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Aliases | TG , AITD3, TGN, thyroglobulin | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 188450; MGI: 98733; HomoloGene: 2430; GeneCards: TG; OMA:TG - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Thyroglobulin (Tg) is a 660 kDa, dimeric glycoprotein produced by the follicular cells of the thyroid and used entirely within the thyroid gland. Tg is secreted and accumulated at hundreds of grams per litre in the extracellular compartment of the thyroid follicles, accounting for approximately half of the protein content of the thyroid gland. [5] Human TG (hTG) is a homodimer of subunits each containing 2768 amino acids as synthesized (a short signal peptide of 19 amino acids may be removed from the N-terminus in the mature protein). [6]
Thyroglobulin is in all vertebrates the main precursor to thyroid hormones, which are produced when thyroglobulin's tyrosine residues are combined with iodine and the protein is subsequently cleaved. Each thyroglobulin molecule contains approximately 16 tyrosine residues, but only around 10 of these are subject to iodination by thyroperoxidase in the follicular colloid. It takes two iodinated tyrosines to make a thyroid hormone molecule; therefore, each Tg molecule forms approximately 5 thyroid hormone molecules. [5]
Thyroglobulin (Tg) acts as a substrate for the synthesis of the thyroid hormones thyroxine (T4) and triiodothyronine (T3), as well as the storage of the inactive forms of thyroid hormone and iodine within the follicular lumen of a thyroid follicle. [7]
Newly synthesized thyroid hormones (T3 and T4) exist as prohormonal modified tyrosine residues of thyroglobulin, which comprise the colloid within the follicle. [8] When stimulated by thyroid stimulating hormone (TSH), the colloid of the follicular lumen is endocytosed into the surrounding thyroid follicular epithelial cells. When endosomes fuse with lysosomes in these cells, Tg is subsequently cleaved by proteases to release thyroglobulin from its T3 and T4 attachments. [9]
Because of the hydrophobic nature of T3 and T4, they are able to then diffuse across the lysosomal membrane and into the cytoplasm. The active forms of thyroid hormone (T3 and T4), are then released into circulation where they are either unbound or attached to plasma proteins. [10] Iodine is recycled back into the follicular lumen where it can continue to serve as a substrate for thyroid hormone synthesis, while the non-modified residues of Tg reenter cellular metabolic pathways. [9]
Metabolism of thyroglobulin occurs in the liver via thyroid gland recycling of the protein. Circulating thyroglobulin has a half-life of 65 hours. Following thyroidectomy, it may take many weeks before thyroglobulin levels become undetectable. Thyroglobulin levels may be tested regularly for a few weeks or months following the removal of the thyroid. [11] After thyroglobulin levels become undetectable (following thyroidectomy), levels can be serially monitored in follow-up of patients with papillary or follicular thyroid carcinoma. [12]
A subsequent elevation of the thyroglobulin level is an indication of recurrence of papillary or follicular thyroid carcinoma. In other words, a rise in thyroglobulin levels in the blood may be a sign that thyroid cancer cells are growing and/or the cancer is spreading. [11] Hence, thyroglobulin levels in the blood are mainly used as a tumor marker [13] [11] for certain kinds of thyroid cancer (particularly papillary or follicular thyroid cancer). Thyroglobulin is not produced by medullary or anaplastic thyroid carcinoma.
Thyroglobulin levels are tested via blood tests including immunoassays and highly-sensitive thyroglobulin (hsTg) assays. [14] These tests are often ordered after thyroid cancer treatment. [11]
In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies (ATAs, alternatively referred to as TgAb). Anti-thyroglobulin antibodies are present in 1 in 10 normal individuals, and a greater percentage of patients with thyroid carcinoma. The presence of these antibodies can result in falsely low (or rarely falsely high) levels of reported thyroglobulin, a problem that can be somewhat circumvented by concomitant testing for the presence of ATAs. The ideal strategy for a clinician's interpretation and management of patient care in the event of confounding detection of ATAs is testing to follow serial quantitative measurements (rather than a single laboratory measurement).
ATAs are often found in patients with Hashimoto's thyroiditis or Graves' disease. Their presence is of limited use in the diagnosis of these diseases, since they may also be present in healthy euthyroid individuals. ATAs are also found in patients with Hashimoto's encephalopathy, a neuroendocrine disorder related to—but not caused by—Hashimoto's thyroiditis. [15]
Thyroglobulin has been shown to interact with Binding immunoglobulin protein. [16] [17]
The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by a thin band of tissue called the isthmus. Microscopically, the functional unit of the thyroid gland is the spherical thyroid follicle, lined with follicular cells (thyrocytes), and occasional parafollicular cells that surround a lumen containing colloid.
Hypothyroidism is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormones. It can cause a number of symptoms, such as poor ability to tolerate cold, extreme fatigue, muscle aches, constipation, slow heart rate, depression, and weight gain. Occasionally there may be swelling of the front part of the neck due to goiter. Untreated cases of hypothyroidism during pregnancy can lead to delays in growth and intellectual development in the baby or congenital iodine deficiency syndrome.
Thyroid neoplasm is a neoplasm or tumor of the thyroid. It can be a benign tumor such as thyroid adenoma, or it can be a malignant neoplasm, such as papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. The estimated number of new cases of thyroid cancer in the United States in 2023 is 43,720 compared to only 2,120 deaths. Of all thyroid nodules discovered, only about 5 percent are cancerous, and under 3 percent of those result in fatalities.
Thyroxine, also known as T4, is a hormone produced by the thyroid gland. It is the primary form of thyroid hormone found in the blood and acts as a prohormone of the more active thyroid hormone, triiodothyronine (T3). Thyroxine and its active metabolites are essential for regulating metabolic rate, supporting heart and muscle function, promoting brain development, and maintaining bone health.
Thyroid-stimulating hormone (also known as thyrotropin, thyrotropic hormone, or abbreviated 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 produced by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid.
Triiodothyronine, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate.
Hashimoto's thyroiditis, also known as chronic lymphocytic thyroiditis, Hashimoto's disease and autoimmune thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed.
Thyroid peroxidase, also called thyroperoxidase (TPO), thyroid specific peroxidase or iodide peroxidase, is an enzyme expressed mainly in the thyroid where it is secreted into colloid. Thyroid peroxidase oxidizes iodide ions to form iodine atoms for addition onto tyrosine residues on thyroglobulin for the production of thyroxine (T4) or triiodothyronine (T3), the thyroid hormones. In humans, thyroperoxidase is encoded by the TPO gene.
Thyroid disease is a medical condition that affects the structure and/or function of the thyroid gland. The thyroid gland is located at the front of the neck and produces thyroid hormones that travel through the blood to help regulate many other organs, meaning that it is an endocrine organ. These hormones normally act in the body to regulate energy use, infant development, and childhood development.
Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism.
Papillary thyroid cancer is the most common type of thyroid cancer, representing 75 percent to 85 percent of all thyroid cancer cases. It occurs more frequently in women and presents in the 20–55 year age group. It is also the predominant cancer type in children with thyroid cancer, and in patients with thyroid cancer who have had previous radiation to the head and neck. It is often well-differentiated, slow-growing, and localized, although it can metastasize.
An antithyroid agent is a hormone inhibitor acting upon thyroid hormones.
Euthyroid sick syndrome (ESS) is a state of adaptation or dysregulation of thyrotropic feedback control wherein the levels of T3 and/or T4 are abnormal, but the thyroid gland does not appear to be dysfunctional. This condition may result from allostatic responses of hypothalamus-pituitary-thyroid feedback control, dyshomeostatic disorders, drug interferences, and impaired assay characteristics in critical illness.
The sodium/iodide cotransporter, also known as the sodium/iodide symporter (NIS), is a protein that in humans is encoded by the SLC5A5 gene. It is a transmembrane glycoprotein with a molecular weight of 87 kDa and 13 transmembrane domains, which transports two sodium cations (Na+) for each iodide anion (I−) into the cell. NIS mediated uptake of iodide into follicular cells of the thyroid gland is the first step in the synthesis of thyroid hormone.
Paired box gene 8, also known as PAX8, is a protein which in humans is encoded by the PAX8 gene.
Follicular thyroid cancer accounts for 15% of thyroid cancer and occurs more commonly in women over 50 years of age. Thyroglobulin (Tg) can be used as a tumor marker for well-differentiated follicular thyroid cancer. Thyroid follicular cells are the thyroid cells responsible for the production and secretion of thyroid hormones.
Thyroid hormones are two hormones produced and released by the thyroid gland, triiodothyronine (T3) and thyroxine (T4). They are tyrosine-based hormones that are primarily responsible for regulation of metabolism. T3 and T4 are partially composed of iodine, derived from food. A deficiency of iodine leads to decreased production of T3 and T4, enlarges the thyroid tissue and will cause the disease known as simple goitre.
Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck, difficulty swallowing or voice changes including hoarseness, or a feeling of something being in the throat due to mass effect from the tumor. However, most cases are asymptomatic. Cancer can also occur in the thyroid after spread from other locations, in which case it is not classified as thyroid cancer.
Iodine is an essential trace element in biological systems. It has the distinction of being the heaviest element commonly needed by living organisms as well as the second-heaviest known to be used by any form of life. It is a component of biochemical pathways in organisms from all biological kingdoms, suggesting its fundamental significance throughout the evolutionary history of life.
Antithyroid autoantibodies (or simply antithyroid antibodies) are autoantibodies targeted against one or more components on the thyroid. The most clinically relevant anti-thyroid autoantibodies are anti-thyroid peroxidase antibodies (anti-TPO antibodies, TPOAb), thyrotropin receptor antibodies (TRAb) and thyroglobulin antibodies (TgAb). TRAb's are subdivided into activating, blocking and neutral antibodies, depending on their effect on the TSH receptor. Anti-sodium/iodide (Anti–Na+/I−) symporter antibodies are a more recent discovery and their clinical relevance is still unknown. 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 TRAb's 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).