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.


METHODS
We performed 24 h serum GH profiles using 20 minute sampling and measured corresponding fasting concentrations of IGF-1 and IGFBP3.


METHODS
Fourteen adult male long-term survivors of childhood brain tumours were studied. All had received high dose cranial irradiation (> or = 30Gy; median 12.8 (range 5.8-14.5) years previously). Nine healthy male volunteers acted as controls.


METHODS
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 micrograms/l vs


METHODS
265 micrograms/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/l vs 9.04 mU/l; 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 strenghtened 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.


CONCLUSIONS
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.
Achermann
J C
JC
London Centre for Paediatric Endocrinology, Middlesex Hospital, London, UK.
Hindmarsh
P C
PC
Brook
C G
CG
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001932:Brain Neoplasms / Q000097:blood* / Q000532:radiotherapy; D016022:Case-Control Studies; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D011879:Radiotherapy Dosage; D018709:Statistics, Nonparametric; D017741:Survivors
D015415:Biomarkers; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone