Pathogenesis of Graves' ophthalmopathy: the role of autoantibodies.
ABSTRACT The clinical manifestations of Graves' ophthalmopathy (GO) stem from a combination of increased orbital fat and extraocular muscle volume within the orbital space. Fibroblasts residing within orbital tissues are thought to be targets of autoimmune attack in the disease. Thyrotropin receptor (TSHr) mRNA and functional protein have been demonstrated in orbital fibroblasts from both normal individuals and GO patients, with higher levels present in the latter. Autoantibodies directed against TSHr or the insulin-like growth factor-1 (IGF-1) receptor have been implicated in GO pathogenesis. Evidence from our laboratory suggests that monoclonal TSHr autoantibodies (TRAbs) are potent stimulators of adipogenesis in GO orbital cells. Therefore, it is possible that circulating TRAbs in Graves' patients both stimulate overproduction of thyroid hormones and increase orbital adipose tissue volume. Antibodies to the IGF-1 receptor appear to impact GO pathogenesis through recruitment and activation of T-cells and stimulation of hyaluronan production, processes that play key roles in the development of inflammation and increased orbital tissue swelling. Although originally thought to represent another causative agent, antibodies to extraocular muscles are now generally thought to be secondary to extraocular muscle inflammation and damage.
Article: Orbit-Thyroid Relationship
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ABSTRACT: Introduction. The definition of severity and activity of Graves' ophthalmopathy (GO) comprises different parameters. The aim of this study is to select the most appropriate severity and activity criteria, respectively scores and to investigate a possible correlation among them. Subjects and methods. The study included 51 patients with GO (43 females, 8 males), mean age 46.8±11.2 years. The patients were evaluated by: clinical exam, laboratory parameters (TSH, FT4, FT3, thyroid autoantibodies) and imagistic means, performed in selected cases (CT or MRI). Results. The GO activity was assessed by the clinical activity score (CAS). We quantified the EUGOGO severity criteria, by allotting points for each selected parameter. According to the recommended criteria, the cases were divided into active (n=26) and inactive forms (n=25). There were no significant statistical differences regarding CAS between euthyroid cases (n=14) and dysthyroid cases (n=37). Serum thyroid receptor antibodies (TRAb) levels did not correlate with CAS or severity scores. Severity scores correlated significantly with CAS (Pearson correlation index 0.546, r2=0.290, p=0.0001). Conclusion. Active forms of GO showed higher severity scores than the inactive ones. The severity scores correlated significantly with CAS scores. Neither CAS, nor severity scores correlated significantly with the severity of thyrotoxicosis.