Cancer Mortality Following Treatment for Adult Hyperthyroidism
Abstract
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 (131)I 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 (131)I 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 (131)I. 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 (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.
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There is concern for thyroid malignancy following RAI therapy.
“Following RAI therapy, there have been reports of new-onset GD (up to 4% prevalence) (263) as well as concern for thyroid malignancy (254,264,265) and a very minimal increase in late nonthyroid malignancy (265).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [264]
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- Authors
- Ron, E.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Ron, Elaine
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 1998-07-22
- Volume
- 280
- Issue
- 4
- Pages
- 347
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2101280599
- Cited by
- 377
- References
- 26
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11 · 2023: 5 · 2022: 11 · 2021: 15 · 2020: 24 · 2019: 20 · 2018: 8 · 2017: 10 · 2016: 11 · 2015: 14 · 2014: 8 · 2013: 10 · 2012: 14
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Clinic
- National Institutes of Health (n01cp041060-006)
- National Cancer Institute (N01-CP-41060)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- hyperthyroidism, radioiodine therapy, iodine-131, cancer mortality, Graves' disease, toxic nodular goiter, antithyroid drugs, thyroid cancer, lung cancer, breast cancer, kidney cancer, long-term follow-up
- MeSH terms
- Adult, Female, Follow-Up Studies, Humans, Hyperthyroidism, Iodine Radioisotopes, Male, Neoplasms, Neoplasms, Radiation-Induced, Retrospective Studies, Risk, Poisson Distribution, Likelihood Functions
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