Recent insights into the pathogenesis and management of thyroid-associated ophthalmopathy.
OBJECTIVE
To identify and critique the most recent experimental findings regarding the pathogenesis and therapy of thyroid-associated ophthalmopathy.


RESULTS
Much of the recent work in this field has focused on identifying genetic alterations associated with the phenotypes of Graves' disease and thyroid-associated ophthalmopathy and investigating their functional consequences. Identified candidate genes include CD40, cytotoxic T-lymphocyte antigen-4, protein tyrosine phosphatase-22, human leukocyte antigen-major histocompatibility complex and those associated with the X-chromosome. Efforts to generate a complete rodent model of Graves' disease continue with little progress. These uniformly involve the immunization of animals with the thyrotropin receptor. Studies conducted in vitro have focused on the actions of cytokines in orbital fibroblasts, the potential role of the insulin-like growth factor-1 receptor and activating antibodies directed against it as a fibroblast and T cell activation pathway. Reports continue to appear examining the potential relationship between the thyrotropin receptor and orbital adipogenesis. Regarding therapy for thyroid-associated ophthalmopathy, small molecules and antibodies disrupting cytokine pathways and lymphocyte function are currently under examination and have yielded promising albeit preliminary results.


CONCLUSIONS
Thyroid-associated ophthalmopathy remains a vexing medical problem, the pathogenesis of which remains uncertain. A number of obstacles continue to plague major advances, not least of which is the absence of a robust animal model. A few new insights seem to represent departure from traditional thinking about this disease and may herald important innovation.
Gianoukakis
Andrew G
AG
Division of Endocrinology and Metabolism, Harbor-UCLA Medical Center, Torrance, California 90502, USA.
Smith
Terry J
TJ