In Graves disease, affecting about 0.25% of the US population, the body produces stimulatory antibodies that mimic thyroid-stimulating hormone (TSH) and activate TSH receptors of the thyroid gland (TSH, itself, is made in the pituitary gland). This leads to the uncontrolled production of various thyroid hormones. In other cases, inhibitory antibodies that block the TSH receptor may be made. Or patients may have both antibody types in which case the relative potency of the two antibody types determines the manifestations of the disease.

 Auto-antibodies also stimulate the growth of the thyroid gland leading to one clinical sign of  Grave's disease, hyperthyroidism  (enlargement of the thyroid). Grave's disease is the most common cause of hyperthyroidism. Other symptoms are exophthalmos (protruding of the eyes) and swelling of the peri-orbital tissues. The enlargement involves the muscles around the eyes and retrobulbar connective tissue.  What causes the production of these auto-antibdoies is unknown but clearly genetic factors are involved since families often show a history of Grave's disease and autoimmune thyroiditis. In may be that bacterial or viral infection or some environmental factor triggers the production of antibodies in genetically-predisposed people. For example some types of E. coli have receptors proteins that bind TSH. It may be that antibodies raised against the bacterial surface  during an infection, cross-react with TSH receptors which would likely have similar epitopes. Why the eyes become involved is still obscure but one possibility is that thyroglobulin has similarities in certain parts of the molecule to an enzyme called acetylcholinesterase and antibodies against the two proteins cross-react. This enzyme is found in the ocular muscles (although it is also found in other muscles as well). It appears that  patients with the inhibitory type of anti-TSH receptor antibodies are more likely to have the ophthalmological manifestations of Grave's disease. The disease is more common in females than males and the incidence peaks in the teens.

Grave's disease involved exophthalmus and swelling of the peri-orbital tissues © Bristol Biomedical Image Archive. Used with permission