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Extrathyroidal Manifestations of Graves’ Disease: The Thyrotropin Receptor Is Expressed in Extraocular, But Not Cardiac, Muscle Tissues¹

Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Center, University of Melbourne, Heidelberg, Victoria 3084, Australia

Address all correspondence and requests for reprints to: Dr. Albert G. Frauman, Clinical Pharmacology and Therapeutics Unit, Department of Medicine, Austin and Repatriation Medical Center, University of Melbourne, Austin Campus, Heidelberg, Victoria 3084, Australia. E-mail: nicola{at}austin.unimelb.edu.au

The existence of an autoantigen common to Graves’ disease and its associated extrathyroidal manifestations has been proposed. As the TSH receptor (TSHR) is the primary target for autoimmunity against the thyroid in Graves’ disease, much effort has gone into investigating the role of TSHR messenger ribonucleic acid (mRNA) transcripts in extrathyroidal tissue, particularly in the orbit. A high stringency RT-PCR technique had previously been employed by our laboratory to demonstrate the presence of full-length and splice variant TSHR mRNA in extraocular muscle (EOM). This technique demonstrated selective amplification of TSHR mRNA transcripts in thyroid and EOM, but not in abdominal muscle, kidney, or brain tissue. We used this technique in the present study to investigate the reported presence of TSHR mRNA transcripts in cardiac tissue. After removal of all visible fat from muscle tissues, high stringency RT-PCR was performed, and we found no TSHR transcripts in the muscle of any chamber of the normal human heart. In addition, in situ hybridization on fresh-frozen and paraffin-embedded sections confirmed the presence of TSHR transcripts in thyroid and EOM, but not in abdominal or cardiac muscle. These findings support the hypothesis that the TSHR is a shared antigen in the thyroid and EOM, but not in cardiac muscle.

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