ADJUVANT RECOMBINANT HUMAN GROWTH-HORMONE STIMULATES INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 SECRETION IN CRITICALLY ILL TRAUMA PATIENTS

The early catabolic phase of severe injury is associated with acute growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) deficiency. The metabolic half-life of circulating IGF-1 is prolonged by its binding to IGFBP-3. The role of this binding protein in nutritionally repleted multiple-injury patients has not been previously evaluated. We have measured plasma levels of these polypeptides and nitrogen (N) balance in 18 adult (15 males/3 females; mean age, 45 years), severely injured, hyper-metabolic, and highly catabolic trauma patients within 48 to 60 hours after injury, when they were receiving maintenance fluids without calories or N and during 6 days of total parenteral nutrition (TPN). Before instituting TPN, the patients were randomized to receive (group H, n = 9) or not to receive (group C, 9) daily recombinant human growth hormone (rhGH), 0.15 mg/kg IM. Adjuvant rhGH significantly increases plasma levels of GH, IGF-1, IGFBP-3, and insulin. In addition, it shows better improvement in N balance. The bioavailability of IGF-1 is increased, as indicated by the decrease in IGFBP-3:IGF-1 ratio. A significant correlation between IGF-1 and IGFBP-3 levels is present in the trauma patients who received TPN and rhGH. A GH/IGF-1/IGFBP-3 axis that closely regulates the metabolic status of the patient is established in trauma.