title: The growth hormone-insulin-like growth factor axis in adult patients with Prader Willi syndrome.
abstract: OBJECTIVE
  Prader Willi syndrome (PWS) is a genetic disorder characterised by short stature, extreme obesity, body composition abnormalities and behavioural problems. Hypothalamic dysfunction with low growth hormone (GH) secretion and low levels of GH-related growth factors is common. However, the interpretation is difficult because of the concomitant obesity, which in itself has important effects on the GH-IGF-I-system. We therefore analysed free and total IGF-I, total IGF-II and their binding proteins in obese PWS adults before and during 12 months GH treatment. Seventeen adults, 9 men and 8 women, 17-32 years of age with a mean BMI of 35+/-2.3 kg/m(2) participated. All had clinical PWS. They were randomized to treatment with placebo or GH (Genotropin, Pharmacia) 0.8 IU (0.26 mg) for one month, and then 1.6 IU (0.53 mg) for 5 months. Subsequently GH doses were individually titrated to normal levels for age. Overnight fasting levels of free and total IGF-I, total IGF-II, GH-binding protein (GHBP) and IGF-binding proteins (IGFBP)-1, -2 and -3 were measured by RIA at baseline and after 6 and 12 months GH treatment. Mean levels+/-SEM of free IGF-I were 1.02+/-0.12 microg/L as compared to a reference value of 0.95+/-0.15 microg/L, while mean total IGF-I was 128+/-15 microg/L (212+/-14 microg/L) and total IGF-II was 704+/-45 microg/L (825+/-34 microg/L). Mean IGFBP-2 158+/-24 microg/L (764+/-72 microg/L) and GHBP 2.65 nmol/L (1.71+/-0.3 1nmol/L). IGFBP-1 and IGFBP-3 levels were normal. Both free and total IGF-I increased significantly during GH treatment, while IGF- and GH-binding proteins as well as total IGF-II remained unchanged.
  
  
  CONCLUSIONS
  Low total IGF-I and, in relation to the obesity, low free IGF-I, low total IGF-II and non-suppressed IGFBP-1 are consistent with the concept that PWS patients have a partial GH deficiency, which can be corrected by GH replacement.
authors.affiliation: Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm 17176, Sweden. charlotte.hoybye@ks.se
authors.forename: Charlotte
authors.initials: C
authors.lastname: Höybye
authors.forename: Jan
authors.initials: J
authors.lastname: Frystyk
authors.forename: Marja
authors.initials: M
authors.lastname: Thorén
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005260:Female; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000378:metabolism* / Q000627:therapeutic use*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D009765:Obesity / Q000378:metabolism; D011218:Prader-Willi Syndrome / Q000188:drug therapy* / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I