Triiodothyronine (T3) is a hormone produced in part by the follicular cells of the thyroid gland, and in part synthesized in the peripheral body tissues starting from the other thyroid hormone, thyroxine (T4). Triiodothyronine, a molecule characterized by 3 iodine units, circulates in the blood bound to specific plasma proteins, and only a small part is free from this bond (free triiodothyronine or fT3). Given that the most active fraction of the hormone at the metabolic level is precisely the free one, it is preferable to measure fT3 in blood tests, rather than T3. Free triiodothyronine or fT3, together with free thyroxine or fT4, is a useful test for monitoring the endocrine activity of the thyroid. In the presence of free triiodothyronine or high fT3 there will be a condition of hyperthyroidism.
Total triiodothyronine (T3) is high when it exceeds 200 ng / dL (or 3.08 nmol / L according to the SI unit of measurement, the International System of Units)
Free or free triiodothyronine (fT3) is high when it exceeds 4.8 pg / ml (or 7.4 pmol / L according to the SI unit of measurement, the International System of Units)
FT3, or free triodothyronine, should be measured to evaluate thyroid function and identify any alterations both in the sense of thyroid hyperactivity (hyperthyroidism), with high fT3, and in the case of hypofunction (hypothyroidism), with reduced levels of fT3; this test must be associated with the dosage of thyrotropin, or TSH, and of fT4, or free thyroxine, essential for understanding the real activity of the thyroid and the possible causes of its malfunction.
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There triiodothyronine, commonly defined T3, together with thyroxine (T4) represent the hormones produced by the thyroid gland, a gland found on the neck on either side of the trachea. Triiodothyronine has a molecular structure based on 3 iodine molecules, and is produced starting from thyroglobulin, a precursor located in the colloid of the thyroid follicles. However, the blood levels of T3 do not depend only on thyroid production: in fact, a large part of T3 (more than 80%) is produced at the peripheral level, starting from the other thyroid hormone, thyroxine or T4, thanks to the activity of a group of specific enzymes, the deiodases. This class of enzymes works by subtracting an iodine molecule from thyroxine, thereby converting it to T3. Triiodothyronine is present in less quantity than T4 in the blood, but has a higher metabolic activity. This hormone is highly lipophilic, i.e. it is soluble in fatty substances but does not dissolve in water and water-based substances such as blood.
In order to travel in the bloodstream, triiodothyronine must move bound to specific proteins, the main of which is (Thyroid Binding Globlulin, TBG. Two other plasma proteins important for the transport of T3 in the blood are albumin and transthyretin. To express its real biological and metabolic activity, triiodothyronine must necessarily detach itself 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 hyperthyroidism, the total amount of T3 will be increased compared to normal values, but a total T3 / free T3 ratio will be observed shifted in favor of the protein-bound fraction, due to a compensatory mechanism that tries to "buffer" the excess of thyroid hormones by sequestering as much as possible in plasma proteins.
The blood values of T3 and fT3 are regulated byhypothalamus pituitary thyroid axis, a sophisticated mechanism that regulates the levels of thyroid hormones. Thanks to this mechanism, the hormones fT3 and fT4 are kept in the normal levels by thyrotropin (thyroid stimulating hormone or thyrotropin, abbreviated to TSH) released by the pituitary gland, which in turn is regulated by the thyrotropin-releasing hormone (Thyrotropin releasing hormone, abbreviated to TRH) produced by the thalamus.
When, for various reasons, there is an excessive production of thyroid hormones, the pituitary intervenes by decreasing the production of TSH, so as to decrease the productive thrust towards the thyroid and to restore thyroxine and triiodothyronine to normal values. As soon as the values of fT3 and fT4 return to normal, TSH quickly returns to the norm. Sometimes, however, this regulation mechanism does not work, or it works but it is not sufficient to balance an excessive increase in thyroxine and triiodothyronine. In this case, we will have a hyperthyroidism with low TSH values. Other times, there is an excessive production of TSH, independent of the thyroid function, which exaggerates the production of T3. In this case we will have a situation of hyperthyroidism with high levels of TSH.
The other mechanism that our body uses to limit the effects of thyroid hormones, and in particular of triiodothyronine, is to act on the activity ofenzyme that largely produces it, that is the deiodase and in particular of the 5-deiodase, thus limiting the conversion from T4 and T3.
The main causes of high T3 and high fT3 are:
Basedow-Graves disease: or diffuse toxic goiter, is an autoimmune disease characterized by the presence of antibodies directed against the TSH hormone receptor. The reaction of the antibodies causes the thyroid to produce thyroxine and triiodothyronine in an abnormal and disproportionate way. In addition, this abnormal stress can cause the formation of an enlargement of the thyroid gland, defined as thyroid goiter. Graves' disease is often characterized by hyperthyroidism, and in laboratory tests by high fT4 and fT3, low TSH and anti-TSH receptor antibody positivity.
Thyroiditis: are diseases of an inflammatory nature of the thyroid, and can have an infectious cause (as in the case of acute or sub-acute thyroiditis) or more frequently autoimmune (as in the case of chronic thyroiditis), which leads in the initial stages to the release of large quantities of T3 and T4. These diseases then evolve into a secondary phase of hypothyroidism, as the inflammation in the long run "destroys" the tissue of the thyroid gland which is unable to produce sufficient quantities of hormones. In autoimmune thyroiditis there is a frequent finding of anti-thyroid antibodies, in particular of antibodies to thyroperoxidase (anti TPO) is antibodies to thyroglobulin anti TGB), usually associated withLow TSH and high values of fT3 and fT4. The most common forms of thyroiditis are Hashimoto's thyroiditis (which in its early stage of hyperthyroidism is called Hashitoxicosis), postpartum thyroiditis and silent lymphocytic thyroiditis. In non-autoimmune thyroiditis (e.g. De Quervain's subacute thyroiditis or in acute bacterial thyroiditis), anti-thyroid antibodies are found less frequently than in autoimmune thyroiditis.
Toxic adenoma, toxic nodular goiter: it is also said Plummer's disease, is a benign neoplasm of the thyroid gland, characterized by a single nodule (uninodular goiter) or multiple nodules (multinodular goiter) which may behave as a cold, and therefore non-secretory (i.e. non-producing) nodule, or may produce large amounts of T3 and T4 completely unregulated by the hormonal compensation mechanism. At the level of the blood tests they will be evident High T3 / T4 and fT3 / fT4, and reduced TSH levels.
Incorrect dose of HRT, other drugs: in patients who are taking thyroid replacement therapy, i.e. in therapy with thyroxine (e.g. Eutirox), the response to blood tests of high fT3 and fT4 and low TSH it may be the consequence of too high a dose of the drug.
Familial non-autoimmune hyperthyroidism: it is a hereditary disorder, linked to the mutation of a gene encoding the TSH receptor. The thyroid no longer responds to the classical TSH-mediated hormonal control mechanism produced by the pituitary, and begins to produce thyroid hormones in an exaggerated and uncontrolled way. The pituitary will decrease TSH production to try to limit the elevated levels of fT3 and fT4. The blood tests are therefore found high thyroxine and triodothyronine and low TSH.
Ovarian teratoma: it is a neoplasm of the ovaries, in which there is growth of embryonic tissues (in our case of thyroid tissue). This tumor is not always malignant, and causes a state of hyperthyroidism for production not thyroid of triodothyronine and thyroxine resulting drop in TSH is increase in T3 / T4 and fT3 / fT4.
Pituitary adenoma: also called pituitary adenoma: sometimes the cells of the anterior lobe of the pituitary become autonomous and are subject to uncontrolled growth. An adenoma is therefore formed in the adenohypophysis, that is, a benign nodule that can produce large quantities of TSH. The blood tests are therefore found High TSH and high fT4 and fT3, and typical signs and symptoms of hyperthyroidism may arise.
Hyperpituitarism:in case of pituitary hyperfunction, a large quantity of high pituitary hormones will be released into the bloodstream. As already seen for TSH-secreting pituitary adenoma, the affected person will suffer from defined secondary hyperthyroidism, characterized by high values of TSH and fT4 and high fT3.
TSH-secreting tumors: some neoplasms, such as cancer al lung, to prostate or al otherwise, they can produce TSH hormone within them, which, once it enters the blood, will stimulate the thyroid to produce thyroxine and triiodothyronine. This mechanism is called paraneoplastic syndrome, which is a set of signs and symptoms caused by a neoplasm in an organ far from the site of tumor development.
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The finding of high values of thyroid hormones, and in particular of free and total triiodothyronine (fT3 and T3) allows to identify a state of hyperthyroidism. The main symptoms in the presence of high fT3 and high fT4 are:
- excitement and increased reactivity
- intense sweating
- weight loss
- difficulty falling asleep and / or frequent nocturnal awakenings
- vision disturbances (photophobia)
- alteration of the menstrual cycle
- widespread itching
- hot flashes
- exophthalmos and eyelid swelling
The analysis is carried out starting from a blood sample through a venous blood sample. You don't need to fast before the exam. Since some medications can alter free and total triiodothyronine values, you should warn your doctor about all medications you are taking at the time of the exam.
Numerous drugs can decrease or increase the levels of T3 and fT3: among these there are estrogens (and therefore drugs such as the contraceptive pill), drugs that lower triglycerides such as chlorofibrate, methadone. It should also be remembered that a pregnant woman may have slightly increased T3 and fT3 values, since it tends to increase the synthesis of the precursor molecule thyroglobulin.
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Tags: Laboratory medicine Blood