A patient who has been taking Korlym (mifepristone) for two months—what laboratory tests and evaluations should be performed to monitor therapy?

Monitoring Requirements for Korlym (Mifepristone) at 2 Months

Monitor serum potassium levels 1-2 weeks after any dose change and periodically thereafter, assess for clinical signs of adrenal insufficiency (not cortisol levels), check thyroid function tests, and in females perform gynecologic evaluation for vaginal bleeding or endometrial changes. 1

Critical Laboratory Monitoring

Serum Potassium (Priority #1)

• Check potassium 1-2 weeks after starting or increasing dose, then periodically 1
• Hypokalemia occurred in 44% of patients in clinical trials 1
• This can occur at any time during treatment, not just early on
• If hypokalemia develops despite supplementation, add mineralocorticoid antagonists (spironolactone or eplerenone) 1

Thyroid Function Tests

• Monitor TSH levels regularly 2
• 19% of patients developed TSH elevations above normal range in clinical trials 1
• Most remained asymptomatic and TSH normalized after discontinuation
• Adjust thyroid hormone replacement as needed if patient is already on therapy 2

Clinical Monitoring (Cannot Use Cortisol Levels)

Adrenal Insufficiency Assessment

This is the most critical pitfall with mifepristone: cortisol levels remain elevated and cannot be used to diagnose adrenal insufficiency 2, 3

Monitor for these clinical signs:

• Weakness
• Nausea and decreased appetite
• Increased fatigue
• Hypotension
• Hypoglycemia 1

The 2021 Lancet Diabetes & Endocrinology consensus guideline emphasizes that "cortisol measurements are not helpful for dosing or safety monitoring" with mifepristone, and "only clinical features can be used" to detect adrenal insufficiency 2. This is fundamentally different from other Cushing's medications.

Female-Specific Monitoring

Gynecologic Evaluation

• Assess for vaginal bleeding at each visit 1
• Consider transvaginal ultrasound to evaluate endometrial thickness
• In clinical trials, endometrial thickness increased from mean 6.14 mm to 15.7 mm in premenopausal women 1
• 38% developed endometrial hypertrophy above normal limits 1
• Refer to gynecology if vaginal bleeding occurs 1

Additional Monitoring Considerations

Drug Interactions Review

• Review all concomitant medications carefully 2
• Mifepristone has extensive drug-drug interactions via CYP3A4 1
• If patient is on strong CYP3A inhibitors (ketoconazole, itraconazole, ritonavir, etc.), maximum dose should be limited to 900 mg/day 1

Clinical Response Assessment

Since cortisol levels cannot guide therapy, assess:

• Blood glucose control and weight (primary therapeutic targets) 2
• Blood pressure changes 2
• Improvement in Cushingoid features 2

Lipid Panel

• Monitor HDL-cholesterol levels 1
• Reductions in HDL-C were observed in clinical trials, though levels returned to baseline after discontinuation

Tumor Surveillance (If Cushing's Disease)

Monitor ACTH levels and consider pituitary imaging 2

• ACTH levels typically increase ≥2-fold during treatment 2
• In long-term studies, 3 patients with macroadenomas showed tumor progression up to 25 months 2
• This did not correlate with ACTH increases, so regular imaging may be warranted for macroadenomas

Common Pitfall to Avoid

Do not order cortisol levels (serum, urinary free cortisol, or late-night salivary cortisol) to monitor treatment response or safety. These remain elevated with mifepristone due to its mechanism as a glucocorticoid receptor antagonist and will mislead clinical decision-making 2, 3. The 2015 Endocrine Society guideline explicitly states that "practitioners cannot use hormonal measurements to guide efficacy or to diagnose adrenal insufficiency" with mifepristone 3.