ACQUIRED GROWTH-HORMONE RESISTANCE IN PATIENTS WITH HYPERCATABOLISM

Sepsis, surgery and critical illness are associated with an increased catabolic rate, which if prolonged delays recovery and increases morbi dity and mortality. There is evidence that changes in the GH/IGF-I axi s are permissive to protein catabolism. Critically ill, septic patient s have high basal levels of GH, low levels of IGF-I and its carrier bi nding protein IGFBP-3, high levels of an inhibitory binding protein, I GFBP-1, and increased serum protease activity which reduces the affini ty of IGFBP-3 for IGF-I. Overall there is a reduction in the indirect IGF-I-mediated anabolic actions of GH and an increase in the direct ca tabolic actions of GH. These physiological changes may be adaptive whe n a sick patient is fasting; however, the availability of modem intens ive care means that these changes are no longer an advantage. GH and I GF-I, in pharmacological doses, promote positive nitrogen balance, in both animal models and man. Preliminary studies with IGF-I in postsurg ical patients suggest that it may provide a practical therapy. Future studies need to focus on outcome measures in relation to the use of GH and IGF-I as anabolic therapies.