Assessment of Hypothalamic-Pituitary Function in Women after External Head Irradiation

To account for hypopituitarism in patients who received 60Co head irradiation for nasopharyngeal neoplasia, hypothalamic-pituitary function was evaluated in 12 women, aged 19–40 yr, 1–13 yr after the irradiation. The hypothalamicpituitary area received a dose of about 6000–6500 rads. Serum basal LH and FSH levels as well as their responses to 25 µg iv LRH were measured by RIA and the results were compared with responses in the early follicular phase of 5 normal cycling women. In 8 of the 12 patients, serum LH, FSH, and PRL levels were also measured before and during the fourth day of clomiphene administration (100 mg/day for 5 days). Among the 12 irradiated patients, 3 had oligomenorrhea, 3 had amenorrhea, and 8 had galactorrhea. The mean basal LH (5.80 ± 0.68 mlU/ml) and FSH (6.23 ± 0.79 mlU/ml) levels and the mean LRH-stimulated peak for LH (31.33 ± 4.26 mlU/ml) and FSH (14.84 ± 1.80 mlU/ml) were significantly (P < 0.01) lower than those of normal controls. The magnitude of individual gonadotropin responses to LRH was variable; however, an evident increase of LH and FSH was observed in all but one of the patients after LRH injection. Three patients showed normal basal LH and FSH levels as well as normal responses to LRH. Two patients showed normal basal FSH and FSH responses to LRH but subnormal LH and LHresponse. Seven patients showed subnormal basal LH and FSH levels and subnormal responses to LRH. One patient, who received head irradiation at the age of 6 yr, exhibited primary amenorrhea, markedly low basal LH and FSH levels and almost no response to LRH injection. Basal PRL levels were elevated, particularly in five patients who showed galactorrhea. Significant increases in LH (P < 0.01) and FSH (P < 0.05) levels but no significant change in PRL levels were observed during clomiphene administration. These results suggest the presence of a hypothalamic lesion and a possible pituitary lesion in the irradiated women. The marked impairment of prepubertal gonadotropin secretion after irradiation suggests that the immature hypothalamus and pituitary may be particularly radiosensitive. The data suggest the existence of a negative feedback relationship of the hypothalamic- pituitary area in these patients.