What is the approach to rule out primary aldosteronism?

Approach to Rule Out Primary Aldosteronism

The most effective approach to rule out primary aldosteronism begins with screening using the plasma aldosterone-to-renin activity ratio in patients with specific risk factors, followed by confirmatory testing and subtype differentiation if positive. 1

When to Screen for Primary Aldosteronism

Screening is recommended in patients with hypertension who have any of the following:

• Resistant hypertension (requiring ≥3 medications for control)
• Hypokalemia (spontaneous or substantial diuretic-induced)
• Incidentally discovered adrenal mass
• Family history of early-onset hypertension
• Stroke at a young age (<40 years) 1

Screening Process

Step 1: Prepare the Patient

• Ensure normal serum potassium levels before testing
• Maintain unrestricted salt intake
• Withdraw mineralocorticoid receptor antagonists (spironolactone, eplerenone) for at least 4 weeks 1
• Other medications that may interfere should be considered for temporary discontinuation when possible

Step 2: Initial Screening Test

• Measure plasma aldosterone concentration (PAC) and plasma renin activity (PRA)
• Calculate the aldosterone-to-renin ratio (ARR)
• A positive screen is defined as:
  • ARR >30 (when PAC is reported in ng/dL and PRA in ng/mL/h)
  • AND plasma aldosterone concentration >10 ng/dL 1

Confirmatory Testing

If screening is positive, confirmatory testing is required to definitively diagnose primary aldosteronism:

Option 1: Intravenous Saline Suppression Test

• Infuse 2L of normal saline over 4 hours
• Measure plasma aldosterone at completion
• Failure to suppress aldosterone confirms the diagnosis 1

Option 2: Oral Salt Loading Test

• Patient maintains high sodium diet
• Collect 24-hour urine for aldosterone
• Elevated urinary aldosterone despite salt loading confirms the diagnosis 1

Subtype Differentiation

Once primary aldosteronism is confirmed, determine if it's unilateral or bilateral:

Step 1: Adrenal Imaging

• CT scan of adrenal glands
• Note: CT alone is insufficient for final determination in most cases 1

Step 2: Adrenal Venous Sampling (AVS)

• Gold standard for differentiating unilateral from bilateral disease
• Essential before considering surgery
• Should be performed at centers with expertise in this procedure
• Measures aldosterone and cortisol from both adrenal veins 1

Treatment Based on Subtype

Unilateral Disease (Aldosterone-Producing Adenoma)

• Laparoscopic adrenalectomy is treatment of choice
• Resolves hypertension in ~50% of patients
• Improves BP control in virtually all patients 1

Bilateral Disease (Idiopathic Hyperaldosteronism)

• Medical therapy with mineralocorticoid receptor antagonists:
  • Spironolactone (first-line): 25-100 mg daily, titrate as needed
  • Eplerenone: alternative if spironolactone side effects occur 1

Common Pitfalls to Avoid

1. Missing the diagnosis by only screening patients with hypokalemia (up to 80% of patients with primary aldosteronism have normal potassium levels)

2. Incorrect test interpretation due to:

   • Failure to withdraw interfering medications
   • Not ensuring normal potassium levels before testing
   • Relying solely on ARR without considering absolute aldosterone level

3. Proceeding directly to surgery based on CT findings alone without AVS confirmation (25% of patients would undergo unnecessary adrenalectomy) 1

4. Inadequate preparation for screening tests, leading to false results

5. Overlooking familial forms of hyperaldosteronism, particularly in young patients with family history of early hypertension

Early diagnosis and appropriate treatment of primary aldosteronism are crucial as they can reverse target organ damage, improve cardiovascular outcomes, and potentially cure hypertension in patients with unilateral disease.