PASC Score Does Not Guide MRA Dosing in Primary Aldosteronism
The Primary Aldosteronism Severity Classification (PASC) score is not used to determine mineralocorticoid receptor antagonist dosing—instead, dosing is guided by blood pressure control, potassium normalization, and tolerability, with standard starting doses of spironolactone 50-100 mg daily (titrating up to 300-400 mg daily) or eplerenone 50-100 mg daily (titrating up to 200-300 mg daily). 1, 2
Standard MRA Dosing Algorithm for Primary Aldosteronism
First-Line Therapy: Spironolactone
- Start spironolactone at 50-100 mg once daily for bilateral primary aldosteronism or unilateral disease when surgery is not an option 2
- Titrate upward based on blood pressure response and potassium levels, with maximum doses reaching 300-400 mg daily if necessary 2
- Lower starting doses of 12.5-25 mg daily may be appropriate to minimize side effects and maximize compliance, particularly in patients at higher risk for hyperkalemia 3, 4
Alternative Therapy: Eplerenone
- Start eplerenone at 50-100 mg daily—substantially higher than heart failure dosing (25 mg)—reflecting the need to overcome autonomous aldosterone excess in primary aldosteronism 2
- Titrate to 200-300 mg daily as needed for blood pressure control 1
- Eplerenone requires twice-daily dosing due to shorter half-life but causes fewer anti-androgenic side effects (gynecomastia, erectile dysfunction, menstrual irregularities) compared to spironolactone 5, 6, 7
Third-Line Option: Amiloride
- Use amiloride 5-10 mg once or twice daily if both spironolactone and eplerenone are not tolerated, primarily to control hypokalemia 1
Monitoring Requirements
Initial Monitoring
- Check serum potassium and creatinine within 2-3 days of initiation or dose increases 1, 2
- Repeat at 7 days, then monthly for the first 3 months 1
- Continue monitoring every 3 months thereafter 2
Dose Adjustment Thresholds
- If potassium rises above 5.5 mEq/L: Reduce dose by 50% or switch to alternate-day dosing 1, 2
- If potassium exceeds 6.0 mEq/L: Discontinue MRA immediately 1, 2
- If creatinine rises above 2.5 mg/dL (men) or 2.0 mg/dL (women): Discontinue MRA 1, 2
Critical Contraindications and Precautions
Absolute Contraindications
- Avoid spironolactone in patients with eGFR <30 mL/min due to prohibitive hyperkalemia risk 1
High-Risk Situations Requiring Closer Monitoring
- Combining MRAs with ACE inhibitors or ARBs substantially increases hyperkalemia risk—monitor potassium closely 1
- Elderly patients with multiple comorbidities should receive standard dosing but with more frequent monitoring 1
- Patients with diabetes, chronic kidney disease, or concurrent NSAID use have elevated hyperkalemia risk 8
Expected Treatment Outcomes
Blood Pressure Response
- Medical therapy with adequate MRA doses achieves blood pressure improvement in virtually 100% of patients 1, 9
- Complete blood pressure normalization occurs in approximately 50% of patients, similar to surgical cure rates 1, 2
Reversal of Target Organ Damage
- MRAs reverse aldosterone-specific cardiovascular damage including left ventricular hypertrophy, albuminuria, and carotid intima-media thickness 2, 9
- Early diagnosis and treatment improve cure rates and reduce long-term cardiovascular complications 2
Common Pitfalls to Avoid
- Never rely on PASC scores for dosing decisions—these are not validated for determining MRA doses 1
- Do not underdose MRAs—primary aldosteronism requires higher doses than heart failure (eplerenone 50-100 mg vs 25 mg starting dose) 2
- Avoid initiating MRAs without establishing a monitoring plan—hyperkalemia can develop rapidly, especially with concurrent RAAS inhibitors 1
- Do not assume hypokalemia must be present—approximately 50% of primary aldosteronism cases have normal potassium levels 8
- Delayed diagnosis leads to irreversible vascular remodeling that may cause residual hypertension even after appropriate treatment 2