There triiodothyronine (T3), is a hormone produced by the thyroid gland, which is produced thanks to the stimulating action of TSH (thyrotropin or thyrotropic hormone) produced by the pituitary gland. Triiodothyronine travels in the blood bound to specific proteins, and only a small part, free triiodothyronine (fT3) circulates in the blood not associated with these transporters. However, free triiodothyronine is the fraction of the hormone that is really active, and, together with the measurement of fT4 or free thyroxine, it is a useful test to know the functionality of the thyroid. In the presence of free triiodothyronine or low fT3 you will have a condition of hypothyroidism.
Free and total triiodothyronine (fT3 and T3) they are measured as second level tests after the measurement of fT4 and T4 (free and total thyroxine) to evaluate thyroid function and identify any alterations due to both reduced thyroid function (hypothyroidism) and increased thyroid function (hyperthyroidism).
There triiodothyronine, also called T3 together with thyroxine (T4) they represent the thyroid hormones, substances produced at the level of the thyroid, a gland located on the neck, on the sides of the trachea. Triiodothyronine has a molecular structure based on 3 iodine molecules, and is produced by the follicular cells of the thyroid, starting from a precursor molecule, the thyroglobulin, which is crammed into the colloid of the thyroid follicles. However, the blood levels of T3 do not depend only on thyroid production: in fact, a good part of T3 (over ¾ of the total production) is obtained at the peripheral level, starting from the other thyroid hormone, thyroxine (T4), thanks to activity of a class of specific enzymes, the deiodases. This group of enzymes works by subtracting an iodine molecule from thyroxine, thereby converting it to triiodothyronine. T3 is present in less quantity than T4 in the blood, but has a greater metabolic activity. This hormone is highly lipophilic, ie it dissolves in fatty substances but not in water and in aqueous substances such as blood. In order to be transported in the bloodstream, triiodothyronine must therefore travel bound to specific proteins, the main one being TBG (Thyroid Binding Globlulin). Two other plasma proteins that contribute to the transport of T3 in the blood are albumin and transthyretin. To express its real biological and metabolic activity, triiodothyronine must necessarily separate from the transport proteins; the protein-free or "free" fraction of T3 is called fT3, and is the substance that is commonly measured in blood tests, as it better expresses the activity of the thyroid. In hyportyroidism, the total amount of T3 will be reduced compared to normal values, but a total T3 / free T3 ratio will be observed shifted in favor of the protein-free fraction, due to a compensation mechanism that tries to "buffer" the deficiency of thyroid hormones by releasing as much as possible of circulating plasma proteins.
The values of T3 and fT3 are regulated by a sophisticated mechanism called hypothalamus pituitary thyroid axis, which allows the body to optimize the production of thyroid hormones. Thanks to this system, the hormones fT3 and fT4 are kept in the normal range from TSH (thyroid stimulating hormone or thyrotropin), produced at the level of the pituitary gland, which in turn is regulated by the production of TRH (Thyrotropin releasing hormone or thyrotropin releasing hormone) produced at the thalamic level.
When, for various reasons, the thyroid gland produces thyroid hormones in reduced quantities, the pituitary gland increases the production of TSH, so as to increase the productive impulse of the thyroid gland and to restore the values of thyroxine and triiodothyronine to normal. As soon as the T3 / fT3 and T4 / fT4 values return to normal, the TSH also returns to normal values. Sometimes, however, this self-regulation system is defective, or it is not sufficient to remedy the deficiency of thyroxine and triiodothyronine. In this case, we will have a hypothyroidism with high TSH values. Less frequently, there is a drop in TSH production not related to thyroid function, but to a defect in pituitary production. As a result, adequate production of T3 and T4 will be lacking, and we will have a situation of hypothyroidism with Low TSH.
Unlike thyroxine or T4, whose production is solely linked to TSH, the levels of T3 (and secondarily of fT3) also depend largely on the activity ofdeiodinase enzyme and in particular of 5-deiodinase, primarily responsible for the conversion from T4 to T3.
The main causes of low T3 and low fT3 are:
Autoimmune thyroiditis: these inflammatory thyroid diseases are the most common cause of hypothyroidism: They are characterized by an inflammatory process that affects the thyroid gland, secondary to an abnormal immune response caused by our own organism, which does not recognize the thyroid cells and attacks them by damaging them. Hypothyroidism from thyroiditis is characterized by High TSH, low fT3 and fT4 and presence of anti-thyroid antibodies , that is the antibodies to thyroperoxidase (anti TPO), antibodies to TSH receptor (anti TSH) e antibodies to thyroglobulin anti TGB). Hasimoto's thyroiditis is the most frequent autoimmune thyroiditis.
Poor iodine intake: a raw material, iodine, is essential for the production of thyroxine and triiodothyronine: if it is not introduced into the body in adequate quantities with food, the thyroid will not be able to produce normal quantities of T3 and T4. In some parts of Italy, foods are less rich in iodine than indicated by the FDA, which is why table salt is added with small amounts of iodine.
Viral thyroiditis: are inflammatory processes affecting the thyroid gland, linked to a viral infection that causes sub-acute thyroiditis. A classic example is De Quervain's thyroiditis, which occurs in two distinct phases: at first the thyroid is stimulated by the inflammatory process and produces thyroid hormones even in excess, resulting in low TSH in the blood. Later, the thyroid enters a phase of less activity, and is often no longer able to maintain adequate levels of thyroid hormones. In this more prolonged phase, it is therefore common to find High TSH and triiodothyronine and thyroxine decreased.
Thyroidectomy or chemical destruction of the thyroid: in case of neoplasms or diseases that require partial or total removal of the thyroid, there will be a block in the production of thyroid hormones (low or no fT3 and fT4). This, if not corrected by adequate drug replacement therapy, will result an increased production of TSH on the part of the pituitary. In addition to surgical removal, this can also occur in the case of thyroid destruction by drugs such as radioactive iodine, or following its damage after radiation therapy (for example following radiotherapy sessions aimed at neoplasms located in the vicinity of the neck ).
Congenital hypothyroidism: in some individuals the thyroid gland presents a malformation from birth which results in reduced activity and a situation of hypothyroidism, which must be corrected immediately to allow psychophysical development.
Peripheral conversion deficiency of triiodothyronine T3:in situations of stress, in prolonged fasting, in infections, and above all in chronic diseases, it frequently happens that peripheral conversion from T4 to T3 is deficient. The reasons for this deficit defined as low T3 syndrome or low T3 syndrome, should be sought among the following hypothetical causes: alterations of the hypothalamus-pituitary axis (due to the action of proinflammatory cytokines which act at the hypothalamic level, reducing the production of TRH), reduction of the transport proteins of thyroid hormones, inhibition of the with transport proteins and hormone uptake by cells, inhibition of membrane transport of thyroid hormones, reduced levels and effects of thyroid hormones in many target organs due to decreased cell uptake and reduced expression of cellular receptors for thyroid hormones, reduction of the deiodinase activity of the three deiodinases (D1, D2, D3) due to acute phase proinflammatory cytokines, and finally decrease of the nocturnal peak of TSH due to a decrease in TRH and a simultaneous increase in cortisolemia. Furthermore, deiodinases, the enzymes responsible for the peripheral transformation of thyroxine into triiodothyronine, function if there is an appropriate amount of selenium: in patients with chronic diseases this trace element is often missing, compromising the normal function of these enzymes. Even some drugs, such as amiodarone, inhibit the action of 5-deiodinoase: here is that in patients treated with amiodarone with appropriate thyroid function and normal TSH and T4 / fT4 values, an isolated T3 deficiency may be found. / fT3.
Medicines: there are some drug therapies that can impair the production of thyroid hormones, with low total and free thyroxine blood levels, and inducing a secondary increase in blood levels of thyrotropin (TSH). Among these the most frequent is amiodarone, an iodine-rich antiarrhythmic drug that can cause both hypothyroidism and hyperthyroidism. As already mentioned, amiodarone has an inhibiting action on the deiodinase enzyme which converts thyroxine into triiodothyronine. Other drugs that can generate this side effect are interferon (mainly used in antiviral therapy and in immunohematological therapy), and the lithium, a psychiatric drug used in the treatment of psychiatric conditions such as bipolar disorder or in some types of headache.
Inadequate thyroid replacement hormone therapy: patients with recognized hypothyroidism, who are on replacement therapy with thyroid hormones (for example with Eutirox, the most used drug in Italy), must carry out periodic blood checks, to regulate the therapy. Often the dose of thyroid hormones taken is insufficient, this will be reflected in the finding of low fT3 (low free triiodothyronine) and low fT4 (low free thyroxine) in the blood.
Storage diseases: these are quite rare pathologies, in which substances that damage the tissues and make it malfunctioning accumulate in the thyroid. As a consequence of the biohumoral tests we will have low fT4 and fT3, and, due to the secondary pituitary response, High TSH. Among the diseases that deposit at the thyroid level we remember amyloidosis, which causes the deposit of low molecular weight proteins produced by the organism in an anomalous way that accumulate between the intracellular spaces of the gland and damage it, and hemochromatosis, characterized from iron storage.
Pregnancy: during pregnancy there is an increase in circulating estrogen, which stimulates the production of proteins that carry the hormones T3 and T4 in the circulation. Consequently on the one hand the fraction of thyroid hormones "bound" to these transport proteins increases, on the other hand the fraction of thyroid hormones "free" in the blood decreases, and therefore there is a decrease in fT3 and fT4 in the bloodstream.
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The finding of low values of free and total triiodothyronine (fT3 and T3), if also associated with reduced values of free and total thyroxine (fT4 and T4) allows us to diagnose the presence of hypothyroidism. The main symptoms in the presence of low fT4 and low fT3 are:
- Low cold tolerance
- Instability of mood
- Tendency to depressed mood
- Easy fatigue
- Increased body weight
- Dry and fragile skin
- Loss of eyebrows (especially the outer part)
- Thin and brittle nails
- Irregularity of the menstrual cycle
- Increased fat (especially the cholesterol)
- Memory loss
If, on the other hand, there is an isolated decrease in fT3 and T3, with fT4 / T4 and / or TSH in the normal range, probably there is no picture of hypothyroidism as described above, but only a transformation deficit from T4 to T3. This, as already explained in the previous paragraphs, often happens in case of chronic diseases, in states of malnutrition, or during therapy (the most frequent is with amiodarone), which inhibit the action of deiodases, enzymes that convert thyroxine (T4) in triiodothyronine (T3).
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The examination is carried out starting from a blood sample obtained with a venous sampling. It is not necessary to fast before the exam. It is known that some drugs can alter the values of free and total thyroxine. Therefore, if you are taking any type of medication, it is advisable to notify the doctor of the therapy in progress.
Some drugs can alter the actual measurement of free and total triiodothyronine values in the blood. These include anabolic steroids, androgens, anti-thyroid drugs (propylthiouracil and methimazole, which obviously will inhibit the production of thyroid hormones), interferon alpha, interleukin 2, lithium, some beta-blocking drugs (for example propanolol) and phenytoin ;
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