Thyroid-associated ophthalmopathy (TAO) is a vexing and poorly understood 
autoimmune process involving the upper face and tissues surrounding the eyes. In 
TAO, the orbit can become inflamed and undergo substantial remodeling that is 
disfiguring and can lead to loss of vision. There are currently no approved 
medical therapies for TAO, the consequence of its uncertain pathogenic nature. 
It usually presents as a component of the syndrome known as Graves' disease 
where loss of immune tolerance to the thyrotropin receptor (TSHR) results in the 
generation of activating antibodies against that protein and hyperthyroidism. 
The role for TSHR and these antibodies in the development of TAO is considerably 
less well established. We have reported over the past 2 decades evidence that 
the insulin-like growth factorI receptor (IGF1R) may also participate in the 
pathogenesis of TAO. Activating antibodies against IGF1R have been detected in 
patients with GD. The actions of these antibodies initiate signaling in orbital 
fibroblasts from patients with the disease. Further, we have identified a 
functional and physical interaction between TSHR and IGF1R. Importantly, it 
appears that signaling initiated from either receptor can be attenuated by 
inhibiting the activity of IGF1R. These findings underpin the rationale for 
therapeutically targeting IGF1R in active TAO. A recently completed therapeutic 
trial of teprotumumab, a human IGF1R inhibiting antibody, in patients with 
moderate to severe, active TAO, indicates the potential effectiveness and safety 
of the drug. It is possible that other autoimmune diseases might also benefit 
from this treatment strategy.