EFFECTS OF CRANIAL IRRADIATION ON HYPOTHALAMIC-PITUITARY FUNCTION - A 5-YEAR LONGITUDINAL-STUDY IN PATIENTS WITH NASOPHARYNGEAL CARCINOMA

The effects of cranial irradiation on hypothalamic-pituitary function were studied over a 5-year period in 31 adult patients with nasopharyngeal carcinoma. The estimated radiotherapy doses to the hypothalamus and pituitary were 3979 +/- 78 (+/- SD) and 6167 +/- 122 cGy, respectively. Within 2 years of radiotherapy, significant impairment in the secretion of growth hormone gonadotrophins, corticotrophin and thyrotrophin were evident and 14 per cent of patients developed hyperprolactinaemia. Using life table analysis, the cumulative probability of endocrine dysfunction was estimated to be 62 per cent after 5 years with deficiencies in growth hormone, gonadotrophins, corticotrophin and thyrotrophin found in 63.5, 30.7, 26.7 and 14.9 per cent of patients, respectively. Growth hormone deficiency was the earliest endocrine dysfunction observed. Hyperprolactinaemia was uncommon in the male patients but occurred in five of eight women within 3 years of cranial irradiation. The alterations in gonadotrophin secretion suggest a defect in the pulsatile release of gonadotrophin releasing hormone. Twenty-eight patients developed a hypothalamic pattern of delayed thyrotrophin response to thyrotrophin releasing hormone one year after radiotherapy - four subsequently became hypothyroid. Patients who received radiotherapy for cervical lymph nodes were at greater risk of developing hypothyroidism. Thus, in these patients with no pre-existing disease in the hypothalamic-pituitary region, progressive impairment in hypothalamic pituitary function leading to endocrine dysfunction requiring treatment occurs in 50 per cent of patients 5 years after cranial irradiation. Regular endocrine assessment should be performed in all patients following cranial irradiation.