title: Pituitary-independent effect of octreotide on IGF1 generation.
abstract: BACKGROUND
  Somatostatin analogues are frequently used for medical treatment of acromegaly. The rationale for their use is based on the inhibition of pituitary GH secretion; however, there is in vitro evidence that octreotide also acts to inhibit hepatic IGF1 generation.
  
  
  OBJECTIVE
  We studied the pituitary-independent effects of octreotide on IGF1 generation in 11 severely GH-deficient (GHD) humans (age 38, range 23-52; seven males; body mass index 24.7+/-3 kg/m(2); peak-stimulated GH <3 microg/l; 3+/-1 pituitary hormone deficiencies) on a stable dose of GH replacement (0.4+/-0.1 mg) for at least 6 months. Patients were studied before and after 50 microg of s.c. octreotide three times a day for 7 days.
  
  
  RESULTS
  At study entry, all patients had total IGF1 within age- and gender-related reference range (SDS 0.4+/-1.0). Octreotide treatment resulted in a significant decrease in total IGF1 (by 18%, 208+/-89 vs 173+/-62 microg/l, P=0.04), free IGF1 (by 13%, 0.83+/-0.36 vs 0.70+/-0.33 microg/l, P=0.01) and IGFBP3 (6%, 4475+/-745 vs 4209+/-912 microg/l, P=0.02). Octreotide suppressed fasting insulin from 8.1+/-3.4 to 6.3+/-4.1 mU/l (P=0.01) and was associated with an increase in fasting glucose from 5.2+/-0.9 to 5.8+/-0.9 mmol/l (P<0.01). IGFBP1 increased by 84% from 42+/-26 to 95+/-52 microg/l (P=0.04).
  
  
  CONCLUSIONS
  Our study demonstrates that octreotide induces a significant decrease in IGF1 in severely GHD adults on a fixed dose of GH replacement. This is the evidence for a non-pituitary action of octreotide on the GH/IGF1 axis, most likely by antagonising the action of GH on hepatic IGF1 generation and indirectly, by suppressing insulin secretion.
authors.affiliation: Department of Endocrinology, Christie Hospital, Manchester, UK. anapokrajac@yahoo.co.uk
authors.forename: Ana
authors.initials: A
authors.lastname: Pokrajac
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Trainer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis / Q000235:genetics; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology*; D010902:Pituitary Gland / Q000502:physiology*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D015282:Octreotide