Editing Graves' disease (section)

==Mechanism==
Thyroid-stimulating immunoglobulins recognize and bind to the TSH receptor, which stimulates the secretion of thyroxine (T4) and triiodothyronine (T3).  Thyroxine receptors in the pituitary gland are activated by the surplus hormone, suppressing additional release of TSH in a negative feedback loop.  The result is very high levels of circulating thyroid hormones and a low TSH level.{{citation needed|date=July 2022}}

===Pathophysiology===
[[File:Histopathology of Graves' disease - medium mag.jpg|thumb|Histopathology of a case of Graves' disease. It shows marked hyperplasia of [[thyroid follicular cell]]s, generally more so than [[toxic multinodular goitre]], forming papillae into the thyroid follicles, and with scalloping of the peripheral colloid.]]
Graves' disease is an [[autoimmunity|autoimmune]] disorder, in which the body produces [[antibody|antibodies]] that are specific to a [[self-protein]] - the receptor for thyroid-stimulating hormone. (Antibodies to thyroglobulin and to the [[thyroid hormone]]s T3 and T4 may also be produced.)

These antibodies cause hyperthyroidism because they bind to the TSHr and [[chronic (medicine)|chronically]] stimulate it. The TSHr is expressed on the [[thyroid follicular cell]]s of the thyroid gland (the cells that produce thyroid hormone), and the result of chronic stimulation is an abnormally high production of T3 and T4. This, in turn, causes the clinical symptoms of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.

The infiltrative exophthalmos frequently encountered has been explained by postulating that the thyroid gland and the extraocular muscles share a common antigen, which is recognized by the antibodies. Antibodies binding to the extraocular muscles would cause swelling behind the eyeball.

The "orange peel" skin has been explained by the infiltration of antibodies under the skin, causing an inflammatory reaction and subsequent fibrous plaques.

'''The three types of autoantibodies to the TSH receptor are:'''

# '''Thyroid stimulating immunoglobulins:''' these antibodies (mainly IgG) act as long-acting thyroid stimulants (LATS), activating the cells through a slower and more drawn out process compared to TSH, leading to an elevated production of thyroid hormone.
# '''Thyroid growth immunoglobulins:''' these antibodies bind directly to the TSH receptor and have been implicated in the growth of thyroid follicles.
# '''Thyrotrophin binding-inhibiting immunoglobulins:''' these antibodies inhibit the normal union of TSH with its receptor.
#* Some actually act as if TSH itself is binding to its receptor, thus inducing thyroid function.
#* Other types may not stimulate the thyroid gland, but <u>prevent</u> TSI and TSH from binding to and stimulating the receptor.
Another effect of hyperthyroidism is bone loss from osteoporosis, caused by an increased excretion of calcium and phosphorus in the urine and stool. The effects can be minimized if the hyperthyroidism is treated early. [[Thyrotoxicosis]] can also augment calcium levels in the blood by as much as 25%. This can cause stomach upset, excessive urination, and impaired kidney function.<ref>{{cite web |url=http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |title=Thyroid Disease, Osteoporosis and Calcium – Womens Health and Medical Information on |publisher=Medicinenet.com |date=2006-12-07 |access-date=2013-02-27 |url-status=live |archive-url=https://web.archive.org/web/20130307133403/http://www.medicinenet.com/script/main/art.asp?articlekey=18637 |archive-date=2013-03-07 }}</ref>