The Effect of Short Stature, Portal Hypertension, and Cholestasis on Growth Hormone Resistance in Children with Liver Disease

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Abstract
Chronic liver disease is associated with GH resistance, which is characterized by high circulating GH and low insulin-like growth factor I (IGF-I) concentrations. Standard GH replacement has no effect on serum IGF-I in pediatric liver disease. The aims were to examine whether GH resistance can be overcome by supraphysiologi- cal GH and to determine whether GH resistance worsens with the progression of liver disease. Thirty children, divided into five groups whose liver disease was at clinically different stages, were studied. They were given 0.2 IU/kgzday GH for 4 days and then 0.4 IU/kgzday for the next 4 days. Serum IGF-I and binding proteins (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 mag- nitude of the response reflected nutritional status and liver dysfunc- tion; in particular, portal hypertension was associated with a poor IGF-I response. There was no change in IGFBP-2. GH resistance begins early in the natural history of childhood liver disease and develops with the progression of liver disease, particu- larly with portal hypertension. It may be partially overcome by su- praphysiological GH administration, but the effect becomes smaller with worsening liver disease. (J Clin Endocrinol Metab 84: 3277- 3282, 1999)

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