Short stature due to growth hormone (GH) deficiency is a common sequelae seen in children who have received cranial/cranialspinal radiation therapy (RT) for treatment of CNS tumors. We, as well as others, have shown that in addition to having growth failure, these children have an earlier, if not frankly precocious, onset of puberty, and that there is a significant positive correlation for age at diagnosis and age at onset of puberty. The experience to date with GH replacement therapy, following high-dose cranial/craniospinal RT has been disappointing. Although brain tumor patients treated with GH demonstrate marginally improved final heights compared to similar patients with GH deficiency who have never been treated with GH, the brain tumor patients have markedly reduced overall changes in height when compared to subjects with idiopathic GH deficiency. The factors which may limit catch-up growth in the irradiated patients include spinal RT, and the fact that irradiated patients often enter puberty at a normal but significantly earlier chronological and bone age than children with idiopathic deficiency. Consequently, the time available for GH therapy is foreshortened and less gain in height is possible . We propose, thus, to utilize a strategy currently being employed to treat patients with GH, deficiency and true precocious puberty, namely combination therapy with a GnRH (hormonal) agonist to suppress puberty and with GH. Although the effects of delay of normally timed puberty on final height are unclear, preliminary data from studies in children with idiopathic GH deficiency and adolescents with short stature have shown promising results. We will determine in patients who have been exposed to high dose cranial irradiation - most of whom are or will be receiving growth hormone therapy - if suppression of the progress of normal puberty with use of GnRH agonist therapy will allow for a final height, more in keeping with these children's genetic potential.
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