Relation between Therapy for Hyperthyroidism and the Course of Graves' Ophthalmopathy
Open accessAbstract
BACKGROUND: The chief clinical characteristics of Graves' disease are hyperthyroidism and ophthalmopathy. The relation between the two and the effect of treatment for hyperthyroidism on ophthalmopathy are unclear. METHODS: We studied 443 patients with Graves' hyperthyroidism and slight or no ophthalmopathy who were randomly assigned to receive radioiodine, radioiodine followed by a 3-month course of prednisone, or methimazole for 18 months. The patients were evaluated for changes in the function and appearance of the thyroid and progression of ophthalmopathy at intervals of 1 to 2 months for 12 months. Hypothyroidism and persistent nyperthyroiaism were promptly corrected. RESULTS: Among the 150 patients treated with radioiodine, ophthalmopathy developed or worsened in 23 (15 percent) two to six months after treatment. The change was transient in 15 patients, but it persisted in 8 (5 percent), who subsequently required treatment for their eye disease. None of the 55 other patients in this group who had ophthalmopathy at base line had improvement in their eye disease. Among the 145 patients treated with radioiodine and prednisone, 50 (67 percent) of the 75 with ophthalmopathy at base line had improvement, and no patient had progression. The effects of radioiodine on thyroid function were similar in these two groups. Among the 148 patients treated with methimazole, 3 (2 percent) who had ophthalmopathy at base line improved, 4 (3 percent) had worsening of eye disease, and the remaining 141 had no change. CONCLUSIONS: Radioiodine therapy for Graves' hyperthyroidism is followed by the appearance or worsening of ophthalmopathy more often than is therapy with methimazole. Worsening of ophthalmopathy after radioiodine therapy is often transient and can be prevented by the administration of prednisone.
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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 [531]
Other studies suggest that ATDs may not adversely impact mild active GO, but they do not address severe GO.
“Other studies suggest that ATDs may not adversely impact mild active GO, but they do not address severe GO (531).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [531]
There is evidence that corticosteroids given concurrently with RAI may prevent worsening of GO in patients with mild active eye disease.
“There is evidence that corticosteroids given concurrently with RAI may prevent worsening of GO in patients with mild active eye disease (531).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [531]
A large, more recent randomized controlled trial studying mainly patients with previously treated GD showed RAI therapy to be associated with an increased risk of GO progression (RR 5.8 in comparison with ATDs) and found the risk to be eliminated with concurrent corticosteroid administration.
“A large, more recent randomized controlled trial studying mainly patients with previously treated GD showed RAI therapy to be associated with an increased risk of GO progression (RR of 5.8 in comparison with ATDs) and found the risk to be eliminated with concurrent corticosteroid administration (531).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [531]
Smoking is the most important known risk factor for the development or worsening of GO, unrelated to type of therapy for GO, and consistent data from several studies show a detrimental effect of smoking on GO in patients treated with RAI.
“Smoking is the most important known risk factor for the development or worsening of GO, unrelated to type of therapy for GO (535), and consistent data from several studies show a detrimental effect of smoking on GO in patients a ATDs or thyroidectomy are also recommended treatment options in each of these scenarios, and they are the preferred choice of therapy in patients with active and moderate-”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [531]
In two different studies, active smokers who received RAI represented the group with the highest incidence (23%-40%) of new GO or deterioration of pre-existing GO during 1 year of follow-up.
“However, in two different studies, active smokers who received RAI represented the group with the highest incidence (23%-40%) of new GO or deterioration of pre-existing GO during 1 year of follow-up (69,531).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [531]
Two randomized controlled trials found the risk of new GO development to be 6/78 (8%) for RAI compared with 1/74 (1%) for ATDs in one study, and 10/32 (32%) for RAI compared with 6/56 (11%) for ATDs and 6/58 (10%) for surgery in an older study.
“Two randomized controlled trials found the risk to be 6/78 (8%) for RAI compared with 1/74 (1%) for ATDs (531) in one study, and 10/32 (32%) for RAI compared with 6/56 (11%) for ATDs and 6/58 (10%) for surgery (532) in the older study.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [531]
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- Authors
- Bartalena, L., Marcocci, C., Bogazzi, F., Manetti, L., Tanda, M. L., Dell'Unto, E., Bruno-Bossio, G., Nardi, M., Bartolomei, M. P., Lepri, A., Rossi, G., Martino, E., & Pinchera, A.
- Affiliations
- University of Pisa (IT)
- National Academies of Sciences, Engineering, and Medicine (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1998-01-08
- Volume
- 338
- Issue
- 2
- Pages
- 73-78
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2024010187
- Cited by
- 715
- References
- 26
- Citations by year
- 2026: 14 · 2025: 20 · 2024: 19 · 2023: 15 · 2022: 26 · 2021: 21 · 2020: 23 · 2019: 20 · 2018: 23 · 2017: 12 · 2016: 32 · 2015: 29 · 2014: 27 · 2013: 27 · 2012: 33
- FWCI
- 24.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- IrInSubria (University of Insubria) (submittedVersion)
- 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 › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- Graves' ophthalmopathy, Graves' disease, hyperthyroidism, radioiodine therapy, methimazole, prednisone
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Combined Modality Therapy, Exophthalmos, Female, Glucocorticoids, Graves Disease, Humans, Iodine Radioisotopes, Male, Methimazole, Middle Aged, Prednisone, Prospective Studies, Antithyroid Agents, Treatment Outcome, Disease Progression
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