title: Acquired growth hormone resistance in patients with hypercatabolism.
abstract: Sepsis, surgery and critical illness are associated with an increased catabolic rate, which if prolonged delays recovery and increases morbidity and mortality. There is evidence that changes in the GH/IGF-I axis are permissive to protein catabolism. Critically ill, septic patients have high basal levels of GH, low levels of IGF-I and its carrier binding protein IGFBP-3, high levels of an inhibitory binding protein, IGFBP-I, and increased serum protease activity which reduces the affinity 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 catabolic actions of GH. These physiological changes may be adaptive when a sick patient is fasting; however, the availability of modern intensive care means that these changes are no longer an advantage. GH and IGF-I, in pharmacological doses, promote positive nitrogen balance, in both animal models and man. Preliminary studies with IGF-I in postsurgical 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.
authors.affiliation: Department of Endocrinology, St. Bartholomew's Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bentham
authors.forename: J
authors.initials: J
authors.lastname: Rodriguez-Arnao
authors.forename: R J
authors.initials: RJ
authors.lastname: Ross
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D013006:Growth Hormone / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000627:therapeutic use; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone