Occurrence of Ophthalmopathy after Treatment for Graves' Hyperthyroidism
Open accessAbstract
BACKGROUND: Ophthalmopathy caused by Graves' disease may first appear or worsen during or after treatment for hyperthyroidism. It is not known, however, whether choosing to treat hyperthyroidism with antithyroid drugs, iodine-131, or surgery affects the development or aggravation of Graves' ophthalmopathy. METHODS: We studied 168 patients with hyperthyroidism caused by Graves' disease, stratified into two age groups--20 to 34 years (54 patients, group 1) and 35 to 55 years (114 patients, group 2). The patients in group 1 were randomly assigned to treatment with methimazole for 18 months or subtotal thyroidectomy, and those in group 2 to either of these two treatments or to iodine-131 therapy. All the patients received thyroxine to avert hypothyroidism, except those treated with iodine-131, who received thyroxine only if hypothyroidism developed. The duration of follow-up was at least 24 months. RESULTS: Twenty-two patients (13 percent) had infiltrative Graves' ophthalmopathy at randomization. During follow-up, ophthalmopathy developed for the first time in 22 patients (13 percent) and worsened in 8 patients (5 percent). The frequency of the development or worsening of ophthalmopathy was similar among the patients in group 1 (medical therapy, 4 of 27 patients [15 percent]; and surgery, 3 of 27 patients [11 percent]). In group 2, ophthalmopathy developed or worsened in 4 of the 38 patients (10 percent) treated medically, 6 of the 37 patients (16 percent) treated surgically, and 13 of the 39 patients (33 percent) given iodine-131 (P = 0.02 for the comparison between the iodine-131 subgroup and the others combined). The risk of the development or worsening of ophthalmopathy increased as pretreatment serum triiodothyronine concentrations increased. CONCLUSIONS: As compared with other forms of antithyroid therapy, iodine-131 is more likely to be followed by the development or exacerbation of Graves' ophthalmopathy.
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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 [532]
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 [532]
The first randomized study of GD patients (13% with mild preexistent GO) assigned to ATDs, surgery, or RAI found the relative risk for deterioration of eye disease to be elevated at 3.2 for RAI compared to ATDs.
“The first randomized study of GD patients (13% with mild preexistent GO) assigned to therapy for hyperthyroidism with ATDs, surgery, or RAI (532) found the relative risk for deterioration of eye disease to be elevated at 3.2 for RAI compared to ATDs.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [532]
There appeared to be no difference in the risk of GO deterioration between ATDs and surgery.
“There appeared to be no difference in such risk between ATDs and surgery.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [532]
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 [532]
Cases of new or worse GO were usually mild, with only 6/168 patients in the second trial requiring specific therapy for GO.
“Fortunately, the cases of new or worse GO were usually mild, with only 6/ 168 patients in this second trial (four in the RAI group, one in the ATD group, and one in the surgical group) requiring specific therapy for GO.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [532]
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References 21 · Cited by 521
Research works printed but not linked: 6
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- Authors
- Tallstedt, L., Lundell, G., Tørring, O., Wallin, G., Ljunggren, J.-G., Blomgren, H., & Taube, A.
- Affiliations
- S:t Eriks Ögonsjukhus (SE)
- ORCID
- Wallin, Göran
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1992-06-25
- Volume
- 326
- Issue
- 26
- Pages
- 1733-1738
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2320293007
- Cited by
- 521
- References
- 21
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 15 · 2023: 12 · 2022: 9 · 2021: 13 · 2020: 18 · 2019: 13 · 2018: 16 · 2017: 5 · 2016: 22 · 2015: 23 · 2014: 15 · 2013: 20 · 2012: 24
- FWCI
- 11.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (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 › Neurology › Myasthenia Gravis and Thymoma
- Keywords
- Graves' ophthalmopathy, Graves' disease, hyperthyroidism, iodine-131 therapy, antithyroid drugs, methimazole, subtotal thyroidectomy, thyroid surgery, triiodothyronine, hypothyroidism, thyroxine
- MeSH terms
- Adult, Female, Follow-Up Studies, Graves Disease, Humans, Hypothyroidism, Iodine Radioisotopes, Male, Methimazole, Middle Aged, Random Allocation, Thyroidectomy, Thyroxine
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