Thyreoglobulin-Antikörper (TAK, Anti-TG): the pathway in the body

Thyreoglobulin-Antikörper (TAK, Anti-TG) is part of the pathway “Thyroid hormones”. This page shows the whole pathway; the station of Thyreoglobulin-Antikörper (TAK, Anti-TG) is highlighted.

Where this laboratory value sits: Iodinated thyroglobulin — in the follicle. At the edge of the follicle, thyroid peroxidase (TPO) attaches iodine to tyrosine units of the large protein thyroglobulin. For this it needs hydrogen peroxide, supplied by the enzyme DUOX2. This creates a hormone store in the follicle. Source 3, 6

In brief

The thyroid hormones T4 and T3 are iodine-containing derivatives of the amino acid tyrosine; their formation is controlled by the pituitary hormone TSH. In the cells, T4 is converted to T3, which changes the reading of certain genes in the nucleus. T3 and T4 in turn curb TSH.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. TRH → TSH In response, the pituitary gland produces TSH and releases it into the blood. TSH reaches the thyroid and stimulates every single step of hormone synthesis there. When little TSH is present, the thyroid works more slowly. Source 1↑ supplies TSH binds to its receptor on the thyroid cell and switches on the uptake of iodide, the formation of thyroglobulin and TPO, and the release of the hormones. Over time, TSH also makes the gland grow. established physiology Source 1, 2, 3
   ⚖ When the balance tips

   too much — If there is a lot of TSH in the blood, the thyroid runs at a higher rate: it brings in more iodide, makes more hormone, and its cells multiply and enlarge.

   too little — If little TSH is present, for example because plenty of T3 and T4 curb the pituitary gland, the thyroid brings in less iodide, releases less hormone, and its cells become smaller.

   established physiology · Source 1

2. TSH → Iodide in the cell NIS · Sodium The transporter NIS brings iodide from the blood into the thyroid cell. It is driven by sodium flowing in at the same time. Only what NIS brings in can become hormone. Source 2, 6↑ supplies Iodide is the raw material of the hormones: the thyroid concentrates it strongly relative to the blood. Only what NIS brings in can be attached to thyroglobulin by TPO. established physiology Source 2, 6
   ⚖ When the balance tips

   too much — If a very large amount of iodide enters the cell, it temporarily curbs iodination and hormone formation itself (Wolff-Chaikoff effect); after a few days the cell turns down NIS and escapes from this brake.

   too little — If little iodide is available, the thyroid makes relatively more T3 than T4, which gets by with less iodine; at the same time TSH rises, and the gland is stimulated more strongly for a long time.

   established physiology · Source 2, 6

3. Iodide in the cell → Iodinated thyroglobulin TPO · Hydrogen peroxide, Haem iron At the edge of the follicle, thyroid peroxidase (TPO) attaches iodine to tyrosine units of the large protein thyroglobulin. For this it needs hydrogen peroxide, supplied by the enzyme DUOX2. This creates a hormone store in the follicle. Source 3, 6↑ supplies Iodinated thyroglobulin is the hormone store of the thyroid: the follicle holds a supply of ready-anchored hormone building blocks from which the gland can sustain its output for a long time. established physiology Source 3
   ⚖ When the balance tips

   too much — If a lot of thyroglobulin is iodinated, TPO needs a lot of hydrogen peroxide; whatever is left over is intercepted in the cell by selenium-containing glutathione peroxidases.

   too little — If little iodine is attached to thyroglobulin, for example because TPO is inhibited or little haem iron is available, the store in the follicle shrinks, and fewer finished hormones form.

   established physiology · Source 3, 6

4. Iodinated thyroglobulin → T4 and T3 TPO (coupling) The same TPO couples pairs of iodinated tyrosines, forming T4 and, in smaller amounts, T3. The cell retrieves the thyroglobulin, frees the hormones and releases them into the blood. Plenty of hormone in the blood curbs TSH release. Source 3, 1↑ supplies The bound hormones form a large reserve in the blood, from which a small free share is continuously replenished. T4 thus stays in circulation for days; it is mainly a precursor, T3 the active form. established physiology Source 4, 1
   ⚖ When the balance tips

   too much — If the thyroid releases a lot of T4 and T3, the hormones curb the release of TSH and TRH via the pituitary gland and hypothalamus until less is produced.

   too little — If little T4 and T3 come from the thyroid, this brake is released: the hypothalamus and pituitary gland release more TRH and TSH and drive the gland harder.

   established physiology · Source 1

5. Free T4 → Free T3 Deiodinase D1, D2 · Selenium Deiodinases remove a single iodine atom from the outer ring of T4. This yields T3, the form that acts at the receptor. The deiodinases carry selenium in their active centre. T3 also curbs the release of TSH. Source 4, 6↑ supplies T3 is the signal that switches genes on or off in the target cell. In the pituitary gland the same T3 curbs the release of TSH and thus regulates its own production. established physiology Source 4, 5, 1
   ⚖ When the balance tips

   too much — If a lot of T3 is present in the cells, energy turnover, heat production and heartbeat speed up; D3 then breaks down more T3, and the release of TSH is curbed.

   too little — If little T3 is present, the dependent genes are read less often, energy turnover and heat production slow down, and the pituitary gland releases more TSH.

   established physiology · Source 5, 4, 1

6. Free T4 → Reverse T3 Deiodinase D3 · Selenium The deiodinase D3 instead removes an iodine atom from the inner ring. The resulting reverse T3 does not fit the receptor and is broken down further. In this way the cell itself sets how much T3 it has. Thus D3 deliberately withdraws hormone from the receptor. Source 4↓ depletes Reverse T3 stands for a breakdown route: D3 inactivates T4 before T3 can be made from it. In this way a tissue deliberately withdraws hormone from the receptor, for example the placenta, which limits transfer to the child. established physiology Source 4
   ⚖ When the balance tips

   too much — If a lot of reverse T3 is formed, correspondingly less T4 is converted into T3; the cells then receive less hormone action, even if enough T4 is present.

   too little — If little T4 is broken down via D3, more of it is available for conversion to T3, and more hormone action reaches the tissue.

   established physiology · Source 4

7. Free T3 → T3 receptor In the nucleus, T3 binds to its receptor (TR). The receptor already sits on specific stretches of DNA, usually together with a second protein. Without T3 it mostly keeps the genes repressed. Source 5↕ both, depending on amount The receptor is a switch: without T3 it mostly keeps the associated genes repressed with braking partner proteins, with T3 it releases them. Depending on the amount of hormone, the same receptor represses or activates. observed in studies Source 5
   ⚖ When the balance tips

   too much — If many receptors are occupied by T3, the associated genes are switched on more often; some others, such as the TSH gene in the pituitary gland, are instead repressed more strongly.

   too little — If little T3 is present, the receptor stays empty on the DNA and actively keeps the genes repressed; in animal models this has a stronger effect than when the receptor is absent altogether.

   observed in studies · Source 5

8. T3 receptor → Gene transcription With T3 bound, the receptor changes shape, releases repressing partner proteins and recruits activating ones. This switches transcription of the associated genes on or off. In this way T3 sets energy turnover, heat production and heart rate. Source 5↑ supplies Through the genes it reads, T3 sets basal metabolic rate, heat production, heartbeat and fat and sugar metabolism; during development it controls the maturation of brain and bone. established physiology Source 5
   ⚖ When the balance tips

   too much — If the T3-dependent genes are read intensively, the cells use more energy and oxygen, more heat is produced, and the heart beats faster and more forcefully.

   too little — If the T3-dependent genes are read little, energy turnover and heat production slow down, the heartbeat becomes calmer, and cholesterol is cleared from the blood more slowly.

   established physiology · Source 5

Further stations

• TRH — from the hypothalamus The hypothalamus, a region of the diencephalon, releases the short hormone TRH. It reaches the pituitary gland by a short route. There TRH stimulates the release of TSH. Source 1↑ supplies TRH binds to receptors on the TSH-producing cells of the pituitary gland and stimulates the formation and release of TSH there. In turn, the thyroid hormones curb the formation of TRH in the hypothalamus. established physiology Source 1
  ⚖ When the balance tips

  too much — If a lot of TRH reaches the pituitary gland, it releases more TSH; at the same time TRH also stimulates the release of the hormone prolactin there.

  too little — If little TRH arrives, the pituitary gland makes less TSH, and the thyroid is stimulated less, even though it is itself fully able to work.

  established physiology · Source 1

• Free T4 — in the target cell In the blood the hormones are almost entirely bound to carrier proteins such as TBG. Only the unbound share, free T4, enters cells via transporters such as MCT8. Each cell makes T3 from it as needed. Source 4↑ supplies Free T4 is the precursor from which each cell makes T3 according to its own needs, or which it inactivates via D3. T4 itself binds only weakly to the receptor. established physiology Source 4
  ⚖ When the balance tips

  too much — If a lot of T4 is present, the deiodinase D2 is broken down faster, because T4 itself marks it for degradation, and more D3 is made; the cell thus converts relatively less T4 into T3.

  too little — If little T4 arrives, D2 persists longer and converts what is there more efficiently into T3; tissues such as the brain thus keep their T3 stable for a while.

  established physiology · Source 4

Cofactors in this pathway

• Iodine — Building block of T4 and T3; the thyroid takes it up as iodide via NIS; with little iodine, relatively more T3 forms Source 2, 6In the ORY catalogue as a laboratory value: Jod (Urin)
• Selenium — As selenocysteine in the active centre of the deiodinases that convert T4 to T3; D3 inactivates T4 and T3 Source 4, 6In the ORY catalogue as a laboratory value: Selen
• Iron — As haem iron, cofactor of thyroid peroxidase, which attaches iodine to thyroglobulin; with little iron it slows Source 6In the ORY catalogue as a laboratory value: Eisen
• Tyrosine — Building block in thyroglobulin to which iodine is attached; two iodinated tyrosines form one hormone Source 3In the ORY catalogue as a laboratory value: Tyrosin
• Sodium — Drives the transporter NIS, which brings iodide into the thyroid cell; without the sodium flow NIS stops Source 2In the ORY catalogue as a laboratory value: Natrium (intrazellulär)

What acts on this pathway

• Thiamazole — Thiamazole inhibits thyroid peroxidase, so less iodine is attached to thyroglobulin. The prescribing information describes exactly this mechanism. Source 7

Sources

1. Ortiga-Carvalho TM, Chiamolera MI et al. Hypothalamus-Pituitary-Thyroid Axis. Compr Physiol 2016 · PubMed 27347897
2. Portulano C, Paroder-Belenitsky M et al. The Na+/I- symporter (NIS): mechanism and medical impact. Endocr Rev 2014 · PubMed 24311738
3. Citterio CE, Targovnik HM et al. The role of thyroglobulin in thyroid hormonogenesis. Nat Rev Endocrinol 2019 · PubMed 30886364
4. Bianco AC, Dumitrescu A et al. Paradigms of Dynamic Control of Thyroid Hormone Signaling. Endocr Rev 2019 · PubMed 31033998
5. Brent GA. Mechanisms of thyroid hormone action. J Clin Invest 2012 · PubMed 22945636
6. Köhrle J. Selenium, Iodine and Iron-Essential Trace Elements for Thyroid Hormone Synthesis and Metabolism. Int J Mol Sci 2023 · PubMed 36834802
7. US prescribing information Thiamazole/Methimazole (DailyMed), section Clinical Pharmacology · Prescribing information

Whole pathway: Thyroid hormones

Related pathways

• Iodine — iodide in the cell
• Vitamin A — gene transcription
• Vitamin C — Selen, Eisen
• 8-OHdG — Selen, Eisen
• Borrelia — Selen, Eisen

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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