Anti-thyroid stimulating hormone receptor antibodies (anti-rTSH)

In what rare situations can the study of AT-TPO and AT-TG be indicated in case of normal thyroid function?

• When, during pregnancy, the level of TSH (thyroid-stimulating hormone) exceeds trimester-specific norms,
• When planning an in vitro fertilization procedure,
• Before prescribing amiodarone, interferon and lithium drugs (since antibody carriers have an increased risk of developing thyroid pathology induced by these drugs)
• To assess the effectiveness of treatment for differentiated thyroid cancer, monitoring of AT-TG levels may be necessary.

Studying the levels of AT-TPO and AT-TG in other situations can be considered redundant, and the interpretation of the results is meaningless.

Author:

Marina Aleksandrovna Sviridonova , endocrinologist

, Ph.D.

Antibodies to TSH receptors

Antibodies to TSH (thyroid-stimulating hormone) receptors are autoantibodies that bind to thyroid-stimulating hormone receptors. Thyroid-stimulating hormone receptors are expressed on the surface of thyroid follicular cells, lymphocytes, adipocytes and fibroblasts. The TSH receptor consists of two glycoprotein subunits (A and B). When TSH binds to the receptor, the production of thyroid hormones and the growth of follicular cells of the thyroid gland are triggered. In the presence of antibodies to the TSH receptor, they bind to the receptor and, thereby, disrupt the implementation of the stimulating effect of TSH on the thyroid gland. There are three types of autoantibodies to the TSH receptor: Stimulating antibodies to the TSH receptor. This type of antibody selectively binds to the A subunit of the receptor and mimics the action of TSH, thereby stimulating the production of thyroid hormones. Stimulating antibodies to the TSH receptor play a major role in the pathogenesis of diffuse toxic goiter (Graves' disease). Blocking antibodies to the TSH receptor. These antibodies selectively bind to the B subunit of the receptor and block the signal from the receptor to stimulate the secretion of thyroid hormones. This type of antibody also prevents TSH from binding to the receptor, which leads to a decrease in thyroid function. This type of antibody is detected in patients with Hashimoto's atrophic thyroiditis and Graves' disease, which occurs with ophthalmopathy. Blocking antibodies can cross the placental barrier and cause transient congenital hypothyroidism. Neutral antibodies to the TSH receptor. These antibodies bind to the receptor but do not block the binding of TSH or other autoantibodies. Neutral antibodies have been identified in patients with Graves' disease; their pathogenetic significance has not been established. In the initial stage of diffuse toxic goiter, antibodies to TSH receptors are detected in 80-85% of patients. In patients with euthyroid goiter, acute, subacute and chronic thyroiditis, antibodies are detected in 10% of cases. The sensitivity of the test is about 80%.

Particular inflammation. What is autoimmune thyroiditis?

When the immune system “takes arms” against normal organs and tissues of the body, we speak of an autoimmune disease. One of these pathologies is autoimmune thyroiditis. We talked about it with the endocrinologist at the Expert Clinic in Rostov-on-Don, Aida Nizamovna Gyulmagomedova.

— Aida Nizamovna, what is autoimmune thyroiditis?

- This is a specific inflammation of the thyroid gland. With this disease, antibodies to the iron are detected in the body. I will give some information about her.

The thyroid gland itself is small, but it is the largest endocrine gland in our body. It consists of two lobes and an isthmus and is shaped like a butterfly. True, sometimes there is an additional, pyramidal, lobe. Each lobe is approximately the size of the nail phalanx of a human thumb. On average, the volume of the thyroid gland in women does not exceed 18 milliliters, in men - no more than 25. It is important to note that the lower limit of its size does not exist today: it can be very small, but at the same time perform its functions properly - in sufficient quantity produce hormones.

Autoimmune thyroiditis was first described by the Japanese physician Hashimoto in 1912, so the disease also has another name - Hashimoto's thyroiditis.

With autoimmune thyroiditis, antibodies to the thyroid gland are detected in the body.

— How common is autoimmune thyroiditis among Russians and in the world?

— The prevalence of carriage of antibodies to the thyroid gland reaches up to 26% in women and 9% in men. Which, however, does not mean that all these people have autoimmune thyroiditis. A study was conducted in the UK in which about three thousand people took part, and this is what was found out. For example, in women the risk of developing the disease was only 2%. That is, out of 100 carriers of elevated levels of antibodies to the thyroid gland, only two developed dysfunction.

— What are the causes of autoimmune thyroiditis? Why does it occur?

- This is a rather complex disease. For some reasons that are still not entirely clear, our immune system begins to perceive the thyroid gland as a foreign organ and produces antibodies to it. They damage the cells that make thyroid hormones. As a result, the amount of hormones decreases and a condition called “hypothyroidism” develops (in simple words - decreased function of the thyroid gland).

You can read more about hypothyroidism in our article

— What are the symptoms of autoimmune thyroiditis?

— Their severity can vary from the complete absence of complaints to severe consequences that are life-threatening for the patient. When thyroid function decreases, almost all organs are affected. The most typical manifestations of the disease include the following symptoms:

• general weakness;
• fatigue;
• weight gain;
• feeling cold for no apparent reason;
• decreased appetite;
• swelling;
• the appearance of hoarseness of voice;
• dry skin;
• increased fragility and hair loss;
• brittle nails.

From the nervous system side, these are complaints such as drowsiness, memory loss, concentration, inability to concentrate, and in some cases depression.

As for the cardiovascular system: there may be a slow pulse, increased diastolic (lower) blood pressure.

Gastrointestinal tract: there is a tendency to chronic constipation.

Reproductive system: women experience menstrual irregularities, infertility, and in some cases termination of pregnancy is possible; in men - erectile dysfunction.

Blood cholesterol levels may be elevated.

Read materials on the topic:

Constipation in adults: looking for causes and getting rid of it Men, there is a way out! How to get back your former strength? Cholesterol Blood Test: Frequently Asked Questions

— How is this disease diagnosed? Are there any tests that can help identify autoimmune thyroiditis?

— Confirming or disproving the diagnosis is quite simple. To do this, you need to determine the level of thyroid-stimulating hormone (TSH) - this is the most important and necessary test for any dysfunction of the thyroid gland, as well as antibodies to TPO (thyroid peroxidase). With normal TSH levels, pathology of this organ can be almost completely excluded. In case of hypothyroidism against the background of autoimmune thyroiditis, the TSH level will be elevated, and free thyroxine (thyroid hormone) will be reduced, according to the feedback principle. This is how most hormones work in our body. What does it mean? When the amount of thyroid hormones in the blood decreases, the pituitary gland, in certain cells of which TSH is formed, “recognizes” this first. “Having caught” the decrease in hormone levels, the pituitary gland cells begin to produce TSH in larger quantities in order to “stimulate” the work of the thyroid gland. Therefore, if you take blood during this period and measure the TSH level, it will be elevated.

The analysis looks quite familiar to everyone - it is donating blood from a vein on an empty stomach.

— Can a diagnosis of “autoimmune thyroiditis” be made with normal hormones?

- Currently, this diagnosis is not valid if hormone levels are normal.

- And if at the same time an analysis was also done for antibodies to the thyroid gland, and they were detected?

— The detection of these antibodies does not always indicate the presence of autoimmune thyroiditis. Their carriage in itself is not a disease. Almost 20% of healthy people can have antibodies to the thyroid gland in their blood. For example, in foreign scientific literature, autoimmune thyroiditis is practically not considered as an independent clinical problem. This needs to be treated only if hypothyroidism develops, that is, decreased thyroid function.

— How is autoimmune thyroiditis treated?

— Treatment consists of compensating for the lack of thyroid hormones in the body. This is called replacement therapy. A person must be given what he lacks - in this case, the missing thyroxine (the main form of thyroid hormones of the thyroid gland). The patient must take modern thyroxine-based medications daily. In their structure, they are completely indistinguishable from our own hormone, which under normal conditions is produced by the thyroid gland. The correct dosage of these drugs prevents all possible adverse consequences of hormone deficiency. Hospitalization is not required. But replacement therapy in cases of the disease is carried out for life, since the normal functioning of the thyroid gland cannot be restored by itself.

— How effective is the use of dietary supplements for autoimmune thyroiditis?

— In the treatment of not only this, but also other diseases, there is no place for dietary supplements. Any conscientious modern doctor must adhere to the principles of evidence-based medicine. In other words, the approach to the prevention, diagnosis and treatment of thyroid diseases is applied based on the available evidence of the effectiveness and safety of drugs. Dietary supplements cannot be used for treatment. This provision is regulated in all countries.

Dietary supplements cannot be used to treat autoimmune thyroiditis

— If this disease is detected in a woman of reproductive age who is planning a pregnancy, the question arises: is it possible to get pregnant with autoimmune thyroiditis?

— Let me remind you: being a carrier of antibodies is not a disease and, accordingly, does not act as an obstacle to pregnancy. However, if a woman who wants to give birth to a child is diagnosed with a dysfunction of the thyroid gland, then it can interfere with pregnancy and gestation. If a woman suffers from hypothyroidism, then the child at birth may have various abnormalities and defects (this includes mental development disorders and growth problems). The child may also have congenital hypothyroidism. Therefore, early detection and treatment of the disease is extremely important.

You can make an appointment with an endocrinologist here. ATTENTION: the service is not available in all cities

Interviewed by Igor Chichinov

The editors recommend

Myths and truth about thyroid diseases A knot will tie, a knot will untie. How dangerous are thyroid nodules? If the thyroid gland is “raging”: what is hyperthyroidism? How to determine that the body does not have enough iodine? When is an ultrasound of the thyroid gland necessary?

For reference

Gulmagomedova Aida Nizamovna

Endocrinologist, nutritionist.

Member of the Russian Association of Endocrinologists, member of the Association of Endocrinologists of the Rostov Region.

Total work experience more than 10 years.

Experience in running the “School of Type 1 and 2 Diabetes.”

Experience in running the School of Proper Nutrition and Weight Loss.

Author of about 20 published works in scientific journals.

Receives at the address: Rostov-on-Don, st. Krasnoarmeyskaya, 262.

Bibliography

1. Lapin S.V. Totolyan A.A. Immunological laboratory diagnosis of autoimmune diseases. Publishing house "Man", St. Petersburg - 2010
2. Tietz Clinical guide to laboratory tests. 4th ed. Ed. Wu ANB- USA, WB Sounders Company, 2006, 1798 p.
3. Conrad K, Schlosler W., Hiepe F., Fitzler MJ Autoantibodies in Organ Specific Autoimmune Diseases: A Diagnostic Reference/PABST, Dresden – 2011.
4. Conrad K, Schlosler W., Hiepe F., Fitzler MJ Autoantibodies in Systemic Autoimmune Diseases: A Diagnostic Reference/PABST, Dresden – 2007.
5. Gershvin ME, Meroni PL, Shoenfeld Y. Autoantibodies 2nd ed./ Elsevier Science – 2006.
6. Shoenfeld Y., Cervera R, Gershvin ME Diagnostic Criteria in Autoimmune Diseases / Humana Press – 2008.
7. Tozzoli, R., Bagnasco, M., & Villalta, D. Thyrotropin Receptor Antibodies / Autoantibodies, 375–383 - 2014
8. Weetman, A. P. (2014). Thyroid disease. / The Autoimmune Diseases, 557–574 - 2014.
9. Test system manufacturer's instructions

Causes

TSH is not produced by the thyroid gland, as the name suggests, but by the pituitary gland. This is a gland located in the brain. When high TSH is detected in women, there can be only two reasons: the pituitary gland produces it on its own or in response to a deficiency in the blood of thyroid hormones - thyroxine (T4) and triiodothyronine (T3).

Most often, excess TSH occurs in response to a lack of T4 and T3. But in some cases, the pituitary gland produces it in large quantities due to the growth of the gland itself. The more cells there are, the more TSH is synthesized.

Detection of autoantibodies to thyroid-stimulating hormone receptors in blood serum, used to diagnose Graves' disease (Graves' disease), autoimmune thyroiditis, as well as transient dysfunction of the thyroid gland in newborns.

Synonyms Russian

Autoantibodies to thyroid-stimulating hormone receptors, thyroid-stimulating immunoglobulin.

English synonyms

Thyroid-stimulating immunoglobulins, TSIs, Thyroid-stimulating hormone receptor antibodies, TSH receptor antibodies, TSHRAbs, TSH binding inhibitor immunoglobulin, TBII.

Research method

Electrochemiluminescent immunoassay (ECLIA).

Determination range: 0.3 - 40 IU/l.

Units

IU/L (international unit per liter).

What biomaterial can be used for research?

Venous blood.

How to properly prepare for research?

Do not smoke for 30 minutes before the test.

General information about the study

Antibodies to TSH receptors (anti-tSH) are a heterogeneous group of autoantibodies that interact with the thyroid stimulating hormone (TSH) receptors of the thyroid gland. Based on their effect on thyroid function, anti-pTTH is divided into stimulating and blocking antibodies. Stimulating anti-pTTHs greatly enhance thyroid function, leading to diffuse goiter and hyperthyroidism. Anti-pTTH blockers interfere with the action of TSH and lead to thyroid atrophy and hypothyroidism. Anti-rTSH are predominantly immunoglobulins of the IgG class and penetrate the placental barrier. Both variants can be detected simultaneously in the blood of the same patient. They are the direct cause of Graves' disease and autoimmune thyroiditis, as well as transient thyroid dysfunction in newborns. A test for antibodies to TSH receptors is a diagnostic test that detects both stimulating and blocking antibodies in the blood.

Anti-rTSH is a clinical and laboratory marker of Graves' disease and is studied in the differential diagnosis of hyperthyroidism syndrome. The presence of anti-rTSH is not typical for other causes of hyperthyroidism, such as toxic nodular goiter, granulomatous thyroiditis, or administration of exogenous thyroxine. Stimulating anti-rTSHs are found in 85-100% of patients with Graves' disease and can serve as a diagnostic criterion. Anti-rTSH concentration reflects disease activity and is associated with the severity of ophthalmopathy. The significance of this test is especially great if the disease has an atypical clinical picture: signs of hyperthyroidism, vaguely palpable goiter, ophthalmopathy against the background of euthyroidism, unilateral ophthalmopathy. The concentration of anti-rTSH decreases when antithyroid drugs are prescribed, and a high rate of titer decline indicates a good response to treatment. The dynamics of anti-rTSH may serve as a basis for adjustment of therapy, including complete withdrawal of antithyroid drugs. In 75-96% of cases of Graves' disease, blocking anti-rTSH is also found. It should be noted that anti-rTSH is not a strictly specific finding for Graves' disease and may also be found in 10-15% of patients with Hashimoto's autoimmune thyroiditis.

The anti-rTSH test plays an important role in the diagnosis of Graves' disease in pregnant women. The danger of Graves' disease during pregnancy is that anti-rTSH crosses the placental barrier and leads to hyperthyroidism in the newborn. Radionuclide scanning of the thyroid gland, one of the main ways to diagnose Graves' disease, is not prescribed to pregnant women. In this situation, anti-rTSH testing is a good alternative to thyroid scintigraphy. Anti-rTSH concentrations are measured in pregnant women with a history of surgery for Graves' disease or radioactive iodine treatment, and in women receiving antithyroid drugs during pregnancy. Like stimulating anti-rTSH, blocking antibodies cross the placenta and can cause transient hypothyroidism in the newborn. For timely diagnosis of autoimmune hypothyroidism in pregnant women, an anti-rTSH test is performed.

In half of the cases of Graves' disease, a relapse of the disease occurs after completing a course of thyreostatic drugs. When assessing the prognosis of relapse, several parameters are used, such as the size of the goiter, the age and gender of the patient, the presence of ophthalmopathy and the level of anti-rTSH. High levels of anti-rTSH are considered to be an unfavorable prognostic factor.

Graves' disease and autoimmune thyroiditis may coexist with other autoimmune conditions such as systemic lupus erythematosus, pernicious anemia, and rheumatoid arthritis. Therefore, if the anti-rTSH test result is positive and autoimmune thyroid disease is diagnosed, it is recommended to conduct additional laboratory tests to exclude concomitant pathology.

What is the research used for?

• For differential diagnosis of hyper- and hypothyroidism syndrome.
• To monitor the treatment of relapse of Graves' disease and make its prognosis.
• To predict the development of transient thyroid dysfunction in newborns.

When is the study scheduled?

• For symptoms of hyperthyroidism: irritability, restlessness, tremor, feeling of irregular heartbeat, oligoamenorrhea, weight loss despite increased appetite, sensitivity to heat, especially in the presence of ophthalmopathy (exophthalmos) and pretibial myxedema of the skin.
• With an atypical clinical picture of Graves' disease: unexpressed signs of hyperthyroidism, vaguely palpable goiter, ophthalmopathy against the background of euthyroidism, unilateral ophthalmopathy.
• For symptoms of hypothyroidism: weakness, drowsiness, impaired concentration and memory, weight gain despite decreased appetite, increased sensitivity to cold, etc.
• When examining pregnant women with a history of surgical treatment of Graves' disease or treatment with radioactive iodine, as well as pregnant women receiving thyreostatic drugs.
• When examining pregnant women with signs of hypothyroidism.

What do the results mean?

Reference values

Reasons for the positive result:

• Graves' disease (Bazedow);
• autoimmune thyroiditis.

Reasons for negative results:

• absence of autoimmune thyroid diseases;
• disease control during treatment.

What can influence the result?

• The concentration of anti-rTSH decreases due to the use of thyrotoxic drugs.

Interpretation

Normally, the level of antibodies in the blood is ≤ 1.75 IU/L. A negative result may indicate the absence of the disease, a low risk of relapse and control of the disease during therapy. At the same time, it should be remembered that a negative result in this case does not exclude the disease. A positive result (> 1.75 IU/L) almost always indicates the development of Graves' disease, since these antibodies are rarely found in healthy individuals. In newborns, this result may indicate transient thyrotoxicosis/hypothyroidism, and in individuals who have been treated for Graves' disease, it may indicate a high risk of relapse when combined with other indicators. In some cases, the presence of antibodies to the thyroid-stimulating hormone receptor has been noted in patients with Hashimoto's thyroiditis.

Possible diseases

The growth of pituitary tissue is possible due to a tumor - adenoma. This is one of the rarest causes of elevated TSH levels in the blood.

The most common causes of elevated TSH:

• hypothyroidism - a lack of thyroid hormones, in response to which the pituitary gland produces more TSH;
• thyroiditis is an inflammation of the thyroid gland, including autoimmune inflammation, to which the pituitary gland reacts.

Diagnosis requires a large-scale examination, since without finding out the cause it is impossible to select a treatment.

Detailed description of the study

The thyroid gland is the most important endocrine organ in humans. Its function is regulated by thyroid-stimulating hormone (TSH), which is secreted by a tiny gland at the base of the brain - the pituitary gland. TSH blocks the production of excess thyroid hormones.

Immune cells typically produce antibodies designed to fight viruses, bacteria or other foreign substances. When the immune system is disrupted, antibodies to TSH hormone receptors are detected. The release of antibodies to the TSH receptor leads to excess production of thyroid hormones, that is, hyperthyroidism. The result is a disease called diffuse toxic goiter, or Graves' disease.

This disease can affect people of both sexes and different ages, but is more common in women under 40 years of age.

Predisposition to diffuse toxic goiter can be inherited. Smoking and severe stress are provoking factors for the development of this disease. There is also an increased risk of developing Graves' disease in pregnant and postpartum women.

Symptoms of Graves' disease include:

• Restlessness and irritability;
• Trembling in hands;
• Intolerance to high temperatures;
• Increased sweating;
• Weight loss despite normal nutrition;
• Enlargement of the thyroid gland (goiter);
• Menstrual irregularities;
• Erectile dysfunction or decreased libido;
• Diarrhea;
• Puffy eyes (Graves' ophthalmopathy);
• Redness of the skin on the legs or feet (Graves' dermopathy);
• Cardiopalmus;
• Sleep disturbance.

A long course of the disease leads to disturbances in the functioning of the heart, decreased bone density and some other complications, so timely detection and treatment of diffuse toxic goiter is necessary.

Determining the level of antibodies to TSH receptors is an important test for identifying Graves' disease. An increase in the number of these antibodies serves as a characteristic sign of this disease, allowing for differential diagnosis with other pathologies of the thyroid gland.

Diagnostics

An increase in TSH is detected by a blood test. Along with this parameter, it is advisable to immediately determine the level of free T3 and T4. This will help you make the correct diagnosis and choose treatment.

A pituitary adenoma is detected on an MRI of the brain. This study is referred if laboratory data did not help to identify the cause of the condition.

A high TSH level in the analysis is not always an indicator of the presence of pathology. It rises after heavy physical activity, so it should be avoided for at least a day before the test. After removal of the gallbladder and hemodialysis, the results may also be distorted. If the attending physician knows about this, he will take all the circumstances into account when deciphering the test results.

The level of TSH in the blood fluctuates depending on the time of day. The maximum level is observed from 2 to 4 am, and the minimum - at 17-18 hours.

Read also: Hypothyroidism: causes, symptoms, treatment