학술논문
Effectiveness of Metyrapone in Treating Cushingʼs Syndrome: A Retrospective Multicenter Study in 195 Patients
Document Type
Academic Journal
Author
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; Mohit, Kumar; Meeran, Karim; Hill, Neil; Rees, Aled; Lansdown, Andrew J.; Trainer, Peter J.; Minder, Anna-Elisabeth H.; Newell-Price, John
Source
The Journal of Clinical Endocrinology & Metabolism. Nov 01, 2015 100(11):4146-4154
Subject
Language
English
ISSN
0021-972X
Abstract
BACKGROUND:: Cushingʼs 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 Cushingʼs 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 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: Cushingʼs 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.