What is the recommended dosage of spironolactone (an aldosterone receptor antagonist) for patients with primary aldosteronism based on their Primary Aldosteronism Severity Classification (PASC) score?

Spironolactone Dosing for Primary Aldosteronism

For primary aldosteronism, initiate spironolactone at 100 mg daily and titrate up to 400 mg daily as needed to control blood pressure and hypokalemia, regardless of PASC score, as the PASC score is a research tool for risk stratification rather than a validated guide for medication dosing. 1

Understanding PASC Score Limitations

The Primary Aldosteronism Severity Classification (PASC) score is a relatively new research tool designed to stratify cardiovascular risk and predict outcomes in primary aldosteronism patients. However, no current guidelines from the American College of Cardiology, American Heart Association, or Endocrine Society recommend using PASC scores to determine spironolactone dosing. 2, 3, 4 Treatment decisions should be based on blood pressure control, potassium normalization, and tolerability rather than risk scores.

FDA-Approved Dosing Algorithm

Initial Dosing

• Start spironolactone at 100 mg daily for primary hyperaldosteronism, administered as a single dose or divided doses. 1
• This starting dose is substantially higher than the 25-50 mg used for heart failure or essential hypertension, reflecting the need to overcome autonomous aldosterone excess. 1, 5

Dose Titration

• Titrate upward to 400 mg daily based on blood pressure response and potassium normalization. 1
• The European Heart Journal recommends starting at 50-100 mg daily and titrating up to 300-400 mg daily if necessary for bilateral disease. 4
• For preoperative management of unilateral disease, use the same 100-400 mg daily range. 1, 6

Maintenance Therapy

• For patients unsuitable for surgery (bilateral disease, surgical contraindications, or patient refusal), continue spironolactone at the lowest effective dose that maintains blood pressure control and normokalemia. 1, 6

Monitoring Requirements

Initial Phase

• Check serum potassium and creatinine within 2-3 days of initiation or dose increases, then again at 7 days. 4
• Continue monthly monitoring for the first 3 months. 4

Ongoing Monitoring

• After stabilization, check potassium and creatinine every 3 months. 4
• Monitor blood pressure at each visit to assess treatment efficacy. 5

Dose Adjustments for Hyperkalemia

• If potassium rises above 5.5 mEq/L, reduce dose by 50% or switch to alternate-day dosing. 4
• Discontinue if potassium exceeds 6.0 mEq/L or creatinine rises above 2.5 mg/dL in men or 2.0 mg/dL in women. 4

Special Populations

Renal Impairment

• In patients with eGFR 30-50 mL/min/1.73 m², consider starting at 25 mg every other day due to hyperkalemia risk. 1
• Avoid use in patients with eGFR <30 mL/min or significant renal dysfunction. 2

Elderly Patients

• For elderly patients with multiple comorbidities (e.g., age >80 years), proceed directly to medical therapy rather than surgery, using standard dosing with closer monitoring. 4
• Perioperative cardiovascular risk is substantially elevated in this population. 4

Alternative Agents When Spironolactone Fails

Eplerenone

• If spironolactone causes intolerable side effects (gynecomastia, erectile dysfunction, menstrual irregularities), switch to eplerenone 50-100 mg daily, titrating up to 200-300 mg daily. 4, 6, 7
• Eplerenone is less potent than spironolactone and often requires twice-daily dosing for adequate blood pressure control. 2, 6

Amiloride

• If both spironolactone and eplerenone are not tolerated, use amiloride 5-10 mg once or twice daily to control hypokalemia. 2, 6
• Add calcium channel blockers or thiazide diuretics as second- or third-line therapy if blood pressure remains uncontrolled. 6, 5

Common Pitfalls to Avoid

• Never rely on hypokalemia presence to guide dosing—50% of primary aldosteronism patients have normal potassium levels. 3
• Do not use heart failure doses (25 mg daily) for primary aldosteronism—these are inadequate to overcome autonomous aldosterone excess. 4, 1
• Avoid combining spironolactone with ACE inhibitors or ARBs without close potassium monitoring, as hyperkalemia risk increases substantially. 2, 3
• Never start spironolactone in patients with potassium >5.0 mEq/L without first correcting hyperkalemia. 1

Expected Outcomes

• Medical therapy achieves blood pressure improvement in virtually 100% of patients when adequate doses are used. 4, 8
• Complete blood pressure normalization occurs in approximately 50% of patients, similar to surgical cure rates. 4
• Spironolactone reverses aldosterone-specific target organ damage, including left ventricular hypertrophy and albuminuria. 4
• Early diagnosis and treatment improve cure rates and reduce cardiovascular complications. 4