Cohort Study on Radioactive Iodine–Induced Hypothyroidism: Implications for Graves' Ophthalmopathy and Optimal Timing for Thyroid Hormone Assessment
Abstract
BACKGROUND: Graves' ophthalmopathy (GO) develops or worsens in up to one-third of patients treated with radioactive iodine (RAI) for Graves' hyperthyroidism. We sought to identify the prevalence of development or worsening of GO in patients treated with RAI for Graves' hyperthyroidism and to identify the risk factors associated with that outcome. METHODS: We identified a retrospective cohort of consecutive patients treated with RAI at Mayo Clinic (Rochester, MN) between 2005 and 2006. We assessed their medical records for evidence of hypothyroidism and development or worsening of GO in the year after therapy. Hypothyroidism was defined as thyrotropin >3.0 mIU/L or free thyroxine <0.8 ng/dL. RESULTS: We identified 291 consecutive patients who received RAI therapy during the study period, with 195 out of 291 having complete follow-up data for a one-year period. GO was present in 46 out of 195 patients (23.6%) at baseline. After RAI treatment, GO developed or worsened in 25 out of 195 patients (12.8%) and it was associated with hypothyroidism at first follow-up (p=0.011) with an odds ratio (OR) of 3.3 [95% confidence interval (CI) 1.3-8.7]. More smokers than nonsmokers developed new or worse GO (17.7% vs. 11.8%), but that difference did not reach statistical significance (p=0.35). Preexisting GO (24% of patients) was associated with a higher risk for negative GO outcome compared with patients who had no GO at baseline (11%; p=0.021). Both development of hypothyroidism by the first visit after RAI therapy (OR 3.6) and preexistent GO (OR 2.8) remained significant in a multivariate analysis. Development of hypothyroidism was more likely in patients with longer duration to first follow-up (p<0.001). By 6-8 weeks after RAI treatment, the prevalence of hypothyroidism was ∼40%, while that of hyperthyroidism was only 20%. CONCLUSIONS: The presence of hypothyroidism at the first assessment of thyroid function after RAI administration is a strong predictor for adverse GO outcome. This risk is highest in patients with preexisting GO. We suggest that in order to prevent clinical hypothyroidism and the associated risk for GO, the optimal time for first measurement of fT4 is before 6 weeks after RAI therapy.
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Hypothyroidism may occur from 4 weeks after RAI, with 40% of patients hypothyroid by 8 weeks and more than 80% by 16 weeks.
“Hypothyroidism may occur from 4 weeks on, with 40% of patients being hypothyroid by 8 weeks and >80% by 16 weeks (106).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [106]
High pretreatment levels of T3 and T4 were each reported to have a predictive role in GO, but these conclusions were not validated by subsequent studies.
“High pretreatment levels of T 3 and T 4 were each reported to have a predictive role in GO, but these conclusions were not validated by subsequent studies (69,106,532,534), suggesting the possibility of higher TRAb values measured on less sensitive assays early-on being partly responsible for this variation.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [106]
Identified risk factors for GO include RAI therapy for hyperthyroidism, untreated hyperthyroidism, smoking, high serum pretreatment TRAb levels, and any delay in treating hypothyroidism after therapy for hyperthyroidism.
“for GO are listed in Table 15, and the most pertinent ones to this discussion are RAI therapy for hyperthyroidism (531,532), untreated hyperthyroidism, smoking, high serum pretreatment TRAb levels (normal <1.75 IU/L, high risk for progression if >8.8 IU/L) (533), and any delay in treating hypothyroidism after therapy for hyperthyroidism (106,534).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [106]
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938 · see citing works
“High pretreatment levels of T3 and T4 were each reported to have a predictive role in GO, but these conclusions were not validated by subsequent studies (69,106,532,534), suggesting the possibility of higher TRAb values measured on less sensitive assays early-on being partly responsible for this variation.”
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Watanabe, N., Noh, J. Y., Kozaki, A., Iwaku, K., Sekiya, K., Kosuga, Y., Matsumoto, M., Suzuki, M., Yoshihara, A., Ohye, H., et al. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2014-4542 · Cited by 35 · see citing works
- Authors
- Stan, M. N., Durski, J. M., Brito, J. P., Bhagra, S., Thapa, P., & Bahn, R. S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Stan, Marius N.
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2013-05
- Volume
- 23
- Issue
- 5
- Pages
- 620-625
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2163962800
- Cited by
- 77
- References
- 15
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 11 · 2021: 11 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 10 · 2015: 2 · 2014: 5 · 2013: 1
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- radioiodine therapy, Graves' ophthalmopathy, post-radioiodine hypothyroidism, Graves' hyperthyroidism, smoking as risk factor
- MeSH terms
- Adult, Female, Follow-Up Studies, Humans, Hyperthyroidism, Hypothyroidism, Iodine Radioisotopes, Male, Middle Aged, Minnesota, Retrospective Studies, Risk Factors, Severity of Illness Index, Thyroid Gland, Thyroid Hormones, Cohort Studies, Prevalence, Disease Progression, Radiopharmaceuticals, Hormone Replacement Therapy, Graves Ophthalmopathy
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