We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients.
- Authors
Daniel, Eleni; Aylwin, Simon; Mustafa, Omar; Ball, Steve; Munir, Atif; Boelaert, Kristien; Chortis, Vasileios; Cuthbertson, Daniel J; Daousi, Christina; Rajeev, Surya P; Davis, Julian; Cheer, Kelly; Drake, William; Gunganah, Kirun; Grossman, Ashley; Gurnell, Mark; Powlson, Andrew S; Karavitaki, Niki; Huguet, Isabel; Kearney, Tara
- Abstract
<bold>Background: </bold>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.<bold>Objective: </bold>The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS.<bold>Design: </bold>This was designed as a retrospective, multicenter study.<bold>Setting: </bold>Thirteen University hospitals were studied.<bold>Patients: </bold>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).<bold>Measurements: </bold>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).<bold>Results: </bold>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 μg/dL] vs 348.6 nmol/L [12.6 μg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 μg/dL] vs 491.1 nmol/L [17.8 μg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 μg/24 h] vs 452.6 nmol/24 h [164 μg/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 μg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 μg/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.<bold>Conclusions: </bold>Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS.
- Subjects
COMBINATION drug therapy; COMPARATIVE studies; CUSHING'S syndrome; DOSE-effect relationship in pharmacology; ENZYME inhibitors; HYDROCORTISONE; RESEARCH methodology; MEDICAL cooperation; PITUITARY tumors; PYRIDINE; RESEARCH; EVALUATION research; TREATMENT effectiveness; RETROSPECTIVE studies; THERAPEUTICS
- Publication
Journal of Clinical Endocrinology & Metabolism, 2015, Vol 100, Issue 11, p4146
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2015-2616