What is the initial treatment for a patient with primary hyperaldosteronism (PHA) and hypertension?

Initial Treatment for Primary Hyperaldosteronism with Hypertension

For patients with primary hyperaldosteronism (PHA) and hypertension, mineralocorticoid receptor antagonists (MRAs), specifically spironolactone at a starting dose of 12.5-25 mg daily (titrated up to 50-100 mg daily as needed), is the initial treatment of choice. 1

Treatment Algorithm Based on PHA Subtype

Step 1: Determine PHA Subtype

• Unilateral PHA (aldosterone-producing adenoma or unilateral hyperplasia)

  • First-line: Laparoscopic adrenalectomy
  • Improves BP in virtually 100% of patients
  • Completely cures hypertension in ~50% of patients 2
  • For patients unsuitable for surgery: Medical management with MRAs

• Bilateral PHA (idiopathic hyperaldosteronism)

  • Medical management with MRAs 2, 1

Step 2: Medical Management with MRAs

Spironolactone (First-line)

• Starting dose: 12.5-25 mg daily 1
• Typical effective dose: 50-100 mg daily 2
• Maximum dose: Can be titrated up to 300-400 mg daily if necessary 2
• FDA indication: 100-400 mg daily for primary hyperaldosteronism 3

Eplerenone (Alternative)

• Consider when spironolactone causes unacceptable side effects
• Starting dose: 25 mg daily
• Typical dose: 25 mg twice daily
• Maximum dose: Up to 200 mg daily 1
• Advantage: Fewer sexual side effects (gynecomastia, erectile dysfunction) 2
• Disadvantage: Less potent than spironolactone, requires twice-daily dosing 2

Monitoring and Management

Initial Monitoring

• Check serum potassium and renal function within 1-2 weeks of starting treatment 1
• Discontinue or reduce potassium supplements when initiating MRAs 1
• Monitor for hyperkalemia, especially when combined with ACE inhibitors 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

Special Considerations

Side Effects Management

• Spironolactone: Common side effects include gynecomastia, decreased libido, impotence in men, and menstrual irregularities in women 4
• Eplerenone: Consider switching to eplerenone if sexual side effects occur with spironolactone 2

Emerging Treatments

• Newer non-steroidal MRAs (finerenone, exarenone) and aldosterone synthase inhibitor (baxdrostat) are being tested for primary aldosteronism 2

Familial Forms

• For glucocorticoid-remediable aldosteronism (Type 1), low-dose dexamethasone can be used, which is safe during pregnancy 2, 1

Clinical Pearls and Pitfalls

• Early diagnosis and treatment achieve higher cure rates and better outcomes 1
• Vascular remodeling from delayed diagnosis may result in residual hypertension even after treatment 2
• Low-dose spironolactone (12.5-25 mg/day) provides significant additive BP reduction even in resistant hypertension 5
• The risk of hyperkalemia increases when serum creatinine is >1.6 mg/dL 1
• In patients with eGFR between 30-50 mL/min/1.73m², consider initiating therapy at 25 mg every other day due to hyperkalemia risk 3