Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome.

Verhelst, J; Trainer, P; Howlett, T; Perry, L; Rees, L; Grossman, A; Wass, J; Besser, G

Journal article

Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome.

Abstract:: OBJECTIVE: To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome. DESIGN: An evaluation of the standard clinical practice at one institution. PATIENTS: Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome. MEASUREMENTS: The acute response to metyrapone was assessed by measuring cortisol, 11-desoxycortisol and ACTH at 0, 1, 2, 3, 4 hours after a test dose of 750 mg of metyrapone. The longer-term effect of metyrapone was judged by measuring serum cortisol at 0900, 1200, 1500, 1800, 2100 and sometimes 2400 h and calculating a mean. RESULTS: A test dose of 750 mg of metyrapone decreased serum cortisol levels within 2 hours in all groups of patients and this effect was sustained at 4 hours. At the same time, serum 11-desoxycortisol levels increased in all patients, while plasma ACTH increased in patients with pituitary Cushing's disease and the ectopic ACTH-syndrome. Fifty-three patients with Cushing's disease were followed on short-term metyrapone therapy (1 to 16 weeks) before other more definitive therapy. Their mean cortisol levels (median 654 nmol/l, range 408-2240) dropped to the target range of less than 400 nmol/l in 40 patients (75%) on a median metyrapone dose of 2250 mg/day (range 750-6000). Metyrapone was given long term in 24 patients with Cushing's disease who had been given pituitary irradiation, for a median of 27 months (range 3-140) with adequate control of hypercortisolaemia in 20 (83%). In 10 patients with adrenocortical adenomas and six with adrenocortical carcinomas, metyrapone in a median dose of 1750 mg/day (range 750-6000) reduced their mean cortisol levels (median 847 nmol/l, range 408-2000) to less than 400 nmol/l in 13 patients (81%). In 18 patients with the ectopic ACTH-syndrome the 'mean cortisol levels', obtained from five or six samples on the test day (median 1023 nmol/l, range 823-6354) were reduced to less than 400 nmol/l in 13 patients (70%), on a median dose of 4000 mg/day (range 1000-6000). Reduction of cortisol levels was clearly associated with clinical and biochemical improvement. The medication was well tolerated. Transient hypoadrenalism and hirsutism were unusual but were the most common side-effects. CONCLUSIONS: In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.

Publication status:: Published

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APA Style

Verhelst, J., Trainer, P., Howlett, T., Perry, L., Rees, L., Grossman, A., Wass, J., & Besser, G. (1991). Short and long-term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome. Clinical Endocrinology, 35(2), 169–178.

MLA Style

Verhelst, J., et al. “Short and Long-Term Responses to Metyrapone in the Medical Management of 91 Patients with Cushing's Syndrome.” Clinical Endocrinology, vol. 35, no. 2, 1991, pp. 169–78.

Chicago Style

Verhelst, J, P Trainer, T Howlett, L Perry, L Rees, A Grossman, J Wass, and G Besser. 1991. “Short and Long-Term Responses to Metyrapone in the Medical Management of 91 Patients with Cushing's Syndrome.” Clinical Endocrinology 35 (2): 169–78.
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