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The thyroid-stimulating hormone receptor (TSHR) has a major importance in thyroid functions, which stimulates or inhibits thyroid hormone from thyroid gland with considerable autoantigens and compose autoimmune thyroid diseases.Understanding activation and differentiation of TSHR antibodies may reveal and resolve various clinic issues that origins from autoimmune thyroid diseases.TSH receptors have a two-chain structure; hydrophilic A-subunit which binds surface of cell membrane and B-subunit which interacts adenylate cyclase and triggered multiple reactions like dimerization and cleavage TSHR; that is a drastic autoantigen that stimulates TSHR-Abs; also considered as a master factor of formation of ophthalmopathy and pretibial myxedema which are decisive clinic features seen in Graves disease.