What are the diagnostic criteria for primary hyperaldosteronism?

Diagnostic Criteria for Primary Hyperaldosteronism

Primary hyperaldosteronism is diagnosed through a three-step process: screening with the aldosterone-to-renin ratio (ARR), confirmatory testing to demonstrate autonomous aldosterone secretion, and subtype differentiation to guide treatment. 1, 2

Step 1: Screening with Aldosterone-to-Renin Ratio (ARR)

Who Should Be Screened

Screen the following high-risk populations 1, 2:

• Resistant hypertension (BP uncontrolled on 3 medications including a diuretic)
• Severe hypertension (BP >180/110 mmHg) 1
• Spontaneous or diuretic-induced hypokalemia (though absent in majority of cases) 1, 2
• Adrenal incidentaloma with hypertension
• Early-onset hypertension or stroke at young age (<40 years)
• Family history of early-onset hypertension or familial hyperaldosteronism

Patient Preparation Before Testing

Critical preparation steps include 1:

• Ensure potassium repletion before testing, as hypokalemia suppresses aldosterone production
• Discontinue interfering medications when clinically feasible:
  • Stop beta-blockers, centrally acting drugs, and diuretics
  • Use long-acting calcium channel blockers and alpha-receptor antagonists as alternatives (minimal ARR interference)
  • Withdraw mineralocorticoid receptor antagonists at least 4 weeks before testing 1, 2
• Maintain unrestricted salt intake and normal serum potassium levels 1, 2

Blood Collection Technique

Proper collection is essential 1:

• Draw blood in the morning
• Patient should be out of bed for 2 hours prior to collection
• Patient should be seated for 5-15 minutes immediately before blood draw
• Blood must be drawn with patient in seated position

Positive Screening Criteria

A positive ARR screening test requires 1, 2:

• ARR ≥30 (when aldosterone measured in ng/dL and plasma renin activity in ng/mL/h)
• Plasma aldosterone concentration ≥10-15 ng/dL (the ratio alone is insufficient)
• Some guidelines suggest using a minimum plasma renin activity of 0.5 ng/mL/h in calculations to improve specificity 1

Important caveat: The ARR has excellent sensitivity and specificity (>90%) when properly performed, but a positive screening test alone is insufficient for diagnosis and requires confirmation 1.

Step 2: Confirmatory Testing

Purpose and Requirement

A positive ARR must be confirmed with additional testing to demonstrate autonomous, non-suppressible aldosterone secretion 1, 2, 3. This distinguishes primary aldosteronism from physiologic aldosterone secretion 1.

Confirmatory Test Options

Choose one of the following 1, 2, 3:

1. Oral sodium loading test with 24-hour urine aldosterone measurement

   • Patient maintains high salt intake
   • Measure 24-hour urinary aldosterone excretion
   • Failure to suppress aldosterone confirms diagnosis

2. Intravenous saline suppression test

   • Administer IV saline infusion
   • Measure aldosterone levels
   • Non-suppressible aldosterone confirms diagnosis

3. Fludrocortisone suppression test

   • 4-day administration of fludrocortisone
   • Failure to reduce plasma aldosterone below threshold confirms diagnosis 4

Testing Conditions

All confirmatory tests require 1, 2:

• Unrestricted salt intake
• Normal serum potassium levels
• Mineralocorticoid receptor antagonists withdrawn ≥4 weeks

Step 3: Subtype Differentiation

Initial Imaging

After biochemical confirmation, perform non-contrast CT scan of the adrenal glands to 1, 2, 3:

• Identify potential adenomas (approximately 50% of cases are unilateral)
• Exclude adrenocortical carcinoma
• Guide further management decisions

Critical pitfall: CT findings alone are insufficient for treatment decisions, as adenomas on imaging can represent hyperplasia, and false positives are common due to nodular hyperplasia 4, 1.

Adrenal Venous Sampling (AVS)

AVS is the gold standard for differentiating unilateral from bilateral disease and should be performed 1, 2, 3:

• Prior to offering adrenalectomy in all patients (up to 25% might undergo unnecessary surgery based on CT alone) 1
• By an experienced radiologist at a tertiary referral center 3, 5
• Especially in patients >40 years of age 2

Treatment Implications Based on Subtype

The subtype determines definitive management 2, 3:

• Unilateral disease (adenoma): Laparoscopic unilateral adrenalectomy is treatment of choice—improves BP in virtually 100% and cures hypertension in approximately 50% 1, 2
• Bilateral disease (hyperplasia): Medical therapy with mineralocorticoid receptor antagonists (spironolactone first-line) 1, 2

Common Diagnostic Pitfalls to Avoid

• Not screening high-risk patients: Only 2-4% of eligible patients get screened 1
• Relying solely on hypokalemia: Absent in the majority of cases; only a small number have hypokalemia at early stages 4, 1
• Proceeding to surgery based on CT alone: Always perform AVS to avoid unnecessary adrenalectomy 1
• Testing without proper medication withdrawal: Interfering medications invalidate results 1, 2
• Inadequate potassium repletion: Hypokalemia suppresses aldosterone and causes false-negative results 1, 2