Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients

Eleni Daniel, Simon Aylwin, Omar Mustafa, Steve Ball, Atif Munir, Kristien Boelaert, Vasileios Chortis, Daniel J Cuthbertson, Christina Daousi, Surya P Rajeev, Julian Davis, Kelly Cheer, William Drake, Kirun Gunganah, Ashley Grossman, Mark Gurnell, Andrew S Powlson, Niki Karavitaki, Isabel Huguet, Tara KearneyKumar Mohit, Karim Meeran, Neil Hill, Aled Rees, Andrew J Lansdown, Peter J Trainer, Anna-Elisabeth H Minder, John Newell-Price

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)
506 Downloads (Pure)


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.

Original languageEnglish
Article numberjc20152616
JournalThe Journal of clinical endocrinology and metabolism
Issue number11
Early online date9 Sept 2015
Publication statusE-pub ahead of print - 9 Sept 2015


Dive into the research topics of 'Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients'. Together they form a unique fingerprint.

Cite this