What is the diagnostic approach for hyperaldosteronism?

Diagnostic Approach for Hyperaldosteronism

Screen high-risk hypertensive patients using the plasma aldosterone-to-renin ratio (ARR), followed by confirmatory testing with saline suppression or oral salt loading, then proceed to adrenal venous sampling to differentiate unilateral from bilateral disease before determining treatment. 1, 2

Who Should Be Screened

Screen for primary aldosteronism in hypertensive 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 1, 2
• Spontaneous or substantial diuretic-induced hypokalemia - though notably absent in 50% of cases, so normal potassium does NOT exclude the diagnosis 1, 3
• Incidentally discovered adrenal mass on CT or MRI 1
• Family history of early-onset hypertension or stroke before age 40 - suggests possible glucocorticoid-remediable aldosteronism 1, 3
• Severe hypertension (BP >180/110 mmHg) 2

Critical pitfall: Do not rely on hypokalemia as a screening trigger - it is absent in the majority of primary aldosteronism cases, yet the disease still causes significant cardiovascular and renal damage. 1, 3

Initial Screening Test: Aldosterone-to-Renin Ratio (ARR)

Patient Preparation Before Testing

• Correct hypokalemia first - low potassium suppresses aldosterone production and causes false negatives 2
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before testing 1, 2
• Stop interfering medications when feasible: beta-blockers, centrally acting drugs, and diuretics should be discontinued 2
• Use non-interfering antihypertensives: long-acting calcium channel blockers and alpha-receptor antagonists minimally affect ARR 2
• Ensure unrestricted salt intake and normal serum potassium levels 1, 2

If medications cannot be stopped, interpret results in the context of the specific drugs the patient is taking. 2

Blood Collection Technique

• Draw blood in the morning after the patient has been out of bed for 2 hours 2
• Patient should be seated for 5-15 minutes immediately before collection 2

Interpreting the ARR

A positive screening test requires BOTH criteria: 1, 2

• ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) - some sources suggest ARR ≥20 has excellent sensitivity and specificity >90% 2
• Plasma aldosterone concentration ≥10-15 ng/dL - this prevents false positives from very low renin levels 1, 2

The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations. 2

Important exception: In patients with severe hypertension and secondary kidney damage, plasma renin activity may escape suppression and appear normal or high-normal, but the ARR remains elevated due to disproportionately high aldosterone levels. 4

Confirmatory Testing

A positive ARR screening test MUST be confirmed with additional testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 1, 2

Confirmatory Test Options

Intravenous saline suppression test: 1, 2

• Infuse 2 liters of normal saline over 4 hours
• Failure to suppress plasma aldosterone below 5 ng/dL confirms the diagnosis
• Perform with unrestricted salt intake and normal serum potassium

Oral sodium loading test: 1, 2

• Administer oral salt loading for 3 days
• Measure 24-hour urine aldosterone
• Elevated urinary aldosterone despite sodium loading confirms autonomous secretion

Subtype Determination: Unilateral vs. Bilateral Disease

After biochemical confirmation, determine whether aldosterone excess is unilateral (surgically curable) or bilateral (medical management). 2, 5

Initial Imaging

• Non-contrast CT scan of the adrenal glands as the initial imaging modality 2

Critical warning: CT findings alone are INSUFFICIENT for treatment decisions - up to 25% of patients might undergo unnecessary adrenalectomy based on CT alone, as adenomas on imaging can represent hyperplasia and false positives are common due to nodular hyperplasia. 2, 3

Adrenal Venous Sampling (AVS)

AVS is mandatory before offering adrenalectomy to definitively distinguish unilateral from bilateral disease. 2, 6

Exception: AVS may be omitted in patients <40 years old when imaging shows a single affected gland and the contralateral gland is normal, as bilateral hyperplasia is rare in this population. 2

• Measure aldosterone concentrations (expressed as aldosterone/cortisol ratio) in each adrenal vein 6
• AVS is more sensitive and specific than cross-sectional imaging or scintigraphy 6

Referral Recommendations

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning. 1, 2

Common Diagnostic Pitfalls

• Not screening high-risk patients - only 2-4% of eligible patients currently get screened 2
• Relying on hypokalemia - absent in 50% of cases 1, 3
• Proceeding to surgery based on CT findings alone - requires AVS confirmation 2, 3
• Testing patients on interfering medications - particularly mineralocorticoid receptor antagonists 1, 2
• Not correcting hypokalemia before testing - suppresses aldosterone and causes false negatives 2