Effect of recombinant human growth hormone and insulin-like growth factor-1 administration on IGF-1 and IGF-binding protein-3 levels in brain injury

Study Objective. To assess the effect of recombinant human growth hormone (rhGH) on the insulin-like growth factor-1 (IGF-1) plasma concentration versus time profile during continuous infusion of recombinant human (rh)IGF-1 to patients with traumatic brain injury (TBI). Setting. University of Kentucky Chandler Medical Center. Patients. Twenty-three patients with TBI (aged 18-59 yrs) with Glascow Coma Scale scores of 4-10. Intervention. Patients were randomized to receive rhIGF-1 0.01 mg/kg/hour and daily subcutaneous doses of rhGH 0.05 mg/kg/day or saline for 14 days. Measurements and Main Results. Plasma concentrations of IGF-1 and IGF-binding protein (BP)-3 were quantified by radioimmunoassay. Patients receiving rhIGF- 1/rhGH reached a peak IGF-1 concentration (1199.3 ± 84.0 μg/L) at 72 hours and maintained it throughout the study. Levels of IGF-1 in the control group did not change significantly above baseline throughout the study. Concentrations of IGFBP-3 were significantly higher after 48 hours in the treated group (5.1 ± 0.4 mg/L) than in controls (2.9 ± 0.5 mg/L) and continued until the end of the study (p<0.05). Conclusion. Infusion of rhIGF- 1 in conjunction with rhGH effectively achieved and maintained supraphysiologic IGF-1 plasma concentrations throughout the dosing period in patients with TBI. It appears that rhGH alters the IGF-1 plasma concentration versus time profile during continuous administration. Although speculative, changes in protein binding of IGF-1 are the most likely mechanism.