Abstract: Purpose/Objective: BACKGROUND: Primary hypothyroidism is a known sequela of head and neck radiotherapy. Hyperfractionation can reduce the delayed effects of radiation injury. The addition of concurrent chemotherapy improves overall outcome in patients with advanced head and neck cancers and thus is being used with increasing frequency. Despite this, the incidence of hypothyroidism in this set of patients remains poorly defined. This study examines the incidence and potential factors predicting the development of thyroid dysfunction in the setting of twice-daily radiation combined with chemotherapy. Materials/Methods: METHODS: Since October 1990, patients at our institution with previously untreated advanced head and neck cancers received hyperfractionated radiotherapy with concurrent 5-FU/Cisplatin on weeks 1 and 5 or 6 of radiotherapy. Baseline pretreatment thyroid-stimulating hormone (TSH) levels were gathered in many patients. Patients with at least 1-year of post-treatment thyroid function tests were retrospectively evaluated. Hypothyroidism was generally defined as a serum (TSH) level > 6 μIU/ml. Results: RESULTS: Twenty-four patients were deemed evaluable. The median follow-up time was 37 months (range, 6.6 - 154). Seven patients (29%) developed hypothyroidism. The median time to the development of hypothyroidism, calculated from the completion of radiotherapy, was 10.5 months (range, 5 - 56). There was no difference in hypothyroidism when the whole thyroid was included in the target volume (n=12) compared to patients where only part of the thyroid was irradiated (n=12, p = 0.29). Furthermore, there was nor correlation between disease recurrence and the development of hypothyroidism (p = 0.157). Age, primary site of disease, and overall stage did not correlate with hypothyroidism in this small study. There was a suggestion that race was correlative as 7 of 16 Caucasian (43.7%) and no African American (n = 7) patients developed hypothyroidism (p = 0.083). Conclusions: CONCLUSIONS: The incidence of hypothyroidism after hyperfractionated radiotherapy and concurrent chemotherapy does not appear to be higher than generally reported without concurrent chemotherapy. The development of hypothyroidism can occur soon after the administration of concurrent chemoirradiation, thus routine testing with serum TSH for follow-up of these patients seems justifiable.