Growth Hormone Secretion and Hypothalamic-Pituitary-Thyroid Axis Function after Cranial Radiotherapy in Children

Background: When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common especially in children than has been appreciated in the past. This study was carried out to evaluate growth hormone secretion and the hypothalamic-pituitary-thyroid axis function in children after cranial radiotherapy. Subjects and Methodology: Twenty children (12 boys and 8 girls) who received cranial/craniospinal radiation therapy were included in this study. Their mean age at the time of therapy was 6 1/2 years (range, 3 to 10 years), and at the time of the study, it was 9 years (range, 5 to 13 years). The mean interval between therapy and testing was 2 years and 4 months (range,1 to 3 years). All the patients were children (<16 years) when tested and the dose of radiation ,delivered to the hypothalamic-pituitary region, ranged from 27 to 45 Gy (1 Gy =100 rads). The serum concentrations of the basal and peak growth hormone, total and free T4, total T3, and basal and peak TSH were measured by radioimmunoassay. A group of 12 agematched healthy children served as control for estimation of the normal range of these hormones. Results: The mean serum basal and peak GH concentrations after stimulation with clonidine in the included patients were significantly lower than those in the control group. Forty-five percent and 65% of the patients had below-normal basal and peak GH secretion respectively. There was a significant inverse correlation between the serum peak GH concentration and both the dose of radiation and the interval between therapy and testing. The mean serum total T4, free T4, and total T3 concentrations in the patients were significantly lower than those in the healthy subjects. Thirty-five percent, 45%, and 25% of the patients had below-normal serum total T4, free T4, and total T3 respectively. There was no significant difference between the 2 studied groups as regards the mean serum basal and peak TSH concentrations in response to stimulation with thyrotropin-releasing hormone. The most common pattern of abnormality in the hypothalamic-pituitary-thyroid axis function (66.66%) was low serum concentration of free T4 and normal basal and peak serum TSH concentrations which is suggestive of hypothalamic hypothyroidism. Negative significant correlations were found between the dose of radiation and serum concentrations of total T4, free T4, and T3, while inverse significant correlation was observed between the interval between radiation and testing and serum free T4 concentration only. In addition , an inverse correlation was found between the age of the patient when treated and both the serum basal and peak TSH concentrations. Conclusion: A large percentage of children develop growth hormone deficiency (GHD) and hypothyroidism within 2 years after receiving doses of cranial radiation ranging from 27 to 45 Gy. Higher doses of radiation and longer interval between therapy and evaluation are associated with higher incidence of both GHD and hypothyroidism. Younger age children are more susceptible to develop hypothyroidism when they are exposed to cranial/craniospinal radiation than older children. Routine testing for possible GHD and thyroid dysfunction should be included in the follow-up procedures of this population and supplement therapy should start as early as necessary.