Thyroxine (T4), is the main hormone of the thyroid gland, which is produced thanks to the stimulating action of TSH (thyrotropic hormone or thyrotropin) produced by the pituitary. 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 useful test if you want to reliably know the functionality of the thyroid. In the presence of free thyroxine or low fT4 you will have a condition of hypothyroidism.
Total thyroxine (T4) is low when it falls below 4.5 μg / dL (or the 58 nmol / L according to the SI unit of measurement, the International System of Units)
Free or free thyroxine (fT4) is low when it falls below 0.8 ng / dL (or 10 pmol / L according to the SI unit of measurement, the International System of 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 T4 or tetraiodothyronine, together with triiodothyronine (T3) they represent the thyroid hormones, substances produced and secreted by the thyroid, a butterfly-shaped gland found on the neck, on either side of the trachea. This substance has a molecular structure based on 4 iodine molecules, and is produced by particular thyroid cells called "follicular", starting from a precursor molecule, the thyroglobulin, which is crammed into the colloid of the thyroid follicles. This hormone is part of the "lipophilic" substances, ie that dissolve in fatty substances but not in water, so it cannot be transported in the blood due to its reduced solubility. Therefore, most of the thyroxine (more than 70%) binds to "thyroxine-binding globulin" (TBG, Thyroxine Binding Globulin), while the remainder travels in the blood associated with two other plasma proteins, albumin and prealbumin (also called transthyretin). Due to the relatively low plasma concentration of thyroid hormones, TBG is rarely saturated more than a quarter of its overall 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 bloodstream. This is definite free thyroxine, or free T4, and is often abbreviated with the abbreviation fT4.
To evaluate thyroid function and thyroid hormone levels with real biological activity, it is useful to measure the free fraction in the blood, i.e. the fT4, instead of absolute levels. In fact, fT4 expresses the amount of thyroxine actually active on the body's metabolism, and is independent of confounding factors such as the increase or decrease in plasma proteins which can alter the measurement of total thyroxine.
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The values of T4 and fT4 are regulated by a sophisticated mechanism called hypothalamus pituitary thyroid axis, which allows the body to regulate 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 pituitary level, which in turn is regulated by the production of TRH (Thyrotropin
releasing hormone or thyrotropin releasing hormone) at the thalamic level. When, for various reasons, the thyroid produces thyroid hormones in defect, the pituitary intervenes by increasing the secretion of TSH, so as to increase the productive impulse to the thyroid gland and to rebalance the values of thyroxine and triiodothyronine. As soon as the values of fT3 and fT4 return to normal, TSH quickly returns to normal. Sometimes, however, this self-regulation mechanism does not work, or is not sufficient to fill the thyroxine and triiodothyronine deficiency. In this case, we will have a hypothyroidism with high TSH values. At other times, there is a drop in TSH production not related to thyroid function, which does not allow adequate production of T4. In this case we will have a situation of hypothyroidism with low levels of TSH.
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The main causes of low T4 and low fT4 are:
Autoimmune thyroiditis: represent the most common cause of hypothyroidism, are characterized by an inflammatory process that affects the thyroid gland, secondary to an abnormal immune response caused by our own body, which does not recognize the thyroid cells and attacks them as if they were hostile organisms. Hypothyroidism from thyroiditis is characterized by high TSH values, low fT4 and the presence of high antithyroid antibody values, which are antibodies to thyroperoxidase (anti TPO or ab TPO), antibodies to TSH receptor (anti TSH) e antibodies to thyroglobulin anti TGB) .. The most important and frequent autoimmune thyroiditis with hypothyroidism is Hashimoto's Thyroiditis.
Upwardefficient contribution iodine: the production of thyroid hormones requires iodine, the essential raw material for the synthesis of thyroxine and triodothyronine. If not enough is introduced into the body through nutrition, the thyroid will not be able to produce enough 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 iodine-based compounds.
Viral thyroiditis (De Quervain's thyroiditis): Thyroid inflammatory process is linked to a viral infection that causes sub-acute thyroiditis, which manifests itself in two distinct phases: at first the thyroid is stimulated by the inflammatory process and produces large quantities of thyroid hormones, resulting in TSH low in blood. Thereafter, the thyroid enters a phase of reduced activity, and is no longer able to maintain adequate levels of thyroid hormones. In this more prolonged phase, it is normal to find High TSH and fT3 and fT4 decreased.
Absence of thyroid gland for surgical (thyroidectomy) or pharmacological causes: in the case of tumors or diseases that require partial or total removal of the thyroid, there will be a partial or total block in the production of thyroid hormones (low or no triiodothyronine and thyroxine). This, if not balanced by proper drug replacement therapy, will cause an increased production of TSH by the pituitary, to try to compensate for the absence of thyroxine and triiodothyronine production. 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 for radiotherapy of tumors located in the vicinity of the neck).
Congenital hypothyroidism: in some people the thyroid has a malformation from birth, causing a situation of hypothyroidism that must be corrected immediately to avoid serious consequences in the development of the child.
Storage diseases: are rare pathologies, in which substances accumulate in the thyroid that damage the tissues and make it malfunctioning. As a consequence the production of T3 and T4 will be reduced, causing a secondary pituitary response with overproduction of 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.
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. Other drugs that can generate this side effect are interferon (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.
Insufficient thyroid replacement hormone therapy: Patients with recognized hypothyroidism, who are on thyroid hormone replacement therapy (the most used drug is Eutirox), must have periodic blood checks to regulate the therapy. Often the dose of thyroid hormones taken is insufficient, this will be reflected by the finding of di fT4 and low fT3 in the blood.
Pregnancy: during pregnancy there is an increase in placental estrogens which stimulate the production of proteins that carry the hormones T3 and T4 into the circulation. Consequently the fraction of thyroid hormones "bound" to transport proteins increases, the "free" fraction in the blood decreases, and therefore there is a decrease in fT4 in the bloodstream.
The finding of low values of thyroid hormones, and in particular of free and total thyroxine (fT4 and T4) allows us to diagnose the presence of hyperthyroidism. The main symptoms in the presence of low fT4 are:
- Low cold tolerance
- Lability of the mood
- Tendency to depression
- Fatigue and weakness
- Weight gain (tendency to gain weight)
- Dry and fragile skin
- Loss of eyebrows (especially the outer part)
- Thin and brittle nails
- Irregularity of the menstrual cycle
- Dyslipidemias (increased cholesterol)
- Memory loss
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.
Some drugs can alter the actual measurement of free and total thyroxine values in the blood. These include heparin, phenylbutazone, phenytoin, lithium, propanolol, quetiapine.
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