Thyroxine (T4) is the main hormone produced by the thyroid gland, following the stimulation of the thyrotropin hormone or THS. Thyroxine travels in the blood bound to specific proteins, and only a small part, free thyroxine (fT4) circulates in the blood not bound to proteins. However, free thyroxine is the fraction of the hormone that is really active, and it is also the most reliable test to carry out if you want to know the functionality of the thyroid. In the presence of free thyroxine or high fT4 you will have a condition of hyperthyroidism.
Total thyroxine (T4) is high when it exceeds 11.2 μg / dL (or the 144 nmol / L according to the SI unit of measurement, the International System Units)
Free or free thyroxine (fT4) is high when it exceeds 2.7 ng / dL (or 35 pmol / L according to the SI unit of measurement, the International System Units)
Free and total thyroxine (fT4 and T4) they are measured to evaluate thyroid function and identify any alterations due to both reduced thyroid function (hypothyroidism) and increased thyroid function (hyperthyroidism); measuring the T4 and fT4 values is also useful for monitoring the appropriateness of thyroid hormone replacement therapy in case of hypothyroidism, or of suppressive therapy in case of hyperthyroidism.
There thyroxine, also called tetraiodothyronine or more commonly T4 and triiodothyronine (T3) represent the thyroid hormones, produced and secreted by the thyroid gland, a butterfly-shaped gland found on the neck. This substance has a molecular structure based on 4 iodine molecules, and is produced by the follicular cells of the thyroid starting from thyroglobulin, a precursor molecule stored in the colloid of the thyroid follicles. This hormone is highly lipophilic, ie it is soluble in fatty substances but does not dissolve in water and theoretically cannot be transported in the blood due to its reduced solubility. Therefore, most of the thyroxine (about three quarters) binds to the "thyroxine-binding globulin" (TBG, Thyroxine Binding Globulin), while the remainder travels in the bloodstream associated with two other plasma proteins, albumin and transthyretin. Due to the relatively low plasma concentration of thyroid hormones, TBG is rarely saturated beyond 25-30% of its total capacity; this means that TBG is present in excess of the amount of thyroid hormones that can bind to it. Only a small part of the total amount of T4 produced by the thyroid (approximately 0.31TT) is therefore free in the blood. This is definite free thyroxine, and is often abbreviated with the initials fT4 (free T4).
To evaluate thyroid function and thyroid hormone levels with real biological activity, it is important to measure the free part in the blood, i.e. the fT4, instead of absolute levels. In fact, fT4 expresses the amount of thyroxine actually active on the body metabolism, and is independent of confounding factors such as the increase or decrease in plasma proteins that can alter the measurement of total thyroxine.
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The blood values of T4 and fT4 are regulated byhypothalamus pituitary thyroid axis, a complex mechanism that regulates the production 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 produced at the pituitary level, which in turn is regulated by the secretion of thyrotropin-releasing hormone (Thyrotropin
releasing hormone, abbreviated to TRH) at the thalamic level. When, for various reasons, the thyroid gland produces excess thyroid hormones, the pituitary intervenes by decreasing the production of TSH, thus decreasing the production impulse to the thyroid gland and rebalancing the values of thyroxine and triiodothyronine. As soon as the values of fT3 and fT4 return to normal, the TSH quickly returns to the normal range. Sometimes, however, this self-regulation mechanism does not work, or is not sufficient to balance the increase in thyroxine and triiodothyronine. In this case, we will have a hyperthyroidism with low TSH values. Other times, there is an abnormal production of TSH not linked to thyroid function, but which exaggerates the production of T4. In this case we will have a situation of hyperthyroidism with high levels of TSH.
The main causes of high T4 and high fT4 are:
Basedow-Graves disease: also called diffuse toxic goiter, is an autoimmune disease caused by the presence of antibodies directed against the TSH hormone receptor. The antibody reaction prompts the thyroid to produce thyroxine and triiodothyronine in an abnormal and exaggerated way. Furthermore, this abnormal stress can cause the formation of an enlargement of the thyroid gland (thyroid goiter). Graves' disease is very frequently characterized by hyperthyroidism, and in laboratory tests by fT4 and high fT3, Low TSH and positivity of anti-TSH receptor antibodies.
Toxic nodular goiter: it is also called Toxic adenoma or 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 (non-producing) nodule, but which often on the other hand, it produces large quantities of thyroid hormones in an uncontrolled and independent way from hormonal regulation. At the level of the blood test we will then have T3 / T4 and fT3 / fT4 high and low TSH levels.
Thyroiditis: is an inflammatory pathology of the thyroid gland, which can be infectious (as in the case of acute or sub-acute thyroiditis) or autoimmune (as in the case of chronic thyroiditis), which leads in the initial stages to the release of large quantities of thyroxine and triodothyronine. These diseases then evolve into a secondary phase of hypothyroidism, as the inflammation in the long run "consumes" the tissue of the thyroid gland. In autoimmune thyroiditis there is a frequent finding of anti-thyroid antibodies like them anti thyroperoxidase and anti thyroglobulin, and on blood tests we can find Low TSH and high values of fT3 and fT4. The most frequent forms are Hashimoto's thyroiditis (which in its initial phase of hyperthyroidism is called Hashitoxicosis), postpartum thyroiditis and silent lymphocytic thyroiditis. In non-autoimmune thyroiditis (for example, De Quervain's subacute thyroiditis or in acute bacterial thyroiditis), anti-thyroid antibodies are not as frequent as in the case of autoimmune.
Too high doses of hormone replacement therapy or other drug therapy: in patients who are already taking thyroid replacement therapy, i.e. who are taking drugs containing thyroxine such as 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. Patients on amiodarone therapy, for the control of common cardiac arrhythmias, or on lithium therapy as psychoactive therapy, may also have a hormonal imbalance characterized by hyperthyroidism.
Familial non-autoimmune hyperthyroidism: this disorder is linked to the mutation of a gene that codes for the TSH receptor, and is an inherited disease. The thyroid escapes the hormonal control of the TSH produced by the pituitary, and begins to produce thyroid hormones in an abnormal way. The pituitary will decrease TSH production to try to limit the elevated levels of fT3 and fT4. We'll have blood tests then high thyroid hormones and low TSH.
Ovarian teratoma: it is a neoplastic disease of the ovaries, characterized by the growth of embryonic tissues and therefore sometimes also of thyroid tissue. This tumor can also have benign characteristics, and causes hyperthyroidism for production not thyroid of thyroxine and triodothyronine resulting TSH reduction is increase in T3 / T4 and fT3 / fT4.
Pituitary adenoma or pituitary adenoma: Sometimes the cells of the anterior pituitary lobe, the adenohypophysis, are subject to uncontrolled growth. A benign nodule is then formed at the level, called adenoma, which, if it consists of TSH-secreting cells, can produce large quantities of thyrotropin. In this case, signs and symptoms of hyperthyroidism will be present, and blood tests will be evident high values of TSH and fT4 and high fT3.
Pituitary hyperfunction: in case of hyperpituitarism, high levels of TSH or thyrotropin will be produced and released into the blood. As already seen for TSH-secreting pituitary adenoma, the affected person will suffer from defined secondary hyperthyroidism, characterized by High TSH, with high triiodothyronine and thyroxine.
TSH-producing neoplasms: some neoplasms, such as those of breasts, of the lung or delthere prostate, can abnormally produce the TSH hormone, which, once it enters the blood, will stimulate the thyroid to produce T3 and T4. 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 thyroxine (fT4 and T4) allows to diagnose the presence of hyperthyroidism. The main symptoms in the presence of high fT4 are:
increased heart rate
difficulty in falling asleep and / or nocturnal awakening
vision disturbances (photophobia)
alteration of the menstrual cycle
exophthalmos and eyelid swelling
possible presence of eyelid swelling
[sociallocker id = ”407 ″] 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 drug therapy, it is good to warn your doctor about all the drugs you are taking.
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Taking amiodarone (an iodine-based antiarrhythmic drug) can alter the production of thyroid hormones resulting in high levels of fT4 and T4.
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