A PROSPECTIVE-STUDY OF HYPOTHALAMUS PITUITARY-FUNCTION AFTER CRANIAL IRRADIATION WITH OR WITHOUT RADIOSENSITIZING CHEMOTHERAPY

Hypopituitarism can occur after cranial irradiation. Combined chemothe rapy (CT) and radiotherapy (RT) have greatly improved the survival of patients with nasopharyngeal carcinoma (NPC). We studied 37 NPC patien ts who received RT and/or CT prospectively to determine if combined CT worsens the radiation damage. Patients were studied before, 6 months, 1 year and 2 years after treatment, with 4 combined hypothalamic rele asing hormones stimulation test and insulin hypoglycemic test. Five de veloped hypothyroidism and 3 developed hyperprolactinemia after treatm ent. The TSH response to TRH progressively increased. In male patients who received RT only, the LH response to GnRH was reduced after RT. T he FSH response to GnRH increased 6 months and 1 year after RT, and re turned to pretreatment level 2 years after RT. In male patients who re ceived RT and CT, after an initial rise 6 months after treatment, both FSH and LH responses to GnRH declined. The ACTH response to ovine CRH was decreased 6 months after RT and remained so later on, while the c ortisol response became prolonged and enhanced progressively after RT. The peak GH response to GRH increased significantly 1 year after RT i n patients who also received CT. The GH response to insulin hypoglycem ia was also increased after RT while the cortisol response remained th e same. In conclusion, cranial irradiation caused a progressive impair ment of the hypothalamus-pituitary-endocrine axes. Combined CT may mas k the radiation damage to GnRH neuron by inducing primary hypogonadism . There may be hippocampal damage in addition to hypothalamo-pituitary damage after cranial irradiation.