title: Growth hormone replacement normalizes impaired fibrinolysis: new insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency.
abstract: BACKGROUND
  Cardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far.
  
  
  OBJECTIVE
  To investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement.
  
  
  METHODS
  Hospital based, interventional, prospective study.
  
  
  METHODS
  Twenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI).
  
  
  METHODS
  Anthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH.
  
  
  RESULTS
  At baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4-13.5) to 22.0(9.0-33.0) nmol/l after one month of treatment; p<0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4-2.6) to 1.9(0.5-8.8) after one year of treatment; p<0.01].
  
  
  CONCLUSIONS
  Growth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications.
authors.affiliation: Clinic of Endocrinology, Clinical Center of Serbia and Medical Faculty, University of Belgrade, Belgrade, Serbia. Electronic address: draganamiljic@yahoo.com.
authors.forename: D
authors.initials: D
authors.lastname: Miljic
authors.forename: P
authors.initials: P
authors.lastname: Miljic
authors.forename: M
authors.initials: M
authors.lastname: Doknic
authors.forename: S
authors.initials: S
authors.lastname: Pekic
authors.forename: M
authors.initials: M
authors.lastname: Stojanovic
authors.forename: G
authors.initials: G
authors.lastname: Cvijovic
authors.forename: D
authors.initials: D
authors.lastname: Micic
authors.forename: V
authors.initials: V
authors.lastname: Popovic
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004393:Dwarfism, Pituitary / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005500:Follow-Up Studies; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007018:Hypopituitarism / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone
keywords: Endothelial t-PA; Fibrinolysis; GH deficiency; GH replacement; Vascular risk in hypopituitarism