Graves disease, the most common cause of goiter and hyperthyroidism in the United States, came to national attention in the early 1990s when former United States President and First Lady, George and Barbara Bush, developed the condition. The etiology of Graves disease is multifactorial, and nongenetic factors are thought to play an important role. Sandra McLachlan and researchers at Cedars-Sinai Medical Center in Los Angeles, California now show that it is an unusual structural feature of the thyrotropin receptor (TSHR) that plays a major role in the development of this disease.
Graves disease is the result of the production of autoantibodies to the TSHR located on the surface of thyroid cells. These antibodies bind the TSHR and stimulate it to overproduce thyroid hormones, which results in hyperthyroidism. In the June 16 issue of the Journal of Clinical Investigation, Sandra McLachlan and her team report that studies in a new adenovirus-mediated animal model of Graves disease revealed that cleavage of the TSHR A subunit can induce or amplify the immune response to the TSHR to a greater extent than the intact TSHR molecule.
The data, increase our understanding as to why autoantibodies specifically arise to the TSHR, stimulate the thyroid, and result in Graves hyperthyroidism. However, the mechanisms responsible for TSHR cleavage will require further exploration.
TITLE: The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim
AUTHOR CONTACT:
Sandra M. McLachlan
Cedars-Sinai Medical Center, Los Angeles, California, USA.
Phone: 310-423-7680
Fax: 310-423-0221
E-mail: mclachlans@cshs.org
View the PDF of this article at: https://www.the-jci.org/press/17069.pdf
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Contact: Brooke Grindlinger
science_editor@the-jci.org
212-342-9006
Journal of Clinical Investigation
16-Jun-2003