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Cushing's Syndrome Treatment

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Table 1. Medical Treatment of Cushing's Syndrome Drug Pros Cons Dose a Steroidogenesis inhibitors Ketoconazole b Quick onset of action Adverse effects: GI, hepatic dyscrasia (death), male hypogonadism; requires acid for biologic activity; DDIs 400–1600 mg/d; q6–8h dosing Metyrapone b Quick onset of action Adverse effects: GI, hirsutism, HT, hypokalemia; accessibility variable across countries 500 mg–6 g/d; q6–8h dosing Mitotane c Adrenolytic; approved for adrenal cancer Slow onset action; lipophilic/long half life, teratogenic Adverse effects: GI and CNS, g ynecomastia, low WBC and T4, ↑LFTs; ↑CBG, DDIs Starting dose 250 mg ; 500 mg–8 g/d Etomidate Intravenous, quick onset of action Requires monitoring in ICU Bolus and titrate Pituitary-directed Cabergoline Adverse effects: asthenia, GI, dizziness 1–7 mg/week Pasireotide d Most successful when UFC <2-fold normal; subcutaneous Adverse effects: diarrhea, nausea, cholelithiasis, hyperglycemia, transient ↑LFTs; ↑QTc interval 600–900 mcg bid Glucocorticoid receptor-directed Mifepristone e Difficult to titrate (no biomarker); abortifacient Adverse effects: fatigue, nausea, vomiting, arthralgias, headache, hypertension, hypokalemia, edema, endometrial thickening 300–1200 mg/d a Except as noted, the lowest dose may be used initially, unless the patient has severe hypercortisolism (UFC >5-times normal), in which case the starting dose may be doubled. b Ketoconazole and metyrapone are approved by the EMA for the treatment of CS. c Mitotane has FDA approval for treatment of adrenal cancer. d Pasireotide has FDA approval for treatment of patients with CD who are not surgical candidates or have failed surgery. e agent is approved in Europe also. e Mifepristone has FDA approval for treatment of patients with CS and diabetes or glucose intolerance who are not surgical candidates or have failed surgery. Other treatments listed here represent off-label uses.

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