title: Systemic and splanchnic metabolic response to exogenous human growth hormone.
abstract: BACKGROUND
  Evidence exists indicating that growth hormone (GH) resistance in some disease states such as hypercatabolic conditions may limit the metabolic benefit associated with recombinant human growth hormone (rhGH) administration. It was the purpose of this study to compare the systemic and splanchnic effects of rhGH in patients with sepsis exhibiting systemic inflammatory response syndrome (SIRS) with the response observed in normal volunteers. Because insulin-like growth factor I (IGF-I) is believed to be the dominant factor responsible for the anabolic effects of rhGH, particular attention was given to this secondary effector.
  
  
  METHODS
  The systemic and splanchnic effects of rhGH (0.15 mg/kg/day) were studied in normal volunteers (n = 5), critically ill patients with sepsis exhibiting SIRS (n = 6), and patients with sepsis exhibiting SIRS while receiving total parenteral nutrition (n = 6). Basal and end study IGF-I, urinary urea excretion, hepatic blood flow, hepatic venous oxygen content, and splanchnic oxygen exchange were measured after a 48-hour course of rhGH.
  
  
  RESULTS
  Fasting basal IGF-I concentrations were reduced by 75% to 83% in patients with sepsis/SIRS relative to normal control subjects. After 48 hours of rhGH, peak IGF-I concentrations were 74% and 76% lower in patients in the Sepsis/SIRS and Sepsis/SIRS + Nutrition groups, respectively, compared with normal control subjects. Despite the attenuated IGF-I rise in patients, urea excretion declined by a similar magnitude in all three groups. Hepatic blood flow remained unaffected, but rhGH administration increased splanchnic oxygen consumption in all groups (control, +57%*; Sepsis/SIRS, +13%; Sepsis/SIRS + Nutr +42%*; *p < 0.05 relative to corresponding basal) resulting in a decline of basal to end therapy hepatic venous oxygen saturation (control, 67 +/- 4% to 62 +/- 11%; Sepsis/SIRS, 51% +/- 14% to 43% +/- 14%*; Sepsis/SIRS + Nutr, 62% +/- 11% to 55% +/- 16%; *p < 0.05 relative to corresponding control value), suggesting that rhGH may induce centrilobular hepatic hypoxia, which may contribute to the diminished IGF-I response.
  
  
  CONCLUSIONS
  Although critically ill patients exhibit an IGF-I increase in response to exogenous rhGH, the rise is markedly attenuated compared with healthy volunteers, indicating the presence of GH resistance. Unexpectedly, the changes in the anabolic hormone IGF-I did not appear to be related to the reduction in urea excretion. This may provide some additional evidence for IGF-I resistance. Finally, rhGH is associated with an augmented splanchnic oxygen consumption but no corresponding increase in regional blood flow. As a result, regional tissue hypoxia may arise and contribute to the impaired or suboptimal IGF-I response pattern.
authors.affiliation: Department of Surgery, VA Medical Center, Detroit, MI 48201, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Dahn
authors.forename: M P
authors.initials: MP
authors.lastname: Lange
mesh_terms: D018806:APACHE; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016638:Critical Illness; D002149:Energy Intake; D006439:Hemodynamics / Q000187:drug effects*; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008102:Liver Circulation / Q000187:drug effects*; D008875:Middle Aged; D009584:Nitrogen / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D010289:Parenteral Nutrition, Total; D011994:Recombinant Proteins / Q000494:pharmacology; D012016:Reference Values; D018805:Sepsis / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D013152:Splanchnic Circulation / Q000187:drug effects*; D018746:Systemic Inflammatory Response Syndrome / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D014508:Urea / Q000652:urine
chemical_list: D002096:C-Peptide; D007328:Insulin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D014508:Urea; D002097:C-Reactive Protein; D009584:Nitrogen; D010100:Oxygen