Cancer mortality following treatment for adult hyperthyroidism

Context.-High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic I-131 to the development of cancer, its extensive medical use indicates the need for additional evaluation. Objective.-To evaluate cancer mortality among hyperthyroid patients, particularly after I-131 treatment. Design.-A retrospective cohort study. Setting.-Twenty-five clinics in the United States and 1 clinic in England. Patients.-A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91% had Graves disease, 79% were female, and 65% were treated with I-131. Main Outcome Measure.-Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. Results.-Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). Conclusions.-Neither hyperthyroidism nor I-131 treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following I-131 treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, I-131 appears to be a safe therapy for hyperthyroidism.