Glucocorticoid Antagonist in Patients With Diabetes or Glucose Intolerance Who Are Not Surgical Candidates or Have Persistent Disease After TSS
STEP 1 — Gather Information
Confirm ACTH-dependent Cushing's disease (CD) via biochemical testing (elevated UFC, lack of suppression on dexamethasone). Assess diabetes/glucose intolerance (HbA1c ≥6.5%, fasting glucose ≥126 mg/dL, or 2‑h OGTT ≥200 mg/dL). Determine surgical candidacy (review comorbidities, prior TSS outcomes, patient preference). If postoperative, obtain latest serum cortisol or UFC to document persistence.
STEP 2 — Rule In / Rule Out
Is the patient NOT a surgical candidate OR does the patient have persistent hypercortisolism after TSS? If YES, proceed to Step 3. If NO, consider first‑line surgery or other second‑line options per guideline.
STEP 3 — Classify or Stratify
Does the patient have diabetes or glucose intolerance? If YES, proceed to Step 4. If NO, consider alternative medical therapy (e.g., steroidogenesis inhibitors) per 6.4a.
STEP 4 — Decide
Administer a glucocorticoid antagonist (mifepristone). Start at 300 mg daily, titrate upward based on clinical response (glucose, weight, blood pressure) up to 1200 mg/day as needed. Monitor for adrenal insufficiency clinically (fatigue, nausea, hypotension) and avoid relying on cortisol levels for efficacy assessment.
Clinical Guardrails / Mimics / Pitfalls
Do not use in pregnancy (abortifacient risk). Watch for hypokalemia, hypertension, edema, and endometrial thickening; correct hypokalemia before and during therapy. Do not rely on UFC or serum cortisol to guide dose; efficacy is assessed via glucose, weight, and blood pressure. Avoid in patients with known adrenal insufficiency unless glucocorticoid replacement is planned.
Concrete Clinical Example
A 48‑year‑old woman with recurrent CD after TSS, HbA1c 8.1%, not a surgical candidate due to severe COPD, started mifepristone 300 mg daily. Titrated to 600 mg daily over 4 weeks; HbA1c improved to 7.0%, weight decreased 4 kg, blood pressure improved, with no signs of adrenal insufficiency.
Source: Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline, Nieman et al., 2015, DOI:10.1210/jc.2015-1818