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.