Pathogenesis of Graves' orbitopathy: a 2010 update.
The most important of the extra-thyroidal manifestations of Graves' disease, Graves' orbitopathy (GO), remains a vexing clinical problem. Treatment of severe active disease has been limited to steroids or radiotherapy. In the relatively rare case where vision is threatened, emergent decompression surgery can be performed. The proptosis, motility, or cosmetic concerns associated with stable GO are commonly remedied with surgical intervention. Substantial obstacles have prevented the development of specific medical therapies for GO, in large part resulting from poor understanding of disease pathogenesis and the absence of preclinical animal models. Fundamental aspects of GO's etiology have been uncovered from studies based in cell culture, extensive analysis of blood constituents, and detailed examination of orbital contents collected at the time of surgical intervention. Many of the published reports resulting from these studies are descriptive and all have failed to yield unifying concepts that integrate the anatomically divergent manifestations of Graves' disease. This brief review covers recent findings of several research groups. While major breakthroughs continue to occur in closely related autoimmune diseases, progress in identifying the pathogenic mechanisms relevant to GO has been limited. As emerging insights into human autoimmunity becomes applied to the study of Graves' disease, we anticipate that improved therapeutic strategies will find their way to our patients with GO.
Smith
T J
TJ
Departments of Ophthalmology and Visual Sciences and Internal Medicine, University of Michigan Medical School, Ann Arbor, MI 48105, USA. terrysmi@med.umich.edu
D018952:Antigens, CD34 / Q000032:analysis; D015551:Autoimmunity; D001854:Bone Marrow Cells / Q000166:cytology; D005347:Fibroblasts / Q000502:physiology; D006111:Graves Disease / Q000532:radiotherapy; D049970:Graves Ophthalmopathy / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects; D008840:Microfilament Proteins / Q000032:analysis; D010641:Phenotype; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D011989:Receptors, Thyrotropin / Q000032:analysis
D018952:Antigens, CD34; D007457:Iodine Radioisotopes; C489183:LSP1 protein, human; D008840:Microfilament Proteins; D011989:Receptors, Thyrotropin; D017526:Receptor, IGF Type 1