thyroglobulin

File:Thyroid hormone synthesis.png, this image traces thyroglobulin from production within the rough endoplasmic reticulum until proteolytic release of the thyroid hormones.]]

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.{{cite web|url=https://www.ncbi.nlm.nih.gov/gene/7038|title=TG thyroglobulin [Homo sapiens (human)] – Gene – NCBI|website=National Center for Biotechnology Information (NCBI)|access-date=2019-09-16}}

Newly synthesized thyroid hormones (T3 and T4) exist as prohormonal modified tyrosine residues of thyroglobulin, which comprise the colloid within the follicle.{{cite journal | vauthors = Tosatto L, Coscia F | title = A glance at post-translational modifications of human thyroglobulin: potential impact on function and pathogenesis | journal = European Thyroid Journal | volume = 11 | issue = 3 | date = June 2022 | pmid = 35544053 | pmc = 9254275 | doi = 10.1530/ETJ-22-0046 }} 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.

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.{{cite journal | vauthors = Gant Kanegusuku A, Araque KA, Nguyen H, Wei B, Hosseini S, Soldin SJ | title = The effect of specific binding proteins on immunoassay measurements of total and free thyroid hormones and cortisol | journal = Therapeutic Advances in Endocrinology and Metabolism | volume = 12 | pages = 2042018821989240 | date = 2021-01-01 | pmid = 33552466 | pmc = 7844449 | doi = 10.1177/2042018821989240 }} 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.{{cite book | vauthors = Rousset BL, Dupuy C, Miot F, Dumont J | chapter = Chapter 2 Thyroid Hormone Synthesis and Secretion |date=2000| chapter-url= http://www.ncbi.nlm.nih.gov/books/NBK285550/| title = Endotext | veditors = Feingold KR, Anawalt B, Boyce A, Chrousos G |publisher=MDText.com, Inc.|pmid=25905405|access-date=2019-09-17}}

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.{{Cite web|url=https://medlineplus.gov/lab-tests/thyroglobulin/|title=Thyroglobulin: MedlinePlus Lab Test Information|website=medlineplus.gov|language=en|access-date=2019-05-06}} After thyroglobulin levels become undetectable (following thyroidectomy), levels can be serially monitored in follow-up of patients with papillary or follicular thyroid carcinoma.{{cite journal | vauthors = Knappe L, Giovanella L | title = Life after thyroid cancer: the role of thyroglobulin and thyroglobulin antibodies for postoperative follow-up | journal = Expert Review of Endocrinology & Metabolism | volume = 16 | issue = 6 | pages = 273–279 | date = November 2021 | pmid = 34693849 | doi = 10.1080/17446651.2021.1993060 }}

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. Hence, thyroglobulin levels in the blood are mainly used as a tumor marker{{cite web | url = http://www.cancer.org/docroot/PED/content/PED_2_3X_Tumor_Markers.asp | publisher = American Cancer Society | title = ACS :: Tumor Markers | access-date = 2009-03-28 | archive-date = 2010-05-13 | archive-url = https://web.archive.org/web/20100513023244/http://www.cancer.org/docroot/ped/content/ped_2_3x_tumor_markers.asp | url-status = dead }} 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.{{cite journal | vauthors = Giovanella L, Castellana M, Trimboli P | title = Unstimulated high-sensitive thyroglobulin is a powerful prognostic predictor in patients with thyroid cancer | journal = Clinical Chemistry and Laboratory Medicine | volume = 58 | issue = 1 | pages = 130–137 | date = December 2019 | pmid = 31444962 | doi = 10.1515/cclm-2019-0654 }} These tests are often ordered after thyroid cancer treatment.

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.{{cite journal | vauthors = Ferracci F, Moretto G, Candeago RM, Cimini N, Conte F, Gentile M, Papa N, Carnevale A | title = Antithyroid antibodies in the CSF: their role in the pathogenesis of Hashimoto's encephalopathy | journal = Neurology | volume = 60 | issue = 4 | pages = 712–714 | date = February 2003 | pmid = 12601119 | doi = 10.1212/01.wnl.0000048660.71390.c6 | s2cid = 21610036 }}

Thyroglobulin has been shown to interact with Binding immunoglobulin protein.{{cite journal | vauthors = Delom F, Mallet B, Carayon P, Lejeune PJ | title = Role of extracellular molecular chaperones in the folding of oxidized proteins. Refolding of colloidal thyroglobulin by protein disulfide isomerase and immunoglobulin heavy chain-binding protein | journal = The Journal of Biological Chemistry | volume = 276 | issue = 24 | pages = 21337–21342 | date = June 2001 | pmid = 11294872 | doi = 10.1074/jbc.M101086200 | doi-access = free }}{{cite journal | vauthors = Delom F, Lejeune PJ, Vinet L, Carayon P, Mallet B | title = Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen | journal = Biochemical and Biophysical Research Communications | volume = 255 | issue = 2 | pages = 438–443 | date = February 1999 | pmid = 10049727 | doi = 10.1006/bbrc.1999.0229 }}

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{{Refend}}

• [https://www2.mrc-lmb.cam.ac.uk/first-look-at-the-atomic-structure-of-thyroglobulin/ First look at the structure of human TG]
• [http://labtestsonline.org/understanding/analytes/thyroglobulin/tab/test/ Thyroglobulin] – Lab Tests Online
• {{KansasHistology|endo|endo11}}
• [http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/thyroid/synthesis.html Overview at colostate.edu]
• {{BUHistology|14302loa}}

{{Globulins}}

{{Glycoproteins}}

{{Tumor markers}}

{{Thyroid hormone receptor modulators}}

Category:Diagnostic endocrinology

Category:Endocrinology

Category:Thyroid

Category:Tumor markers