The Influence of Prior Hyperthyroidism on Euthyroid Graves’ Ophthalmopathy

Termote, Karolien; Decallonne, Brigitte; Mombaerts, Ilse

doi:10.1155/2014/426898

Cited by 8 publications

(7 citation statements)

References 31 publications

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“…32 and 46) (Table 1). This phenomenon is consistent with a few cases called euthyroid Graves' ophthalmopathy (EGO), which is defined as the presence of thyroid-associated ophthalmopathy in patients with normal thyroid function (40,41). Most of the patients with EGO proved to be TRAb-positive (including stimulating and inhibiting antibodies), but the underlying mechanism is currently unknown (41).…”

Section: Discussionsupporting

confidence: 76%

A Promising Mouse Model of Graves' Orbitopathy Induced by Adenovirus Expressing Thyrotropin Receptor A Subunit

Zhang

Ding

et al. 2021

Thyroid

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Background: Graves' orbitopathy (GO) is the most common and serious manifestation of Graves' disease (GD). It is characterized by orbital inflammation and tissue remodeling. Although several GO models have been reported, most lack a full assessment or mechanistic evaluation. Here, we established a promising mouse model mimicking many aspects of human GO with a frequency of 70% and characterized the key role of T cells in the progression of GO. Methods: An adenovirus expressing the human thyrotropin (TSH) receptor A subunit (Ad-TSHRA) was injected in the muscles of female BALB/C mice nine times to induce GO. At predetermined time points, histological examinations of retrobulbar tissues and thyroid glands were performed to dynamically monitor changes; serum autoantibodies and total thyroxine levels were examined to evaluate thyroid function. Flow cytometry of CD4+ T cell subgroups and RNA sequencing (RNA-Seq) of splenocytes were also performed to explore the underlying mechanism. Results: After nine injections, 7 of 10 mice challenged with Ad-TSHRA developed the orbital changes associated with GO. Seven mice manifested retrobulbar fibrosis, and four mice showed adipogenesis. Exophthalmia, conjunctival redness, and orbital lymphocyte infiltration were also observed in a subset of mice. The orbitopathy was first detected after seven injections and followed the hyperplastic change observed in thyroids after four injections. Flow cytometry revealed increased proportions of Th1 cells and decreased proportions of Th2 cells and regulatory T (Treg) cells in the splenocytes of GO mice. This change in CD4+ T cell subgroups was confirmed by orbital immunohistochemical staining. Genes involved in T cell receptor signaling, proliferation, adhesion, inflammation, and cytotoxicity were upregulated in GO mice according to the RNA-Seq; a trend of upregulation of these GO-specific genes was observed in mice with hyperthyroidism without orbitopathy after four injections. Conclusions: A GO mouse model was successfully established by administering nine injections of Ad-TSHRA. The model was achieved with a frequency of 70% and revealed the importance of T cell immunity. A potential time window from Graves' hyperthyroidism to GO was presented for the first time. Therefore, this model could be used to study the pathogenesis and novel treatments for GO.

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Section: Discussionsupporting

confidence: 76%

A Promising Mouse Model of Graves' Orbitopathy Induced by Adenovirus Expressing Thyrotropin Receptor A Subunit

Zhang

Ding

et al. 2021

Thyroid

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“…A number of distinct clinical variants of GO exist, however these are poorly studied and deserve attention. Euthyroid/hypothyroid GO is a variant comprising of patients who are euthyroid, or have overt or subclinical hypothyroidism, before or within 6–12 months after the onset of GO and constitutes 0.2–11% of all cases of GO [ 29 – 33 ]. Patients with GO associated with dermopathy have characteristic skin changes and comprise 1.5% of all cases of GO [ 7 ].…”

Section: Resultsmentioning

confidence: 99%

Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement

Perros

Hegedűs

Bartalena

et al. 2017

Orphanet J Rare Dis

136

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BackgroundGraves’ orbitopathy (GO) is an autoimmune condition, which is associated with poor clinical outcomes including impaired quality of life and socio-economic status. Current evidence suggests that the incidence of GO in Europe may be declining, however data on the prevalence of this disease are sparse. Several clinical variants of GO exist, including euthyroid GO, recently listed as a rare disease in Europe (ORPHA466682).The objective was to estimate the prevalence of GO and its clinical variants in Europe, based on available literature, and to consider whether they may potentially qualify as rare. Recent published data on the incidence of GO and Graves’ hyperthyroidism in Europe were used to estimate the prevalence of GO. The position statement was developed by a series of reviews of drafts and electronic discussions by members of the European Group on Graves’ Orbitopathy. The prevalence of GO in Europe is about 10/10,000 persons. The prevalence of other clinical variants is also low: hypothyroid GO 0.02–1.10/10,000; GO associated with dermopathy 0.15/10,000; GO associated with acropachy 0.03/10,000; asymmetrical GO 1.00–5.00/10,000; unilateral GO 0.50–1.50/10,000.ConclusionGO has a prevalence that is clearly above the threshold for rarity in Europe. However, each of its clinical variants have a low prevalence and could potentially qualify for being considered as a rare condition, providing that future research establishes that they have a distinct pathophysiology. EUGOGO considers this area of academic activity a priority.

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“…In a clinical study conducted by Termote et al , the euthyroid patients developed milder and unilateral ophthalmopathy ( 5 ). The discovery was that previous exposure to high levels of thyroid hormone in euthyroid ophthalmopathy could be associated with proptosis and extraocular muscle restriction ( 5 ). It was also revealed that normal thyroid function influences the course of the GO positively ( 27 ).…”

Section: Clinical Characteristics Of Egdmentioning

confidence: 99%

“…Notably, euthyroid ophthalmopathy can represent the initial stage of thyroid dysfunction. It is also considered that a subset of patients with prior undetermined episodes of transient thyroid abnormalities is identified within the group of euthyroid patients ( 5 ). Long-term follow-up is essential in the management of EGD, and a retrospective study has highlighted that dysthyroidism could occur in 8-25% of patients between 15-45 months from the initial presentation of ophthalmopathy ( 5 ).…”

Section: Introductionmentioning

confidence: 99%

“…It is also considered that a subset of patients with prior undetermined episodes of transient thyroid abnormalities is identified within the group of euthyroid patients ( 5 ). Long-term follow-up is essential in the management of EGD, and a retrospective study has highlighted that dysthyroidism could occur in 8-25% of patients between 15-45 months from the initial presentation of ophthalmopathy ( 5 ). Furthermore, a patient with euthyroid ophthalmopathy was observed for twelve years without developing thyroid dysfunction ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

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A systematic review of euthyroid Graves' disease (Review)

et al. 2021

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Euthyroid Graves' Disease (EGD) is a challenging pathology, due to its atypical clinical manifestations and the absence of abnormal thyroid function. Typically, thyroid ophthalmopathy is associated with elevated thyroid hormone levels and with the presence of thyrotropin receptor antibodies (TRAb) but a low percentage of patients remain euthyroid without developing hyperthyroidism during long-term follow-up periods. Although it is considered a different pathology, it shares a lot of similarities with Graves' disease, rendering the diagnosis more difficult. It is also important to note that ophthalmopathy may be the first clinical manifestation of Graves' disease and that thyroid function examinations do not present abnormalities over a long period. Treatment choices for euthyroid disease do not differ from those described in Graves' ophthalmopathy. However, it is considered that since euthyroid patients develop milder ophthalmic symptoms and their clinical activity score is lower, they tend to have better responses to treatment. Moreover, atypical sight-threatening cases such as exposure keratopathy and dysthyroid optic neuropathy with variable responses to therapy also exist. Disease management consists of a favorable collaboration between ophthalmologists and endocrinologists because patients with EGD can develop thyroid abnormalities over time. In conclusion, the diagnosis of EGD is difficult, clinical manifestations and evolution are variables depending on several factors, including the heterogeneity of TRAb. This review aimed to identify the characteristics of this disease by reviewing the clinical studies and case reports published in previous years.

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The Influence of Prior Hyperthyroidism on Euthyroid Graves’ Ophthalmopathy

Cited by 8 publications

References 31 publications

A Promising Mouse Model of Graves' Orbitopathy Induced by Adenovirus Expressing Thyrotropin Receptor A Subunit

A Promising Mouse Model of Graves' Orbitopathy Induced by Adenovirus Expressing Thyrotropin Receptor A Subunit

Graves’ orbitopathy as a rare disease in Europe: a European Group on Graves’ Orbitopathy (EUGOGO) position statement

A systematic review of euthyroid Graves' disease (Review)

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