title: Hypothalamic abnormalities in patients with pituitary-dependent Cushing's syndrome.
abstract: OBJECTIVE
  We aimed to investigate the pattern of 24-hour ACTH and cortisol secretion in pituitary-dependent Cushing's syndrome and to evaluate the pituitary and hypothalamic contributions to the disease.
  
  
  METHODS
  Five women with Cushing's disease (mean age 35 +/- 5 (SEM) years) and five normal female controls (mean age 25 +/- 2 years) were studied.
  
  
  METHODS
  Plasma ACTH and cortisol levels were measured every 15 minutes for 24 hours using established IRMA and RIA respectively. ACTH and cortisol mean and trough levels, pulse number and amplitude were calculated using established computer software, programmed to identify ACTH and cortisol peaks.
  
  
  RESULTS
  Patients with Cushing's disease had a twofold increase in 24-hour mean cortisol levels and a threefold increase in 24-hour mean ACTH levels (Cushing's 5.9 +/- 1.0, controls 1.9 +/- 0.2 pmol/l, P less than 0.01). This was predominantly mediated by an increase in ACTH pulse amplitude. However, 24-hour ACTH pulse number was also increased (Cushing's 15.2 +/- 2.6, controls 10.6 +/- 1.7, P less than 0.05) due to an increase in pulse number between 1800 and 2400 h. ACTH trough levels were also higher in patients with Cushing's disease (Cushing's 5.3 +/- 1.3, controls 2.3 +/- 0.2 pmol/l, P less than 0.05).
  
  
  CONCLUSIONS
  Twenty-four-hour mean plasma cortisol and ACTH levels are elevated two to three-fold in patients with Cushing's disease. The increase in ACTH pulse amplitude suggests a pituitary abnormality in patients with Cushing's disease. However, the increased ACTH pulse frequency together with elevated trough levels is interpreted as indicating coexisting hypothalamic stimulation (or loss of inhibition).
authors.affiliation: Department of Medicine, University of Birmingham, UK.
authors.forename: P M
authors.initials: PM
authors.lastname: Stewart
authors.forename: R
authors.initials: R
authors.lastname: Penn
authors.forename: R
authors.initials: R
authors.lastname: Gibson
authors.forename: R
authors.initials: R
authors.lastname: Holder
authors.forename: A
authors.initials: A
authors.lastname: Parton
authors.forename: J G
authors.initials: JG
authors.lastname: Ratcliffe
authors.forename: D R
authors.initials: DR
authors.lastname: London
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D003480:Cushing Syndrome / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007031:Hypothalamus / Q000503:physiopathology*; D008875:Middle Aged; D010902:Pituitary Gland / Q000503:physiopathology*; D012636:Secretory Rate / Q000502:physiology
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone