Early Effects of Cranial Irradiation on Hypothalamic-Pituitary Function*

Abstract

Hypothalamic-pituitary function was studied in 31 patients before and after cranial irradiation for nasopharyngeal carcinoma. The estimated radiotherapy (RT) doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 centiGrays, respectively. All patients had normal pituitary function before RT. One year after RT, there was a significant decrease in the integrated serum GH response to insulin-induced hypoglycemia. In the male patients, basal serum FSH significantly increased, while basal serum LH and testosterone did not change. Moreover, in response to LHRH, the integrated FSH response was increased while that of LH was decreased. Such discordant changes in FSH and LH may be explained by a defect in LHRH pulsatile release involving predominantly a decrease in pulse frequency. The peak serum TSH response to TRH became delayed in 28 patients, suggesting a defect in TRH release. Twenty-one patients were reassessed 2 yr after RT. Their mean basal serum T4 and plasma cortisol levels had significantly decreased. Hyperprolactinemia associated with oligomenorrhoea was found in 3 women. Further impairment in the secretion of GH, FSH, LH, TSH, and ACTH had occurred, and 4 patients had hypopituitarism. Thus, progressive impairment in hypothalamic-pituitary function occurs after cranial irradiation and can be demonstrated as early as 1 yr after RT.

Hypothalamic-Pituitary-Adrenal Function following Cranial Irradiation

“…It does appear that ACTH deficiency is quite rare in patients receiving CRT at doses of <50 Gy [7], Previous reports of variable findings of abnormalities in cortisol reserve may be due to the use of different agents to test the HPA axis, as well as the fact that patients have been studied at varied times after treatment [15][16][17][18], Harrop et al [19] found adrenal reserve to be normal in 9 patients treated with high-dose RT for primary brain tumors, whereas Littley et al [20] reported that 3 of 7 adults tested 5-13 years after RT for brain tumors were ACTH-deficient. Lam et al [21] evaluated 31 patients after RT for nasopharyngeal carcinoma treated with doses in the range of 40-60 Gy and found a progressive decrease in basal cortisol levels. The mean integrated cortisol responses did not decrease significantly except in 1 pa tient who had a subnormal response 2 years after RT.…”

Growth and Endocrine Disorders Secondary to Cranial Irradiation

“…Furthermore, according to two prospective studies of patients given radiation doses of more than 3000 cGy, children (21,22) appeared to develop GH deficiency more rapidly than adults (23).…”

Long-term effects of cranial irradiation for childhood malignancy on sleep in adulthood

“…We included assessment of GH status, prolactin (PRL), and leptin expressed per kg body fat mass (Leptin/FM), because a close association of these neuroendocrine parameters with the sleep -wake rhythm has been demonstrated (11 -14). In addition, GH deficiency, hyperprolactinaemia and increased leptin concentrations have been reported in some patients treated with CRT (2,3,15,16). In order to gain insight into possible determinants of sleep changes, we performed stepwise regression analyses, with neuroendocrine status, radiation dose, chemotherapy, age at treatment and post-treatment interval as candidates.…”