Immunopathogenesis of Graves' ophthalmopathy: The role of the TSH receptor

Seethalakshmi Iyer, Rebecca Bahn

Research output: Contribution to journalReview articlepeer-review

75 Scopus citations


Graves' ophthalmopathy is an inflammatory autoimmune disorder of the orbit. The close clinical and temporal relationships between Graves' hyperthyroidism and ophthalmopathy have long suggested that both conditions derive from a single systemic process and share the thyrotropin receptor as a common autoantigen. This receptor is expressed not only in thyroid follicular cells, but also in orbital fibroblasts with higher levels measured in orbital cells from ophthalmopathy patients than in cells from normal individuals. Recent studies from several laboratories have shown that thyrotropin receptor activation in orbital fibroblasts enhances hyaluronic acid synthesis and adipogenesis, both cellular functions that appear to be upregulated in the diseased orbit. The phosphoinositide 3-kinase/Akt signaling cascade, along with other effector pathways including adenylyl cyclase/cAMP, appears to mediate these processes. Future therapies for this condition may involve inhibition of thyrotropin receptor signaling in orbital fibroblasts.

Original languageEnglish (US)
Pages (from-to)281-289
Number of pages9
JournalBest Practice and Research: Clinical Endocrinology and Metabolism
Issue number3
StatePublished - Jun 2012


  • Graves' disease
  • Graves' orbitopathy
  • autoimmune disease
  • thyrotropin receptor
  • thyrotropin receptor autoantibodies

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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