A prospective study of hypothalamus pituitary function after cranial irradiation with or without radiosensitizing chemotherapy

Abstract

Hypopituitarism can occur after cranial irradiation. Combined chemotherapy (CT) and radiotherapy (RT) have greatly improved the survival of patients with nasopharyngeal carcinoma (NPC). We studied 37 NPC patients 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 releasing hormones stimulation test and insulin hypoglycemic test. Five developed hypothyroidism and 3 developed hyperprolactinemia after treatment. The TSH response to TRH progressively increased. In male patients who received RT only, the LH response to GnRH was reduced after RT. The FSH response to GnRH increased 6 months and 1 year after RT, and returned to pretreatment level 2 years after RT. In male patients who received 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 cortisol response became prolonged and enhanced progressively after RT. The peak GH response to GRH increased significantly 1 year after RT in patients who also received CT. The GH response to insulin hypoglycemia was also increased after RT while the cortisol response remained the same. In conclusion, cranial irradiation caused a progressive impairment of the hypothalamus-pituitary-endocrine axes. Combined CT may mask the radiation damage to GnRH neuron by inducing primary hypogonadism. There may be hippocampal damage in addition to hypothalamo-pituitary damage after cranial irradiation.