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Response to growth hormone treatment and final height after cranial or craniospinal irradiation
V Sulmont1, R Brauner, M Fontoura
1Pediatric Endocrinology Unit, Hôpital des Enfants Malades, Paris, France.
Insights
Growth hormone (GH) therapy shows limited final height gains in children treated for cranial irradiation-induced GH deficiency (GHD). Spinal irradiation significantly reduces growth response, suggesting potential improvements with adjusted GH dosing and puberty delay.
Area of Science:
- Pediatric Endocrinology
- Radiation Oncology
- Growth Hormone Therapy
Background:
- Cranial irradiation for non-pituitary tumors frequently causes growth hormone deficiency (GHD).
- Growth hormone (GH) substitutive therapy is a common treatment for GHD in these pediatric patients.
- Understanding factors influencing growth response to GH therapy post-irradiation is crucial.
Purpose of the Study:
- To analyze the growth response to human GH (hGH) therapy in children with GHD post-irradiation.
- To identify factors contributing to decreased growth velocity after cranial irradiation.
- To compare final height outcomes in treated and untreated irradiated children.
Main Methods:
- Studied 100 children (61 boys, 39 girls) who received cranial radiation.
- Fifty-six children with GHD received hGH therapy.
- Compared final heights of 28 hGH-treated patients with untreated irradiated groups (GHD and normal GH secretion).
Main Results:
- Additional spinal irradiation significantly reduced growth response to hGH therapy.
- Height SD score changes with hGH therapy were +0.3 (cranial) and -1.2 (craniospinal).
- GH deficiency caused a mean height loss of 1 SD; spinal irradiation caused a 1.4 SD loss.
Conclusions:
- hGH therapy shows a limited effect on final height in irradiated children, influenced by bone age and early puberty onset.
- Optimizing hGH therapy with higher, fractionated doses may improve outcomes.
- Delaying puberty with GnRH analogs could be beneficial for select irradiated patients.
Abstract:
Growth hormone (GH) deficiency (GHD) induced by cranial irradiation has become a frequent indication of hGH substitutive therapy. This study analyses the growth response to hGH therapy and the factors involved in the decrease in growth velocity observed after cranial irradiation. One hundred children (61 boys and 39 girls) given cranial radiation for pathology distant from the hypothalamo-pituitary area were studied. Fifty-six of them received hGH therapy for GHD resulting in decreased growth velocity. The initial annual height gain in the cranial-irradiated group was comparable to that of patients treated for idiopathic GHD; additional spinal irradiation significantly reduced the growth response. Twenty-eight hGH-treated patients reached final heights which were compared to those of 2 untreated irradiated groups, one with GHD (n = 27) and the other with normal GH secretion (n = 17). The height SD score changes observed in hGH therapy were +0.3 in the cranial (n = 10) and -1.2 SD in the craniospinal (n = 18) groups. GH deficiency had contributed to a mean height loss of 1 SD and spinal irradiation to a loss of 1.4 SD. The small effect of hGH therapy on final height is probably linked to the small bone age retardation at onset of hGH therapy and to the fact that irradiated children entered puberty at a younger age in terms of chronological age (10.6 +/- 0.3 yr in girls and 11.0 +/- 0.3 yr in boys) and bone age (9.6 +/- 0.4 yr in girls and 12.6 +/- 0.3 in boys) than the idiopathic GHD patients. These data suggest that the results of hGH therapy in irradiated children might be improved with higher and more fractionated hGH doses and, in some patients, by delaying puberty using luteinizing hormone releasing hormone analogs.