Graves Disease and Hyperthyroidism WikiOn March 1, 2007, in the UCLA health and medicine section of its website, it was reported that researchers discovered defects in the T-cells of Graves’ disease patients. This discovery could provide a better understanding of Graves’ autoimmune disease and how it damages the body.
To provide some background, certain autoantibodies over-stimulate the thyroid gland and produce excess thyroid hormone, resulting in hyperthyroidism. The normal process of thyroid hormone production is based on a negative feedback loop – that is, thyroid stimulating hormone (TSH), a pituitary hormone, becomes suppressed as thyroid hormones (T4 and T3) rise, or rises when thyroid hormone levels are too low. When the hypothalamus-pituitary-thyroid (HPT) axis is working properly, sans autoantibodies, TSH and thyroid hormone seesaw against each other to provide the body with the precise amount of thyroid hormone needed.
The TSH-mimicking autoantibodies which stimulate the gland are known as stimulating TSH-Receptor antibodies (or stimulating TRAb). They suppress TSH because they stimulate the gland to release an excess amount of thyroid hormone into the body which in turn slows or shuts off the production of TSH by the pituitary gland. Conversely, blocking TSH-R antibodies (blocking TRAb) block the receptor, preventing TSH from stimulating these receptors which can result in both low thyroid hormone levels as well as low TSH (n the latter case because the receptor is occupied by antibody). Some patients have both autoantibody types, that is, both stimulating and blocking TSH-R Ab. Depending on the “profile” of these autoantibodies at any point in the disease, the patient can experience either hyperthyroidism (more stimulating TRAb than blocking TRAb) or hypothyroidism (more blocking TRAb).What’s important here is that the cause is autoimmune in nature, whatever the autoantibody type or metabolic consequences.
Autoimmune disease also causes increased inflammation and tissue damage in the body. Without intervention, thyroid autoimmune disease can cause repeat attacks on thyroid cells and can result in the loss of thyroid function. In other cases, the disease resolves (at least symptomatically) on its own with modest treatment.
The UCLA Jules Stein Eye Institute and Harbor–UCLA Medical Center discovered defects in the T-cells of Graves' disease patients' immune systems. T-cells are necessary to fight infection. However, those who have Graves' disease produce an antibody that is not found in healthy people. According to the published UCLA report, T-cells taken from patients with Graves' disease contain an abnormal surplus of the receptor targeted by this antibody. "An antibody must latch to a specific receptor — like a key into a lock — in order to elicit a cellular response. These receptors mobbed the patients' immune systems, even appearing on T-cells that normally would not produce them."
It is not yet known why cells in Graves' disease create this new antibody, which is found in almost all Graves' disease patients. Under suspicion is that the T-cells themselves produce this antibody which binds to the excess receptors on the T-cells. It also mimics the actions of the hormone IGF-1, which stimulates cell growth while slowing down normal cell death. According to the study, this prolongation of old T-cells could be causing the body to attack itself.
Principal UCLA investigator Dr. Terry Smith said, "We think that the extra receptors allow the new antibody and IGF-1 to disrupt the programming of the T-cells. The antibody provokes the receptor to signal the T-cell to grow and multiply — long after the cell was programmed to die." It is thought that the evolution of this process when repeated over and over results in abnormal T-cells overtaking normal ones, thus resulting in Graves’ disease.
Continued research will include how the receptor is enabling T-cells to live beyond their life span. Ideally, a drug designed to block the receptor from interacting with the T-cells could be developed, eclipsing or slowing down the process of Graves' autoimmunity. At present, there is no cure for Graves' disease, only therapies that address the metabolic nature of the disease. These current therapies either slow down or eliminate the production of thyroid hormone and include antithyroid drugs, thyroidectomy, or radioactive iodine ablation (RAI).
Perhaps the most disfiguring aspect of Graves’ disease is thyroid eye disease (TED), also known as Graves' ophthalmopathy (GO). TED causes the eye to bulge (exophthalmos), often resulting in vision loss, double vision and severe eye pain. Patients with exophthalmos can have problems closing their eyelids as well as experience corneal and optic nerve damage. While surgery can help correct the disfiguring aspects of TED, a future drug treatment that addresses the autoimmune aspect of TED could provide a wholly new approach to it.
Resources: UCLA News, Mar 1, 2007
Armadillo AHSTA.com 25 March 2007 (PDT)
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