Table 2: Medical treatments for Cushing’s syndrome (in clinical use or investigational).

DrugMechanism of actionDose (range)Side effectsSafety monitoring

KetoconazoleInhibits steroidogenesis via inhibition of cytochrome P450 function200–1800 mg per os
(in divided doses, b.i.d.-t.i.d.)
Reversible liver dysfunction, severe liver toxicity, GI disorders, skin rash, loss of libido, impotenceTransaminase, testosterone, and SHBG in men
MetyraponeInhibits 11- 𝛽 hydroxylase in the adrenal gland750–6000 mg per os
(in divided doses, t.i.d.-q.i.d.)
Hirsutism, acne, GI disorders, dizziness, hypertension, edema, hypokalemiaAndrogens, mineralocorticoid, electrolytes
AminoglutethimidePrevents conversion of cholesterol to pregnenolone250–750 mg per os
(in divided doses, b.i.d.-t.i.d.)
Generalized, self-limiting itchy rash, nausea, dizziness, blurred vision, cholestasis, bone marrow suppressionBlood count, thyroid hormones, hepatic function, abdominal US
MitotaneInhibits steroidogenesis via inhibition of cytochrome P450; adrenolytic (high doses)500 mg–12 g per os (daily)Severe nausea, vomiting, diarrhea, rash, somnolence, ataxia, vertigo, dyslipidemiaPlasma mitotane, blood count, electrolytes, liver function, cholesterol
EtomidateInhibits 11- 𝛽 hydroxylase and 17–20 lyase<0.1 mg/kg/hr i.v.Sedative effects, anesthesiaMonitoring by anesthesiologists
Mifepristone (RU-486)Glucocorticoid, androgen, and progesterone receptor antagonist300–1200 mg per os, daily doseHypoadrenalism, hypokalemia, hypertension, irregular menses, endometrial hyperplasiaBlood count, electrolytes, pelvic US
CabergolineD2 receptor agonist1–7 mg per os, weekly doseNausea, vomiting, dizziness, valvulopathyEchocardiogram
OctreotideSomatostatin receptor agonist (isoform 2)200–1000 mcg s.c. t.i.d., or LAR formulation 10–30 mg i.m. every 4 weeksGI disorders, gallstones or biliary sludge, hyperglycemia, sinus bradycardiaGlycaemia, HbA1c, ECG, abdominal US
Pasireotide
(SOM 230)
Somatostatin receptor agonist
(isoforms 1, 2, 3, 5)
600–900 mcg s.c. b.i.d., LAR formulation under investigationGI disorders, gallstones or biliary sludge, hyperglycemia or diabetes mellitus, sinus bradycardiaGlycaemia, HbA1c, Q-T interval, abdominal US
Retinoic acid Inhibits POMC transcription and cell-cycle progressionNo data in vivo in humans in Cushing’s syndromeAnaemia, mucocutaneous and ocular symptomsToxic effects of vitamin A, liver function, blood count
RosiglitazonePPAR- 𝛾 agonist4–16 mg per os, daily dosesWeight increase, edema, somnolence, hirsutismBlood count, transaminase, ECG, echocardiogram
TemozolomideAlkylating agent150–200 mg/m2 per os for 5 days once every 28 days, or 75 mg/m2 daily for 21 days with 7 day breakBone marrow suppression, nausea, vomiting, dizziness diarrhea, rashBlood count, liver and renal function, electrolytes
GefitinibTyrosine kinase inhibitorNo data in vivo in humans in Cushing’s diseaseFatigue, nausea, vomiting, stomatitis, bone pain, dyspnea, interstitial lung diseaseTransaminase, pulmonary toxicity
EverolimusmTOR inhibitor5 mg/dayBone marrow suppression, nausea, angioedema, GI disorders, extremity painLiver and renal function, blood count, glycaemia, HbA1c, lipid profile

b.i.d.: twice daily; t.i.d.: three times daily; q.i.d.: four times daily; i.v.: intravenous; i.m.: intramuscular; s.c.: subcutaneous; POMC: proopiomelanocortin; US: ultrasound; HbA1c: glycated hemoglobin; GI: gastrointestinal.