Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients
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BACKGROUND: Cushing's syndrome is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose.
OBJECTIVE: To assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with Cushing's syndrome.
DESIGN: Retrospective, multicenter.
SETTING: Thirteen university hospitals.
PATIENTS: 195 patients with proven Cushing's syndrome: 115 Cushing's disease (CD), 37 ectopic ACTH (EAS); 43 ACTH-independent disease (Adrenocortical Cancer [ACC] 10; adrenal adenoma [AA] 30; ACTH-independent adrenal hyperplasia (3) Measurements: Biochemical parameters of activity of Cushing's syndrome: mean serum cortisol day-curve (CDC) (target 150-300nmol/L); 09.00h serum cortisol; 24h-UFC.
RESULTS: 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 months, range 3 days to 11.6 years). There were significant improvements on metyrapone - first evaluation to last review: CDC [91 patients, 722.9nmol/L (26.2μg/dl) vs. 348.6nmol/L (12.6μg/dl), p<0001]; 09.00h cortisol [123 patients, 882.9nmol/L (32.0μg/dl) vs. 491.1nmol/L (17.8μg/dl), p<0.0001]; UFC [37 patients, 1483nmol/24h (537μg/24h) vs. 452.6nmol/24h (164μg/24h), p=0.003]. Overall control at last review: 55%, 43%, 46% and 76% of patients who had CDCs, UFCs, 09.00h cortisol <331nmol/L (12.0μg/dl) and 09.00h cortisol <ULN/600nmol/L (21.7μg/dl). Median final dose: CD 1375mg; EAS 1500mg; benign adrenal disease 750mg; ACC 1250mg. Adverse events occurred in 25% of patients, mostly mild GI upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible.
CONCLUSIONS: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in Cushing's syndrome.
|Journal||The Journal of clinical endocrinology and metabolism|
|Early online date||9 Sep 2015|
|Publication status||E-pub ahead of print - 9 Sep 2015|