Endocrine Abstracts

Graves orbitopathy (GO) or thyroid eye disease (TED) is an inflammatory orbitopathy most commonly associated with hyperthyroid autoimmune thyroid disease (Graves’ disease). Most patients have TSHR autoantibodies (TRAb) in their blood. They usually have a stimulating effect and cause hyperthyroidism. About half of the patients also show more or less pronounced eye symptoms. Factors, which are significantly associated with the occurrence of clinically overt orbitopathy include smoking, high TRAb, a long period of hyperthyroidism, and the presence of already mild ocular symptoms. Risk groups can be assessed with TRAb measurement with the new assay technologies (using a monoclonal antibody for binding competition, or with a bioassay) by certain cut off levels at different time points during the course of GO. In vitro experiments showed that stimulation of the TSHR triggers a cross talk to the growth factor receptor IGF1R, which mediate essential pathomechanisms of GO. Targeted therapies for both the TSHR (small molecules, inhibiting antibodies) and the IGF1R (inhibiting antibodies) are in development. However, preventive measures relate to the regulation of the immune system. Results of several trials in the animal model support this. Influencing the gut microbiome or T-cell migration can prevent GO. In addition, local factors such as tissue hypoxia due to the configuration of the bony orbit do also play a decisive role for the extent of inflammation in the orbit. Optimal future treatment address the action of TSHR but also the regulation of the immune system.