What is the recommended testing and treatment approach for Primary Aldosteroneism?

Testing for Primary Aldosteronism

Who Should Be Screened

Screen all patients with resistant hypertension (BP uncontrolled on 3 medications including a diuretic), spontaneous or substantial diuretic-induced hypokalemia, incidentally discovered adrenal mass, family history of early-onset hypertension, or stroke at young age (<40 years). 1, 2

Additional screening indications include:

• Severe hypertension (BP >180/110 mmHg) 2
• Well-controlled hypertension with a first-degree relative with primary aldosteronism 3
• Hypertension with atrial fibrillation or obstructive sleep apnea 3
• Primary aldosteronism is present in up to 20% of patients with resistant hypertension, making this the highest-yield screening population 2, 4

Patient Preparation Before Testing

Ensure patients are potassium-replete before testing, as hypokalemia suppresses aldosterone production and causes false-negative results. 2

Medication Management

• Ideally discontinue interfering medications when clinically safe: beta-blockers, centrally acting drugs, and diuretics should be stopped 2
• Use non-interfering alternatives: long-acting calcium channel blockers and alpha-receptor antagonists minimally affect the aldosterone-renin ratio (ARR) 2
• Mineralocorticoid receptor antagonists must be withdrawn at least 4 weeks before testing 2, 4
• If medications cannot be stopped, interpret results in the context of the specific medications the patient is taking 2

Dietary Requirements

• Patients should have unrestricted salt intake before testing 2, 4
• Normal serum potassium levels must be achieved 2, 4

Initial Screening Test: Aldosterone-Renin Ratio (ARR)

Use the plasma aldosterone-to-renin ratio (ARR) as the initial screening test for all suspected cases. 1, 2, 4

Collection Technique

• Draw blood in the morning (preferably 0800-1000h) with the patient out of bed for 2 hours prior 2, 5
• Patient should be seated for 5-15 minutes immediately before collection 2
• Blood must be drawn with the patient in a seated position 2

Interpretation Criteria

A positive screening test is defined as ARR ≥30 (when aldosterone is in ng/dL and renin activity in ng/mL/h) AND plasma aldosterone concentration ≥10 ng/dL. 2, 4

• An ARR cutoff of 20 ng/dL per ng/mL/hr has excellent sensitivity and specificity (>90%) 2
• The specificity improves if a minimum plasma renin activity of 0.5 ng/mL/h is used in calculations 2
• Critical pitfall: Do not rely solely on hypokalemia as a marker—it is absent in the majority of PA cases 2

Confirmatory Testing

All positive screening tests require confirmatory testing to demonstrate autonomous aldosterone secretion that cannot be suppressed. 2, 4, 6

Confirmatory Test Options

Choose one of the following:

• Intravenous saline suppression test: Administer IV saline and measure plasma aldosterone concentration 2, 4
• Oral sodium loading test: 24-hour urine aldosterone measurement with high salt intake 1, 2
• Fludrocortisone suppression test: Failure to reduce plasma aldosterone below threshold confirms diagnosis 2
• Captopril challenge test 3

Testing Conditions

• Perform with unrestricted salt intake 2, 4
• Ensure normal serum potassium levels 2, 4
• Mineralocorticoid receptor antagonists must be withdrawn at least 4 weeks prior 2, 4

Subtype Determination

After biochemical confirmation, determine if the disease is unilateral or bilateral to guide treatment decisions. 2, 4

Initial Imaging

• Obtain non-contrast CT scan of the adrenal glands to identify potential adenomas and exclude adrenocortical carcinoma 2, 4
• Critical caveat: CT findings alone are insufficient for treatment decisions, as adenomas on imaging can represent hyperplasia and false positives are common 2

Adrenal Venous Sampling (AVS)

Perform AVS prior to offering adrenalectomy in all patients except those <40 years with a single affected gland on imaging (bilateral hyperplasia is rare in this population). 2, 6

• AVS is the gold standard for differentiating unilateral from bilateral disease 4
• Up to 25% of patients might undergo unnecessary adrenalectomy based on CT findings alone 2
• Must be performed by an experienced radiologist 4

Referral Recommendations

Refer all patients with confirmed primary aldosteronism to a hypertension specialist or endocrinologist for further evaluation and treatment. 1, 2, 4

• Multidisciplinary review by endocrinologists, surgeons, and radiologists is recommended when imaging is not consistent with a benign lesion or there is evidence of hormone hypersecretion 2

Common Pitfalls to Avoid

• Underscreening: Only ~2-4% of eligible patients are currently screened despite high prevalence 2, 3
• Testing without proper preparation: Failure to correct hypokalemia or withdraw interfering medications leads to false-negative results 2
• Relying on CT alone for surgical decisions: Always perform AVS before adrenalectomy (except in patients <40 with unilateral adenoma) 2, 6
• Missing normokalemic cases: Most patients with primary aldosteronism are normokalemic 5, 7