Graves' disease causes
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Causes
The trigger for auto-antibody production is not known. There appears to be a genetic predisposition for Graves' disease, suggesting that some people are more prone than others to develop TSH receptor activating antibodies due to a genetic cause. HLA DR (especially DR3) appears to play a significant role.[1]
Since Graves' disease is an autoimmune disease which appears suddenly, often quite late in life, it is thought that a viral or bacterial infection may trigger antibodies which cross-react with the human TSH receptor (a phenomenon known as antigenic mimicry, also seen in some cases of type I diabetes).
One possible culprit is the bacterium Yersinia enterocolitica (a cousin of Yersinia pestis, the agent of bubonic plague). However, although there is indirect evidence for the structural similarity between the bacteria and the human thyrotropin receptor, direct causative evidence is limited.[1] Yersinia seems not to be a major cause of this disease, although it may contribute to the development of thyroid autoimmunity arising for other reasons in genetically susceptible individuals.[2] It has also been suggested that Y. enterocolitica infection is not the cause of auto-immune thyroid disease, but rather is only an associated condition; with both having a shared inherited susceptibility.[3] More recently the role for Y. enterocolitica has been disputed.[4]
The ocular manifestations of Graves disease are more common in smokers and tend to worsen (or develop for the first time) following radioiodine treatment of the thyroid condition. Thus, they are not caused by hyperthyroidism per se; this common misperception may result from the fact that hyperthyroidism from other causes may cause eyelid retraction or eyelid lag (so-called hyperthyroid stare) which can be confused with the general appearance of proptosis/exophthalmos, despite the fact that the globes do not actually protrude in other causes of hyperthyroidism. Also, both conditions (globe protrusion and hyperthyroid lid retraction) may exist at the same time in the hyperthyroid patient with Graves disease.
References
- ↑ 1.0 1.1 Tomer Y, Davies T (1993). "Infection, thyroid disease, and autoimmunity" (PDF). Endocr Rev. 14 (1): 107–20. PMID 8491150.
- ↑ Toivanen P, Toivanen A (1994). "Does Yersinia induce autoimmunity?". Int Arch Allergy Immunol. 104 (2): 107–11. PMID 8199453.
- ↑ Strieder T, Wenzel B, Prummel M, Tijssen J, Wiersinga W (2003). "Increased prevalence of antibodies to enteropathogenic Yersinia enterocolitica virulence proteins in relatives of patients with autoimmune thyroid disease". Clin Exp Immunol. 132 (2): 278–82. PMID 12699417.
- ↑ Hansen P, Wenzel B, Brix T, Hegedüs L (2006). "Yersinia enterocolitica infection does not confer an increased risk of thyroid antibodies: evidence from a Danish twin study". Clin Exp Immunol. 146 (1): 32–8. PMID 16968395.