Abstract:

Graves’ disease is always accompanied by thyroid-associated ophthalmopathy (TAO), and both of them shared the same pathophysiological characteristics, as it has been proved that thyroid\|stimulating hormone receptor (TSHR) plays an essential role not only in the pathogenesis of Graves’ disease but also in that of TAO. TSHR expresses on orbital fibroblasts in the procedure of TAO, in which many factors such as cellular and humeral immunity, thyrotropin stimulating immunoglobulin (TSI), thyroid\|stimulating hormone (TSH), platelet derived growth factor (PDGF) and other thyroid antibodies synergistically initiate the disease via TSHR. The activation of helper T cells recognizing TSHR peptides and ligation of TSHR by TRAb lead to the secretion of inflammatory cytokines and chemokines, and enhanced hyaluronic acid (HA) production and adipogenesis. The resulting connective tissue remodeling results in varying degrees extraocular muscle enlargement and orbital fat expansion. In addition to TSHR, orbital fibroblasts from patients with TAO express high levels of insulin-like growth factors\|1 receptor (IGF-1R). Stimulatory autoantibodies direct against the insulin-like growth factor-1 receptor have been proposed to contribute to orbital fibroblast activation in TAO.