TSH - thyrotropin
The TSH, also called thyrotropin, thyrotropic hormone or thyroid stimulating hormone, is a substance produced by the pituitary gland. Come on TSH values you can guess how the thyroid works: in fact, TSH is the main regulatory substance of the two thyroid hormones: T4 (thyroxine) and T3 (triiodothyronine).
The reference values of TSH they are usually between 0.5 and 4 mIU / L. Depending on the institution or laboratory to which reference is made, these values may present small variations. This site uses as a reference only the most reliable sources in the world. We therefore report the ranges of normality according toauthoritative Medscape portal:
TSH normal values in pediatrics
- Infants born premature (at 28-36 weeks) first week of life: 0.7-27.0 mIU / L
- Children born from 4 days: 1-39 mIU / L
- Babies born from 2-20 weeks: 1.7-9.1 mIU / L
- Children born from 21 weeks to 20 years of age: 0.7-6.4 mIU / L
TSH normal values in adults
- 21-54 years: 0.4-4.2 mIU / L
- 55-87 years: 0.5-8.9 mIU / L
TSH in pregnancy
The range of TSH values during pregnancy varies slightly depending on the time of gestation. Here's what TSH looks like depending on the quarter:
- First quarter: 0.3-4.5 mIU / L
- Second quarter: 0.5-4.6 mIU / L
- Third quarter: 0.8-5.2 mIU / L
The Mayo Clinic, one of the most important research institutes in the world, defines normal TSH values as between 0.3 and 4.2 mIU / L. Here are the normal TSH values stratified by age according to i Mayo Medical Laboratories:
TSH normal values in infants
- 0-5 days: 0.7-15.2 mIU / L
- 6 days-2 months: 0.7-11.0 mIU / L
TSH normal values in children and adolescents
- 3-11 months: 0.7-8.4 mIU / L
- 1-5 years: 0.7-6.0 mIU / L
- 6-10 years: 0.6-4.8 mIU / L
- 11-19 years: 0.5-4.3 mIU / L
TSH normal values in adults
- 20 or more years: 0.3-4.2 mIU / L
TSH is a glycopeptide of approximately 28 KDa in molecular weight.
There TSH concentration in circulation is expressed in thousandths of international units of biological activity per liter of blood (mIU / L). This unit of measurement derives from the way the TSH concentration is assessed.
Thyrotropin levels are initially measured on colloidal tissue isolated from the thyroid gland of a guinea pig (guinea pig); an international unit was defined as the minimum amount of thyrotropin that causes an active biological response (i.e. production of cAMP by stimulation of thyroid adenylate cyclase).
Analyzes for measuring thyrotropin use standardized calibrators according to the guidelines of the World Health Organization (WHO), according to the International Reference Preparation (IRP) 80/558, which contain 7-5µg of purified human pituitary extract, which is the equivalent of 37mIU of thyrotropin.
The measurement of the TSH ultra-sensitive, routinely in many laboratories, involves the use of immunoenzymatic method with microplates including mouse monoclonal anti-TSH antibody used for the solid phase and rabbit anti-TSH antibody for the liquid phase, which react simultaneously with the sample to be examined. The measurement of the TSH ultra-sensitive it then continues with the washing of the kit and the conjugation with tetramethylbenzidine (TMB) for the determination of the concentration through the proportional gradations of color.
The thyrotropic hormone it is produced by the pituitary gland, a small gland found in the skull. If thyroid hormone levels decrease, or if our body is subjected to physical or psychological stress, a part of our brain, the hypothalamus, produces thyrotropy-releasing hormone, also called TRH (thyrotropin-releasing hormone). The TRH acts at the level of the anterior part of the pituitary gland, increasing its production of TSH, which in turn goes to act at the level of the thyroid, stimulating the production of thyroid hormones starting from the molecule thyroglobulinuntil their normal value is restored.
There thyroid it is a butterfly-shaped gland located at the anterior base of the neck, in front of the trachea. Its main function is to produce two types of hormones, the hormone thyroxine (T4) and the hormone triiodothyronine (T3). These hormones then spread through the blood throughout the body, work together to maintain balance and body temperature, contributing to the growth of our body and to the production of energy in the form of heat. When thyroid hormones have reached normal values, the pituitary gland decreases the production of thyroid stimulating hormone, and consequently the thyroid is less stimulated to produce T3 and T4. This mechanism is called "negative feedback".
The production of TSH follows a daytime rhythm, and has a peak in the late evening, and a lower production in the mid-morning hours. The TSH measurement in blood tests is the main test to understand how the thyroid is working: it can be measured alone, or in association with the thyroid hormone T4. When we are in the presence of thyroid hormones and thyrotropin within normal values, it can be assumed with reasonable certainty that the thyroid is normal functioning.
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The thyrotropic hormone is dosed for evaluate thyroid function and identify any alterations in hormonal secretion. TSH, fT3, fT4 are the three hormones that are part of the basic blood analysis panel when you want to investigate the efficiency of the thyroid gland. The altered function linked to an overactive thyroid generates a clinical picture of hyperthyroidism, often with feedback from Low TSH and high fT3 fT4 in the case of overt hyperthyroidism, or Low TSH and normal fT3 fT4 in case of subclinical hyperthyroidism, in the initial phase). A hypofunction of the thyroid instead generates a clinical picture of hypothyroidism, both overt type with high TSH and low fT3 and low fT4, and mild and not yet manifest type (subclinical hypothyroidism, high TSH and normal fT3 fT4); measuring the TSH also serves to monitor the effectiveness of therapy in case of hypothyroidism (monitoring of the thyroid hormone replacement therapy) or hyperthyroidism (monitoring of thyroid suppressive therapy).
TSH analysis is also performed in newborns as a screening test for the diagnosis of congenital thyroid pathologies (the most frequent is thecongenital hypothyroidism). The diagnosis is made through an analysis on a blood sample obtained with a venous sample, which measures the concentration of the TSH hormone. Usually with the same sample the doctor also recommends the dosage of thyroid hormones (T3 and T4, as already mentioned, often indicated in their free or "free" form with the initials fT3 and fT4), which are essential in order to establish the possible cause of altered levels of thyrotropic hormone.
Often these tests are associated with other blood tests: the most frequent are blood count, kidney function (urea and creatinine), mineral salts in the blood (sodium, potassium, less frequently calcium and magnesium), and inflammation parameters, i.e. the erythrocyte sedimentation rate (VES) and the C-reactive protein (PCR). In the suspicion of thyroid autoimmune diseases, anti-thyroid antibodies are usually required, namely the antibody anti thyroglobulin (ab anti-TG), which is a substance from which thyroid hormones are produced, theanti-TSH receptor antibody (ab anti-TSH), and the antibody anti thyroid peroxidase (ab anti-TPO), directed against thyroperoxidase, an enzyme that regulates the synthesis of hormones produced by the thyroid.
From the radiological point of view, if there is an evident morphological alteration (for example a nodule palpable or visible, or a thyroid goiter), or if you want to investigate any alterations in blood tests, the first level exam and aultrasound of the thyroid gland. Only secondarily, if necessary, will it be possible to make one thyroid scintigraphy and possibly a fine needle aspiration.
TSH above normal is associated with a number of medical conditions: in case of high TSH it is always necessary to measure at least one of the two types of thyroid hormones, fT3 or fT4. This allows us to understand if, as happens in most cases, there is a reduced function of the thyroid, ie a hypothyroidism, or if, less frequently, there is a hyperfunction of the thyroid, and therefore a hyperthyroidism.
High TSH causes
A High TSH it can be found both in response to a reduced production of thyroid hormones by the thyroid gland (condition of hypothyroidism), and in the presence of an increased production of TSH, in the pituitary or in other sites (condition of hyperthyroidism). However, it must be said that in the vast majority of cases the High TSH goes with normal or low fT3 and fT4.
Below we will explain what are the main causes of high TSH and differentiate those that lead to a condition of hyperthyroidism (TSH high fT3 fT4 high), from those, more frequent, that lead to a condition of hypothyroidism, initially subclinical (High TSH fT3 normal fT4) and then overt hypothyroidism (TSH high fT3 fT4 low).
Do you want to deepen the topic? We have selected this book that addresses the problem of hypo and hyperthyroidism.
High TSH and normal fT3 fT4: subclinical hypothyroidism
Hypothyroidism it is a disease characterized by a reduced function of the thyroid gland, which therefore produces the thyroid hormones fT3 and fT4 in insufficient quantities. To compensate for this deficiency, the pituitary gland produces greater quantities of TSH, which will therefore be elevated in blood tests. Initially, the increase in thyrotropin production will be enough to stimulate the thyroid more, obtaining a normalization of thyroid hormone levels. At this stage, said subclinical hypothyroidism, blood tests will result High TSH with normal fT3 and fT4.
High TSH and low fT3 fT4: hypothyroidism
When you are in a more advanced stage, the increased levels of TSH will no longer be enough to maintain normal levels of the hormones produced and secreted by the thyroid. In this situation we speak of real or hypothyroidism overt hypothyroidism, and on blood tests we will have high TSH and low values of fT3 and fT4. Often hypothyroidism, if neglected, leads to the formation of thyroid goiter, that is the enlargement of the thyroid gland linked to a continuous stimulation by TSH.
Here are a few causes of high TSH associated with hypothyroidism:
- Congenital hypothyroidism: in 85% of cases due to a structural defect of the thyroid gland, as for thethyroid agenesis (lack of formation of the thyroid gland), for the thyroid dysgenesis (abnormal thyroid development), thethyroid ectopia (thyroid in abnormal location compared to the normal anterior pretracheal position) or for thyroid hypoplasia (poorly represented thyroid tissue). In another 10% of cases it concerns a defect in hormone production, which can be linked to a thyroid difficulty concentrate iodine internally due to the presence of a mutation in the iodine / sodium transporter, to a defect of the intrathyroid peroxidase, rather than a defect of the oxidative condensation of MIT and DIT in thyroxine and triiodothyronine, or to a deficiency of desiodation of iodotyrosines, or finally to the production of abnormal iodized compounds which are metabolically hypoactive. All these cases are characterized by Elevated TSH and reduced or absent thyroid hormones.
- Acute thyroiditis: the acute thyroiditis they are usually related to bacterial or parasitic infections: in children and adolescents they are often linked to structural thyroid abnormalities such as fistulas in the piriform sinus or residues of the thyroglossal duct in adults they are more often caused by the spread of an infection by proximity of the affected site (infection by contiguity from pharyngitis, tonsillitis, mumps etc.) or by blood dissemination (pulmonary, gastrointestinal, soft tissue infections). The most common symptoms are fever and the appearance of latorecervical adenopathies (swelling and / or pain of the lymph nodes in the neck). The therapy is obviously antibiotic which in most cases causes the thyroiditis to regress and restore normal hormone production by the thyroid.
- De Quervain's thyroiditis and subacute thyroiditis: the De Quervain's thyroiditis o granulomatous thyroiditis, often occurs following a viral infection, and sometimes requires cortisone therapy. The most common symptoms are fever, asthenia (tiredness), myalgia (muscle aches). It usually resolves with one restitutio ad integrum, that is, with a return to normal thyroid function. In a 5% of cases, however, a condition of hypothyroidism remains which will require replacement therapy.
- Hashimoto's thyroiditis e chronic thyroiditis: are the most common forms of thyroiditis, in particular the Hashimoto's thyroiditis it represents by far the most frequent inflammatory thyroid disease (in women 3.5 cases per 1000 people). It is a chronic inflammation of the thyroid gland with autoimmune origin, which leads to chronic damage with residual final hypothyroidism. Symptoms may be absent, or be related to the hypothyroidism that develops in this pathology. Diagnosis is based on the finding of anti-thyroid antibodies: antibodies to thyroperoxidase (anti-TPO) and antibodies to thyroglobulin (anti-TGB), as well as low levels of fT3 and fT4 in the blood. Therapy is essentially replacement with levothyroxine (LT4). Other forms of chronic thyroiditis are the postpartum thyroiditis, the silent tyrolidite and the Riedel's thyroiditis. These inflammatory pathologies are characterized by High TSH, low triiodothyronine and thyroxine and possible presence of anti-thyroid antibodies.
- Subtotal or total thyroidectomy (partial or complete removal of the thyroid gland): when a part of the thyroid gland is removed, inadequate production of thyroid hormones by the residual gland is generated. This is even more evident with the removal of the entire thyroid, with a total deficiency of hormones. As a compensation mechanism there is an increase in the pituitary production of TSH. The feedback from High TSH after thyroidectomy it is therefore obvious, and is the signal that drug replacement therapy is not yet at optimal doses.
- Presence of resistance to TSH: resistance to TSH is a pathology that determines a permanent thyroid deficit present at birth. Resistance to TSH is determined by the presence of mutations in the TSH receptor (TSHR; 14q31), which cause a reduced production of thyroid hormones. In this condition then we can find blood tests High TSH and low fT3 fT4.
- Storage diseases: they are rare pathologies, in which substances that damage the tissues and compromise its function accumulate in the thyroid. As a consequence the production of thorium hormones will be deficient, causing a secondary response at the level of the pituitary gland overproduction of TSH. Among the diseases that deposit in the thyroid we remember hemochromatosis, characterized by iron deposition, and amyloidosis, which causes the deposit of low molecular weight proteins produced in an anomalous and unregulated way by the organism that accumulate between the intracellular spaces of the gland by damaging it.
- Insufficient thyroid replacement hormone therapy: it seems obvious but in reality there are many misunderstandings on the subject: patients with a recognized hypothyroidism, who are on thyroid hormone replacement therapy (the most used drug is Eutirox), must carry out periodic blood checks, to regulate therapy. Often the dose of thyroid hormones taken is even slightly insufficient, and this is reflected at the pituitary level with a greater production of thyrotropin, which will be higher than normal. A contrary case, one too high Ft4 dose will tend to lower the levels of thyroid stimulating hormone in the blood. Even with normal thyroid hormones, in the presence of a high TSH it is necessary to consult your doctor or endocrinologist to evaluate whether to slightly modify the dose of thyroid hormones taken daily.
High TSH and high fT3 fT4: hyperthyroidism
Hyperthyroidism is a disease linked to an increased production of thyroid hormones by the thyroid. In the case of a primary hyperthyroidism, in the face of high concentrations of thyroxine and triiodothyronine the pituitary will decrease the production of TSH in order to reduce thyroid activity (low TSH and high thyroxine and triiodothyronine).
In thesecondary hyperthyroidism, it will instead be an excessive production of TSH by the pituitary to stimulate the thyroid in an uncontrolled way: in this situation we will have High TSH and high thyroid hormones. It is this last type of hyperthyroidism which is characterized by high levels of thyrotropin and which we will describe in the next paragraphs.
Here are the causes more frequent than High TSH with hyperthyroidism:
- Hyperpituitarism (increased pituitary TSH production): it may happen that the pituitary gland produces an abnormal amount of hormones, unregulated with respect to the normal pituitary-target organ control mechanism. Hyperpituitarism can be primitive, if the overproduction of hormones is due to secreting masses such as a pituitary adenoma, or it can be, more rarely, secondary, if the excessive hormone production derives from the lack of negative feedback from the hypothalamus. This occurs in rare cases of hypothalamic secreting tumors (TRH producers in our case). The decisive therapy is the surgical one. This condition is characterized by High TSH and high fT3 and fT4.
- Ectopic TSH production: paraneoplastic syndrome which determines the production, at the level of non-pituitary neoplasms (lung, breast, uterus, prostate, gastrointestinal), of a substance similar to TSH.
There are some drug therapies that can inhibit the secretion of hormones by the gland thyroid, consequently inducing an increase in blood levels of thyrotropin (TSH). Among these the most frequent is amiodarone, an iodine-rich antiarrhythmic drug that can cause both the development of hyperthyroidism but also hypothyroidism. Other common 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 certain types of headache.
High TSH in pregnancy
Usually the TSH during pregnancy is normal or slightly below the classical reference values: this is because during pregnancy there are some physiological alterations (increase in TBG (Thyroxin Binding Globulin), presence of chorionic gonadotropin) which tend to slightly reduce TSH values.
The finding of a High TSH in pregnancy it must be carefully evaluated, as it can indicate the presence of hypothyroidism, a metabolic state very harmful for the future newborn, since it can compromise the correct somato-neural development. If the thyroid is unable to provide adequate production of T3 and T4, it will be necessary to compensate with supplementary therapy with supportive levothyroxine (Eutirox, Tirosint, etc. ..).
There are particular conditions that must be carefully monitored and which have an increased probability of leading to gestational hypothyroidism. Given that a TSH check before conceiving a child should be done in all cases, the major ones instructions to perform the TSH check during pregnancy are as follows:
- Over 30 years of age
- History of family or personal thyroid dysfunction
- History of previous thyroid surgery.
- Symptoms of thyroid dysfunction or presence of thyroid goiter
- Positivity of antibodies to thyroperoxidase (anti TPO).
- Type 1 diabetes mellitus and / or other autoimmune disorders.
- History of miscarriage or preterm labor.
- History of radiation therapy with irradiation to the head or neck.
- Severe obesity with body mass index (BMI) greater than 40 kg / m2.
- Use of drugs such as amiodarone or lithium
- Recent administration of iodinated contrast medium.
- Residence in an area known to have moderate to severe iodine deficiency.
The feedback from High TSH in pregnancy should always be investigated: the most frequent cause of high TSH in pregnancy is the Hashimoto's thyroiditis.
The TSH values to define a hypothyroidism during gestation are:
Full-blown hypothyroidism in pregnancy:
- TSH greater than or equal to 2.5 mIU / L with reduced FT4; or
- a TSH greater than or equal to 10 mIU / L with any FT4.
Subclinical hypothyroidism in pregnancy:
TSH between 2.5 and 10 mIU / L with normal FT4 concentration.
In case of overt hypothyroidism during the pregnancy, there's a increased risk of: preterm birth, low weight and delayed neurocognitive development of the child at birth and above all increased risk of miscarriage (60% of spontaneous abortions in severe untreated hypothyroidism). It also increases the frequency of arterial hypertension for the mother. There replacement therapy with levothyroxine it is highly recommended to reduce the incidence of all these complications.
In case there is only subclinical hypothyroidism during the pregnancy, an increased risk of complications has been noted in women with anti-thyroperoxidase (anti-tpo) antibodies. Replacement therapy should be considered in this case.
Please note: for the women who were already in replacement therapy with levothyroxine, the dose should be increased during pregnancy, usually by 30% in autoimmune hypothyroidism and by 50% in people with hypothyroidism after partial or total removal of the thyroid (partial or total thyroidectomy).
High TSH symptoms
As already mentioned, high TSH is often not accompanied by particular symptoms, especially if the thyroid hormones are still normal, as in the case ofsubclinical hypothyroidism. In the phase of overt hypothyroidism, however, high TSH is associated with a condition of low fT3 and fT4, which may manifest itself with various signs and symptoms. The main symptoms of high TSH and low fT3 fT4 (hypothyroidism) are listed below:
- Less tolerance to cold
- Mood instability and tendency to depression
- Weight gain
- Dry and fragile skin
- Loss of eyebrows (especially the outer part)
- Finer and more fragile nails
- Constipation (constipation)
- Carpal tunnel syndrome,
- Irregularity of the menstrual cycle,
- Increase of cholesterol,
- Memory loss.
In other, less frequent cases, when the High TSH is associated with high levels of thyroid hormones, we will have the classic symptoms hyperthyroidism, related to the increased dose of circulating thyroxine and triiodothyronine. The main symptoms of high TSH with high fT3 fT4 are listed below:
- Agitation and anxiety
- Nervousness and irritability
- Tremor, especially in the hands
- Alterations at the menstrual level
- Presence of exophthalmos
- Possible presence of eyelid swelling
- Hot flashes
Below normal TSH is associated with a number of medical conditions: in case of low TSH it is always necessary to measure at least one of the two types of thyroid hormones, fT3 or fT4. This allows us to understand if, as happens in most cases, there is an increased function of the thyroid, ie a hyperthyroidism accompanied by high fT4 and T4, or if there is reduced thyroid function, and therefore a hypothyroidism, accompanied by low T3 and fT3 and low T4 and fT4.
Low TSH causes
A Reduced TSH it can be found both in response to an increased production of thyroid hormones by the thyroid gland (condition of hyperthyroidism), and in the presence of a reduced production of TSH, caused by a hypofunction in the pituitary or hypothalamic level. However, it must be said that in the vast majority of cases the Low TSH goes with high fT3 and fT4.
Below we will explain what are the main causes of low TSH and differentiate those that lead to a condition of hyperthyroidism (Low TSH fT3 high fT4) from those that lead to a condition of hypothyroidism (TSH low fT3 fT4 low).
Low TSH and high fT3 fT4: hyperthyroidism
Here are some conditions with Low TSH and hyperthyroidism:
- Basedow-Graves disease: it is a pathology characterized by hyperthyroidism with the presence of abnormal antibodies, aimed at the TSH receptor (TSH receptor antibodies or ab anti-TSH). These antibodies cause persistent stimulation of the thyroid receptors for the TSH hormone resulting in overactivity of the thyroid with increased production of thyroxine and triiodothyronine. Therapy can be pharmacological, with drugs such as propityluracil or methimazole (Tapazole) which reduce the activity of the thyroid gland, or based on radioiodine, that is of a radioactive isotope of iodine (iodine 131) which irreversibly damages the thyroid cells, and finally surgical, with partial or total removal of the tyrosis. In addition to the typical symptoms of hyperthyroidism, ocular pathology (ophthalmopathy or basedowian exophthalmosor, with protruding eyeballs) and a skin pathology (dermopathy or pretibial myxedema).
- Thyroiditis in the stage of thyrotoxicosis: thyroiditis is an inflammatory process in the thyroid gland, which can be infectious (such as acute or sub-acute thyroiditis) or autoimmune (such as chronic thyroiditis). In autoimmune thyroiditis there is a frequent finding of antibodies to thyroperoxidase and antibodies to thyroglobulin, and are characterized by Low TSH and high values of fT3 and fT4. The most frequent forms are Hashimoto's thyroiditis, postpartum thyroiditis and silent lymphocytic thyroiditis. In non-autoimmune thyroiditis (e.g. acute bacterial thyroiditis or De Quervain's subacute thyroiditis), anti-thyroid antibodies are found much less frequently.
- Toxic nodular goiterGoiter is an enlargement of the thyroid volume, which can be generalized (diffuse thyroid struma or diffuse goiter) or nodular (uninodular or multinodular). Toxic nodular goiter consists of a thyroid nodule that no longer responds to intra-thyroid regulation mechanisms or to pituitary TSH control. The toxic goiter nodule can secrete large amounts of thyroid hormones causing the typical symptoms of hyperthyroidism. At this juncture we will have High T3 and T4 and reduced TSH.
- Too high doses of hormone replacement therapy or other drug therapy: incorrect intake of thyroid replacement therapy, (the most commonly used drug, Levothyroxine or L-thyroxine, carries the trade name of Eutirox, Tiracrin, Tirosint, Tiche, Syntroxine), can lead to the finding of elevated thyroid hormone levels and reduced TSH . Classic example, the finding of Low TSH after thyroidectomy it is often linked to an exaggerated dose of replacement therapy. Even patients on lithium therapy for psychoactive therapy, or with amiodarone, for the control of cardiac arrhythmias, may have a hormonal imbalance in the hyperthyroid sense.
- Ovarian teratoma: it is a neoplasm composed of embryonic tissues and therefore potentially also of thyroid type tissue, with ovarian localization. This tumor can also be benign, and causes hyperthyroidism for production not thyroid of T3 and T4, resulting in TSH reduction.
- Familial non-autoimmune hyperthyroidism: this disorder is linked to the mutation of a gene that codes for the TSH receptor, and is transmitted in an inherited manner. The thyroid then escapes the pituitary hormone control, and begins to produce thyroid hormones in an uncontrolled way. As a result, the pituitary will decrease TSH production to attempt to limit the elevated levels of fT3 and fT4. We'll have blood tests then Low TSH and normal ft3 ft4.
- Hyperemesis gravidarum: the suppression of TSH by hCG may be part of the picture of hyperemesis gravidarum, a pathology responsible for many hospitalizations in the first months of pregnancy. From the thyroid hormonal point of view there is a reduction up to the complete suppression of TSH, elevated concentrations of FT4 and disabling symptoms such as severe recurrent vomiting, weight loss, dehydration, dysionemia (alterations in the level of blood minerals) and ketonuria.
- Choriocarcinoma: useful to measure chorionic gonadotropin (hCG), follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
- Subclinical hyperthyroidism: in the initial phase, hyperthyroidism occurs only with low thyrotropin values which are accompanied by normal levels of T3 and T4: then low TSH and normal Ft3 and fT4.
Low TSH and low fT3 fT4: hypothyroidism
Here are the causes of Low TSH with hypothyroidism:
Dysfunctions of the pituitary gland: if the pituitary, despite good thyroid function, does not produce adequate levels of thyrotropin (TSH), the production of fT3 and fT4 will be negatively affected. In this case we speak of secondary hypothyroidism, characterized by low levels of TSH, fT3 and fT4 .
Dysfunction of the hypothalamus: it can rarely happen that the hypothalamus does not function properly, not producing adequate levels of TRH. Consequently, the pituitary is not adequately stimulated to produce the right amount of TSH. Again we will have Low TRH, low TSH and low fT3 and fT4.
Low TSH in pregnancy
The finding of a Low TSH in pregnancy is often physiological: the TBG (Thyroxin Binding Globulin or thyroxine binding protein), which is none other than the transporter protein of thyroid hormones in the blood, due to the increased circulating levels of estrogen, in turn increases its plasma concentrations. The increased levels of circulating T3 and T4 exert a mild suppressive effect on TSH.
At the same time, the chorionic gonadotropin (hCG or human Chorionic Gonadotropin) produced by the placenta has an inhibiting effect on TSH production. This happens because hCG has a molecular structure that resembles that of the thyroid stimulating hormone and therefore acts on the thyroid TSH receptors activating the production of thyroid hormones, which in turn inhibit the release of TSH at the pituitary level. Here are the two reasons why physiologically is found Low TSH in pregnancy.
Having adequate levels of thyroid hormones circulating during gestation is important to ensure proper neurological and somatic development of the fetus. For this reason the thyrotropic hormone should be checked periodically, and the finding of Low TSH during pregnancy it must always be deepened with further analysis.
In fact, a percentage ranging from 0.1 to 3% of pregnancies may be subject, during the course, to the appearance of gestational hyperthyroidism, often associated with hyperemesis gravidarum. The other most frequent causes of hyperthyroidism in pregnancy are the Graves' disease and toxic uninodular or multinodular goiter.
L'gradually increasing hyperthyroidism increases the risk of perinatal death, the risk of preterm birth or even miscarriage, the development of hypertension in pregnancy, and a low birth weight of the baby. It is also dangerous for the mother as it increases the incidence of maternal heart failure. For this reason hyperthyroidism during pregnancy should always be investigated to distinguish the cause and start the most appropriate therapy, checking the TSH every 2-4 weeks at the start of therapy, every 4-6 weeks after reaching the target value.
Low TSH symptoms
Low TSH, if not accompanied by elevated thyroid hormone values (therefore a condition of subclinical hyperthyroidism), often does not involve particular symptoms. If, on the other hand, there are high values of fT3 and fT4, it will manifest itself with the typical symptoms of hyperthyroidism. So here are the main ones symptoms of low TSH with fT3 fT4 high:
- Easy Irritability
- State of anxiety
- Presence of palpitations (presence of extrasystoles or ectopic beats, up to real arrhythmias)
- Tremor in the limbs
- Changes in the menstrual cycle
- Exophthalmos (eye protruding)
- Possible presence of eyelid swelling
- Hyperhidrosis (profuse sweating)
- Thinness and weight loss
- Hot flashes
In the less frequent case of low TSH levels associated with reduced fT3 and fT4, we may have the classic symptoms hypothyroidism. Here are the main ones symptoms of low TSH with low fT3 fT4:
- Instability of mood
- Less tolerance to cold
- Weight gain
- Fragility of skin and nails
- Loss of eyebrows (especially the outer part)
- Constipation (constipation)
- Irregularity of the menstrual cycle,
- Increase in blood cholesterol levels
- Memory loss.
TSH reflex (TSH reflex or TSH-r)
The TSH reflex, Reflex TSH or TSH-r, is nothing more than a diagnostic protocol that provides for the execution of the TSH blood assay initially without the simultaneous analysis of the thyroid hormones: in case the TSH should be altered, with the same blood draw the dosage of thyroid hormones is then performed.
If you detect a TSH low reflex, i.e. less than 0.5 mIU / l, thyroxine (T4) is also dosed in its free form fT4, and then, if this falls within normal values, also triiodothyronine (T3).
If, on the other hand, a TSH high reflex, that is higher than 4 mIU / l, the dosages of free thyroxine fT4 and antibodies to thyroperoxidase (anti-TPO) are added. If the anti-thyroperoxidase antibodies are found to be normal, proceed with the third step, that is the dosage of the anti-thyroglobulin antibodies (anti-TGB).
Conversely, a TSH relfex (TSH-r) with normal values it does not require the execution of further tests. This allows you to avoid the expense of the dosage of thyroid hormones in case they are found normal values of TSH relfex.
But be careful: use the protocol TSH reflex, with a cascade sequence of examinations, is useful and effective in people without a diagnosis of known thyroid disease, who carry out the examination because they belong to a population at risk, or because they suffer from non-specific symptoms, or for simple screening.
It is not appropriate run the TSH reflex for people who already know they have a thyroid problem or who in any case have a strong suspicion of thyroid disease: in these cases it is useless to resort to TSH reflex protocol: are performed directly thyrotropin, thyroxine and triiodothyronine without delay.
Recombinant TSH (hr TSH)
The Recombinant TSH (hr TSH) is a synthetic TSH obtained with the recombinant DNA technique and is used as a drug in a test that involves the dosage of thyroglobulin. In patients undergoing thyroidectomy there is a tendency to keep the TSH in the low levels of the norm, to avoid an excessive stimulus by the latter on any thyroid cells left after the operation. In this way, however, the production of thyroglobulin by any residual tumor cells could also be masked (because it is too low).
The recombinant TSH test serves to solve this problem by temporarily stimulating any residual cells to produce thyroglobulin, which is then measured with blood analysis. The test involves the administration of Thyrogen (thyrotropin alfa) in two intramuscular administrations 24 h apart from each other, with subsequent blood sampling to measure thyroglobulin.
How is the TSH test performed?
The examination is carried out starting from a blood sample obtained with a venous sampling. It is not necessary to fast before the exam. As some medications can interfere with TSH measurement, you should warn your doctor about all ongoing drug therapy.
Certain drugs or substances can alter the TSH measurement, either by increasing or decreasing the blood concentrations.
As for the drugs that can increase TSH on blood tests, here are the main ones:
- Amiodarone (amiodarone-induced hypothyroidism): amiodarone is an iodine-rich drug used for the treatment and prophylaxis of ventricular cardiac arrhythmias, supraventricular cardiac arrhythmias such as paroxysmal supraventricular tachycardias, atrial fibrillation and atrial flutter. Amiodarone can lead to an excess of iodine in the circulation resulting in a thyroid defense mechanism that leads to a decrease or blockage of the functionality of the thyroid gland (Wolff-Chaikoff effect). The pituitary in turn will respond to thyroid deficiency with increased TSH secretion.
- Dopamine antagonists: for example the antiemetics domperidone and metoclopramide, dopaminergic D2 receptor antagonists.
- Chlorpromazine: antipsychotic of the phenothiazine class, used in various psychiatric diseases such as schizophrenia, the manic phase of bipolar disorder and other psychoses.
- Haloperidol: neuroleptic of the butyrophenones family, it is also an antagonist of the dopaminergic D2 receptor, as well as an antagonist of alpha-adrenergic receptors.
THE medications which can decrease the levels of TSH instead they are the following:
- Thyroxine exogenous: e.g. levothyroxine (L-T4), which is the left-handed isomer of thyroxine (T4), is the main drug used for the treatment of hypothyroidism, whose main trade name is Eutirox)
- Amiodarone (therapy amiordarone early; thyrotoxicosis induced byamiodarone): as already mentioned above, amiodarone is an antiarrhythmic drug rich in iodine, with a structure similar to the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Amiodarone can cause a state of hyperthyroidism (AIT: amiodarone–induced thyrotoxicosis) resulting in a reduction in TSH due to two different mechanisms: an excessive synthesis of thyroid hormones induced by the increased intake of iodine from amiodarone in people with a thyroid already with pre-existing subclinical dysfunction (AIT type 1), while the second is a release of thyroid hormones previously formed during a destructive thyroid inflammatory process, caused by the therapy with amiodarone itself (AIT type 2).
- Glucocorticoids: class of steroid hormones, naturally produced in humans in the fasciculated area of the adrenal cortex. Synthetic glucocorticoids are drugs with powerful anti-inflammatory and immunosuppressive action, used in a wide range of pathologies, including rheumatological, immunological diseases, allergic reactions, eye diseases, chronic inflammatory gastro-intestinal diseases, therapy against rejection in transplants. organ, skin diseases, treatment of bronchial asthma and chronic obstructive pulmonary disease.
- Dopamine: neurotransmitter substance produced by the body, it belongs to the catecholamine family. It is used as a drug with haemodynamic activity and vasoconstrictor and inotropic effect.
- Levodopa: L-dopa or 3,4-dihydroxy-1-phenylalanine, is an intermediate product of the dopamine synthesis pathway. In pharmacology it is used as a dopamine prodrug for Parkinson's disease therapy.
- Dopamine agonists: drugs with action on dopaminergic receptors, used in many clinical contexts, first of all Parkinson's disease (among the most used thel ropinirole, trade name Requip, and pramipexole, trade name Mirapexin). Another dopamine agonist drug is apomorphine (trade names Uprima, Ixensee, Taluvian), which is often used as a cure for erectile dysfunction.
- Pyridoxine: pyridine derivative of the dell familyto vitamin B (vitamin B6, sometimes also called pyridoxamine). Present in supplements and multivitamin concentrates.