Hypothalamic-pituitary-thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma

The aim of this study is to investigate the status and dose-volume relationship of hypothalamic-pituitary-thyroid dysfunction induced by intensity-modulated radiotherapy (IMRT) for adult patients with nasopharyngeal carcinoma (NPC). The hormone levels of 98 patients treated with IMRT were retrospectively reviewed. Hormone values including prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone, adrenocorticotropic hormone, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were tested. The pituitary and thyroid glands were re-contoured to obtain dose-volume histograms. The relationship between the dose distributions and hormone values was analyzed, as well as combined chemotherapy, age, gender, stages and interval time. The median follow-up period was 17 months. Median values of mean radiation dose to the pituitary and thyroid were 51.2 and 49.72 Gy. Evidences of hormone disorder were found in 54.1 % patients. About 33.7 % patients experienced dysfunction of TSH, 20.4 % of sexual axis and 11.2 % of PRL. Twenty-nine patients presented central hypothyroidism, while 4 patients developed primary hypothyroidism. Dosimetric analysis showed that thyroid axis was significantly associated with Vt30-50 and Dmean of thyroid, V40 (p = 0.000) was the most significant parameters. In addition, TSH and FT4 were correlated with volume of pituitary receiving above 55 Gy (Vp55; p = 0.014, 0.035). Vp55 was most significantly influencing factor of PRL axis (p = 0.044) and gonad axis (p = 0.047). TSH dysfunction was more common with interval time longer than 10 months and age older than 45 years in both univariate and multivariate analysis. FSH and PRL were affected by both gender (p = 0.009, 0.001) and age (p = 0.004, 0.012). Hormone changes were not affected by either clinical stages or combined chemotherapy. At the era of IMRT, a high rate of endocrine deficiency was still seen. Hypothalamic-pituitary-thyroid dysfunction is more common in NPC patients. Regular monitoring is needed.