
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension or stroke at young age (<40 years)

Prevalence note: Primary aldosteronism is present in up to 20% of patients with resistant hypertension, making screening in this population particularly high-yield 2, 3

Algorithmic Approach

1. Order initial screening labs: Plasma aldosterone, plasma renin activity, serum potassium, serum sodium 1
2. Ensure proper preparation: Potassium-replete, unrestricted salt, medications adjusted if possible 2, 3
3. Interpret ARR: Positive if ≥30 AND aldosterone ≥10 ng/dL 1
4. If positive, order confirmatory test: Saline suppression or oral salt loading 1
5. If confirmed, refer to specialist: Endocrinologist or hypertension specialist for subtype determination with adrenal imaging and possible adrenal venous sampling 1