What is the recommended screening and treatment approach for patients suspected of having primary aldosteronism?

Primary Aldosteronism Screening and Treatment Approach

The aldosterone-to-renin ratio (ARR) is the recommended initial screening test for primary aldosteronism in patients with hypertension, particularly those with resistant hypertension, hypokalemia, or early-onset hypertension, with an ARR ≥20 ng/dL per ng/mL/hr considered positive when plasma aldosterone is ≥10 ng/dL. 1

Screening Indications

Screening for primary aldosteronism should be performed in patients with:

• Resistant hypertension
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Hypertension with adrenal incidentaloma
• Early-onset hypertension or family history of early-onset hypertension
• Severe hypertension (>180/110 mmHg) - with prevalence up to 12% in this group 2
• Patients with BP not controlled on multiple medications

Diagnostic Algorithm

Step 1: Screening with ARR

• Morning collection (preferably between 8-10 AM)
• Patient should be seated for 5-15 minutes before collection
• Ensure patient is potassium-replete
• Two approaches for medication management:
  1. Conduct ARR testing without changing medications and interpret results in context of current medications
  2. Discontinue interfering medications when feasible (beta-blockers, diuretics, clonidine, alpha-methyldopa) 2, 1

Step 2: Confirmatory Testing

If ARR is positive (≥20 ng/dL per ng/mL/hr with plasma aldosterone ≥10 ng/dL), perform one of the following confirmatory tests:

• Intravenous saline suppression test
• Oral salt-loading test with 24-hour urine aldosterone measurement
• Fludrocortisone suppression test 1

Step 3: Imaging

• Non-contrast CT scan of adrenal glands (or MRI if CT is contraindicated) to identify adrenal nodules 1

Step 4: Subtype Differentiation

• Adrenal vein sampling (AVS) is the gold standard for distinguishing between unilateral and bilateral aldosterone production
• AVS is particularly important for patients:
  • Age >40 years
  • Normal-appearing adrenal glands on imaging
  • Discordance between biochemical and imaging results 1

Treatment Approach

For Unilateral Disease

• Laparoscopic adrenalectomy is the treatment of choice
• Improves blood pressure in virtually 100% of patients
• Achieves complete cure of hypertension in ~50% of patients 1

For Bilateral Disease or Non-Surgical Candidates

• Medical therapy with mineralocorticoid receptor antagonists:
  • Spironolactone: Initial dose 25-100 mg daily, can be titrated up to 400 mg daily
  • Eplerenone: Alternative option with fewer anti-androgenic side effects
• Monitor for hyperkalemia, especially in patients with reduced renal function 1, 3

Specific Spironolactone Dosing for Primary Hyperaldosteronism

• For preoperative treatment: 100-400 mg daily
• For long-term maintenance therapy: Lowest effective dosage determined for the individual patient 3

Clinical Pitfalls and Considerations

1. Underdiagnosis: Primary aldosteronism is significantly underdiagnosed, with screening rates as low as 2-4% even in high-risk groups 2

2. Medication Interference: Several medications can affect ARR results:

   • Beta-blockers and central alpha-2 agonists can suppress renin and falsely elevate ARR
   • Diuretics can increase renin and falsely lower ARR
   • When testing on medications, interpretation must account for these effects 1

3. False Positives: Very low renin levels can falsely elevate ARR; plasma aldosterone should be at least 10 ng/dL for a positive test 1

4. Monitoring During Treatment:

   • Regular monitoring of blood pressure, serum potassium, and renal function
   • Titrate medication to achieve target blood pressure
   • Watch for hyperkalemia, especially at initiation of therapy and with dose increases 1

5. Referral Considerations: Patients with suspected primary aldosteronism should be considered for referral to specialized centers with expertise in hypertension management for further testing 2

Primary aldosteronism is associated with increased cardiovascular risk beyond that attributed to hypertension alone, making proper diagnosis and treatment essential for reducing morbidity and mortality.