Radioiodine-Associated Exacerbation of Graves' Orbitopathy in the Japanese Population: Randomized Prospective Study
Abstract
CONTEXT: Exacerbation of Graves' orbitopathy (GO) after radioiodine (RAI) therapy has been examined in some populations but has not been fully described in Japanese populations. OBJECTIVE: The purpose of this study was to clarify the characteristics of GO exacerbation after RAI therapy and the effectiveness of low-dose prophylactic corticosteroid (PCS). DESIGN AND SETTING: This was a prospective randomized study in Tokyo, Japan. PATIENTS: Between June 2011 and June 2012, 295 patients with Graves' disease with either inactive GO or no GO received RAI therapy. Of these, 147 received no PCS (PCS-Off group), whereas 148 received low-dose PCS (starting dose, 15 mg/day of prednisolone) for 6 weeks (PCS-On group). We used magnetic resonance imaging to thoroughly evaluate GO before and 1 year after RAI therapy. MAIN OUTCOME MEASURES: Outcomes of GO 1 year after RAI therapy were determined. RESULTS: GO exacerbation occurred in 29 patients (9.8%), and only 7 patients (2.4%) required ophthalmic treatment. No significant difference in the frequency of GO exacerbation was seen between the groups (PCS-On group: n = 18 [12.1%]; PCS-Off group: n = 11 [7.5%]; P = .17). Significant prognostic factors were identified as thyroid-stimulating antibody (by 100% linear increase: risk ratio, 1.15; 95% confidence interval, 1.07-1.24; P = .0003) and clinical activity score (≥1 vs 0: risk ratio, 6.40; 95% confidence interval, 2.17-19.7; P = .0009). CONCLUSION: Exacerbation of GO after RAI therapy in the Japanese population appears less common than in other populations. Low-dose PCS did not produce a significant preventive effect and appeared insufficient. Patients presenting with risk factors would thus be recommended to receive higher-dose PCS.
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Several randomized trials have identified the risk of GO development or progression after RAI therapy for hyperthyroidism to be between 10% and 39%.
“Several randomized trials have identified the risk of GO development or progression after RAI therapy for hyperthyroidism to be between 10% and 39% (69,540).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [540]
In the Japanese trial, most GO cases were mild, and only 7 cases (2.4%) required GO-directed therapy.
“Ultimately, most GO cases were mild, and only 7 cases (2.4%) required GO-directed therapy.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [540]
In a recent Japanese trial, the rate of disease progression in the absence of risk factors was low (4.2%) and not impacted by glucocorticoid therapy.
“The rate of disease progression in the absence of risk factors was low (4.2%) and not impacted by glucocorticoid therapy.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [540]
The presence of risk factors for GO (high thyroid stimulating antibody, CAS ≥1) increased the risk of progression, again without a benefit from low-dose steroid prophylaxis.
“The presence of risk factors for GO (high thyroid stimulating antibody, CAS ‡1) increased that risk, again without a benefit from low-dose steroid prophylaxis.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [540]
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Research works printed but not linked: 1
- Diana T, Kanitz M, Lehmann M, Li Y, Olivo PD, Kahaly GJ. Stan- dardization of a bioassay for thyrotropin receptor stimulating au- toantibodies. Thyroid. 2015;25:169 -175.
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Sorted by citations
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
“A recent trial from Japan (540) randomized patients without GO or inactive GO (i.e., CAS 3 or T2-weighted imaging T2SIR £1) to receive either glucocorticoid prophylaxis with low-dose prednisolone (on average 0.28 mg/kg per day tapered rapidly over 6 weeks) or no prophylaxis at all.”
BackgroundInfluentialBartalena, L., Baldeschi, L., Boboridis, K., Eckstein, A., Kahaly, G. J., Marcocci, C., Perros, P., Salvi, M., & Wiersinga, W. M. (2016) · European Thyroid Journal · doi:10.1159/000443828 · Cited by 943 · see citing works
De Leo, S., Lee, S. Y., & Braverman, L. E. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00278-6 · Cited by 883 · see citing works
- Authors
- Watanabe, N., Noh, J. Y., Kozaki, A., Iwaku, K., Sekiya, K., Kosuga, Y., Matsumoto, M., Suzuki, M., Yoshihara, A., Ohye, H., Kobayashi, S., Kunii, Y., Mukasa, K., Sugino, K., Inoue, T., & Ito, K.
- Affiliations
- Ito Hospital (JP)
- Corresponding author
- Watanabe, Natsuko
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-07
- Volume
- 100
- Issue
- 7
- Pages
- 2700-2708
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W1841138620
- Cited by
- 35
- References
- 41
- Citations by year
- 2025: 5 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 4 · 2016: 8
- FWCI
- 3.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15K09296)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Neurology › Myasthenia Gravis and Thymoma
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- Graves' ophthalmopathy, Graves' disease, radioiodine therapy, disease exacerbation, prophylactic corticosteroids, prednisolone, thyroid-stimulating antibodies, clinical activity score, prognostic factors, Japanese patients
- MeSH terms
- Adult, Aged, Female, Graves Disease, Humans, Iodine Radioisotopes, Japan, Male, Middle Aged, Prednisolone, Radiation Injuries, Disease Progression, Chemoprevention, Graves Ophthalmopathy, Young Adult
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