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Original Contribution
July 22/29, 1998

Cancer Mortality Following Treatment for Adult Hyperthyroidism

Author Affiliations

From the Radiation Epidemiology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Md (Drs Ron, Wong, and Boice and Mss Doody and Curtis); The New York Hospital–Cornell Medical Center, New York, NY (Dr Becker and Ms Warshaver); Vanderbilt University, Nashville, Tenn (Dr Brill); Harvard University School of Public Health, Boston, Mass (Dr Goldman); Research Triangle Institute, Research Triangle Park, NC (Mr Harris†); George Washington University, Washington, DC (Dr Hoffman); Mayo Clinic, Rochester, Minn (Dr McConahey); University of Cincinnati Medical Center, Cincinnati, Ohio (Dr Maxon); and the University of Southern California, Los Angeles (Dr Preston-Martin). Dr Wong is currently a private statistical consultant in Burbank, Calif. Dr Boice is currently with the International Epidemiology Institute, Rockville, Md.
Dr Harris is deceased.

JAMA. 1998;280(4):347-355. doi:10.1001/jama.280.4.347

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 131I 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 131I 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 131I.

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 131I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following 131I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, 131I appears to be a safe therapy for hyperthyroidism.