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

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.

• Authors: 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
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 100 Issue 11 Pg. 4146-54 (Nov 2015) ISSN: 1945-7197 [Electronic] United States
• PMID: 26353009 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Hydrocortisone
• Metyrapone

Topics

• 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, adverse effects, therapeutic use)
• Humans
• Hydrocortisone (blood, urine)
• Infant
• Male
• Metyrapone (administration & dosage, adverse effects, therapeutic use)
• Middle Aged
• Pituitary Neoplasms (drug therapy)
• Retrospective Studies
• Treatment Outcome
• Young Adult