What labs should be ordered for a patient with suspected hyperaldosteronism, particularly one presenting with resistant hypertension or hypokalemia?

Laboratory Evaluation for Hyperaldosteronism

Order a morning aldosterone-to-renin ratio (ARR) as the initial screening test, collected after the patient has been out of bed for 2 hours and seated for 5-15 minutes, with a positive screen defined as ARR ≥20-30 and plasma aldosterone ≥10-15 ng/dL. 1, 2

Initial Screening Test: Aldosterone-to-Renin Ratio

• The ARR is the screening test of choice because it has excellent sensitivity and specificity (>90%) for detecting primary aldosteronism, with a high negative predictive value 1, 2

• Collect blood in the morning (ideally 0800-1000 hours) with the patient seated for 5-15 minutes immediately before the blood draw 1, 2

• The patient should be out of bed for at least 2 hours prior to collection 1, 2

• A positive screening result requires BOTH an ARR ≥20-30 ng/dL per ng/mL/hr AND a plasma aldosterone concentration ≥10-15 ng/dL 1, 2

• The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1, 2

Additional Baseline Laboratory Tests

• Basic metabolic panel including serum sodium, potassium, chloride, bicarbonate, glucose, blood urea nitrogen, and creatinine 1

• Urinalysis to assess for proteinuria and other renal abnormalities 1

• Review prior potassium levels, as hypokalemia increases the likelihood of primary aldosteronism, though hypokalemia is absent in approximately 50% of cases 1, 2

Critical Patient Preparation Before Testing

Potassium Repletion

• Ensure the patient is potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 1, 2

• Target serum potassium in the 4.0-5.0 mEq/L range to optimize test sensitivity 2

Medication Management

• Ideally, discontinue interfering medications when clinically feasible, though testing can proceed on current medications with careful interpretation 1, 2, 3

• Mineralocorticoid receptor antagonists (spironolactone, eplerenone) must be withdrawn at least 4 weeks before testing if confirmatory testing is planned 1, 2

• Beta-blockers and centrally acting drugs (clonidine, methyldopa) suppress renin and cause false-positive ARR results 1, 4

• ACE inhibitors and ARBs raise renin levels and can cause false-negative ARR results, though if renin remains suppressed despite these medications, it increases test sensitivity 1, 2

• Potassium-wasting diuretics raise renin and can cause false-negative results 1

• Long-acting calcium channel blockers and alpha-receptor antagonists (prazosin, doxazosin) minimally interfere with ARR and are safe alternatives 1, 2, 4

Dietary Considerations

• Encourage unrestricted (liberal) salt intake before testing 1, 2

• Testing should be performed with normal sodium intake, as sodium restriction raises aldosterone and renin (potentially lowering ARR), while sodium loading lowers aldosterone and renin (potentially raising ARR) 1

Confirmatory Testing (After Positive ARR)

All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed with sodium loading. 1, 2

Confirmatory Test Options

• Intravenous saline suppression test: Infuse 2L of 0.9% normal saline over 4 hours; failure to suppress plasma aldosterone below 5 ng/dL confirms the diagnosis 1, 2

• Oral sodium loading test: High-salt diet (>200 mEq sodium/day for 3 days) with 24-hour urine collection for aldosterone; urinary aldosterone >12-14 mcg/24h confirms the diagnosis 1, 2

• Fludrocortisone suppression test: Considered the most sensitive confirmatory test, though less commonly used due to complexity 1, 5

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

Screening for Pheochromocytoma (If Indicated)

• If the adrenal mass has ≥10 Hounsfield units on non-contrast CT or the patient has signs/symptoms of catecholamine excess, measure plasma free metanephrines or 24-hour urinary metanephrines 1

• Values >2 times the upper limit of normal are highly suggestive of pheochromocytoma 1

Common Pitfalls to Avoid

• Do not rely on the presence or absence of hypokalemia alone to screen for primary aldosteronism, as it is absent in 50% of confirmed cases 1, 2

• Do not skip confirmatory testing after a positive ARR, as the specificity is low due to common low-renin states from volume expansion or dietary salt excess 1, 2

• Do not proceed directly to imaging without biochemical confirmation, as imaging alone is insufficient for diagnosis and can lead to unnecessary surgery in up to 25% of patients 2

• Do not perform confirmatory testing while the patient is taking mineralocorticoid receptor antagonists, as they must be withdrawn for at least 4 weeks 1, 2

• If medications cannot be safely discontinued, interpret ARR results in the context of the specific medications the patient is taking 1, 2, 3

Next Steps After Confirmation

• Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination (unilateral vs. bilateral disease) 1, 2

• Subtype determination requires high-resolution CT or MRI of the adrenal glands, followed by adrenal venous sampling in most patients >40 years old to distinguish unilateral adenoma (surgical candidate) from bilateral hyperplasia (medical management) 1, 2