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Old 09-15-2018, 06:30 AM
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rss IGF - Insulin-like growth factor-I receptor and thyroid-associated ophthalmopathy.

Insulin-like growth factor-I receptor and thyroid-associated ophthalmopathy.

Endocr Rev. 2018 Sep 11;:

Authors: Smith TJ, Janssen JAMJL

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 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 thyrotropin receptor (TSHR) through which they can be activated by TSH and the GD-specific pathogenic antibodies that underpin thyroid over-activity. Fibrocytes also express insulin-like growth factor-I receptor (IGF-IR) with which TSHR forms a physical and functional signaling complex. Notably, inhibiting 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 while 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. Targeting IGF-IR with specific biologic agents may represent a paradigm shift in the therapy of TAO.


PMID: 30215690 [PubMed - as supplied by publisher]



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