Thyroglobulin


 * Not to be confused with is_associated_with::Thyroxine-binding globulin, a is_associated_with::carrier protein responsible for carrying the thyroid hormones in the blood.

Thyroglobulin (Tg) is a 660 is_associated_with::kDa, dimeric is_associated_with::protein produced by the follicular cells of the thyroid and used entirely within the is_associated_with::thyroid gland. Thyroglobulin protein accounts for approximately half of the protein content of the thyroid gland.

Each thyroglobulin molecule contains approximately 100-120 tyrosyl (is_associated_with::Tyrosine) residues. However, because only a small number (>20) of these tyrosine residues are subject to iodination by is_associated_with::thyroperoxidase in the follicular is_associated_with::colloid, each Tg molecule is only able to form very small amounts of thyroid hormone (5-6 molecules of either T4 and T3).

Function
Tg is used by the thyroid gland to produce the is_associated_with::thyroid hormones is_associated_with::thyroxine (T4) and is_associated_with::triiodothyronine (T3). The active form of triiodothyronine, 3, 5, 3' triiodothyronine, is produced both within the thyroid gland and in the periphery by 5'-deiodinase (which has been referred to as is_associated_with::tetraiodothyronine 5' deiodinase). It is presumed that Tg and thyroid are also an important storage of iodine for all body needs, in particular, for many iodine-concentrating organs such as breast, stomach, salivary glands, thymus, choroid plexus and cerebrospinal fluid, etc. (see is_associated_with::iodine in biology).

Tg is produced by the thyroid epithelial cells, called is_associated_with::thyrocytes, which form spherical follicles. Tg is secreted and stored in the follicular lumen.

Via a reaction with the is_associated_with::enzyme is_associated_with::thyroperoxidase, iodine is covalently bound to is_associated_with::tyrosine residues in thyroglobulin molecules, forming is_associated_with::monoiodotyrosine (MIT) and is_associated_with::diiodotyrosine (DIT).
 * is_associated_with::Thyroxine is produced by combining two moieties of DIT.
 * is_associated_with::Triiodothyronine is produced by combining one molecule of MIT and one molecule of DIT.

Small globules of the follicular colloid (Tg) are endocytosed (hormone (TSH)-mediated) and is_associated_with::proteases in is_associated_with::lysosomes digest iodinated thyroglobulin, releasing T3 and T4 within the thyrocyte cytoplasm. The T3 and T4 are then transported across (TSH-mediated) the basolateral thyrocyte membrane, into the bloodstream, by an unknown mechanism while the lysosome is recycled back to the follicular lumen.

Clinical significance
Thyroglobulin levels in the blood are mainly used as a is_associated_with::tumor marker for certain kinds of is_associated_with::thyroid cancer (particularly papillary or follicular thyroid cancer). Thyroglobulin is not produced by medullary or anaplastic thyroid carcinoma.

Circulating thyroglobulin has a half-life of 65 hours. Following thyroidectomy, it may take many weeks before thyroglobulin levels become undetectable. After thyroglobulin levels become undetectable following thyroidectomy, levels can be serially monitored. A subsequent elevation of the thyroglobulin level is an indication of recurrence of papillary or follicular thyroid carcinoma.

Metabolism of thyroglobulin occurs in the liver and via thyroid gland recycling of the protein.

Tg antibodies
In the clinical laboratory, thyroglobulin testing can be complicated by the presence of anti-thyroglobulin antibodies (ATA), frequently 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 on thyroglobulin testing. This problem can be somewhat circumvented by testing for the presence of anti-thryroglobulin antibodies. In patients with anti-thyroglobulin antibodies, a better strategy is to not rely on any single lab result but instead to follow serial quantitative measurements. This can help a clinician/clinical pathologist interpret a test and manage patient care, even with the presence of the confounding factor of anti-thyroglobulin antibodies.

Anti-thyroglobulin antibodies are often found in patients with is_associated_with::Hashimoto's thyroiditis or is_associated_with::Graves' disease. These antibodies are of limited use in the diagnosis of these diseases, since they may also be present in healthy is_associated_with::euthyroid individuals. Anti-Tg antibodies are also found in patients with Hashimoto's encephalopathy, a neuroendocrine disorder related to - but not caused by - Hashimoto's thyroiditis.

Interactions
Thyroglobulin has been shown to interact with is_associated_with::Binding immunoglobulin protein.