title: Insulin-like growth factor-I and insulin-like growth factor binding protein-3 cotreatment versus insulin-like growth factor-I alone in two brothers with growth hormone insensitivity syndrome: effects on insulin sensitivity, body composition and linear growth.
abstract: OBJECTIVE
  Growth hormone insensitivity syndrome (GHIS) is caused by a defective growth hormone receptor (GHR) and is associated with insulin-like growth factor-I (IGF-I) deficiency, severely short stature and, from adolescence, fasting hyperglycemia and obesity. We studied the effects of treatment with IGF-I in either a 1:1 molar complex with IGFBP-3 (IGF-I/BP-3-Tx) or with IGF-I alone (IGF-I-Tx) on metabolism and linear growth.
  
  
  METHODS
  Two brothers, compound heterozygous for a GHR gene defect, were studied. After 8 months without treatment, we examined the short- and long-term effects of IGF-I/BP-3-Tx and, subsequently, IGF-I-Tx on 12-hour overnight levels of IGF-I, GH, insulin, IGFBP-1, insulin sensitivity by hyperinsulinemic euglycemic clamp, body composition by dual-energy X-ray absorptiometry and linear growth.
  
  
  RESULTS
  Mean overnight levels of insulin decreased and IGFBP-1, a measure of hepatic insulin sensitivity, increased on both regimens, but was more pronounced on IGF-I-Tx. Insulin sensitivity by clamp showed no consistent changes. Lean body mass increased and abdominal fat mass decreased in both subjects on IGF-I-Tx. However, the changes were inconsistent during IGF-I/BP-3-Tx. Height velocity was low without treatment, increased slightly on IGF-I/BP-3-Tx and doubled on IGF-I-Tx.
  
  
  CONCLUSIONS
  Both modalities of IGF-I improved determinants of hepatic insulin sensitivity, body composition and linear growth rate; however, IGF-I alone seemed to be more efficient.
authors.affiliation: Pediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institute and Hospital, Stockholm, Sweden. klas.ekstrom@karolinska.se
authors.forename: Klas
authors.initials: K
authors.lastname: Ekström
authors.forename: Christine
authors.initials: C
authors.lastname: Carlsson-Skwirut
authors.forename: E Martin
authors.initials: EM
authors.lastname: Ritzén
authors.forename: Peter
authors.initials: P
authors.lastname: Bang
mesh_terms: D000293:Adolescent; D001823:Body Composition / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D004338:Drug Combinations; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D046150:Laron Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage; D035781:Siblings
chemical_list: D004338:Drug Combinations; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I