What blood work is required to screen for primary aldosteronism?

Blood Work for Primary Aldosteronism Screening

The screening test for primary aldosteronism requires a paired morning plasma aldosterone concentration and plasma renin activity (or direct renin concentration) to calculate the aldosterone-to-renin ratio (ARR). 1

Core Laboratory Tests Required

Primary Screening Test

• Plasma aldosterone concentration (PAC) measured in ng/dL 1
• Plasma renin activity (PRA) measured in ng/mL/h 1
• Calculate the aldosterone-to-renin ratio (ARR) by dividing PAC by PRA 1, 2

Supporting Laboratory Tests

• Basic metabolic profile including serum sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, and creatinine 1
• Serum potassium must be checked and corrected to normal range before testing, as hypokalemia suppresses aldosterone production and causes false negatives 1, 2, 3

Interpretation Criteria

Positive Screening Results

• ARR ≥30 when aldosterone is in ng/dL and renin activity in ng/mL/h 1
• Plasma aldosterone concentration must be ≥10 ng/dL (some sources suggest ≥15 ng/dL) in addition to the elevated ratio to interpret as positive 1, 2
• Alternative cutoff: ARR >20 when aldosterone is ≥16 ng/dL and PRA <0.6 ng/mL/h suggests primary aldosteronism 1

The American Heart Association guidelines note that an ARR of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism 2, though the most commonly used cutoff remains 30 1.

Critical Pre-Test Preparation

Patient Conditions

• Correct hypokalemia to normal range before testing 1, 2, 3
• Unrestricted salt intake (liberal salt diet) for optimal sensitivity 1, 2, 3
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before testing 1, 2

Medication Management

Medications that should be stopped when feasible:

• Beta-blockers (suppress renin, causing false positives) 2, 3
• Diuretics (stimulate renin, causing false negatives) 2, 3
• Centrally acting drugs 2

Acceptable alternatives during testing:

• Long-acting calcium channel blockers (verapamil slow-release) 2, 3
• Alpha-receptor antagonists (prazosin, doxazosin) 2, 3
• Hydralazine 3

Medications causing false negatives (stimulate renin): ACE inhibitors, ARBs, dihydropyridine calcium blockers, and diuretics 1, 3. However, the American Heart Association notes that if renin remains suppressed despite ACE inhibitor or ARB use, this actually increases the sensitivity of the test 1.

Medications causing false positives (suppress renin): NSAIDs, alpha-methyldopa, clonidine 3.

Collection Timing and Positioning

• Morning collection (preferably between 0800-1000h) 2, 4
• Patient should be out of bed for 2 hours prior to collection 2
• Seated position for 5-15 minutes immediately before blood draw 2
• Some protocols recommend 2-4 hours upright posture before collection 3

Common Pitfalls to Avoid

Testing Errors

• Do not rely on hypokalemia as a screening criterion - it is absent in the majority of primary aldosteronism cases and has low negative predictive value 1
• Do not interpret elevated ARR alone - very low renin levels can artificially elevate the ratio; plasma aldosterone must meet minimum threshold 1
• Poor reproducibility - ARR values can vary almost five-fold between measurements taken under identical conditions, so repeat testing is essential before proceeding to confirmatory tests 5

Medication Interference

• If medications cannot be stopped, interpret results in the context of specific medications the patient is taking 2
• Research shows that under random medication (especially ACE inhibitors and ARBs), ARR sensitivity drops to only 22.2% with the standard cutoff, though specificity remains 98.7% 5

Special Populations

• Females have higher ratios than males 3
• False positives can occur during luteal menstrual phase and with oral contraceptives containing ethinylestradiol/drospirenone (but only when using direct renin concentration, not PRA) 3
• Renal dysfunction and advancing age can produce false positive results 3

Next Steps After Positive Screening

• Confirmatory testing is mandatory - a positive ARR is only a screening test 1, 2
• Options include intravenous saline suppression test or oral salt-loading test with 24-hour urine aldosterone measurement 1, 2
• Refer to hypertension specialist or endocrinologist for confirmatory testing and further evaluation 1, 2