Growth hormone response to a growth hormone-releasing hormone stimulation test in a population-based study following cranial irradiation of childhood brain tumors.
Children with brain tumors are at high risk of developing growth hormone deficiency (GHD) after cranial irradiation (CI) if the hypothalamus/pituitary (HP) axis falls within the fields of irradiation. The biological effective dose (BED) of irradiation to the HP region was determined, since BED gives a means of expressing the biological effect of various irradiation treatment schedules in a uniform way. Hypothalamic versus pituitary damage as cause of GHD was distinguished in 62 patients by comparing the growth hormone (GH) peak response to an insulin tolerance test (ITT)/arginine stimulation test and the GH response to a growth hormone-releasing hormone (GHRH) stimulation test. Peak GH response to a GHRH test was significantly higher (median 7.3 mU/l; range: 0.5--79.0 mU/l) than that of an ITT/arginine test (median 4.7 mU/l; range: 0.01--75.0 mU/l) (p = 0.017). Peak GH after a GHRH test was significantly inversely correlated to follow-up time (r(s) = -0.46, p < 0.0001) and to BED (R(s) = -0.28, p = 0.03), and both were found to be of significance in a multivariante regression analysis. We speculate that a significant number of patients developed hypothalamic radiation-induced damage to the GHRH secreting neurons, and secondary to this the pituitary gland developed decreased responsiveness to GHRH following CI in childhood.
Schmiegelow
M
M
Department of Growth and Reproduction, Juliane Marie Centre, National University Hospital, Rigshospitalet, Copenhagen, Denmark. rho4642@rh.dk
Lassen
S
S
Poulsen
H S
HS
Feldt-Rasmussen
U
U
Schmiegelow
K
K
Hertz
H
H
Müller
J
J
D000293:Adolescent; D001120:Arginine; D001921:Brain / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000528:radiation effects; D007223:Infant; D008297:Male; D010902:Pituitary Gland / Q000528:radiation effects; D011832:Radiation Injuries / Q000378:metabolism; D012062:Relative Biological Effectiveness; D013997:Time Factors
D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine