A High TSH it is almost always indicative of hypothyroidism. The causes and symptoms of high TSH are explained in this article. The TSH (thyrotropin or thyrotropic hormone) is a substance produced by the anterior part of the pituitary gland, the adenohypophysis. It is the fundamental hormone that regulates the functionality and efficiency of the thyroid, which is stimulated to produce thyroid hormones (T3 or triiodothyronine and T4 or thyroxine) starting from the precursor molecule thyroglobulin. The measurement of thyroid hormones during blood tests is carried out on the free fraction of these hormones, which in turn reflects the total amount of T3 and T4 present in the circulation. It is therefore more correct to refer to thyroid hormones with the terminology fT3 (free T3) and fT4 (free T4).
The TSH is high when it exceeds 4 mIU / L.
The TSH it is dosed to evaluate thyroid function and identify any alterations both in the sense of hyperactivity of the thyroid gland (hyperthyroidism) and in case of hypofunction (hypothyroidism); measuring TSH also serves to monitor the effectiveness of therapeutic treatment in case of hypothyroidism (monitoring of thyroid hormone replacement therapy) or hyperthyroidism (monitoring of thyroid suppressive therapy).
Not infrequently we find the indication in the doctor's prescriptions or in blood tests TSH reflex or TSH reflex: it is good to clarify that this wording does not indicate a particular type of TSH, but simply indicates to the laboratory that a protocol can be implemented that helps to optimize medical costs: therefore, only the TSH is measured first and then, if the value of the latter it is altered, we continue with the dosage, on the same blood sample, of the thyroid hormones. Hence TSH reflex and TSH both indicate thyrotropin hormone.
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), either in the presence of an increased production of TSH, at the pituitary level 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).
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.
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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.
Symptoms of High TSH and Low Thyroid Hormones.
So what are the main ones symptoms of high TSH and low fT3 fT4 (hypothyroidism)?
The symptoms of high TSH are:
- 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.
Symptoms of high TSH and elevated thyroid hormones
What are the main ones symptoms of high TSH with high fT3 fT4?
In this case, the symptoms of high TSH are:
- 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
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.
What Factors Affect TSH Dosage?Hemolysis chance of the blood sample.
Daily changes in blood TSH levels: the highest levels are found around 10 pm, while basal levels are measurable at 10 am.
Recent radioactive iodine therapy.
Many drug therapies they can alter the TSH measurement. The following are the drugs that can most commonly raise TSH levels on blood tests:
- sodium nitroprusside,
- potassium iodide,
- iodized radiographic contrast medium,
- oral antidiabetics such as sulfonylureas,
- intravenous administration of TRH (thyroid-releasing hormone)
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