Abstract：
:Thyroid-associated ophthalmopathy (TAO) is a complex disease process presumed to emerge from autoimmunity occurring in the thyroid gland, most frequently in Graves disease (GD). It is disfiguring and potentially blinding, culminating in orbital tissue remodeling and disruption of function of structures adjacent to the eye. There are currently no medical therapies proven capable of altering the clinical outcome of TAO in randomized, placebo-controlled multicenter trials. The orbital fibroblast represents the central target for immune reactivity. Recent identification of fibroblasts that putatively originate in the bone marrow as monocyte progenitors provides a plausible explanation for why antigens, the expressions of which were once considered restricted to the thyroid, are detected in the TAO orbit. These cells, known as fibrocytes, express relatively high levels of functional TSH receptor (TSHR) through which they can be activated by TSH and the GD-specific pathogenic antibodies that underpin thyroid overactivity. Fibrocytes also express insulin-like growth factor I receptor (IGF-IR) with which TSHR forms a physical and functional signaling complex. Notably, inhibition of IGF-IR activity results in the attenuation of signaling initiated at either receptor. Some studies suggest that IGF-IR-activating antibodies are generated in GD, whereas others refute this concept. These observations served as the rationale for implementing a recently completed therapeutic trial of teprotumumab, a monoclonal inhibitory antibody targeting IGF-IR in TAO. Results of that trial in active, moderate to severe disease revealed dramatic and rapid reductions in disease activity and severity. The targeting of IGF-IR with specific biologic agents may represent a paradigm shift in the therapy of TAO.
journal_name
Endocr Revjournal_title
Endocrine reviewsauthors
Smith TJ,Janssen JAMJLdoi
10.1210/er.2018-00066subject
Has Abstractpub_date
2019-02-01 00:00:00pages
236-267issue
1eissn
0163-769Xissn
1945-7189pii
5094009journal_volume
40pub_type
杂志文章,评审abstract：:Rats bearing transplantable Walker 256 carcinoma provide an opportunity to assess thyroid function and activity during an interval of time when the tumor has not affected growth rate. Rats with tumor have decreased serum T4 and T3 concentration and decreased serum FT4 and FT3 as well. These changes are due to a decrea...
journal_title：Endocrine reviews
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更新日期：1994-08-01 00:00:00
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journal_title：Endocrine reviews
pub_type： 杂志文章,评审
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更新日期：2019-08-01 00:00:00
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journal_title：Endocrine reviews
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更新日期：2014-02-01 00:00:00
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journal_title：Endocrine reviews
pub_type： 杂志文章,评审
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更新日期：2011-06-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2002-12-01 00:00:00
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更新日期：2007-12-01 00:00:00
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更新日期：2018-02-01 00:00:00
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更新日期：2005-04-01 00:00:00
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更新日期：1998-02-01 00:00:00
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