What is the initial workup for a patient suspected of having hyperaldosteronism?

Hyperaldosteronism Workup

Initial Screening Test

Screen with the aldosterone-to-renin ratio (ARR) as the first-line test, 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, 2

Who Should Be Screened

Screen the following high-risk populations:

• Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) - present in up to 20% of these patients 1, 2
• Hypertension with spontaneous or diuretic-induced hypokalemia (though hypokalemia is absent in the majority of cases) 1, 2
• Severe hypertension (BP >180/110 mmHg) 1
• Adrenal incidentaloma with hypertension 1, 2
• Early-onset hypertension or stroke at young age (<40 years) 2, 3
• Family history of early-onset hypertension or familial hyperaldosteronism 2, 3

Patient Preparation Before ARR Testing

Medication Management

• Withdraw mineralocorticoid receptor antagonists at least 4 weeks before testing 1, 2
• Stop beta-blockers, centrally acting drugs, and diuretics when feasible 1
• Use long-acting calcium channel blockers and alpha-receptor antagonists as alternatives as they minimally interfere with ARR 1
• If medications cannot be stopped, interpret results in the context of the specific medications being taken 1, 3

Metabolic Preparation

• Ensure patient is potassium-replete before testing, as hypokalemia suppresses aldosterone production 1, 2
• Maintain unrestricted salt intake 1, 2
• Normalize serum potassium levels 1, 2

Collection Technique

• Collect blood in the morning (ideally 0800-1000h) 1
• Patient should be out of bed for 2 hours prior to collection 1
• Patient seated for 5-15 minutes immediately before collection 1
• Draw blood with patient in seated position 1

Confirmatory Testing

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

Choose one of the following confirmatory tests:

• Intravenous saline suppression test 1, 2
• Oral sodium loading test with 24-hour urine aldosterone measurement 1, 2
• Fludrocortisone suppression test (failure to reduce plasma aldosterone below threshold confirms diagnosis) 1

All confirmatory testing should be performed with unrestricted salt intake and normal serum potassium levels 1, 2

Subtype Determination After Biochemical Confirmation

Initial Imaging

• Perform non-contrast CT scan of the adrenal glands to identify potential adenomas and exclude adrenocortical carcinoma 1, 2
• CT/MRI findings alone are insufficient for treatment decisions, as imaging can miss aldosterone-producing adenomas or show non-functioning nodules 3

Adrenal Venous Sampling (AVS)

• AVS is mandatory before offering adrenalectomy to distinguish unilateral from bilateral disease 1, 2
• Up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 1
• Exception: Patients <40 years with a single unilateral adenoma on imaging may proceed to surgery without AVS, as bilateral hyperplasia is rare in this population 1
• AVS should be performed by an experienced radiologist 2

Common Pitfalls to Avoid

• Do not rely solely on hypokalemia as a marker - it is absent in the majority of cases 1
• Do not skip confirmatory testing - an elevated ARR alone is not diagnostic 1, 2
• Do not use CT findings alone for subtype determination in patients >40 years 1, 3
• Avoid testing patients on mineralocorticoid receptor antagonists without appropriate withdrawal period 1, 2
• Be aware that false positive ARR results can occur with low-renin states, certain medications, and advanced age 3

Referral Considerations

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