Browse by author
Lookup NU author(s): Dr Stephen Ball
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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.
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
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
Altmetrics provided by Altmetric