How do you evaluate for hyperaldosteronism?

Evaluation for Hyperaldosteronism

The evaluation for hyperaldosteronism should begin with plasma aldosterone concentration (PAC) and plasma renin activity (PRA) measurement to calculate the aldosterone-renin ratio (ARR), followed by confirmatory testing if positive. 1

Initial Screening

Who to Screen

Screen for primary aldosteronism in patients with:

• Resistant hypertension (BP remains >140/90 mmHg despite ≥3 antihypertensive medications)
• Hypokalemia (spontaneous or diuretic-induced)
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension
• Stroke at young age (<40 years)
• Hypertension with first-degree relative with primary aldosteronism
• Hypertension with atrial fibrillation or obstructive sleep apnea 1, 2

Initial Testing

1. Measure paired morning plasma aldosterone concentration (PAC) and plasma renin activity (PRA)

   • Ensure patient has unrestricted salt intake
   • Normalize serum potassium before testing
   • Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks 1
   • Consider effects of other medications:
     • ACE inhibitors/ARBs: elevate PRA
     • Beta-blockers: lower renin levels
     • Direct renin inhibitors: lower renin levels 1

2. Calculate aldosterone-renin ratio (ARR)

   • ARR > 30 (when PAC in ng/dL and PRA in ng/mL/hour) suggests primary aldosteronism
   • PAC should be at least 10-16 ng/dL for a positive test to be meaningful 1

Confirmatory Testing

If ARR is elevated, proceed with one of these confirmatory tests:

1. Saline suppression test:

   • Administer 2L normal saline IV over 4 hours
   • Measure PAC after infusion
   • Normal response: PAC suppresses to <5 ng/dL
   • Primary aldosteronism: PAC remains elevated (>10 ng/dL) 1, 2, 3

2. Oral salt loading test:

   • Patient maintains high-salt diet for 3 days
   • Measure 24-hour urinary aldosterone
   • Primary aldosteronism: elevated urinary aldosterone despite salt loading 1, 2

3. Captopril challenge test:

   • Administer captopril and measure PAC before and after
   • Primary aldosteronism: PAC fails to suppress adequately 2

4. Fludrocortisone suppression test:

   • Administer fludrocortisone for 4 days with salt loading
   • Measure PAC
   • Primary aldosteronism: PAC fails to suppress 2

Subtype Classification

If confirmatory testing is positive:

1. Adrenal CT or MRI:

   • To identify adrenal adenoma or hyperplasia
   • Note: Imaging alone is not reliable for distinguishing unilateral from bilateral disease 1

2. Adrenal vein sampling (AVS):

   • Gold standard for differentiating unilateral from bilateral disease
   • Measure aldosterone/cortisol ratio from each adrenal vein
   • Should be performed in all surgical candidates except possibly young patients (<40 years) with clear unilateral adenoma on imaging 1, 4

3. Postural stimulation test (less commonly used):

   • Measure PAC supine and after 2-4 hours of upright posture
   • Aldosterone-producing adenoma: PAC typically doesn't increase >30%
   • Idiopathic hyperaldosteronism: PAC typically increases >30% 5

Common Pitfalls and Caveats

1. Don't rely on hypokalemia - approximately 25% of patients with primary aldosteronism have normal potassium levels 3, 5

2. Medication interference - several medications can affect ARR results:

   • Mineralocorticoid receptor antagonists: falsely elevate PAC
   • Beta-blockers and direct renin inhibitors: suppress renin, potentially causing falsely elevated ARR
   • ACE inhibitors and ARBs: increase renin, potentially causing falsely low ARR 1

3. False positives in ARR can occur with:

   • Very low renin states (e.g., volume expansion, dietary salt excess)
   • Advanced age
   • Chronic kidney disease 1

4. Adrenal vein sampling interpretation requires expertise and should be performed at centers with experience in the procedure 1, 4

5. CT imaging alone is insufficient for determining surgical candidacy in most cases, as it cannot reliably distinguish between unilateral and bilateral disease 1, 4

Management Based on Subtype

• Unilateral disease (usually aldosterone-producing adenoma): Laparoscopic adrenalectomy
• Bilateral disease (usually idiopathic hyperaldosteronism): Medical management with mineralocorticoid receptor antagonists (spironolactone or eplerenone) 1, 2