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Thyroid-stimulating hormone Thyroid-stimulating hormone (also known as thyrotropin, TSH, or TSH for human TSH) is a pituitary hormone that stimulates the thyroid gland to produce thyroxine (T4 ), and then triiodothyronine (T3) which stimulates the metabolism of almost every tissue in the body.It is a glycoprotein hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland. TSH receptor The TSH receptor is found mainly on thyroid follicular cells. Stimulation of the receptor increases T3 and T4 production and secretion. Stimulating antibodies to this receptor mimic TSH and cause Graves' disease. In addition, hCG shows some crossreactivity to the TSH receptor and therefore can stimulate production of thyroid hormones. In pregnancy, prolonged high concentrations of hCG can produce a transient condition termed gestational hyperthyroidism. This is also the mechanism of trophoblastic tumors increasing the production of thyroid hormones Regulation of thyroid hormone levels TSH stimulates the thyroid gland to secrete the hormone thyroxine (T4), which has only a slight effect on metabolism. T4 is converted to triiodothyronine (T3), which is the active hormone that stimulates metabolism. About 80% of this conversion is in the liver and other organs, and 20% in the thyroid itself.TSH is secreted throughout life but particularly reaches high levels during the periods of rapid growth and development.The hypothalamus, in the base of the brain, produces thyrotropinreleasing hormone (TRH). TRH stimulates the pituitary gland to produce TSH. Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release.The concentration of thyroid hormones (T3 and T4) in the blood regulates the pituitary release of TSH; when T3 and T4 concentrations are low, the production of TSH is increased, and, conversely, when T3 and T4 concentrations are high, TSH production is decreased. This is an example of a negative feedback loop. Any inappropriateness of measured values, for instance a low-normal TSH together with a low-normal T4 may signal tertiary disease and a TSH to TRH pathology. Elevated reverse T3 (RT3) together with low-normal TSH and low-normal T3, T4 values, which is regarded as indicative for euthyroid sick syndrome, may also have to be investigated for chronic subacute thyroiditis (SAT) with output of subpotent hormones. Absence of antibodies in patients with diagnoses of an autoimmune thyroid in their past would always be suspicious for development to SAT even in the presence of a normal TSH because there is no known recovery from autoimmunity. Anti-thyroid Autoantibodies Thyroid microsomal antibodies were discovered in 1964, which were subsequently renamed anti-TPO antibodies due to the identification of their autoantigen. Antithyroid autoantibodies (or simply anti-thyroid antibodies) are autoantibodies targeted against one or more components of the thyroid. The most clinically relevant antithyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies), thyrotropin receptor antibodies (TRAbs) and thyroglobulin antibodies. TRAbs are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Graves' disease and Hashimoto's thyroiditis are commonly associated with the presence of anti-thyroid autoantibodies. Although there is overlap, anti-TPO antibodies are most commonly associated with Hashimoto's thyroiditis and activating TRAbs are most commonly associated with Graves' disease. Thyroid microsomal antibodies were a group of anti-thyroid antibodies, they were renamed after the identification of their target antigen (TPO). Anti-thyroid peroxidase (anti-TPO) antibodies are specific for the autoantigen TPO, a 105kDa glycoprotein that catalyses iodine oxidation and thyroglobulin tyrosyl iodination reactions in the thyroid gland. Most antibodies produced are directed to conformational epitopes of the immunogenic carboxyl-terminal region of the TPO protein, although antibodies to linear epitopes have been seen. Anti-TPO antibodies are the most common anti-thyroid autoantibody, present in approximately 90% of Hashimoto's thyroiditis, 75% of Graves' disease and 10-20% of nodular goitre or thyroid carcinoma. Also, 10-15% of normal individuals can have high level anti-TPO antibody titres. High serum antibodies are found in active phase chronic autoimmune thyroiditis. Thus, an antibody titer can be used to assess disease activity in patients that have developed such antibodies.The majority of anti-TPO antibodies are produced by thyroid infiltrating lymphocytes, with minor contributions from lymph nodes and the bone marrow. They cause thyroid cell damage by complement activation and antibody dependent cell cytotoxicity. Effect on human reproduction The presence of anti-thyroid antibodies is associated with an increased risk of unexplained subfertility, miscarriage, recurrent miscarriage, preterm birth and maternal Postpartum thyroiditis .Activating TSH receptor antibodies were discovered.