56 NEUROENDOCRINE ALTERATIONS INDUSCED BY CRANIAL IRRADIATION (CR) IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA (LLA)

Abstract

In order to investigate the effects produced by external CR on neuroendocrine systems,GH secretion, in response to hypothalamic stimulation (clonidine, 0.15 mg/m2, per os) and to direct pituitary challenge (GRF-29, Serono, Spain, 1 μg/kg, iv bolus), and TSH and PRL responses to TRH (200 ug, iv bolus) were evaluated in 7 children, 3 years after previous CR for LLA (dose= 2400 rads). Growth velocity was also periodically evaluated. Mean age at diagnosis was 4.2 years (range : 9 months to 8 y.). Hormones in plasma were measured by sensitive IRMA. RESULTS (mean ± SD).- Growth velocity, as expressed by SD under the mean for age, was impaired in all patients. -3.05 ± 1.8, GH peaks elicited by clonidine and GRF-29 were similar : 13.8 ± 6.1, and 15.5 ± 10.8,ng/ml,respectively. Either basal or stimulated TSH and PRL were between normal limits, TSH; O' = 1.6 ± 1.1, peak = 7.8 ± 5.3, μU/ml; PRL : O' = 5.4 ± 2.1, peak = 22.5 ± 14.8, ng/ml. Individually, while in 6 patients a normal GH response to clonidine was observed, 3 of them exhibited a poor response of the hormone to GRF challenge (peaks : 7.4, 9.2, 2, ng/ml). CONCLUSIONS.- The fact that GH secretion appeared to be normal when explored either from the hypothalamus or directly at pituitary level, suggests that CR (at the dcse utilised) did not affect the endogenous GHRH-GH pathway. Given that, in spite of the fact that thyroideal status was also normal, growth velocity is consistently impaired in these children it is tempting to speculate that CR affected the suprahypothalamic structures that, governing the interplay between GHRH and somatostatin, lead to the normal pattern of spontaneous GH secretion. Additionally, the fact that in 3 cases there was not observed significant GH response to GRF, but normal response to clonidine, supports our previous hypothesis on HSR and GRF tests (Bevesa, J Endoc Inv, 10, Suppl 3,27,87)