Thyroid toxicity of treatment for Hodgkin's disease

Thyroid disease, especially hypothyroidism, is one of the more frequently encountered late endocrine sequelae of treatment for Hodgkin's disease. We analyzed the thyroid function of 177 patients (92 male and 85 female) who had been treated for Hodgkin's disease between 1970 and 1995; their median age was 38 years (range 18-74) and their median time after therapy was 6 years (range 1-20). Thirty-five (20%) patients were treated with chemotherapy alone (mainly COPP/ABVD), 44 (25%) with radiotherapy (RTX) alone, and 98 (55%) received combined modality treatment according to the protocols of the German Hodgkin's Disease Study Group. All patients had been without evidence of disease for at least 1 year. They were evaluated between 1994 and 1997 for thyroid disease by clinical examination, thyroid function tests, and ultrasound imaging if indicated. Overall, 48 patients (27%) were found to have subclinical (36 patients, 20%) or overt (12 patients, 7%) hypothyroidism. No patient in the group treated with chemotherapy alone developed hypothyroidism, in contrast to 15 of 44 (34%) patients treated with radiotherapy alone and 33 of 98 (34%) patients treated with the combined modality approach who did. All patients with hypothyroidism had received some form of supradiaphragmatic radiation except one patient who underwent infradiaphragmatic RTX but with preceding hemithyroidectomy for staging purposes. After an average follow-up of 6 years, 27% of patients treated for Hodgkin's disease with either radiotherapy alone or a combination of radiotherapy and chemotherapy developed hypothyroidism. Supradiaphragmatic radiation, but not the use of chemotherapy alone, is associated with an increased risk for hypothyroidism. Evaluation of thyroid function after therapy is important, and appropriate substitution medication should be initiated.