What is the appropriate workup for aldosteronism (primary aldosteronism)?

Workup for Primary Aldosteronism

Screen high-risk hypertensive patients with a morning aldosterone-to-renin ratio (ARR), proceed to confirmatory testing if ARR >30 with aldosterone ≥10 ng/dL, then perform adrenal CT followed by adrenal venous sampling to differentiate unilateral from bilateral disease before deciding on surgery versus medical therapy. 1

Who Should Be Screened

Screen the following patient populations for primary aldosteronism:

• Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) 1, 2
• Severe hypertension (BP >180/110 mmHg) 1
• Hypokalemia (spontaneous or diuretic-induced) 1, 2
• Adrenal incidentaloma with hypertension 1, 2
• Family history of early-onset hypertension or stroke <40 years 1, 2
• Atrial fibrillation or obstructive sleep apnea with hypertension 3

Primary aldosteronism affects up to 20% of patients with resistant hypertension, yet only 2-4% of eligible patients are actually screened—a critical missed opportunity. 1, 3

Step 1: Initial Screening Test (ARR)

Patient Preparation

• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 1
• Medication adjustments (when clinically feasible):
  • Stop beta-blockers, centrally acting drugs, and diuretics 1
  • Continue long-acting calcium channel blockers and alpha-receptor antagonists (minimal ARR interference) 1
  • Discontinue mineralocorticoid receptor antagonists at least 4 weeks before testing 1
• If medications cannot be stopped, interpret results in the context of the specific drugs being used 1

Blood Collection Protocol

• Timing: Morning collection (ideally 0800-1000h) 4
• Patient positioning: Out of bed for 2 hours, then seated for 5-15 minutes immediately before blood draw 1
• Salt intake: Unrestricted (normal dietary sodium) 1

Interpretation Criteria

A positive screening test requires BOTH:

• ARR ≥30 (when aldosterone in ng/dL and renin activity in ng/mL/h) 1, 2
• Plasma aldosterone concentration ≥10-15 ng/dL 1, 2

The ARR has >90% sensitivity and specificity at these thresholds. 1 Higher ARR values (>100) dramatically reduce false-positive rates and may obviate confirmatory testing in some cases. 5

Important caveat: Do not rely solely on hypokalemia as a marker—it is absent in the majority of primary aldosteronism cases. 1

Step 2: Confirmatory Testing

A positive screening test requires demonstration of autonomous aldosterone secretion that cannot be suppressed. 1, 6

Confirmatory Test Options

Choose one of the following:

• Oral sodium loading test: 24-hour urine aldosterone measurement after 3 days of high-salt diet (>200 mEq/day sodium) 1, 3
• Intravenous saline suppression test: 2L normal saline infused over 4 hours with plasma aldosterone measurement 1, 3
• Fludrocortisone suppression test: Failure to suppress plasma aldosterone below threshold after fludrocortisone administration 1, 3
• Captopril challenge test: Measure aldosterone and renin before and after captopril administration 3, 5

All confirmatory testing should be performed with normal serum potassium levels and unrestricted salt intake. 1

Step 3: Subtype Differentiation

After biochemical confirmation, determine whether disease is unilateral or bilateral to guide treatment decisions. 1, 6

Adrenal CT Imaging

• Initial imaging: Non-contrast CT scan of adrenal glands 1
• Critical limitation: CT findings alone are insufficient for treatment decisions, as adenomas on imaging can represent hyperplasia and false positives are common due to nodular hyperplasia 1

Adrenal Venous Sampling (AVS)

AVS is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease, as up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone. 1, 6

Exception: AVS can be bypassed in patients <40 years with imaging showing a single affected gland, as bilateral hyperplasia is rare in this population. 1

Referral Considerations

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 3 A multidisciplinary review by endocrinologists, surgeons, and radiologists is recommended when imaging is not consistent with a benign lesion or there is evidence of hormone hypersecretion. 1

Common Pitfalls to Avoid

• Not screening high-risk patients: Only 2-4% of eligible patients get screened despite high prevalence 1
• Testing without potassium repletion: Causes false-negative results 1
• Relying on hypokalemia alone: Absent in most cases 1
• Proceeding to surgery based on CT alone: Requires AVS confirmation to avoid unnecessary adrenalectomy 1, 6
• Discontinuing all antihypertensives unnecessarily: ARR can be performed while continuing most medications 7