Effect of cranial irradiation on hypothalamus-pituitary function: follow-up study one year after radiotherapy

Hypothalamic pituitary functions were studied in 24 patients before, 6 months after and 1 year after cranial irradiation with or without radiosensitizing chemotherapy for nasopharyngeal carcinoma (NPC). The estimated average total dose was 5,000 cGy to the hypothalamus and pituitary gland. The radiosensitizing chemotherapy used was endoxan, 4,900 +/- 873 mg (mean +/- SD) and/or methotrexate, 113 +/- 30 mg. All patients had normal pituitary function before radiotherapy. There was a progressive increase in baseline serum thyrotropin (TSH) after radiotherapy. The basal serum follicle stimulating hormone (FSH) was significantly increased 6 months after radiotherapy and remained so at 1 year after radiotherapy. The TSH response to thyrotropin-releasing hormone (TRH) also progressively increased after radiotherapy, suggesting primary hypothyroidism due to neck irradiation. The peak serum TSH response to TRH became delayed after radiotherapy, suggesting a defect in TRH release. In male patients who did not receive chemotherapy, the LH response to luteinizing hormone-releasing hormone (LHRH) decreased after radiotherapy. After an initial rise in the FSH response to LHRH 6 months after radiotherapy, there was a reduction in the FSH response at 1 year. This suggests a defect in LHRH pulsatile release. However, in male patients who received radiosensitizing chemotherapy, both the FSH and LH responses to LHRH had declined at 1 year after radiotherapy, as compared with their responses at 6 months. However, these were still higher than those obtained before radiotherapy. This suggests further GnRH neuron damage, which was previously masked by chemotherapy-induced primary hypogonadism. The adrenocorticotropic hormone (ACTH) response to ovine corticotropin-releasing hormone (CRH) had not changed further at 1 year after radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)