GROWTH-HORMONE INSENSITIVITY ASSOCIATED WITH ELEVATED CIRCULATING GROWTH HORMONE-BINDING PROTEIN IN CHILDREN WITH ALAGILLE SYNDROME AND SHORT STATURE

The purpose of this study was to assess GH sensitivity in children wit h Alagille syndrome (syndromic intrahepatic bile duct paucity) by exam ining their response to short term administration of recombinant human GH (rhGH). Serum levels of insulin-like growth factor-I (IGF-I) were low despite elevated overnight integrated serum GH concentrations. Adm inistration of rhGH (0.05 mg/kg-day for 3 days) to four growth-retarde d children with Alagille syndrome did not significantly alter the seru m concentrations of IGF-I and insulin, blood urea nitrogen, or urinary calcium excretion. In contrast, circulating IGF-I increased 2-fold in two children with Alagille syndrome and normal stature. In the contro l group, consisting of when prepubertal children with GH deficiency, t he predicted changes in response to rhGH in serum concentrations of IG F-I and insulin, urea nitrogen, and urinary calcium excretion were obs erved. Serum GH-binding protein levels, measured by a ligand-mediated immunofunctional assay, were significantly higher in children with Ala gille syndrome than in children with cirrhosis or GH deficiency. We co nclude that growth-retarded children with Alagille syndrome are insens itive to GH. The growth disturbances and metabolic defects may be due in part to failure to increase IGF-I concentrations in response to GH, implying that growth-retarded children with Alagille syndrome may ben efit from IGF-I treatment.