What laboratory tests are used to diagnose aldosteronoma in an adult patient with resistant hypertension and possible hypokalemia?

Laboratory Testing for Aldosteronoma Diagnosis

The aldosterone-to-renin ratio (ARR) is the initial screening test for aldosteronoma, requiring both ARR ≥20-30 and plasma aldosterone concentration ≥10-15 ng/dL for a positive screen, followed by mandatory confirmatory testing with saline suppression or oral sodium loading to demonstrate autonomous aldosterone secretion. 1

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

Patient Preparation Before Testing

• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production and causes false-negative results—this is a critical step that cannot be skipped. 1

• Collect blood in the morning (ideally 0800-1000 hours) after the patient has been out of bed for at least 2 hours and seated for 5-15 minutes immediately before blood draw. 1

• Patients should have unrestricted (liberal) salt intake before testing to avoid false results. 1

Medication Management

• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) at least 4 weeks before testing—this is mandatory. 1

• Discontinue beta-blockers, centrally acting drugs, and diuretics when clinically feasible, as these suppress renin and cause false-positive results. 1

• Safe alternatives that minimally interfere with ARR include long-acting calcium channel blockers (verapamil slow-release) and alpha-receptor antagonists (prazosin, doxazosin, hydralazine). 1

• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking. 1

Interpretation Thresholds

• A positive screening test requires BOTH:

  • ARR ≥20-30 ng/dL per ng/mL/hr 1
  • AND plasma aldosterone concentration ≥10-15 ng/dL 1

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

• An ARR of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) for confirming hyperaldosteronism. 1

Common Diagnostic Pitfall

• Do not rely on hypokalemia as a screening trigger or diagnostic criterion—it is absent in approximately 50% of primary aldosteronism cases. 1 Normal potassium does not exclude the diagnosis. 1

Confirmatory Testing (Mandatory After Positive ARR)

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

Confirmatory Test Options

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

• Oral sodium loading test: Administer oral salt loading with measurement of 24-hour urine aldosterone; this is an alternative confirmatory method. 1

• Fludrocortisone suppression test: Failure to reduce plasma aldosterone below threshold confirms autonomous production. 1

Critical Requirements During Confirmatory Testing

• Testing must be performed with unrestricted salt intake and normal serum potassium levels. 1

• Potassium supplementation during salt challenge testing is essential to maintain serum potassium in the 4.0-5.0 mEq/L range, as hypokalemia suppresses aldosterone and leads to false-negative results. 1

Subtype Determination After Confirmation

Initial Imaging

• Obtain non-contrast CT scan of the adrenal glands as initial imaging to identify unilateral adenoma versus bilateral hyperplasia. 1

• Critical caveat: CT findings alone are insufficient for treatment decisions—adenomas on imaging can represent hyperplasia, and false positives are common due to nonfunctioning nodular masses. 1, 2

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

• Exception: AVS may be omitted in patients <40 years when imaging shows a single affected gland, as bilateral hyperplasia is rare in this population. 1

Who Should Be Screened

Screen the following high-risk populations for aldosteronoma: 1

• Resistant hypertension (BP not controlled on 3 medications including a diuretic)—prevalence up to 20% 1
• Severe hypertension (BP >180/110 mmHg) 1
• Spontaneous or substantial diuretic-induced hypokalemia 1
• Incidentally discovered adrenal mass with hypertension 1
• Family history of early-onset hypertension or stroke at age <40 years 1

Referral Pathway

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

Key Distinction: Primary vs. Secondary Hyperaldosteronism

• Primary aldosteronism: Elevated aldosterone with suppressed renin (high ARR >30) 3
• Secondary hyperaldosteronism: Both aldosterone and renin elevated together (low ARR), suggesting renovascular hypertension or renal disease 4, 3

This distinction is critical because primary aldosteronism causes dramatically worse cardiovascular outcomes than primary hypertension at equivalent blood pressure levels, including 3.7-fold increase in heart failure, 4.2-fold increase in stroke, and 12.1-fold increase in atrial fibrillation. 1