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, like tumor marker for thyroid neoplasms. The feedback from low thyroglobulin it is to be considered a sign of thyroid hypofunction and, if it occurs after thyroidectomy, having low thyroglobulin is a normal finding.
Thyroglobulin normal values
The normal values of thyroglobulin differ according to the country or the 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 are between 3 ng / mL and 40 ng / mL (µg / L). 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 (also called 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 lining i thyroid follicles. The thyroglobulin molecule contains a total of 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).
In fact, inside the follicles the tyrosine residues of thyroglobulin 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 (referred to simply as 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 make up the thyroid hormonesi, and their free fractions, namely 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 colloidal level even for weeks, and then re-enter the thyrocytes and be hydrolyzed by enzymes such as proteases and peptidases to form single molecules of thyroxine and triiodothyronine, ready for release into the bloodstream.
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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 intake of iodine is around 150 mg. For pregnant or breastfeeding women, the average recommended daily intake is slightly higher.
Normally the recommended average daily dose is safely taken with the diet, without having to resort to supplementation with supplements or iodized salt.
Iodine is absorbed in the intestine and then collected in the thyroid gland, using a transporter (iodine-dependent thyroid Na-K ATPase) that concentrates iodine against the gradient 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.
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What is thyroglobulin and why is it tested
There thyroglobulin (TBG) is a glycoprotein produced exclusively by the follicular cells of the thyroid. Thyroglobulin is therefore a marker of the presence of thyroid follicular cells, and NOT of thyroid cancer. Its use for the screening of thyroid carcinoma (ie to try to identify the presence of tumor) is therefore not useful, while it is very useful for the post-operative follow-up in the operated patient for differentiated thyroid neoplasia.
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 any recurrence of thyroid cancer (recurrence of thyroid cancer, in this case after having been with very low or undetectable values stably, thyroglobulin becomes detectable again).
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 anti-thyroglobulin antibodies because, if present, they reduce the usefulness of the analysis of thyroglobulin as a tumor marker!
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.
Low Thyroglobulin Symptoms
What are the symptoms of low thyroglobulin? In case of hypothyroidism, with reduced production of thyroid hormones, the symptoms will be:
- Less tolerance to cold
- Mood instability and tendency to depression
- Tiredness (asthenia)
- Weight gain (tendency to gain weight)
- Dry and fragile skin
- Loss of eyebrows (especially the outer part)
- Finer and more fragile nails
- Constipation (constipation)
- Greater incidence of carpal tunnel syndrome
- Irregularity of the menstrual cycle,
- Increase of cholesterol (hypercholesterolemia)
- Increased triglycerides (hypertriglyceridaemia)
- Memory loss.
In case there is a response from low thyroglobulin after thyroidectomy, this is absolutely normal, and should not be associated with specific symptoms.
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