title: Glucocorticoid replacement therapy and fibrinolysis in patients with hypopituitarism.
abstract: BACKGROUND
  Hypopituitarism is associated with increased cardiovascular mortality, and it has been suggested that unphysiological glucocorticoid replacement regimens might contribute to this risk. Traditional glucocorticoid replacement regimens have often led to excessive serum cortisol levels. The hypercortisolaemia of Cushing's syndrome is associated with an increased risk of thromboembolism.
  
  
  OBJECTIVE
  To examine whether short-term higher-dose hydrocortisone replacement regimens adversely affect the fibrinolytic system.
  
  
  METHODS
  Crossover study comparing tailored low-dose (LD) glucocorticoid regimen (mean, 17·5 mg hydrocortisone daily), with a traditional high-dose (HD, 30-mg hydrocortisone daily) regimen for 2 weeks.
  
  
  METHODS
  Ten patients with hypopituitarism and ACTH deficiency - median (range) age, 59 (41-75) years - and 10 age- and sex-matched controls. Nine patients had growth hormone deficiency (five replaced), nine patients had TSH deficiency (nine replaced), eight had gonadotrophin deficiency (five replaced). During the study, other pituitary hormone replacement therapy remained unchanged. Patients with acromegaly and Cushing's syndrome were excluded.
  
  
  METHODS
  Hourly serum cortisol for 11 h, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen levels after 2 weeks of treatment with both LD and HD regimens.
  
  
  RESULTS
  No overall significant differences were found between the three groups using the Kruskal-Wallis test: PAI-1: [median (range)] HD, 25 (5-53) ng/ml; LD, 21 (4-56) ng/ml; controls, 27 (8-51); P = 0·3; tPA: HD, 10 (5-15) ng/ml; LD, 10 (4-13) ng/ml; controls 10 (3-13); P = 0·46; and fibrinogen: HD, 2·5 (1·8-3·5) g/l; LD, 3·0 (2·3-4·4) g/l; controls, 2·6 (1·6-3·2): P = 0·97 In addition, no significant differences between HD and LD using Wilcoxon's paired test; PAI-1 (P = 0·91), tPAag (P = 0·47) and fibrinogen (P = 0·09).
  
  
  CONCLUSIONS
  An increased dose of hydrocortisone for 2 weeks creates excessive glucocorticoid exposure, but does not significantly affect fibrinolytic-coagulation parameters.
authors.affiliation: Department of Diabetes and Endocrinology, Bradford Teaching Hospitals NHS Foundation Trust, Duckworth Lane, Bradford, UK. steve.peacey@bthft.nhs.uk
authors.forename: Steven R
authors.initials: SR
authors.lastname: Peacey
authors.forename: Dianne
authors.initials: D
authors.lastname: Wright
authors.forename: Mo
authors.initials: M
authors.lastname: Aye
authors.forename: Robert
authors.initials: R
authors.lastname: Moisey
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000009:adverse effects; D007018:Hypopituitarism / Q000097:blood* / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D005938:Glucocorticoids; D006854:Hydrocortisone