Diagnosis of Primary Aldosteronism
Screen with the aldosterone-to-renin ratio (ARR) as the initial test, requiring both ARR ≥20-30 and plasma aldosterone ≥10-15 ng/dL for a positive screen, followed by mandatory confirmatory testing with saline suppression or oral sodium loading, then adrenal venous sampling to determine laterality before treatment decisions. 1
Who Should Be Screened
Screen the following high-risk populations, as primary aldosteronism affects 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension 2, 1:
- Resistant hypertension (BP uncontrolled on 3 medications including a diuretic) 1
- Severe hypertension (BP >180/110 mmHg) 1
- Spontaneous or diuretic-induced hypokalemia (though absent in 50% of cases) 2, 1
- Adrenal incidentaloma discovered on imaging 2, 1
- Family history of early-onset hypertension or stroke at age <40 years 2, 1
- Young-onset hypertension (<30-40 years without traditional risk factors) 1
Patient Preparation Before Testing
Medication Management
Discontinue interfering medications when clinically feasible 1:
- Stop beta-blockers, centrally acting drugs, and diuretics (suppress renin, cause false-positives) 1
- Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks before any testing 1
- Consider stopping ACE inhibitors/ARBs for 2 weeks (increase renin, cause false-negatives) 1
Use these safe alternatives during washout 1:
- Long-acting calcium channel blockers (verapamil slow-release)
- Alpha-receptor antagonists (prazosin, doxazosin, hydralazine)
If medications cannot be stopped, interpret results in the context of the specific drugs the patient is taking 1.
Metabolic Preparation
- Ensure potassium repletion to 4.0-5.0 mEq/L before testing, as hypokalemia suppresses aldosterone production and causes false-negative results 1
- Encourage unrestricted (liberal) salt intake before testing 1
Initial Screening Test: Aldosterone-to-Renin Ratio (ARR)
Blood Collection Technique
Collect blood in the morning (0800-1000 hours) with the patient out of bed for 2 hours prior and seated for 5-15 minutes immediately before blood draw 1.
Interpretation Criteria
A positive screening test requires BOTH 1:
- ARR ≥20-30 (when aldosterone measured in ng/dL and renin activity in ng/mL/h)
- Plasma aldosterone concentration ≥10-15 ng/dL
The specificity improves if minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 1.
Confirmatory Testing
All positive ARR screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed 1. Choose one of the following:
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 high-sodium diet (>200 mEq/day) for 3 days with 24-hour urine aldosterone measurement; aldosterone >12-14 mcg/24 hours confirms the diagnosis 1, 3.
Fludrocortisone Suppression Test
Failure to reduce plasma aldosterone below threshold after fludrocortisone administration confirms the diagnosis 1.
Perform confirmatory testing with unrestricted salt intake and normal serum potassium levels 1.
Subtype Determination
Initial Imaging
Obtain non-contrast CT scan of the adrenal glands as the first step to identify unilateral adenoma versus bilateral 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, 4.
Exception: AVS can be bypassed in patients <40 years when imaging shows a single affected gland, as bilateral hyperplasia is rare in this population 1.
Critical Pitfalls to Avoid
- Never rely on hypokalemia alone for screening, as it is absent in approximately 50% of primary aldosteronism cases 2, 1
- Never proceed to surgery based on CT findings alone without AVS confirmation 1
- Never perform confirmatory testing while patient is on mineralocorticoid receptor antagonists without a 4-week washout period 1
- Never test without ensuring potassium repletion, as hypokalemia suppresses aldosterone and causes false-negatives 1
- Never skip confirmatory testing after a positive ARR, as the screening test alone has low specificity 1
Referral Pathway
Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for subtype determination and treatment planning 1, 5.
Clinical Significance
Primary aldosteronism causes dramatically worse outcomes than primary hypertension at equivalent blood pressure levels, including a 3.7-fold increase in heart failure, 4.2-fold increase in stroke, 6.5-fold increase in myocardial infarction, and 12.1-fold increase in atrial fibrillation 2, 1. Early diagnosis and treatment with either unilateral adrenalectomy or mineralocorticoid receptor antagonists can reverse these aldosterone-specific target organ damages 2, 4.