The effect of short stature, portal hypertension, and cholestasis on growth hormone resistance in children with liver disease

Chronic liver disease is associated with GH resistance, which is characteri zed by high circulating GH and low insulin-like growth factor I (IGF-I) con centrations. Standard GH replacement has no effect on serum IGF-I in pediat ric liver disease. The aims were to examine whether GH resistance can be ov ercome by supraphysiological GH and to determine whether GH resistance wors ens with the progression of liver disease. Thirty children, divided into five groups whose liver disease was at clinic ally different stages, were studied. They were given 0.2 IU/kg.day GH for 4 days and then 0.4 IU/kg.day for the next 4 days. Serum IGF-I and binding p roteins (IGFBPs) were measured by immunoassay. IGF-I was lower in all study groups than in normal controls. IGF-I, IGFBP-3 , and acid-labile subunit rose in response to GH. The magnitude of the resp onse reflected nutritional status and liver dysfunction; in particular, por tal hypertension was associated with a poor IGF-I response. There was no ch ange in IGFBP-2. GH resistance begins early in the natural history of childhood liver diseas e and develops with the progression of liver disease, particularly with por tal hypertension. It may be partially overcome by supraphysiological GH adm inistration, but the effect becomes smaller with worsening liver disease.