Treatment of Cushing disease: overview and recent findings

Figures & data

Table 1 Drugs with adrenolytic properties used in treatment of CD

Agent	Doses	Results/peculiar effects	Side effects/limits
Metyrapone	750–6,000 mg/daily	Effective	Hypoadrenalism, nausea, abdominal pain, hirsutism, acne No longer available in United States/compassionate use in Europe
Ketoconazole	400–1,200 mg/daily	Effective Slow onset of action	Gastrointestinal upset, rashes, elevation of hepatic serum transaminases, gynecomastia, reduced libido in men
Aminoglutethimide	250 mg/2–3 times daily	Less efficient in CD compared with the other causes of CS, often used as an adjunct to metyrapone	Self-limited pruritic rash, nausea, somnolence, dizziness, blurred vision, hypothyroidism, several potential medication interactions Cholestasis and bone marrow suppression are rare side effects No longer available
Mitotane	500 mg–12 g/daily	Effective (commonly used in cancer) Gradual dose titration, taken during meals	Adrenal insufficiency, gastrointestinal upset, neurological disturbances, elevation of hepatic enzymes, hypercholesterolemia, hyperuricemia, gynecomastia, prolonged bleeding time, change in hormone-binding globulins, teratogenicity
Etomidate		Effective	Case reports in pediatric population

Abbreviations: CD, Cushing disease; CS, Cushing syndrome.

Table 2 Drugs centrally active (reduction of ACTH secretion) with therapeutic potential in CD

Agent	Doses	Results/peculiar effects	Side effects/limits
Somatostatin analogs
Octreotide	100–300 μg/daily	Ineffective in clinical studies	Gastrointestinal discomfort, gall stones, hyperglycemia, GH deficit?
Pasireotide	600 μg twice daily	Phase 2 study shows promising results
Dopamine agonists
Bromocriptine	3–30 mg/daily	Poor long-term results but renewed interest	Nausea and postural hypotension Cardiac valve dysfunction?
Cabergoline	1–7 mg/wk	More efficacious than bromocriptine	Postural hypotension Cardiac valve dysfunction?
Histamine and serotonin antagonists
Cyproheptadine	4–24 mg/daily	Small series, rarely effective	Sedation, weight gain
5-HT2 antagonist
Ritanserin		No sustained effects in most patients
PPAR-γ receptor agonists
Rosiglitazone	4–16 mg/daily	In vitro success not reproduced in clinical practice
Pioglitazone	45 mg daily

Abbreviations: ACTH, adrenocorticotropin hormone; CD, Cushing disease; GH, growth hormone; PPAR-γ, peroxisome proliferator-activated receptor-γ; 5-HT, 5-hydroxytryptamine.