A possible role for the thyrotropin receptor in thyroid-associated ophthalmopathy

Clinical observations and several lines of investigation suggest a possible role for the thyroid stimulating hormone receptor (TSHr) as an autoantigen in thyroid-associated ophthalmopathy (TAO) and pretibial dermopathy. The close temporal relationship between the onset of hyperthyroidism and of the extrathyroidal manifestations of Graves' disease suggests that there may be an antigen common to the thyroid, the orbit and the skin. That this antigen could be the TSHr is supported by the data from several laboratories demonstrating RNA transcripts in orbital and dermal cells that encode either variant or intact TSHr extracellular domain. The majority of the studies that examine cells in culture demonstrate that the fibroblast is the TSHr transcript-bearing cell. Areas of controversy include whether TSHr protein is expressed in extrathyroidal tissues, and, if so, whether the receptor is 'functional' in these tissues. In summary, whether the TSHr actually serves as an orbital and dermal antigen in TAO and pretibial dermopathy is unknown and awaits definitive studies.