What is the workup for primary hyperaldosteronism?

Primary Hyperaldosteronism Workup

The workup for primary hyperaldosteronism should include screening with aldosterone-to-renin ratio, confirmatory testing, and adrenal vein sampling prior to considering surgical intervention. 1, 2

Initial Screening

Who to Screen

• Patients with resistant hypertension
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Adrenal incidentaloma
• Hypertension with family history of early-onset hypertension
• History of stroke at a young age (<40 years)
• Patients with unilateral adrenal masses 1, 2

Screening Test

• Aldosterone-to-renin ratio (ARR) is the preferred screening test
  • Typical cutoff: >20-30 when aldosterone is reported in ng/dL and plasma renin activity in ng/mL/h
  • Requires aldosterone >15-16 ng/dL for proper interpretation
  • Most sensitive when patients are on ACE inhibitors or ARBs (these elevate renin; if renin remains suppressed, it increases sensitivity) 1, 2

Important: Certain medications affect ARR interpretation:

• Mineralocorticoid receptor antagonists (raise aldosterone)
• Direct renin inhibitors and β-blockers (lower renin)
• Continue ACE inhibitors or ARBs during testing if possible 1

Confirmatory Testing

If ARR is positive, one of the following confirmatory tests should be performed:

• Intravenous saline suppression test
• Oral salt-loading test with 24-hour urine aldosterone
• Fludrocortisone suppression test 2, 3

Subtype Determination

Imaging

• Non-contrast CT scan as first-line imaging to distinguish benign from indeterminate lesions
• If indeterminate, proceed to washout CT or chemical-shift MRI
• Imaging helps identify adrenal adenomas or hyperplasia 1, 2

Adrenal Vein Sampling (AVS)

• Critical step: AVS is recommended prior to offering adrenalectomy in patients with primary aldosteronism 1
• Gold standard for distinguishing between unilateral and bilateral aldosterone production
• Essential for patients with:
  • Age >40 years
  • Normal-appearing adrenal glands on imaging
  • Discordance between biochemical and imaging results 2, 3, 4

Treatment Options

Surgical Management

• Laparoscopic unilateral adrenalectomy for patients with confirmed unilateral disease
  • Can improve BP control in nearly 100% of patients
  • Cures hypertension in approximately 50% of cases
  • Minimally-invasive surgery (MIS) should be performed when feasible 1, 2, 5

Medical Management

• For bilateral adrenal hyperplasia or patients unsuitable for surgery:
  • Mineralocorticoid receptor antagonists:
    • Spironolactone (100-400 mg daily) as first-line
    • Eplerenone as alternative (less side effects but less potent) 2, 6
  • May add calcium channel blockers, ACE inhibitors, or ARBs if needed 2

Follow-up Management

• Regular monitoring of:
  • Blood pressure
  • Serum potassium levels
  • Renal function
  • Signs of cardiovascular damage 2

Common Pitfalls to Avoid

1. Inadequate screening: Failing to screen high-risk patients (resistant hypertension, hypokalemia)
2. Medication interference: Not accounting for medications that affect the ARR
3. Skipping AVS: Proceeding to surgery based on imaging alone can lead to inappropriate adrenalectomy in ~25% of cases 1
4. Inadequate follow-up: Even after successful treatment, patients require monitoring for blood pressure control and electrolyte balance

By following this structured approach to primary hyperaldosteronism workup, clinicians can accurately diagnose and appropriately treat this common but often undiagnosed cause of secondary hypertension.