title: One year growth hormone replacement therapy does not alter colonic epithelial cell proliferation in growth hormone deficient adults.
abstract: OBJECTIVE
  Increased colonic epithelial cell proliferation has been found in various conditions associated with increased risk of colorectal cancer including acromegaly. In a placebo-controlled study we determined the effect of growth hormone (GH) replacement therapy in GH deficient adults on the colonic epithelial proliferation rate.
  
  
  METHODS
  Sixteen GH deficient adults were randomised to low dose GH therapy (1 U (0.5 mg) subcutaneously per day, n = 5), high dose GH therapy (2 U daily, n = 5) or placebo (n = 6) during 6 months. Thereafter, all patients were treated with 2 U of GH daily during a 6-months open extension period.
  
  
  METHODS
  Plasma Insulin-like growth hormone I (IGF-I) and IGF binding protein 3 (IGF BP3) concentrations were measured using commercial RIA kits. The colonic epithelial proliferation rate, expressed as overall crypt labelling index (LI) using 5-bromo-2'-deoxyuridine (BrdU) immunostaining, was determined at baseline, after 6 months treatment and at the end of the 6 months open extension period.
  
  
  RESULTS
  IGF-I rose from 8.9 +/- 6.7 to 34.6 +/- 20.0 nmol/l after 6 months in 8 GH treated patients (P < 0.01 from baseline; P < 0.01 from change with placebo). In the extension study, plasma IGF-I was also increased in the patients who previously received placebo (P < 0.02, n = 5). LI was evaluable in 14 biopsies at baseline, in 16 after 6 months and in 14 after 12 months. Overall crypt LI did not change in 8 GH treated patients after 6 months (P > 0.40 from baseline; P > 0.80 from change with placebo). In the extension study, overall crypt LI was also unchanged in those patients who received GH after placebo (n = 5, P > 0.40) and in those who continued GH replacement (n = 9, P > 0.60; P > 0.80 from change in initially placebo treated patients). Separate evaluation of the LI at the basal, mid and luminal portions of the colonic crypts also did not reveal any effect of GH treatment on BrdU labelling.
  
  
  CONCLUSIONS
  Six to 12 months of GH replacement therapy, aimed to increase plasma IGF-I into the (high) physiological range, does not adversely affect colonic epithelial cell proliferation as a biomarker for the risk of development of colorectal cancer.
authors.affiliation: Department of Internal Medicine, Divisions of; Endocrinology, University Hospital Groningen, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Beentjes
authors.forename: B A
authors.initials: BA
authors.lastname: van Gorkom
authors.forename: W J
authors.initials: WJ
authors.lastname: Sluiter
authors.forename: E G
authors.initials: EG
authors.lastname: de Vries
authors.forename: J H
authors.initials: JH
authors.lastname: Kleibeuker
authors.forename: R P
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000328:Adult; D002455:Cell Division / Q000187:drug effects; D003106:Colon / Q000187:drug effects / Q000473:pathology*; D003110:Colonic Neoplasms / Q000209:etiology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005260:Female; D013006:Growth Hormone / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use; D020249:Hormone Replacement Therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D013006:Growth Hormone