Does autoimmunity against thyroglobulin play a role in the pathogenesis of Graves' ophthalmopathy: a review

While most authors believe that autoimmunity against the TSH receptor expressed in the orbital connective tissue cells is the main reaction that leads to the development of ophthalmopathy in patients with Graves' hyperthyroidism, an older hypothesis that deserves fresh consideration is based on the notion that thyroglobulin (Tg) in the thyroid gland passes in a retrograde fashion to the orbit where it is recognized by Tg autoantibodies, leading to inflammation. Here, we review new evidence that supports a role of Tg and propose a new hypothesis based on the notion that Tg is targeted in the orbit leading to a complex cascade of reactions that leads to Graves' ophthalmopathy.