Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients

Eleni Daniel; Simon Aylwin; Omar Mustafa; Steve Ball; Atif Munir; Kristien Boelaert; Vasileios Chortis; Daniel J Cuthbertson; Christina Daousi; Surya P Rajeev; Julian Davis; Kelly Cheer; William Drake; Kirun Gunganah; Ashley Grossman; Mark Gurnell; Andrew S Powlson; Niki Karavitaki; Isabel Huguet; Tara Kearney; Kumar Mohit; Karim Meeran; Neil Hill; Aled Rees; Andrew J Lansdown; Peter J Trainer; Anna-Elisabeth H Minder; John Newell-Price

doi:10.1210/jc.2015-2616

Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients

Eleni Daniel, Simon Aylwin, Omar Mustafa, Steve Ball, Atif Munir, Kristien Boelaert, Vasileios Chortis, Daniel J Cuthbertson, Christina Daousi, Surya P Rajeev, Julian Davis, Kelly Cheer, William Drake, Kirun Gunganah, Ashley Grossman, Mark Gurnell, Andrew S Powlson, Niki Karavitaki, Isabel Huguet, Tara KearneyKumar Mohit, Karim Meeran, Neil Hill, Aled Rees, Andrew J Lansdown, Peter J Trainer, Anna-Elisabeth H Minder, John Newell-Price

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Abstract

BACKGROUND: Cushing's syndrome 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: To assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with Cushing's syndrome.

DESIGN: Retrospective, multicenter.

SETTING: Thirteen university hospitals.

PATIENTS: 195 patients with proven Cushing's syndrome: 115 Cushing's disease (CD), 37 ectopic ACTH (EAS); 43 ACTH-independent disease (Adrenocortical Cancer [ACC] 10; adrenal adenoma [AA] 30; ACTH-independent adrenal hyperplasia (3) Measurements: Biochemical parameters of activity of Cushing's syndrome: mean serum cortisol day-curve (CDC) (target 150-300nmol/L); 09.00h serum cortisol; 24h-UFC.

RESULTS: 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 months, range 3 days to 11.6 years). There were significant improvements on metyrapone - first evaluation to last review: CDC [91 patients, 722.9nmol/L (26.2μg/dl) vs. 348.6nmol/L (12.6μg/dl), p<0001]; 09.00h cortisol [123 patients, 882.9nmol/L (32.0μg/dl) vs. 491.1nmol/L (17.8μg/dl), p<0.0001]; UFC [37 patients, 1483nmol/24h (537μg/24h) vs. 452.6nmol/24h (164μg/24h), p=0.003]. Overall control at last review: 55%, 43%, 46% and 76% of patients who had CDCs, UFCs, 09.00h cortisol <331nmol/L (12.0μg/dl) and 09.00h cortisol <ULN/600nmol/L (21.7μg/dl). Median final dose: CD 1375mg; EAS 1500mg; benign adrenal disease 750mg; ACC 1250mg. Adverse events occurred in 25% of patients, mostly mild GI 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 Cushing's syndrome.

Original language	English
Article number	jc20152616
Journal	The Journal of clinical endocrinology and metabolism
Volume	100
Issue number	11
Early online date	9 Sept 2015
DOIs	https://doi.org/10.1210/jc.2015-2616
Publication status	E-pub ahead of print - 9 Sept 2015

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Daniel, E., Aylwin, S., Mustafa, O., Ball, S., Munir, A., Boelaert, K., Chortis, V., Cuthbertson, D. J., Daousi, C., Rajeev, S. P., Davis, J., Cheer, K., Drake, W., Gunganah, K., Grossman, A., Gurnell, M., Powlson, A. S., Karavitaki, N., Huguet, I., ... Newell-Price, J. (2015). Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients. The Journal of clinical endocrinology and metabolism, 100(11), Article jc20152616. Advance online publication. https://doi.org/10.1210/jc.2015-2616

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abstract = "BACKGROUND: Cushing's syndrome 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: To assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with Cushing's syndrome.DESIGN: Retrospective, multicenter.SETTING: Thirteen university hospitals.PATIENTS: 195 patients with proven Cushing's syndrome: 115 Cushing's disease (CD), 37 ectopic ACTH (EAS); 43 ACTH-independent disease (Adrenocortical Cancer [ACC] 10; adrenal adenoma [AA] 30; ACTH-independent adrenal hyperplasia (3) Measurements: Biochemical parameters of activity of Cushing's syndrome: mean serum cortisol day-curve (CDC) (target 150-300nmol/L); 09.00h serum cortisol; 24h-UFC.RESULTS: 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 months, range 3 days to 11.6 years). There were significant improvements on metyrapone - first evaluation to last review: CDC [91 patients, 722.9nmol/L (26.2μg/dl) vs. 348.6nmol/L (12.6μg/dl), p<0001]; 09.00h cortisol [123 patients, 882.9nmol/L (32.0μg/dl) vs. 491.1nmol/L (17.8μg/dl), p<0.0001]; UFC [37 patients, 1483nmol/24h (537μg/24h) vs. 452.6nmol/24h (164μg/24h), p=0.003]. Overall control at last review: 55%, 43%, 46% and 76% of patients who had CDCs, UFCs, 09.00h cortisol <331nmol/L (12.0μg/dl) and 09.00h cortisol <ULN/600nmol/L (21.7μg/dl). Median final dose: CD 1375mg; EAS 1500mg; benign adrenal disease 750mg; ACC 1250mg. Adverse events occurred in 25% of patients, mostly mild GI 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 Cushing's syndrome.",

author = "Eleni Daniel and Simon Aylwin and Omar Mustafa and Steve Ball and Atif Munir and Kristien Boelaert and Vasileios Chortis and Cuthbertson, {Daniel J} and Christina Daousi and Rajeev, {Surya P} and Julian Davis and Kelly Cheer and William Drake and Kirun Gunganah and Ashley Grossman and Mark Gurnell and Powlson, {Andrew S} and Niki Karavitaki and Isabel Huguet and Tara Kearney and Kumar Mohit and Karim Meeran and Neil Hill and Aled Rees and Lansdown, {Andrew J} and Trainer, {Peter J} and Minder, {Anna-Elisabeth H} and John Newell-Price",

year = "2015",

month = sep,

day = "9",

doi = "10.1210/jc.2015-2616",

language = "English",

volume = "100",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

publisher = "Endocrine Society",

number = "11",

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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, A-EH & Newell-Price, J 2015, 'Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients', The Journal of clinical endocrinology and metabolism, vol. 100, no. 11, jc20152616. https://doi.org/10.1210/jc.2015-2616

TY - JOUR

T1 - Effectiveness of metyrapone in treating Cushing's Syndrome

T2 - a retrospective multicenter study in 195 patients

AU - Daniel, Eleni

AU - Aylwin, Simon

AU - Mustafa, Omar

AU - Ball, Steve

AU - Munir, Atif

AU - Boelaert, Kristien

AU - Chortis, Vasileios

AU - Cuthbertson, Daniel J

AU - Daousi, Christina

AU - Rajeev, Surya P

AU - Davis, Julian

AU - Cheer, Kelly

AU - Drake, William

AU - Gunganah, Kirun

AU - Grossman, Ashley

AU - Gurnell, Mark

AU - Powlson, Andrew S

AU - Karavitaki, Niki

AU - Huguet, Isabel

AU - Kearney, Tara

AU - Mohit, Kumar

AU - Meeran, Karim

AU - Hill, Neil

AU - Rees, Aled

AU - Lansdown, Andrew J

AU - Trainer, Peter J

AU - Minder, Anna-Elisabeth H

AU - Newell-Price, John

PY - 2015/9/9

Y1 - 2015/9/9

N2 - BACKGROUND: Cushing's syndrome 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: To assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with Cushing's syndrome.DESIGN: Retrospective, multicenter.SETTING: Thirteen university hospitals.PATIENTS: 195 patients with proven Cushing's syndrome: 115 Cushing's disease (CD), 37 ectopic ACTH (EAS); 43 ACTH-independent disease (Adrenocortical Cancer [ACC] 10; adrenal adenoma [AA] 30; ACTH-independent adrenal hyperplasia (3) Measurements: Biochemical parameters of activity of Cushing's syndrome: mean serum cortisol day-curve (CDC) (target 150-300nmol/L); 09.00h serum cortisol; 24h-UFC.RESULTS: 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 months, range 3 days to 11.6 years). There were significant improvements on metyrapone - first evaluation to last review: CDC [91 patients, 722.9nmol/L (26.2μg/dl) vs. 348.6nmol/L (12.6μg/dl), p<0001]; 09.00h cortisol [123 patients, 882.9nmol/L (32.0μg/dl) vs. 491.1nmol/L (17.8μg/dl), p<0.0001]; UFC [37 patients, 1483nmol/24h (537μg/24h) vs. 452.6nmol/24h (164μg/24h), p=0.003]. Overall control at last review: 55%, 43%, 46% and 76% of patients who had CDCs, UFCs, 09.00h cortisol <331nmol/L (12.0μg/dl) and 09.00h cortisol <ULN/600nmol/L (21.7μg/dl). Median final dose: CD 1375mg; EAS 1500mg; benign adrenal disease 750mg; ACC 1250mg. Adverse events occurred in 25% of patients, mostly mild GI 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 Cushing's syndrome.

AB - BACKGROUND: Cushing's syndrome 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: To assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with Cushing's syndrome.DESIGN: Retrospective, multicenter.SETTING: Thirteen university hospitals.PATIENTS: 195 patients with proven Cushing's syndrome: 115 Cushing's disease (CD), 37 ectopic ACTH (EAS); 43 ACTH-independent disease (Adrenocortical Cancer [ACC] 10; adrenal adenoma [AA] 30; ACTH-independent adrenal hyperplasia (3) Measurements: Biochemical parameters of activity of Cushing's syndrome: mean serum cortisol day-curve (CDC) (target 150-300nmol/L); 09.00h serum cortisol; 24h-UFC.RESULTS: 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 months, range 3 days to 11.6 years). There were significant improvements on metyrapone - first evaluation to last review: CDC [91 patients, 722.9nmol/L (26.2μg/dl) vs. 348.6nmol/L (12.6μg/dl), p<0001]; 09.00h cortisol [123 patients, 882.9nmol/L (32.0μg/dl) vs. 491.1nmol/L (17.8μg/dl), p<0.0001]; UFC [37 patients, 1483nmol/24h (537μg/24h) vs. 452.6nmol/24h (164μg/24h), p=0.003]. Overall control at last review: 55%, 43%, 46% and 76% of patients who had CDCs, UFCs, 09.00h cortisol <331nmol/L (12.0μg/dl) and 09.00h cortisol <ULN/600nmol/L (21.7μg/dl). Median final dose: CD 1375mg; EAS 1500mg; benign adrenal disease 750mg; ACC 1250mg. Adverse events occurred in 25% of patients, mostly mild GI 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 Cushing's syndrome.

U2 - 10.1210/jc.2015-2616

DO - 10.1210/jc.2015-2616

M3 - Article

C2 - 26353009

SN - 0021-972X

VL - 100

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 11

M1 - jc20152616

ER -

Effectiveness of metyrapone in treating Cushing's Syndrome: a retrospective multicenter study in 195 patients

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