There thyroglobulin  (Tgb or Tg) is a glycoprotein that is produced by thyroid cells, and is a precursor substance for the synthesis of hormones triiodothyronine (T3) is thyroxine (T4). It is used, like calcitonin, as a tumor marker for thyroid cancer.

Before starting, some technical data that are of particular interest to professionals, but which are important to be given in order to understand the functions and clinical usefulness of the thyroglobulin.

There thyroglobulin (also defined human thyroglobulin or hTg) is an iodinated glycoprotein weighing 660 KDa made up of two units or dimers of 115 tyrosine residues each, and is produced in the basal portion of the thyroid follicular cells (thyrocytes), the epithelial cells that line the thyroid follicles.

There molecule of thyroglobulin it contains in total about 5000 amino acids; approximately 8% -10% of the total mass of thyroglobulin is given by carbohydrates, while 0.2% -1% is linked to the iodine content (varies according to the amount of iodine introduced with the diet).

Once produced, it is stored in the thyroid follicles, the "cisterns" of glycoprotein material called colloid, the walls of which consist of a single layer of thyrocytes.

Thyroglobulin contained in the colloid, a homogeneous glycoprotein material of the thyroid follicles. 1: follicles, 2: follicular epithelium, 3: endothelial cells

Thyroglobulin: normal values

THE normal thyroglobulin values differ according to the country or geographical area of belonging: in fact, the values are affected by the daily intake of iodine taken with food,

Using the Certified Reference Material-457 (CRM-457) standards, in subjects with normal thyroid function (euthyroid) without antibodies to thyroglobulin (AbTg) living in countries with adequate iodine intake, normal thyroglobulin values They are included between 3 ng / mL and 40 ng / mL (µg / L). To be more precise, given that an amount of thyroglobulin equal to 1 ng / ml per gram of thyroid is estimated, and considering that the thyroid usually lost 20-25 grams, the reference range should generally be included between 20-25 ng / ml.

Low thyroglobulin values (less than 10 ng / mL) are found in approximately 8% of the general population. In neonates, the thyroglobulin level can be physiologically high (values between 36 ng / mL and 48 ng / mL) for up to 48 hours after birth (Medscape).

Thyroglobulin: mechanism of formation

As already mentioned, the production of thyroglobulin occurs by the follicular cells of the thyroid, under the stimulus of the hormone thyroid stimulant or thyrotropin (TSH).

In the thyroid follicles the tyrosine residues are iodinated (i.e. they are added with iodine atoms) to form 3-monoiodotyrosine (MIT) and 3,5-diiodotyrosine (DIT).

A molecule of monoiodiotyrosine and one of diiodiotyrosine joining together inside the follicular lumen will then compose the 3,5,3′-triiodothyronine (simply defined triiodothyronine or T3) while if instead two residues of DIT join together it will give rise to a molecule of tetraiodothyronine (called thyroxine or T4).

T3 and T4 constitute the thyroid hormones, and their free fractions, i.e. free triiodothyronine (fT3) and free thyroxine (fT4) constitute the part with greater biological activity of the same. About 70% of the iodine contained in thyroglobulin is within the precursors MIT and DIT, while the remaining 30% is contained in the molecules of thyroxine and triiodothyronine.

Thyroglobulin can remain stored at the level colloidal even for weeks, and then re-enter the thyrocytes when the body needs to produce new thyroid hormones. In this case, in fact, under the action of TSH, thyroid follicular cells “recover” thyroglobulin from the follicles through endocytosis, and hydrolyze it with enzymes such as proteases and peptidases to form single molecules of thyroxine and triiodothyronine, ready for release into the bloodstream.

What is thyroglobulin and why is it tested

There thyroglobulin (TBG) it is produced exclusively by the follicular cells of the thyroid. Thyroglobulin it is therefore a marker of the presence of thyroid follicular cells, and NOT of thyroid cancer. Its use for screening for differentiated thyroid cancer (i.e. to try to identify the presence of cancer) it is therefore not useful, while it is very useful for post-operative follow-up in the operated patient for differentiated neoplasia of the thyroid.

There thyroglobulin therefore it is mainly used as a tumor marker, to evaluate the efficacy of therapies in people affected by differentiated thyroid tumors, and to monitor any relapses in patients already treated. Neoplasms of the thyroid gland that produce thyroglobulin in significant quantities are the so-called thyroid carcinomas differentiated, i.e. the papillary thyroid cancer and follicular thyroid cancer: they are formations that synthesize thyroglobulin causing an increase in measurable concentrations in the blood. It should be borne in mind that not all thyroid cancers synthesize thyroglobulin, for example, medullary thyroid cancer is monitored by another substance, the calcitonin.

Measurement of thyroglobulin should be done before surgical removal of the thyroid gland in case of carcinoma. It is then requested after removal to see if there is any thyroid tissue still in place (in this case measurable levels of thyroglobulin persist, rather than being very low or absent). Thyroglobulin can then be measured at regular intervals to monitor the possible return of thyroid cancer (recurrence of thyroid cancer, in this case after having been with very low or undetectable values stably, thyroglobulin becomes detectable again).

High thyroglobulin

What does it mean to have high thyroglobulin? The finding of elevated thyroglobulin values must always be carefully evaluated, since one of the causes of an increase in blood analysis values is thyroid cancer. It should also be said, however, that there are many pathologies, not necessarily cancerous, that can lead to high thyroglobulin values, such as thyroiditis or a state of hyperthyroidism.

High Thyroglobulin: Causes

Here are the most frequent causes of high thyroglobulin:

  • Papillary thyroid cancer: it is the most frequent thyroid carcinoma, in fact it represents about 80% of thyroid neoplasms. It is often not enveloped in a capsule, and occurs in multiple (multifocal) nodules. Diagnosis is made throughultrasound of the thyroid gland, and often with a subsequent one fine needle aspiration thyroid on the thyroid nodule suspected. Therapy is surgical (hemithyroidectomy, i.e. removal of half of the thyroid gland, or total removal, i.e. total thyroidectomy), followed or not by metabolic radiotherapy with iodine. Papillary carcinoma of the thyroid gland leads to the release of thyroglobulin into the blood, therefore common will be the finding of high thyroglobulin 
  • Follicular thyroid cancer:  approximately 10% of thyroid cancers are follicular carcinomas. They are neoplasms often limited to one single thyroid nodule which may have an external capsule, and are spread through the blood (to the bones and lungs mainly) rather than the lymphatic route. Also for this tumor the therapy is basically surgical and metabolic with radioiodine. As mentioned for papillary thyroid cancer, the follicular carcinoma thyroid leads to the finding in the circulation of elevated thyroglobulin.
  • Metastasis of papillary carcinoma or follicular carcinoma of the thyroid gland: the metastases of thyroid tumors, being made up of tumor tissue identical to that of intra-thyroid neoplasms, cause the release of thyroglobulin into the bloodstream, with the finding of elevated thyroglobulin values in the blood.
  • Thyroid cancer recurrence: thyroglobulin is especially useful for controlling thyroid tumors treated with surgery (partial or total thyroidectomy) and / or with metabolic radiotherapy (radioiodine), are not present again in the thyroid gland or in other sites (appearance of metastases). If high thyroglobulin is found, relapse (return) of the disease is suspected
  • Hyperthyroidism: an increased activity of the thyroid gland, producing a high amount of thyroid hormones it also leads to a greater production of the precursor substance of T3 and T4, that is thyroglobulin. It is therefore not uncommon to find one high thyroglobulin in the course of hypertoriodism
  • Subacute thyroiditis: acute stage thyroiditis often leads to a state of thyrotoxicosis with release of thyroid hormones by the thyroid tissue damaged by the inflammatory process. in this phase the thyroglobulin contained in the damaged thyroid follicles is also released, with evidence of tElevated ireoglobulin in the blood. Most thyroiditis are autoimmune, and are characterized by the presence of antibodies to thyroid peroxidase and to thyroglobulin.
  • Benign adenoma: often from thyroid hormone-producing follicular thyroid adenoma, there is also release of thyroglobulin, with high thyroglobulin being found in blood tests.
  • Cigarette smoking:  not infrequently there may be an overactivation of the thyroid gland in smokers, leading to even minimal overproduction of thyroglobulin and thyroid hormones. In some cases you will have an elevated thyroglobulin, albeit slightly, compared to normal values.

Please note: the presence of high thyroglobulin therefore it does not automatically mean having thyroid cancerThere are many other causes that can increase thyroglobulin levels in the blood. A finding of high thyroglobulin should lead to further investigations, such as the complete picture of thyroid function, image test (thyroid ultrasound, thyroid scintigraphy in an econd step), but without forgetting that the diagnosis of thyroid neoplasia is always histological, and not through blood tests.

The above also explains why currently Thyroid cancer screening is not helpful by measuring the thyroglobulin,  precisely because of its poor specificity (in other words, due to the fact that it can be high for causes very different from thyroid cancer).

Back to the introduction

T.Low ireoglobulin

What it means to have low thyroglobulin? Low values of thyroglobulin they can be normal values, for example after thyroidectomy, or in any case after a process that has damaged the thyroid. Often the dosage of thyroglobulin is required precisely to check that the values remain low, as an increase in the same could mean a relapse of neoplastic thyroid disease.

Low thyroglobulin: causes

The most frequent causes of low thyroglobulin I'm:

  • Outcomes of thyroidectomy (surgical removal of the thyroid): as already mentioned, thyroglobulin is a marker of the presence of thyroid follicular cells. Thyroidectomy, which involves removing part or all of the thyroid gland, is followed by finding low or no thyroglobulin on blood tests.
  • Factitic thyrotoxicosis (voluntary or involuntary intake of excessive amounts of thyroid hormones): the intake of thyroid hormones puts the thyroid gland "at rest": in this situation it is possible to find low thyroglobulin values.
  • Congenital hypothyroidism with goiter: the most frequent cause of congenital hypothyroidism is endemic cretinism, a severe iodine deficiency linked to the reduced iodine content in water and food. Another, less frequent cause are genetic defects that lead to impaired synthesis of thyroid hormones and cause hypothyroidism with goiter. In all these cases, blood tests may show evidence of low thyroglobulin.

Thyroglobulin and iodine

The iodine, a fundamental molecule for the production of thyroid hormones, is a rare element, poorly represented at ground level; consequently, the normal human diet is low in iodine. The total body reserve of iodine is around 20-30 mg. In an average adult, the recommended average daily amount of iodine is about 150 mg. For pregnant or breastfeeding women, the average recommended daily intake is slightly higher. The table salt that we normally take with meals is added with iodine to help us reach the recommended daily dose.

Iodine is absorbed in the intestine and then collected in the thyroid, concentrating in the thyroid follicles. The ratio of thyroid iodine to serum iodine, which is normally 25: 1, depends on the action of this membrane carrier molecule and the action of TSH.

Thyroglobulin and recombinant TSH (rh TSH)

The dosage of the thyroglobulin must always be related to that of TSH, the level of which must be kept very low, or in any case in the low part of the normal range, through replacement therapy with thyroid hormones that the thyroidectomized patient must take due to the removal of the thyroid.

Keeping the TSH low induces a very low production of thyroglobulin in normal thyroid follicular cells but also in some thyroid tumors very dependent on the action of TSH. To prevent this reduced production masking the presence of tumor recurrence (i.e. to prevent the tests finding a false negative) we resort to the use of recombinant human TSH test.

This test involves the intramuscular administration of recombinant TSH and the subsequent measurement of serum thyroglobulin: in the case of tumor cells, stimulation with TSH will allow an increase in the production of thyroglobulin which will then be detectable in blood analyzes.

The drug usually used for the stimulation test is 0.9 mg Thyrogen (thyrotropin alfa), in two intramuscular administrations 24 hours apart, with subsequent blood sampling to measure thyroglobulin.

The measurement of TBG after recombinant TSH test, combined with ultrasound of the neck, is the optimal standard for monitoring patients who have undergone total thyroidectomy and any subsequent radiotherapy with Iodine 131.


sometimes the organism produces autoantibodies to thyroglobulin (anti-Tg), which are self-antibodies produced by the body against thyroglobulin. They are produced by our body in an unpredictable way and not linked to lifestyle, and once in the circulation they bind to the blood thyroglobulin, interfering with its measurement. It is therefore necessary to measure the antibodies to thyroglobulin because, if present, reduce the usefulness of thyroglobulin analysis as a tumor marker!

And now let's answer together some of the most frequently asked questions regarding thyroglobulin.

What is thyroglobulin used for?

Thyroglobulin serves as a precursor for the formation of the thyroid hormones T3 and T4, as well as for storing inactive forms of thyroid hormones and iodine within the colloid of the thyroid follicles.

What does it mean if my thyroglobulin is high?

Although thyroglobulin can be altered for many types of diseases, high thyroglobulin can be a wake-up call for the presence of papillary or follicular thyroid cancer.

When we can talk about indosable or negative thyroglobulin.

Undetectable serum Tgb is defined as unstimulated thyroglobulin of less than 1 ng / mL measured at least 5 weeks after total thyroidectomy and at least 3 months (3-11 months; median 6 months) after any adjuvant radiotherapy (source).

  1. Vania 4 years ago

    Hello, I am a 40-year-old mother and in 2010 I underwent total thyroidectomy for hyperthyroidism and papillary K export with active focus in metastases. Subsequently I was subjected to radioiodine 131. In the last blood test, in the anti TSH receptor Ab I as a result <0.10 IU / L on a reference value of <0.55 and as known chemiluminescence. So the exam went well? Thanks

    • Testlevels 3 years ago

      Yes, it is a value to be considered negative, i.e. antibodies to TSH receptor are not present.

  2. Lydia 4 years ago

    Hello, in April 2016 I underwent total thyroidectomy followed by a result of 'follicular neolpasia with uncertain neoplastic potential'. I did the control exams yesterday with the following results: TSH 2.55 CALCINEMIA 9.1 TIREOGLOBULINA 5.16 (in July it was at 2.90). Is the rise in the latter worrying?

    • Testlevels 4 years ago

      Hi, the increase in thyroglobulin must be absolutely investigated, starting with an ultrasound of the thyroid. In any case, always refer to your doctor or to the specialist who follows you. Best regards

  3. Art 4 years ago

    Hello I am a 25 year old mama. A few days ago I did the analysis. And the antibodies to Thyroglobulin are 879 ....... the norm and (0-40). What does it mean. Thanks

    • Testlevels 4 years ago

      It means there are antibodies attacking the thyroid. How is TSH? and thyroid hormones? to see the tests at the treating doctor or endocrinologist specialist. Best regards.

  4. El 4 years ago

    Is the Abtg value a <15 to be considered within the norm? The reference values are from 0.00 to 60.00 (I think). all other values are normal.
    Thank you in advance

    • Testlevels 4 years ago

      Yes, a negative value is normal for antibodies to thyroglobulin. Best regards

  5. Ilaria 4 years ago

    Hi I did the tests for the thyroid and these are the results: T3-2.78 T4-0.70 TSH -2.08
    Anti thyroglobulin 4.5
    Anti thyroid peroxidase 2.8
    Can you tell me if these are worrying values since I have to wait a while for the endocrinologist visit. Thank you

    • Testlevels 4 years ago

      Units of measurement are lacking, in any case thyroxine is slightly reduced, tsh and ft3 appear to be normal, anti-thyroid antibodies normal. Always refer to your doctor. Best regards

  6. Tina 4 years ago

    Hi, on August 1st I had to undergo iodine therapy but today I discovered that from the analysis of rutin IODURIA at 400 came out. Yet I have eaten correctly for twenty days and I don't explain how it could happen. They gave me the continuation of the diet and hospitalization for Iorio at the end of September. Help me understand, thank you

  7. Giovanna 5 years ago

    Hi, I was operated on in October 2015 for follicular variant papillary carcinoma ……. Radioiodine in December. The anti-thyrooglobulin antibodies before surgery were at about 1100 ....... Post surgery they started to go down .... to go up a little after the radiotherapy and go down ... Now they are at 125 ..... Thyroglobulin is always less than 0.04 ....... Is it normal as a path? Or do I have to think that there is still some thyroid tissue? Tsh 0.01 and ft4 1.49.

    • Testlevels 5 years ago

      It can be a normal path, in any case it is difficult to give a definitive answer. Follow scrupulously the diagnostic and follow-up path provided by your doctors. Best regards.

  8. Sofia 5 years ago

    Hi !!! I redid the tests for the thyroid ft4 tsh normal but the antitereoglobulin from 37.10 and passed after 1 year to 386 !!! yesterday I did the echo again and the nodules have a normal shape and size Thursday I have the endocrinologist .... I'm afraid !!!

    • Testlevels 5 years ago

      Hi, the unchanged ultrasound is a good sign, good luck for the endocrinological visit.

  9. vincenza 5 years ago

    Hi a friend noticed that I have an enlarged neck so I did an ultrasound of the neck which shows a picture of thyroid I did tests: ft3 5.3 pmol / L ft3 4.5 pmol / L then decreased tsh 64.87 globulin shot 405 ng / mL antithyroidoglobulin 3 antithyrooperoxidase 1407 ui / mL is it just thyroiditis or do I have to think that there is more below? Thank you in advance

    • Testlevels 5 years ago

      Hi, it could be an autoimmune thyroiditis, please refer to your doctor who will be able to interpret the analyzes even in the light of the complete ultrasound report of the neck.

  10. Tai 5 years ago

    Hi I did the tests for the thyroid picture and all the values are normal except the thyroglobulin which is high. What can it indicate?

    • Testlevels 5 years ago

      Hi, why did you have these tests? the picture must probably be completed with the execution of thyroid echo. Show the tests to your general practitioner or the specialist who follows you. Best regards.

  11. FAUSTA 5 years ago


    • Testlevels 5 years ago

      I would say you don't have to worry. In any case, always show the tests to your doctor.

  12. Danica 5 years ago

    Good evening,
    Operated in August 2014 for papillary variant with oxyphilic cells, metabolic radio performed after 3 months, after radio exams always normal if we exclude difficulties in lowering the Tsh. After the Tg test a few days ago, the thyroglobulin is less than 0.09, and the Anti Tg antibodies are at 11 (they have always been zero after the metabolic radio), so I ask you, in general, they should not remain at zero antibodies too? In post thyroidectomy patients are usually no anti-Tg produced if they take up thyroglobulin?

    • Testlevels 5 years ago

      Hi, let's say that the presence of high levels of antibodies to thyroglobulin can interfere with the dosage of blood thyroglobulin, making it difficult to monitor any relapses. In his case the antibodies are positive, but at a very low dose. In any case, the picture can be completed with a radiological investigation. In any case, always refer to your doctor. Best regards

  13. Adriana 5 years ago

    Good morning
    From a control examination carried out on an ICD carrier but without thyroid symptoms except overweight, the following showed:
    Ft4 9.2
    AbTG 204
    Ab TPO <35
    Tsh 3.84

    What indication can this be?
    Thanks to the availability

    • Testlevels 5 years ago

      Hi, TSH, free thyroxine and anti-thyroperoxidase antibodies are normal, the anti-thyroglobulin is a little increased, but in the absence of symptoms it can mean nothing. Always have the examinations seen by the attending physician.

  14. William 5 years ago

    I underwent a total thyroidectomy for papillary carcinoma in the right lobe in September 2015, followed in January 2016 by radiometabolic therapy with radioactive iodine. I would say that everything went well in this regard, at least so they told me, today after 3 months from the therapy I performed blood tests for scruple, the TSH is at 0.04 the same value as before the radiotherapy, and the hormone values I'm fine, what worries me is antiTG which is 423, before the radiotherapy it was 300 more or less…. So I don't know what to think…. I must say that the real check-up with the oncologist I have at the end of July .... I wait without problems or do I start running like when I discovered the problem of carcinoma?

    • Testlevels 5 years ago

      Dear user, the increase in antibodies prudently suggests that she anticipate the visit with the oncologist. In any case, refer to the attending physician who knows your history in depth. Best regards

  15. Leonardo 5 years ago

    Hi another information, if it were a relapse, is there a probability that it also affected other organs or not?
    Thanks in advance for your reply.

    • Testlevels 5 years ago

      We really hope not! The dosage of thyroglobulin also serves this purpose, to detect minimal signs of "activity" at an early stage ..

  16. Leonardo 5 years ago

    Hi, my girlfriend was operated on about two years ago for thyroid cancer.
    After the operation, he underwent iodine therapy and for these two years his thyroglobulin was always low.
    The last analysis the value was 0.09 while in those made two weeks ago the value of thyroglobulin rose to 0.90!
    Is this almost certainly a relapse?
    Will he have to do an iodine cycle again?
    Compared to the latest analyzes, his tsh is high.
    I look forward to your reply.

    • Testlevels 5 years ago

      Hi, it cannot be said that it is definitely a relapse, but the probability is not low. In any case, ultrasound of the thyroid, together with the test with recombinant TSH (Thyrogen), are the most appropriate investigations to understand what it is. Consult your endocrinologist who will suggest the most appropriate procedure. Best regards

  17. Charles 5 years ago

    Hello, I am 54 years old, I had a thyroidectomy for a thyroid cancer follicular thyroid cancer in 2011, I had also done radiotherapy after thyroidectomy, a and in the first two years the thyroid tumor markers were in place, the thyroglobulin was low or absent. Even hours, 5 years after the removal of the thyroid, I have always checked the blood values of the tumor type atg analysis, and a month ago a very high thyroglobulin came out (high chemiluminescence method). What do these high tumor values mean? should i do other thyroid cancer markers? Is elevated thyroglobulin a signal of thyroid cancer recurrence?

    • Testlevels 5 years ago

      SAlve, absolutely yes. It is necessary to exclude that the increase in thyroglobulin is due to a recurrence of the disease. Contact your trusted endocrinologist immediately to repeat ultrasound and complete thyroid biohumoral panel. Best regards

  18. luvara 5 years ago

    I had the thyroid export I had 2 multiple folicular calcinoma I had radiotherapy now I have low tsh and high ft4 and tyroglibulin at 56

    • admin 5 years ago

      Hi, the data are indicative of a picture of hyperthyroidism with low TSH and high fT4. You are taking levothyroxine replacement therapy (Eutirox?). I imagine that the value you reported of thyroglobulin is expressed in ng / ml or in µg / L: it is a value above the norm, after thyroidectomy thyroglobulin should be suppressed or measurable in minimal quantities. Have you recently had a follow-up ultrasound? please show the tests to your doctor and follow his instructions. Best regards

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