Pathophysiology of Graves’ Ophthalmopathy: The Cycle of Disease

Hyperthyroidism in Graves ’ disease is due to the binding of stimulatory autoantibodies to the TSH receptor (TSHr) on thyroid follicular cells. The stimulation of this G proteincoupled receptor by autoantibodies leads to excessive and uncontrolled production of thyroid hormone. Our understanding of Graves ’ disease has increased remarkably after the cloning in 1989 of TSHr (1–3). This achievement led to insights regarding TSHr biology, including the unique two-subunit structure of this receptor that may render it especially prone to autoimmune attack (4). In contrast, the pathophysiology of Graves ’ ophthalmopathy (GO) and thyroid-associated pretibial dermopathy (PTD) is less well understood. However, studies by several groups have begun to unravel the many complex factors contributing to development of these ocular and dermal manifestations of Graves ’ disease.