Lesson 3: Autoimmune Thyroid Disease
Thyroid Antibodies
Graves’ disease, Hashimoto’s thyroiditis, idiopathic thyroid failure and Hashitoxicosis are all closely associated and sometimes overlapping syndromes that cause symptoms of thyroid disease.
In Graves’ disease, a predominance of stimulating TSH receptor antibodies causes hyperthyroidism. In Hashimoto’s thyroiditis, which is autoimmune hypothyroidism, and idiopathic thyroid failure, blocking TSH receptor antibodies, thyroglobulin and/or TPO antibodies contribute to hypothyroidism.
In Hashitoxicosis, patients primarily have Hashimoto’s thyroiditis, but they also have the stimulating TSH receptor antibodies that cause Graves’ disease. This causes hypothyroidism with transient or temporary symptoms of hyperthyroidism whenever the stimulating antibody titers rise.
Thyroglobulin and TPO Antibodies Most patients with an AITD have a combination of different thyroid antibodies. The antibodies that predominate determine what current thyroid disease a person will have. Thyroglobulin and TPO antibodies contribute to thyroid cell destruction and inflammation. These antibodies are present in high concentrations in people with Hashimoto’s thyroiditis or idiopathic thyroid failure.
In addition, these antibodies are seen in patients with Hashimoto’s encephalopathy. In this condition, the antibodies destroy brain cells rather than thyroid cells, causing a type of dementia that responds well to corticosteroid medications. Corticosteroids slow the immune system, reducing thyroid antibody production. Thyroglobulin and TPO antibodies are also seen in 70 to 90 percent of patients with Graves’ disease although usually, lower titers are seen.
If patients with Graves’ disease continue to produce thyroglobulin and/or TPO antibodies long after their immune system stops producing the stimulating antibodies that cause Graves’ disease, these patients will move into autoimmune hypothyroidism.
Similarly, patients with Hashimoto’s thyroiditis who begin producing the stimulating antibodies associated with Graves’ disease, they’ll have Hashitoxicosis. If they begin to produce less thyroglobulin and TPO antibodies and more stimulating TSH receptor antibodies, they will develop Graves’ disease.
TSH Receptor Antibodies TSH receptor antibodies are thyroid antibodies that react with a protein known as the TSH receptor, which is found on thyroid cells. Normally, the pituitary hormone thyrotropin or TSH reacts with this receptor, ordering the thyroid cell to produce and release more thyroid hormone.
Stimulating TSH receptor antibodies are also known as thyroid stimulating immunoglobulins or TSI. TSI cause Graves’ disease and they also occur in Hashitoxicosis. TSI stimulate the TSH receptor to keep producing high amounts of thyroid hormone regardless of the body’s needs or requirements for thyroid hormone. Blood tests for TSI can be used to diagnose Graves’ disease and help determine when the patient is in remission.
Blocking TSH receptor antibodies block both the pituitary hormone TSH and TSI antibodies from reacting with the TSH receptor on thyroid cells. Blocked, TSH and TSI are prevented from causing thyroid hormone production. Blocking antibodies, therefore, reduce the influence of TSI. Some people with very high TSI levels will have mild hyperthyroidism because they also have high levels of blocking antibodies.
People with equal amounts of both stimulating and blocking TSH receptor antibodies will have normal thyroid function. However, if their levels are higher or lower than what they usually run, they’ll have symptoms of thyroid disease. Because both stimulating and blocking TSH receptor antibodies contribute to thyroid eye disease, these people have a high risk for clinically significant eye disease.
People who primarily have blocking TSH receptor antibodies will have hypothyroidism when these antibodies predominate. TSH is prevented from ordering thyroid cells to produce thyroid hormone. Thyroid hormone levels continue to fall and TSH continues to rise in this condition until thyroid replacement hormone is administered.
Blocking TSH receptor antibodies can be measured with a test for thyrotropin blocking antibodies or TBA. TSH is another name for thyrotropin. Tests that measure total TSH receptor antibodies or thyroid binding inhibiting immunoglobulins or TBII are able to measure the total concentration of both stimulating and blocking TSH receptor antibodies. If the TSI level is only slightly elevated and the total TSH receptor antibody level is markedly elevated, this would show that blocking antibodies are also present.
