Daniel, E. orcid.org/0000-0003-4699-420X, Aylwin, S., Mustafa, O. et al. (25 more authors) (2015) Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 100 (11). pp. 4146-4154. ISSN 0021-972X
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 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.
Conclusions: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 the Endocrine Society. This is an author produced version of a paper subsequently published in Journal of Clinical Endocrinology and Metabolism. Uploaded in accordance with the publisher's self-archiving policy. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number HRA PHARMA, FRANCE UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 May 2017 09:52 |
Last Modified: | 28 Mar 2018 23:14 |
Published Version: | https://doi.org/10.1210/jc.2015-2616 |
Status: | Published |
Publisher: | Oxford University Press |
Refereed: | Yes |
Identification Number: | 10.1210/jc.2015-2616 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:115220 |