title: 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.
  
  
  METHODS
  An evaluation of the standard clinical practice at one institution.
  
  
  METHODS
  Ninety-one patients with Cushing's syndrome: 57 pituitary-dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome.
  
  
  METHODS
  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.
authors.affiliation: Department of Endocrinology, St Bartholomew's Hospital, London, UK.
authors.forename: J A
authors.initials: JA
authors.lastname: Verhelst
authors.forename: P J
authors.initials: PJ
authors.lastname: Trainer
authors.forename: T A
authors.initials: TA
authors.lastname: Howlett
authors.forename: L
authors.initials: L
authors.lastname: Perry
authors.forename: L H
authors.initials: LH
authors.lastname: Rees
authors.forename: A B
authors.initials: AB
authors.lastname: Grossman
authors.forename: J A
authors.initials: JA
authors.lastname: Wass
authors.forename: G M
authors.initials: GM
authors.lastname: Besser
mesh_terms: D000182:ACTH Syndrome, Ectopic / Q000097:blood / Q000188:drug therapy; D000236:Adenoma / Q000097:blood; D000293:Adolescent; D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000188:drug therapy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000097:blood / Q000188:drug therapy; D003350:Cortodoxone / Q000097:blood; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy*; D003864:Depression, Chemical; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008797:Metyrapone / Q000627:therapeutic use*; D008875:Middle Aged; D013997:Time Factors
chemical_list: D000324:Adrenocorticotropic Hormone; D003350:Cortodoxone; D006854:Hydrocortisone; D008797:Metyrapone