Pathophysiology of thyroid-associated orbitopathy

Thyroid-associated orbitopathy, the most common extrathyroidal manifestation of Graves' disease, is characterized by orbital in-flammatory infiltration and activation of orbital fibroblasts, which mediates de novo adipogenesis, excessive production of hyalur-onan, myofibroblast differentiation and ultimately tissue fibrosis. Interactions among T cells, B cells, and orbital fibroblasts result in their activation and perpetuation of orbital inflammation as well as tissue remodelling. T helper 17 cells belong to a newly identified pathogenic CD4 thorn T cell subset which possesses prominent pro -inflammatory and profibrotic capabilities. Thyroid stimulating hormone receptor/insulin-like growth factor-1 receptor crosstalk and the downstream signalling pathways of both receptors represent the major mechanisms leading to activation of orbital fibroblasts. Thyroid stimulating hormone receptor autoantibody is the disease specific biomarker of great clinical relevance and utility. There is growing evidence that oxidative stress, gut microbiome and epigenetics also play a role in the pathogenesis and their manipulation may represent novel therapeutic strategies.(c) 2022 Elsevier Ltd. All rights reserved.