New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved]
Thyroid-associated ophthalmopathy (TAO), a localized periocular manifestation of the autoimmune syndrome known as Graves’ disease, remains incompletely understood. Discussions of its pathogenesis are generally focused on the thyrotropin receptor, the proposed role for which is supported by substanti...
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2018-02-01
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| Series: | F1000Research |
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| Online Access: | https://f1000research.com/articles/7-134/v1 |
| _version_ | 1819174914132803584 |
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| author | Terry J Smith |
| author_facet | Terry J Smith |
| author_sort | Terry J Smith |
| collection | DOAJ |
| description | Thyroid-associated ophthalmopathy (TAO), a localized periocular manifestation of the autoimmune syndrome known as Graves’ disease, remains incompletely understood. Discussions of its pathogenesis are generally focused on the thyrotropin receptor, the proposed role for which is supported by substantial evidence. Considerations of any involvement of the insulin-like growth factor-I receptor (IGF-IR) in the disease are frequently contentious. In this brief, topically focused review, I have attempted to provide a balanced perspective based entirely on experimental results that either favor or refute involvement of IGF-IR in TAO. Discussion in this matter seems particularly timely since the currently available treatments of this disfiguring and potentially sight-threatening disease remain inadequate. Importantly, no medical therapy has thus far received approval from the US Food and Drug Administration. Results from a very recently published clinical trial assessing the safety and efficacy of teprotumumab, an inhibitory human anti–IGF-IR monoclonal antibody, in active, moderate to severe TAO are extremely encouraging. That double-masked, placebo-controlled study involved 88 patients and revealed unprecedented clinical responses in the improvement of proptosis and clinical activity as well as a favorable safety profile. Should those results prove reproducible in an ongoing phase III trial, therapeutic inhibition of IGF-IR could become the basis for paradigm-shifting treatment of this vexing disease. |
| first_indexed | 2024-12-22T20:46:32Z |
| format | Article |
| id | doaj.art-b4e95bda4dd34cb0a381e0b3aa557a5c |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-22T20:46:32Z |
| publishDate | 2018-02-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-b4e95bda4dd34cb0a381e0b3aa557a5c2022-12-21T18:13:12ZengF1000 Research LtdF1000Research2046-14022018-02-01710.12688/f1000research.12787.113855New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved]Terry J Smith0Department of Ophthalmology and Visual Sciences, Kellogg Eye Center and Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USAThyroid-associated ophthalmopathy (TAO), a localized periocular manifestation of the autoimmune syndrome known as Graves’ disease, remains incompletely understood. Discussions of its pathogenesis are generally focused on the thyrotropin receptor, the proposed role for which is supported by substantial evidence. Considerations of any involvement of the insulin-like growth factor-I receptor (IGF-IR) in the disease are frequently contentious. In this brief, topically focused review, I have attempted to provide a balanced perspective based entirely on experimental results that either favor or refute involvement of IGF-IR in TAO. Discussion in this matter seems particularly timely since the currently available treatments of this disfiguring and potentially sight-threatening disease remain inadequate. Importantly, no medical therapy has thus far received approval from the US Food and Drug Administration. Results from a very recently published clinical trial assessing the safety and efficacy of teprotumumab, an inhibitory human anti–IGF-IR monoclonal antibody, in active, moderate to severe TAO are extremely encouraging. That double-masked, placebo-controlled study involved 88 patients and revealed unprecedented clinical responses in the improvement of proptosis and clinical activity as well as a favorable safety profile. Should those results prove reproducible in an ongoing phase III trial, therapeutic inhibition of IGF-IR could become the basis for paradigm-shifting treatment of this vexing disease.https://f1000research.com/articles/7-134/v1Retinal, Vitreous & Macular Disorders |
| spellingShingle | Terry J Smith New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved] F1000Research Retinal, Vitreous & Macular Disorders |
| title | New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved] |
| title_full | New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved] |
| title_fullStr | New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved] |
| title_full_unstemmed | New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved] |
| title_short | New advances in understanding thyroid-associated ophthalmopathy and the potential role for insulin-like growth factor-I receptor [version 1; referees: 2 approved] |
| title_sort | new advances in understanding thyroid associated ophthalmopathy and the potential role for insulin like growth factor i receptor version 1 referees 2 approved |
| topic | Retinal, Vitreous & Macular Disorders |
| url | https://f1000research.com/articles/7-134/v1 |
| work_keys_str_mv | AT terryjsmith newadvancesinunderstandingthyroidassociatedophthalmopathyandthepotentialroleforinsulinlikegrowthfactorireceptorversion1referees2approved |