Thyroid hormones
The thyroid hormones function via a well-studied set of nuclear receptors, termed the thyroid hormone receptors. These receptors, together with corepressor molecules, bind DNA regions called thyroid hormone response elements (TREs) near genes. This receptor-corepressor-DNA complex can block gene transcription. Triiodothyronine (T3), which is the active form of thyroxine(T4), goes on to bind to receptors. The deiodinase catalyzed reaction removes an iodine atom from the 5' position of the outer aromatic ring of Thyroxine's (T4) structure. When triiodothyronine (T3) binds a receptor, it induces a conformational change in the receptor, displacing the corepressor from the complex. This leads to recruitment of coactivator proteins and RNA polymerase, activating transcription of the gene.
Hashimoto's thyroiditis
Given the relatively non-specific symptoms of initial hypothyroidism, Hashimoto's thyroiditis is often misdiagnosed as depression, cyclothymia, PMS, chronic fatigue syndrome, fibromyalgia and, less frequently, as erectile dysfunction or an anxiety disorder. On gross examination, there is often presentation of a hard goiter that is not painful to the touch; other symptoms seen with hypothyroidism, such as periorbital myxedema, depend on the current state of progression of the response, especially given the usually gradual development of clinically relevant hypothyroidism. Testing for thyroid-stimulating hormone (TSH), free T3, free T4, and the anti-thyroglobulin antibodies (anti-Tg), anti-thyroid peroxidase antibodies (anti-TPO, or TPOAb) and anti-microsomal antibodies can help obtain an accurate diagnosis. Earlier assessment of the person may present with elevated levels of thyroglobulin owing to transient thyrotoxicosis, as inflammation within the thyroid causes damage to the integrity of thyroid follicle storage of thyroglobulin; TSH secretion from the anterior pituitary increases in response to a decrease in negative feedback inhibition secondary to decreased serum thyroid hormones. Typically T4 is the preferred thyroid hormone test for hypothyroidism. This exposure of the body to substantial amounts of previously isolated thyroid enzymes is thought to contribute to the exacerbation of tolerance breakdown, giving rise to the more pronounced symptoms seen later in the disease. Lymphocytic infiltration of the thyrocyte-associated tissues often leads to the histologically significant finding of germinal center development within the thyroid gland.