December 12, 2019
3 min read

Associations urge caution after controversial radioactive iodine findings

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Kristien Boelaert

The Society for Endocrinology and the British Thyroid Association issued a joint statement urging caution when interpreting a recent study linking radioactive iodine therapy to cancer mortality among people with hyperthyroidism.

The retrospective analysis, published in July in JAMA Internal Medicine and reported by Healio, suggested that organ-absorbed doses of radioactive iodine used to treat hyperthyroidism were associated with an increased risk for death from all solid cancers, including breast cancer. The study conclusions raised concerns among patients and clinicians, according to the statement authors, who noted some limitations of the research.

“This retrospective analysis of data from the large multicenter Cooperative Thyrotoxicosis Therapy Follow-up Study suggests a modest increase in potential risk of death from cancer in people who receive radioiodine therapy for hyperthyroidism,” Kristien Boelaert, MD, PhD, MRCP, head of the Institute of Metabolism and Systems Research and a Reader in Endocrinology at the University of Birmingham, U.K., and colleagues wrote in the statement, published in Clinical Endocrinology. “These findings have obviously raised considerable concern, as radioiodine is one of the key treatment options in hyperthyroidism, particularly in those who relapse or have disease that is difficult to control. Experience with radioiodine is longstanding, and it is a widely used treatment modality for hyperthyroidism. The conclusion in this paper ... has naturally caused anxiety for both patients and clinicians. Whilst the work in the study is innovative and detailed, the Society for Endocrinology (SFE) and the British Thyroid Association (BTA) are concerned that the conclusion will need to be interpreted cautiously.”

The Society for Endocrinology and the British Thyroid Association issued a joint statement urging caution when interpreting a recent study linking radioactive iodine therapy to cancer mortality among people with hyperparathyroidism.

Modest association observed

For the study, researchers created a 24-year extension of the Cooperative Thyrotoxicosis Therapy Follow-Up Study to evaluate site-specific and solid cancer mortality among 18,805 adults with no cancer history at baseline (mean age, 49 years; 78% women; 93.7% Graves’ disease). The study included patients from the U.S. and U.K. with hyperthyroidism who were enrolled between 1946 and 1964 and initially followed up through 1968. After 1968, participants were asked to return to clinics every 2 years. Causes of death were identified through Dec. 31, 2014.

Researchers found that the risk for death from all solid cancers increased by 6% with each 100 mGy dose of radioactive iodine to the stomach (RR = 1.06; 95% CI, 1.02-1.1). The risk for death from breast cancer also increased with each radioactive iodine dose, with a 12% increased risk for death for every 100 mGy dose to the breast (RR = 1.12; 95% CI, 1.003-1.3). Excluding breast cancer, all other solid cancers combined had a 5% increased risk for death per 100 mGy dose to the stomach (RR = 1.05; 95% CI, 1.01-1.1).


Researchers found that for every 1,000 patients with hyperthyroidism treated at age 40 years who received typical radioactive iodine doses (150 mGy to 250 mGy) to the stomach, an additional 19 (95% CI, 3-40) to 32 (95% CI, 5-66) solid cancer cases could occur.

Findings questioned

However, Boelaert and colleagues noted that the lack of a hyperthyroidism control group makes it difficult to ascertain whether the increase in cancer risk is a consequence of hyperthyroidism and poor disease control or due to radioactive iodine use.

Additionally, the complex, mathematical model used in the study to calculate the absorbed radioactive iodine dose was novel, but not validated, Boelaert and colleagues wrote. The model was based on a “series of assumptions” on thyroid gland weight and radioactive iodine update measures among a small sample of patients, according to researchers. The analysis also did not correct for important confounders for cancer risk, such as smoking, obesity, alcohol intake and biochemical disease severity. Further, excess solid cancer risk is not observed after administration of substantially higher doses of radioactive iodine among people with thyroid cancer.

“In this context, it would be unfortunate if patients were deprived of the option of rapid, effective control of their hyperthyroidism with radioiodine, due to concerns of cancer risk,” the statement authors wrote. “Overall, on the basis that current evidence shows no excess cancer risk, it would be reasonable to continue with current approaches to the management of hyperthyroidism, whilst further, appropriately controlled studies are undertaken.”

The researchers concluded that they support efforts to construct large national databases of radioiodine-treated hyperthyroid patients to assess cancer outcomes. – by Regina Schaffer

Disclosure: Boelaert reports no relevant financial disclosures.