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Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients

Lookup NU author(s): Dr Stephen Ball

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Abstract

Background: Cushing's syndrome (CS) 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: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS.Design: This was designed as a retrospective, multicenter study.Setting: Thirteen University hospitals were studied.Patients: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3).Measurements: Measurements included biochemical parameters of activity of CS: mean serum cortisol "day-curve" (CDC) (target 150-300 nmol/L); 9 AM serum cortisol; 24-hour urinary free cortisol (UFC).Results: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 +/- 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 mu g/dL] vs 348.6 nmol/L [12.6 mu g/dL]; P < .0001); 9 AM cortisol (123 patients, 882.9 nmol/L [32.0 mu g/dL] vs 491.1 nmol/L [17.8 mu g/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 mu g/24 h] vs 452.6 nmol/24 h [164 mu g/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 AM cortisol less than 331 nmol/L (12.0 mu g/dL), and 9 AM cortisol less than upper limit of normal/600 nmol/L (21.7 mu g/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal 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 CS.


Publication metadata

Author(s): Daniel E, Aylwin S, Mustafa O, Ball S, Munir A, Boelaert K, Chortis V, Cuthbertson DJ, Daousi C, Rajeev SP, Davis J, Cheer K, Drake W, Gunganah K, Grossman A, Gurnell M, Powlson AS, Karavitaki N, Huguet I, Kearney T, Mohit K, Meeran K, Hill N, Rees A, Lansdown AJ, Trainer PJ, Minder AEH, Newell-Price J

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology & Metabolism

Year: 2015

Volume: 100

Issue: 11

Pages: 4146-4154

Print publication date: 01/11/2015

Online publication date: 09/09/2015

Acceptance date: 02/09/2015

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: The Endocrine Society

URL: http://dx.doi.org/10.1210/jc.2015-2616

DOI: 10.1210/jc.2015-2616


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