The role of the thyrotropin (TSH) receptor in the immunopathogenesis of GO
Circulating TSH receptor stimulatory autoantibodies recognize the receptor on fibroblasts residing within the orbit. Ligation of the receptor results in activation of the phosphoinositide-3-kinase (P13K)/Akt signaling cascade, as well as others, including the adenylyl cyclase (AC)/cAMP pathway. This leads to increased production of hyaluronic acid (HA) by these cells and the development of new fat cells from a subset of adipocyte precursors. In addition, insulinlike growth factor (IGF-I) and other growth factors and cytokines within the orbit may modulate these processes. This results in accumulation of HA and edema within the orbit and expansion of the orbital fat volume, leading to the varied clinical expressions of the disease. Iyer S, et al. Immunopathogenesis of Graves' ophthalmopathy: The role of the TSH receptor. Best Practice & Research. Clinical Endocrinology & Metabolism. 2012; 26(3):281-289. Used with permission.