{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:13:41Z","timestamp":1787022821178,"version":"build-2736575974"},"reference-count":198,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:p>Thyroid-associated ophthalmopathy (TAO) is a vexing and poorly understood autoimmune process involving the upper face and tissues surrounding the eyes. In TAO, the orbit can become inflamed and undergo substantial remodeling that is disfiguring and can lead to loss of vision. There are currently no approved medical therapies for TAO, the consequence of its uncertain pathogenic nature. It usually presents as a component of the syndrome known as Graves\u2019 disease where loss of immune tolerance to the thyrotropin receptor (TSHR) results in the generation of activating antibodies against that protein and hyperthyroidism. The role for TSHR and these antibodies in the development of TAO is considerably less well established. We have reported over the past 2 decades evidence that the insulin-like growth factorI receptor (IGF1R) may also participate in the pathogenesis of TAO. Activating antibodies against IGF1R have been detected in patients with GD. The actions of these antibodies initiate signaling in orbital fibroblasts from patients with the disease. Further, we have identified a functional and physical interaction between TSHR and IGF1R. Importantly, it appears that signaling initiated from either receptor can be attenuated by inhibiting the activity of IGF1R. These findings underpin the rationale for therapeutically targeting IGF1R in active TAO. A recently completed therapeutic trial of teprotumumab, a human IGF1R inhibiting antibody, in patients with moderate to severe, active TAO, indicates the potential effectiveness and safety of the drug. It is possible that other autoimmune diseases might also benefit from this treatment strategy.<\/jats:p>","DOI":"10.1530\/jme-17-0276","type":"journal-article","created":{"date-parts":[[2017,12,22]],"date-time":"2017-12-22T20:20:38Z","timestamp":1513974038000},"page":"T29-T43","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":60,"title":["40 YEARS OF IGF1: IGF1 receptor and thyroid-associated ophthalmopathy"],"prefix":"10.1530","volume":"61","author":[{"given":"Michelle","family":"Mohyi","sequence":"first","affiliation":[{"name":"1Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry J","family":"Smith","sequence":"additional","affiliation":[{"name":"1Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA"},{"name":"2Division of Metabolism, Endocrine, and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref111","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1172\/JCI116621","article-title":"Insulin-like growth factor-1 stimulation of lymphopoiesis","volume":"92","year":"1993","journal-title":"Journal of Clinical Investigation"},{"key":"ref1751","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1510030","article-title":"Graves\u2019 disease","volume":"375","year":"2016","journal-title":"New England Journal of Medicine"},{"key":"ref1251","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.maturitas.2016.08.012","article-title":"Insulin growth factor (IGF) 1, IGF-binding proteins and ovarian cancer risk: a systematic review and meta-analysis","volume":"94","year":"2016","journal-title":"Maturitas"},{"key":"ref601","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1172\/JCI200420997","article-title":"Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis","volume":"114","year":"2004","journal-title":"Journal of Clinical Investigation"},{"key":"ref811","first-page":"160008","article-title":"Thyroid antibody-negative euthyroid Graves\u2019 ophthalmopathy","volume":"2016","year":"2016","journal-title":"Endocrinology, Diabetes and Metabolism Case Reports"},{"key":"ref691","first-page":"1857","article-title":"Thyrotropin receptor messenger ribonucleic acid is expressed in most brown and white adipose tissues in the guinea pig.","volume":"130","year":"1992","journal-title":"Endocrinology"},{"key":"ref841","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1146\/annurev-pathol-012513-104713","article-title":"Mechanisms of autoimmune thyroid diseases: from genetics to epigenetics","volume":"9","year":"2014","journal-title":"Annual Review of Pathology"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"7427","DOI":"10.1073\/pnas.1202064109","article-title":"Human fibrocytes coexpress thyroglobulin and thyrotropin receptor","volume":"109","year":"2012","journal-title":"PNAS"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1016\/0014-5793(87)80169-2","article-title":"Photoaffinity labelling of the TSH receptor on FRTL5 cells","volume":"215","year":"1987","journal-title":"FEBS Letters"},{"key":"ref1411","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.ecl.2009.01.006","article-title":"The thyroid-stimulating hormone receptor: impact of thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies on multimerization, cleavage, and signaling","volume":"38","year":"2009","journal-title":"Endocrinology Metabolism Clinics of North America"},{"key":"ref511","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1210\/en.2008-0878","article-title":"Characterization of thyrotropin receptor antibody-induced signaling cascades","volume":"150","year":"2009","journal-title":"Endocrinology"},{"key":"ref971","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.2174\/13816128113199990595","article-title":"Advances in targeting insulin-like growth factor signaling pathway in cancer treatment","volume":"20","year":"2014","journal-title":"Current Pharmaceutical Design"},{"key":"ref1811","doi-asserted-by":"crossref","first-page":"7834","DOI":"10.1016\/S0021-9258(20)89525-8","article-title":"Thyrotropin and insulin-like growth factor I regulation of tyrosine phosphorylation in FRTL-5 cells. 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