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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.

journal_name

Clin Endocrinol (Oxf)

journal_title

Clinical endocrinology

authors

Verhelst JA,Trainer PJ,Howlett TA,Perry L,Rees LH,Grossman AB,Wass JA,Besser GM

doi

10.1111/j.1365-2265.1991.tb03517.x

keywords:

subject

Has Abstract

pub_date

1991-08-01 00:00:00

pages

169-78

issue

eissn

0300-0664

issn

1365-2265

journal_volume

pub_type

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