The relationship between the growth hormone and insulin-like growth factor axis in long-term survivors of childhood brain tumours

OBJECTIVE We compared IGF-1 and IGFBP3 concentrations in a group of adults treated for brain tumours in childhood with those of matched controls, and investigated the relationship between the GH secretory pattern and IGF-1/IGFBP3 concentrations in the entire group. DESIGN We performed 24 h serum GH profiles using 20 minute sampling and measured corresponding fasting concentrations of IGF-I and IGFBP3. PATIENTS Fourteen adult male long-term survivors of childhood brain tumours were studied. All had received high dose cranial irradiation (greater than or equal to 30Gy; median 12.8 (range 5.8-14.5) years previously). Nine healthy male volunteers acted as controls. MEASUREMENTS IGF-1 and IGFBP3 concentrations were measured at 06.00 hours. Peak and trough GH activity within the GH profile was analysed by a distribution method which determined the concentration at or below which the serum GH concentration in the profile spent 95% (peak) and 5% (trough) of the total time. RESULTS Serum IGF-1 levels were significantly lower in the irradiated group (Irradiated: 200 mu g/l vs Control: 265 mu g/l; P = 0.001) but the difference in serum IGFBP3 (Irradiated: 2.3 mg/l vs Controls: 2.77 mg/l; P = 0.03) was less marked. Peak GH activity was lower in the irradiated subjects (2.59 mU/I vs 9.04 mU/I; P = 0.0004) and correlated strongly with IGF-1 (r = 0.62; P = 0.002) but less so with IGFBP3 (r = 0.35; P = 0.09). This was strengthened when the range of activity within the profle (peak - trough) was considered. Trough GH activity had a nonsignificant negative correlation with IGF-1 and IGFBP3 levels. CONCLUSION The difference in serum IGF-1 concentrations between irradiated subjects and controls was greater than the difference in serum IGFBP3. Peak GH activity and the range of activity within the profile correlated strongly with IGF-1 concentrations but less so with IGFBP3.