Risk of Solid Cancer Death Not Influenced by Hyperthyroidism Treatment

Results of a new analysis suggest there was no association between treatment modality with solid cancer mortality in patients with hyperthyroidism.

A comparison of radioactive iodine, antithyroid drug, and surgical treatments with solid cancer mortality, results indicate the association noted between radioactive iodine treatment and solid cancer mortality was dose-dependent rather than based on modality of treatment.

“After accounting for known sources of bias, we observed no significant differences in risk across treatment groups based on external and internal cohort comparisons, and notably, we found no evidence of an increased risk of solid cancer death associated with use of antithyroid drugs,” wrote study investigators.

Based on the results of previous studies, debate exists over the long-term health effects of radioactive iodine and antithyroid drug treatments compared with surgery for hyperthyroidism. To further understand this subject, a team of investigators from the National Institutes of Health designed a study using data from a large cohort study of patients with hyperthyroidism to evaluate associations between treatment received and risk of solid cancer death.

For the purpose of the analysis, investigators chose to pull data from the Cooperative Thyrotoxicosis Therapy Follow-up Study (CTTFUS), which was a study of patients treated from hyperthyroidism from 1946-1964 in the US and the United Kingdom. The original CTTFUS cohort contained 35,593 patients with hyperthyroidism treated with the aforementioned therapies, of which 31,363 were included in their study. Of the 31,363 patients, 79.4% were female, the mean age was 46.9 years, the mean follow-up time was 26 years, and 90.9% of patients had Graves disease.

Use of antithyroid drugs, either alone or in combination with other treatments, was reported in 71.3% of the study cohort. In comparison, radioactive iodine use and surgery were recorded in 62.5% and 43.6% of patients, respectively. The goal of the investigators' analyses was to assess standardized mortality ratios (SMRs) of solid cancer in each treatment group. Investigators also planned internal comparisons using hazard ratios adjusted for age, sex, and underlying diagnosis.

Results of the analyses indicated solid SMRs were not increased in any of the treatment groups and no significant hazard ratios were observed across treatment groups after exclusion of patients with prior cancers. Specific SMRs were 0.82 (95% CI, 0.66-1.00) for surgery only, 0.90 [95% CI, 0.74-1.09) for antithyroid drugs only, 0.88 (95% CI, 0.84-0.94) for antithyroid drugs and surgery, 0.90 (95% CI, 0.84-0.96) for radioactive iodine only, 0.66 (95% CI, 0.52-0.85) for surgery and radioactive iodine, 0.94 (95% CI, 0.89-1.00) for antithyroid drugs and radioactive iodine, and 0.85 (95% CI, 0.75-0.96) for antithyroid drugs, surgery, and radioactive iodine.

Investigators pointed out the results of their analysis indicated hazard ratios for solid cancer mortality increased significantly among radioactive iodine-treated patients across levels of total administered activity (HR, 1.08 per 370 MBq; 95% CI, 1.03-1.13 per 370 MBq). Furthermore, this apparent association increased in strength among patients treated with radioactive iodine only (HR, 1.19 per 370 MBq; 95% CI, 1.09-1.30 per 370 MBq).

“After controlling for known sources of confounding, the study found no significant differences in the risk of solid cancer mortality by treatment group,” investigators wrote. “However, among RAI-treated patients, a modest positive association was observed between total administered activity and solid cancer mortality, providing further evidence in support of a dose-dependent association between RAI and solid cancer mortality.”

This study, “Association of Radioactive Iodine, Antithyroid Drug, and Surgical Treatments With Solid Cancer Mortality in Patients With Hyperthyroidism,” was published in JAMANetwork Open.