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

The journal of clinical endocrinology and metabolism, 2015-11, Vol.100 (11), p.4146-4154 [Peer Reviewed Journal]

Copyright © 2015 by the Endocrine Society ;Copyright © 2015 by The Endocrine Society ;ISSN: 0021-972X ;EISSN: 1945-7197 ;DOI: 10.1210/jc.2015-2616 ;PMID: 26353009

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Title:
Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients
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
Subjects: ACTH-Secreting Pituitary Adenoma - drug therapy ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Cushing Syndrome - drug therapy ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Enzyme Inhibitors - administration & dosage ; Enzyme Inhibitors - adverse effects ; Enzyme Inhibitors - therapeutic use ; Humans ; Hydrocortisone - blood ; Hydrocortisone - urine ; Infant ; Male ; Metyrapone - administration & dosage ; Metyrapone - adverse effects ; Metyrapone - therapeutic use ; Middle Aged ; Pituitary Neoplasms - drug therapy ; Retrospective Studies ; Treatment Outcome ; Young Adult
Is Part Of: The journal of clinical endocrinology and metabolism, 2015-11, Vol.100 (11), p.4146-4154
Description: 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.
Publisher: United States: Endocrine Society
Language: English
Identifier: ISSN: 0021-972X
EISSN: 1945-7197
DOI: 10.1210/jc.2015-2616
PMID: 26353009
Source: GFMER Free Medical Journals
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Effectiveness of Metyrapone in Treating Cushing's Syndrome: A Retrospective Multicenter Study in 195 Patients

Copyright © 2015 by the Endocrine Society ;Copyright © 2015 by The Endocrine Society ;ISSN: 0021-972X ;EISSN: 1945-7197 ;DOI: 10.1210/jc.2015-2616 ;PMID: 26353009

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