Thyroid Abnormalities after Therapy for Hodgkin's Disease in Childhood

BACKGROUND: Involvement of the thyroid gland is an important morbidity of therapy for Hodgkin's disease, which should be well recognized by caretakers of these patients. However, the roles of age at the time of therapy for Hodgkin's disease, chemotherapy, treatment with reduced dose of radiation and lymphangiography in causing thyroid abnormalities have not been defined. MATERIALS AND METHODS: Eighty-nine pediatric and young adult patients (less than 21 years old at diagnosis) with Hodgkin's disease who were treated with either radiation alone (57 patients), radiation and chemotherapy (20 patients), or chemotherapy alone (12 patients) at the University of Minnesota between 1971 and 1986 were periodically evaluated. RESULTS: The median age at diagnosis was 14 years, and the median duration of follow up was 11 years. Of 89 patients evaluable for thyroid abnormalities, 51 patients developed biochemical hypothyroidism. The median time to development of hypothyroidism was six years. The estimated actuarial risk of developing hypothyroidism was 60% at 11 years. Radiation to the thyroid region was associated with an elevated risk of development of hypothyroidism (relative risk = 9.9), with patients receiving mantle irradiation alone developing hypothyroidism earlier (median time 2.5 years) than patients receiving combined modality treatment (median time 6 years; p = 0.001). Dose of radiation was the chief correlate for the development of hypothyroidism (relative risk increasing by 1.02/Gy; p < 0.001). Age, gender, chemotherapy and prior lymphangiography were not shown to be significant risk factors for the development of hypothyroidism. Four patients were diagnosed with thyroid nodules, (diagnosed 7.6 to 14.3 years after treatment of Hodgkin's disease), with histology showing multinodular goiter (2), single colloid nodule (1) and papillary carcinoma (1). Transient hyperthyroidism developed in two patients 8 and 13 months after treatment for Hodgkin's disease. CONCLUSIONS: There is a high risk for development of thyroid disease after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation of such patients.