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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 J+Clin+Endocrinol+Metab
2015 ; 100
(11
): 4146-54
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Effectiveness of Metyrapone in Treating Cushing s Syndrome: A Retrospective
Multicenter Study in 195 Patients
#MMPMID26353009
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 AE
; Newell-Price J
J Clin Endocrinol Metab
2015[Nov]; 100
(11
): 4146-54
PMID26353009
show ga
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 ?g/dL] vs 348.6 nmol/L [12.6
?g/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 ?g/dL] vs
491.1 nmol/L [17.8 ?g/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537
?g/24 h] vs 452.6 nmol/24 h [164 ?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 ?g/dL), and 9 am cortisol less than upper limit of
normal/600 nmol/L (21.7 ?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.
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