How is primary aldosteronism managed?

Management of Primary Aldosteronism

The treatment of primary aldosteronism depends on whether the condition is unilateral or bilateral, with laparoscopic adrenalectomy recommended for unilateral disease and mineralocorticoid receptor antagonists (MRAs) for bilateral disease. 1

Diagnostic Approach

Before initiating treatment, proper diagnosis and subtype determination are essential:

1. Screening: Aldosterone-to-Renin Ratio (ARR) is the primary screening test

   • Cutoff value: ARR > 30 with plasma aldosterone ≥ 10 ng/dL
   • Ensure unrestricted salt intake, normal serum potassium
   • Withdraw mineralocorticoid receptor antagonists for ≥4 weeks before testing 2, 1

2. Confirmatory Testing: Either intravenous saline suppression test or oral salt-loading test 2, 1

3. Subtype Determination:

   • Initial adrenal CT imaging
   • Adrenal venous sampling to definitively determine if aldosterone production is unilateral or bilateral 2, 1

Treatment Algorithm

1. Unilateral Disease (Aldosterone-producing adenoma or unilateral hyperplasia)

• First-line treatment: Laparoscopic adrenalectomy 2, 1, 3
  • Improves blood pressure in virtually 100% of patients
  • Completely cures hypertension in approximately 50% of patients 2
  • Reverses left ventricular hypertrophy and other target organ damage 4

2. Bilateral Disease (Bilateral adrenal hyperplasia)

• First-line treatment: Mineralocorticoid receptor antagonists 2, 1, 3

  • Spironolactone: Start at 12.5-25 mg daily, titrate up to 50-100 mg daily or up to 200 mg if necessary 1, 3
  • Eplerenone: Alternative with fewer sexual side effects, start at 25 mg daily, requires twice-daily dosing, less potent than spironolactone 1

• Add-on therapy if blood pressure not controlled:

  • Potassium-sparing diuretics (amiloride or triamterene)
  • Calcium channel antagonists 5, 6

3. Special Cases

• Preoperative management: Spironolactone 100-400 mg daily 3
• Unsuitable for surgery: Long-term maintenance therapy with spironolactone at lowest effective dose 3
• Glucocorticoid-remediable aldosteronism: Low-dose dexamethasone 1

Monitoring

• Initial monitoring:

  • Check serum potassium and renal function within 1-2 weeks of starting treatment
  • Monitor potassium at 3 days and 1 week after initiating therapy, then monthly for first 3 months 1

• Long-term monitoring:

  • Regular assessment of blood pressure control
  • Periodic measurement of serum potassium and renal function
  • Watch for side effects: gynecomastia, sexual dysfunction, menstrual irregularities 1

Important Considerations

• Side effects of MRAs:

  • Spironolactone: Gynecomastia, breast tenderness, sexual dysfunction, menstrual irregularities
  • Both MRAs: Risk of hyperkalemia, especially with renal impairment or concomitant ACE inhibitors 1, 4

• Treatment efficacy:

  • Medical treatment of bilateral forms appears to be as effective as surgical treatment of unilateral forms for controlling hypertension and preventing cardiovascular and renal morbidities 6
  • Early diagnosis and treatment are crucial as vascular remodeling from delayed diagnosis may result in residual hypertension even after treatment 1

• Dosage considerations:

  • For primary hyperaldosteronism, higher doses of spironolactone (100-400 mg daily) may be needed initially, especially for preoperative management 3
  • For long-term maintenance, the lowest effective dose should be determined individually 3

Pitfalls to Avoid

• Underdiagnosis: Primary aldosteronism is significantly underdiagnosed, representing 5-13% of hypertension cases but with fewer than 1% of patients being diagnosed and treated 7

• Medication interference: Be aware that certain medications can interfere with ARR testing:

  • MRAs raise aldosterone levels
  • Direct renin inhibitors and β-blockers lower renin levels 1

• Inadequate monitoring: Close monitoring of electrolytes and renal function is essential when starting MRAs, especially when combined with ACE inhibitors 1

• Delayed treatment: Prompt diagnosis and treatment mitigate aldosterone-specific target organ damage and improve outcomes 8