What is the best medication to treat primary hyperaldosteronism (aldosterone excess)?

Best Blood Pressure Medication for Primary Hyperaldosteronism

Spironolactone is the first-line medication for treating primary hyperaldosteronism, with a starting dose of 25-50 mg daily that can be titrated up to 100-400 mg daily as needed for blood pressure control. 1, 2, 3

Treatment Algorithm Based on Disease Subtype

For Bilateral Disease (Idiopathic Hyperaldosteronism)

• Start spironolactone 25-100 mg daily as the cornerstone of medical therapy 1, 2, 3
• Titrate the dose at two-week intervals based on blood pressure response 3
• Maximum doses of 300-400 mg daily may be necessary for adequate control 2, 4
• Spironolactone is specifically identified as the preferred agent for primary aldosteronism in major guidelines 1, 2

For Unilateral Disease

• Laparoscopic adrenalectomy remains the treatment of choice for surgical candidates 2, 5
• However, medical therapy with spironolactone achieves equivalent long-term outcomes to surgery in terms of blood pressure control, cardiovascular outcomes, and kidney function 5
• For patients who are not surgical candidates (elderly, multiple comorbidities, patient preference), proceed directly to spironolactone therapy 2, 5

Alternative Medication: Eplerenone

Eplerenone (50-100 mg daily in 1-2 doses) is the preferred alternative when patients develop sexual side effects on spironolactone 1, 2

• Eplerenone has equal effectiveness to spironolactone for blood pressure control 2
• It causes significantly less gynecomastia, breast tenderness, erectile dysfunction, and menstrual irregularities compared to spironolactone 1, 2, 6
• The main limitation is that eplerenone often requires twice-daily dosing for adequate blood pressure lowering 1

Critical Safety Monitoring

Before Initiating Treatment

• Verify serum potassium ≤5.0 mEq/L 2
• Confirm serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min 2
• Discontinue all potassium supplements 2

Monitoring Schedule

• Check potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months 2
• Subsequently monitor every 3 months if stable 2

Common Pitfalls and Contraindications

Avoid These Dangerous Combinations

• Do not combine with potassium supplements or potassium-sparing diuretics due to severe hyperkalemia risk 1, 2, 3
• Use extreme caution when combining with ACE inhibitors or ARBs - requires close monitoring for hyperkalemia 1, 2, 3
• Avoid NSAIDs or COX-2 inhibitors due to increased risk of hyperkalemia and renal dysfunction 2, 3
• Do not use with lithium - spironolactone reduces lithium clearance and causes toxicity 3

Renal Function Considerations

• Use with caution if eGFR <45 mL/min 1, 2
• Avoid in significant renal dysfunction (creatinine >2.5 mg/dL) 2

Additional Agents for Resistant Cases

If blood pressure remains uncontrolled on maximum-dose spironolactone:

• Add amiloride or triamterene (potassium-sparing diuretics) 4
• Add calcium channel blockers (amlodipine, nifedipine) 1, 4

Why This Matters for Outcomes

Early diagnosis and treatment with mineralocorticoid receptor antagonists reverses aldosterone-specific target organ damage, including left ventricular hypertrophy, albuminuria, and carotid intima-media thickness 5

Delayed treatment leads to irreversible vascular remodeling that causes residual hypertension and cardiovascular/renal complications even after appropriate treatment is initiated 2, 5

Blood pressure improves in virtually 100% of patients treated with adequate doses of mineralocorticoid receptor antagonists, with complete normalization occurring in approximately 50% of cases 2, 5