Graves Disease

Epidemiology

Graves' disease (Basedow's disease, diffuse toxic goiter) is a systemic autoimmune disease, a symptom that develops due to the production of antibodies to the thyroid stimulating hormone receptor (TSH), clinically manifested by a thyroid lesion (thyroid gland) with the development of thyrotoxicosis syndrome in combination with an extra thyroid pathology and, anesthesia, anemia, a combination of thyroid gland and thyroid gland. The simultaneous combination of all components of the systemic autoimmune process is relatively rare and is not obligatory for diagnosis. In most cases, the greatest clinical significance in Graves' disease (BH) is a lesion of the thyroid gland. The disease was first described by Robert James Graves in 1835 in Dublin (Ireland), and in 1840 by the German physician Karl Adolf von Basedow in Merseburg (Germany) ("Merseburg Triad of Bazedov" - exophthalmos, tachycardia, goitre).

In the USA and England, the frequency of new cases of HB varies from 30 to 200 cases per 100 thousand people per year. Women get BG 10-20 times more often. In regions with normal iodine supply, HB is the most common cause of persistent thyrotoxic

for, and in iodine-deficient regions in the etiological structure of the toxic goiter, BG competes with the functional autonomy of the thyroid gland (nodular and multinodular toxic goiter). As evidenced by the experience of the Endocrinological Scientific Center of the Ministry of Public Health of the Russian Federation, BG is one of the main reasons for the appealability of the population for endocrinological assistance. Diffuse toxic goiter accounts for up to 80% of all cases of thyroid hyperfunction and is most common at the age of 40 years.

In Russia, the term "diffuse toxic goiter" is traditionally used as a synonym for the term "Graves disease" ("Basedow's disease"), which is not devoid of a number of significant drawbacks. First, it characterizes only a macroscopic (diffuse goiter) and a functional (toxic goiter) change of the thyroid gland, which is not obligatory for Graves' disease: on the one hand, there may be no increase in the gland, on the other - the goiter may not be diffuse. Secondly, a diffuse increase in the thyroid gland in combination with thyrotoxicosis can occur in other diseases, in particular in the so-called diffuse functional autonomy.

The use of the broader term "disease" (and not just "toxic goiter") in relation to the disease under discussion is most likely more justified, since it more strongly emphasizes the systemic nature of the autoimmune process. In addition, the term "Graves disease" is traditionally the most commonly used throughout the world, and "Bazedov disease" in German-speaking countries.

Tiology

To date, it has become almost obvious that the last stage in the pathogenesis of Graves disease is the production of thyroid stimulating immunoglobulins (TSI), which bind to the TSH receptor (rTTG) and activate it. Many of the immunological aspects of Graves' disease are similar to those with classic autoimmune thyroiditis (autoimmune hypothyroidism), and these diseases are in some cases found in the same family. At the same time, the factors that determine the development of various variants of autoimmune thyroid disease of streets with a similar genetic predisposition remain unknown to date.

Genetic factors

Concordance in identical twins due to Graves disease is 20-30%, while the role of genetic predisposition in its pathogenesis compared to environmental factors reaches 80%. The risk of developing the disease for siblings is about 5-10%, while for HbA-identical sibs - only 7%, which is significantly less than for identical twins, and suggests that the HbA complex genes make a very moderate contribution to the genetic predisposition to Graves disease. Many studies have identified the association of Graves disease with HbAH3 in individuals of the European race and various associations of other HbA alleles for other ethnic groups.

The second and currently the last genome, the polymorphism of which is associated with Graves' disease, is CHA-4, which encodes a key regulatory molecule on the surface of T-lymphocytes, the function of which is the completion of the immune response. In mice lacking the CHA-4 gene,

developing lymphoproliferative disease and a number of changes in the immune system, indicating the importance of this gene for immune tolerance. Nevertheless, the association of SPA-4 alleles with Graves disease is even less than for HbA, and is somewhat different than with other organ-specific autoimmune diseases.

To date, many potential predisposition loci for Graves disease have been described: they are localized on chromosomes 14d31, 18d21, 20d11, Xp11 and Xd21. The international consortium for the genetics of thyroid diseases, which is currently completing the analysis of more than 700 pairs of siblings with autoimmune thyropathies, did not confirm the significance of the connection of any of the previously described loci with the development of Graves' disease. In this regard, it remains to conclude that genetic predisposition is indeed of great importance in the development of Graves disease, but it is a question of multiple inheritance, in which each factor makes an insignificant contribution to the total amount, and therefore it is extremely difficult to identify . We know the most significant loci (HLA ^ I and CHA-4) by today's notions, but none of them can explain the pathogenesis of the thyroid lesion.

Environmental factors

Patients with Graves disease stress events in life over the past year, indicate more often than those included in the control group, which still does not fully show the role of stress in the pathogenesis of this disease.

A significant increase in iodine consumption in the regions of iodine deficiency, on the one hand, can lead to an increase in the incidence of thyrotoxicosis due to decompensation of the functional autonomy of the thyroid gland and, on the other hand, to accelerate the manifestation of Graves disease in predisposed individuals. Smoking has a weak association with an increase in the incidence of Graves disease, but it is the most important risk factor for the manifestation and progression of endocrine ophthalmic

Mopathy (EOP). From a scientific point of view, iatrogenic causes contributing to the development of Graves disease are of great interest. In particular, several cases of development of the disease have been described against the background of the administration of immunomodulators, such as p-interferon (p - ^^, and against the background of intensive antiretroviral therapy (and in clinical practice it is necessary to differentiate Graves disease from the thyrotoxic phase of cytokin-induced thyroiditis , which against the background of therapy with interferon drugs develops much more often than Graves' disease).

A no less interesting example is the development of Graves' disease in a third of patients with multiple sclerosis who receive treatment with monoclonal antibodies to T-cells. In this case, in the pathogenesis of Graves disease, induction of an autoimmune response may be of importance due to a shift in the TI1 / TI2 ratio or a change in T-regulatory cells. Another example of an induced immunological shift could in principle be the simultaneous remission of Graves disease and allergic diseases. This suggests that enhanced TI2 response is an unfavorable indicator. This data is attractive because potentially, by interfering with immunoregulatory processes, it would be possible to achieve remission of Graves disease, but this poses a hidden threat of induction such TM-dependent diseases as multiple sclerosis and type 1 diabetes mellitus.

Antibodies to the TSH receptor

The current nomenclature of antibodies to the TSH receptor (at-rTTG) has created some confusion (Table 1). At-rTTG cloning significantly advanced our understanding of the principles of the interaction of antigen and antibody and allowed us to create significantly more sophisticated test systems. However, a complete understanding of the structural and functional relationships of at-rTTG with the receptor itself has not been achieved due to the lack of monoclonal antibodies to human rTTG. Moreover, there are no acceptable systems for determining stimulating antibodies to rTTG (as opposed to antibodies that simply can bind with rttg). Another problem is that, despite the considerable efforts made in this direction, there is currently no adequate animal model that would fully correspond to Graves' disease.

The TSH receptor is a molecule associated with the G-protein, which consists of 379 amino acids of the ectodomain, 7 chains linked to the membrane and a short intracellular tail. The receptor is assembled by splitting a single chain synthesized on the membrane.

Nomenclature of antibodies to the TSH receptor

Nomenclature Acronym Type of study

Long-acting LATS (Long-acting Stimulation of the release of radioactively labeled thyroid stimulator thyroid stimulator) iodine from the thyroid of mice

Antibodies, TSAb Antibody stimulation of the production of adenylate cyclase stimulating the thyroid gland (Thyroid (cAMP) on thyroid sections, in thyrocyte culture, (rTTG) stimulating antibodies) cell lines (for example, PAL-B) or cells into which rTTG is injected

Antibodies, TBAb Antibody suppression of the production of adenylate cyclase blocking the thyroid gland (Thyroid blocking (cAMP), which in the same system is stimulated by (rTTG) antibodies) by adding TSH

Immunoglobulins, TBII Suppression of antibody binding of labeled TSH inhibiting (TSH binding inhibiting with its receptors binding of TSH immuno-globulins)

Antibodies, TSH-R binding Flow cytometry using cells that bind rTTG antibodies into which rTTG is introduced (less sensitive - immunoprecipitation) to the A and B subunits with a loss of about 50 amino acids from the C-terminus. Subunit A forms a large part of the ectodomain, and subunit B forms the rest of the receptor, after which they are connected by disulfide bridges. The subunit A in the culture of thyrocytes is given above the surface and can be isolated and chemically stabilized in a form in which it will react with antibodies and, thus, can be used to determine them.

Antibodies that stimulate rTTG bind exclusively to the ^ terminal fragment of its molecule, and those antibodies that block the receptor, preventing its binding to TSH, exclusively to the C-terminal fragment, while the epitopes for those and other antibodies largely overlap each other, and the degree of this overlay may depend on the conformational changes of the entire protein. Published evidence that there may be a third variant of binding antibodies to the receptor, in which the antibody binds it without any functional consequences. Consequently, there may be antibodies that can later be detected by newer methods in patients in whom these antibodies have not been previously determined by older methods. Taking into account the possibility of alternating production of different variants of at-rTTG, it becomes clear that rTTG and its antibodies possess exceptional and unusual properties, the study of which will bring us closer to elucidating the pathogenesis of Graves' disease.

Other components of the immune response

In Graves' disease in the thyroid gland, a polyclonal T-cell response is detected, as evidenced by the microheterogeneity of the transcripts of the T-lymphocyte V receptor gene. This concerns the heterogeneity of both T-cells and thyroid autoantigens. Up to 80% of patients with Graves disease have antibodies (and, therefore, CD4 + T cells) that react with thyroid peroxidase (at-TPO). Anti-thyroglobulin (at-TG) antibodies are found with a slightly lower frequency.

Contrary to the initial assumption that both Graves' disease and Hashimoto thyroiditis often detect antibodies to the sodium iodide symporter, the proportion of such patients does not exceed 30%. At the same time, such antibodies are unlikely to have any functional significance in pathology, as there is still no data on their transplacental transfer.

By itself, the thyroid gland is the place where autoantibody synthesis is carried out, but only in the later stages of the disease. It is not entirely clear which cytokine profile - TI 1 or TI2 - can be expressed in the thyroid gland, which may be due to the long duration and diversity of the autoimmune response. The thyroid cells themselves express a number of pro-inflammatory molecules in response to cytokines and sublethal complement attacks, which can occur in Graves' disease (HbA class II antigens, adhesion molecules and CD40). As a result, thyrocyte itself can influence the progression of the autoimmune process. Apparently, the individual features of the regulation of these interactions are at least one of the determinants of different clinical course of Graves' disease, in particular its severity, the degree of increase in the thyroid gland and the prediction of the effectiveness of thyrostatic therapy.

Clinical picture

The classical Merseburg triad (goiter, tachycardia, exophthalmos), described by Karl Basenedov, occurs in approximately 50% of patients. Approximately 2 / s of cases of GH develops after the age of 30 years, at least 5 times more often in women. In separate populations (Japan, Sweden), BG manifests itself almost in half of the cases during the first year after birth.

As mentioned, the clinical picture of BG is determined by thyrotoxicosis syndrome, which is characterized by weight loss, often with increased appetite, sweating, tachycardia and a feeling of heartbeat, internal anxiety, nervousness, trembling hands, and sometimes the entire body, general and muscle weakness, rapid fatigue and a number of other symptoms described in detail in the literature. In contrast to the multinodular toxic goiter, which is associated with functional autonomy of the thyroid gland, with BG, there is usually a short history: symptoms develop and progress quickly and in most cases lead the patient to a doctor within 6-12 months. In elderly patients, thyrotoxicosis of any genesis often occurs oligo- or monosymptomatically (evening subfebrile, arrhythmias) or even atypical (anorexia, neurological symptoms). In a palpatory study, approximately 80% of patients can detect an increase in the thyroid gland, sometimes quite significant.

In some cases, BG in the first place may appear manifestations of EOP (marked exophthalmos, often having an asymmetrical character, diplopia when looking sideways or up, tearing, feeling of "sand in the eyes", eyelid edema). It should be noted here that the presence of a pronounced EOP in a patient makes it possible to establish the patient’s etiological diagnosis almost without fail according to the clinical picture, since among the diseases occurring with thyrotoxicosis, EOP is combined only with HD.

Diagnostics

In typical cases, the diagnosis of BG does not cause significant difficulties. If the patient is suspected of having thyrotoxicosis, he is shown to determine the level of TSH by a highly sensitive method (functional sensitivity of at least 0.01 mU / l). When detecting a low level of TSH, the patient is determined by the level of St. T4 and St. T3: if at least one of them is elevated - this is a manifest thyrotoxicosis, if both indicators are normal - subclinical.

After confirming the presence of thyrotoxicosis in the patient, an etiological diagnosis is carried out aimed at identifying the specific disease that caused it.

Diagnosis of BG

Mandatory studies to confirm the diagnosis (minimum set)

Determination of the level of TSH, sv. T4 and St. T3 for proving thyrotoxicosis - ultrasound of the thyroid gland

In the presence of EOP, the diagnosis of BG can be considered confirmed, and a further diagnostic search aimed at determining the cause of thyrotoxicosis is usually inappropriate.

Control study

Determination of the level of St. T4 and St. T3, and further TSH level during the first 6-12 weeks with an interval of 6-12 weeks
Complete blood count, gamma-GT and ALT levels
Ultrasound of the thyroid gland in the presence of data for its increase, but at least once a year

The feasibility of determining the dynamics of the at-rTTG level has not been proven to date.

Nevertheless, this study makes sense to conduct before the abolition of thyreostatics, since a significantly elevated level of at-RTTG indicates a high risk of recurrence of thyrotoxicosis.

Differential diagnosis of BG

Functional autonomy of the thyroid gland
Subacute thyroiditis
Painless ("silent") thyroiditis
Pregnancy
Postpartum thyroiditis
Destructive (iodine-induced) thyroiditis

In most cases, this is a multinodular (nodal) toxic goiter. It is important to note that the detection of a nodal formation in the thyroid gland itself in a patient with thyrotoxicosis does not exclude BG. In some cases, on the contrary, there is a diffuse FA occurring without the formation of nodules. The main importance in the differential diagnosis is scintigraphy, in which, in the case of FA, "hot" nodes and / or uneven enhancement of the isotope capture are detected. FA is more common in the older age group, with no EOP, and, as a rule, at-rTTG.

Acute onset, pain in the neck, radiating to the back of the head and ears, severe tenderness of the thyroid gland, low-grade fever, increased ESR, lymphocytosis, decreased isotope trapping during scintigraphy, a rapid effect of glucocorticoid therapy (Krajl test).

Clinical manifestations of thyrotoxicosis are rare, but hormonal studies reveal typical changes that often do not go beyond subclinical thyrotoxicosis. Reduction of isotope accumulation according to scintigraphy.

Normal pregnancy is accompanied by a decrease in the level of TSH in the first and, often, second trimester. Levels of sv. T4 and St. T3 is normal, while levels of total T4 and T3 are naturally elevated. When treating GH, before prescribing thyreostatics, young women need to make sure that they are not pregnant (!).

A variant of painless thyroiditis that occurs in the first six months after birth. It should be remembered that the most common cause of impaired thyroid function in the postpartum period is precisely postpartum thyroiditis.

May occur when supraphysiological doses of iodine are ingested (contrast agent, amiodarone, etc.). The hormonal shift can be significant, due to the iodine deposition in the fatty tissue - long.

The key to a correct diagnosis is the lack of accumulation of the radiopharmaceutical during thyroid scintigraphy, anamnestic indication of the administration of iodine-containing drugs. Ultrasound imaging for BG has no specific features and is characteristic of most autoimmune thyroid diseases. According to the scintigraphy at BG, diffuse enhancement of the isotope capture by the gland is detected. As with other autoimmune diseases of the thyroid gland, high levels of classical antithyroid antibodies, at-TPO and at-TG (not less than 70-80% of cases) can be determined in HB. Thus, the detection of classical antithyroid antibodies does not allow to distinguish GH from chronic autoimmune, postpartum, and painless ("silent") thyroiditis, but it can, together with other signs, significantly help in the differential diagnosis of GH and functional autonomy (FA) of the thyroid gland. It should be remembered that at-TPO and at-TG can be found in healthy people without any thyroid disease. The determination of the at-rTTG level is of greater diagnostic value.

Treatment

First of all, when planning treatment, it is necessary to clearly understand that in HB this is an autoimmune disease caused by the development of antibodies to rTTG by the immune system. Contrary to this, it is often necessary to come across the idea that the surgical removal of a part of the thyroid gland (subtotal resection) in itself can cause a remission of the disease (that is, essentially an autoimmune process). Although both BG surgery and radioactive iodine therapy should ideologically be perceived only as the removal from the body of the target organ of autoimmune aggression, eliminating thyrotoxicosis.

Advantages and disadvantages of the main treatments for Graves disease

Criteria Thyrostatics Radioactive 1311 Surgical Treatment

Efficiency 20-30% 80-95%> 95% as treatment in a properly selected first-line patient group

Achievement 2-4 weeks 4-8 weeks Preparation of euthyroidism thyreostatics is necessary

Hypothyroidism 15% after 15 years Purpose of treatment, depending on the dose Purpose of the operation: 100% - after thyroidectomy, about 80% - after subtotal resection with 15-20% probability of thyrotoxicosis recurrence

Side effects, 5% - small; <1% 1-4%, complications <1% - severe

In pregnant women, a dose titration regimen Contraindicated Practically not used, but it is possible in the second trimester

With a large goiter. High risk of recurrence. Greater activity needs to be introduced. Fast effect. TAO Does not have a possibility of weighting. It does not have an effect on the course. There is no effect especially in smokers and, contrary to popular belief, there is no evidence that contributes to remission.

In children Treatment of the first Treatment of the third Treatment of the second choice

Conservative therapy

It is prescribed to achieve euthyroidism before surgical treatment, as well as, in certain groups of patients, as a basic long course of treatment, which in some cases leads to persistent remission. It makes sense to plan long-term conservative therapy by far not all patients. First of all, we are talking about patients with a moderate increase in thyroid volume (up to 40 ml) without serious thyroid-toxic complications. An important condition for the planning of long-term thyrostatic therapy is the patient's readiness to follow the recommendations of the doctor (compliance) and the availability of qualified endocrinological care. Conservative therapy is not advisable to plan in patients with nodules in the thyroid gland more than 1-1.5 cm, as well as in the presence of pronounced complications of thyrotoxicosis (atrial fibrillation, thyrotoxic myocardiodystrophy, severe circulatory failure, osteoporosis, etc.). It is practically meaningless and, most importantly, unsafe for the patient to prescribe repeated courses of conservative treatment in the development of a relapse of thyrotoxicosis after 12-24 months of thyreostatic therapy.

For many decades, in the clinical practice, thionamide preparations such as thiamazole (metizol, methimazole, tyrosol, mercazole) and propylthiouracil (PTU, propitsil) have been used as the main thyreostatics for many decades. The key mechanism of action of thionamides is that, when they enter the thyroid, they suppress the action of thyroid peroxidase, inhibit the oxidation of iodine, iodination of ti-reoglobulin and condensation of iodotyrosines. As a result, the synthesis of thyroid hormones is stopped and thyrotoxicosis is stopped. Along with this, it is hypothesized that thionamides (primarily tiamazole) have effects on the immunological changes that develop in HB. In particular, it is assumed that thionamides affect the activity and number of some lymphocyte subpopulations, reduce the immunogenicity of thyroglobulin by reducing its iodization, reduce the production of prostaglandins E2, I-1, I-6 and the production of thyrocyte heat shock proteins. It is precisely this that is associated with the fact that in a properly selected group of patients with GD, while thionamides maintain euthyroidism for 12-24 months in approximately 20-30% of cases, we can expect the development of stable remission of the disease.

The most accepted two regimens for prescribing thyrostatics are: constant titration of the dose of the drug prescribed as monotherapy ("block" scheme), and its appointment at a relatively large dose in combination with thyroxine to maintain euthyroidism ("block and replace" scheme). The long-term results of treatment with both methods in terms of the likelihood of sustained remission are the same, however, in the case of the block and replace scheme, the maximum likelihood of remission is reached after a 6-month course of therapy, whereas similar indicators for monotherapy in dose titration are achieved only after 18-24 months treatment. At the beginning of a course of conservative therapy, including when preparing a patient for an operation, thionamides are prescribed in relatively large doses: 30-40 mg of thiamazole (for 2 doses) or 300-400 mg of vocational schools (for 3-4 doses). Against the background of such therapy, after 4-6 weeks in 90% of patients with moderate thyrotoxicosis, it is possible to achieve a euthyroid state, the first sign of which is the normalization of the level of St. T4. The level of TSH may remain low for a long time, which should not serve as a criterion for the lack of complete compensation for thyrotoxicosis in patients preparing for surgical treatment. For the period before reaching euthyroidism, and often for a longer period, the majority of patients are advisable to prescribe beta-blockers.

When conducting conservative therapy after the normalization of the level of St. T4 the patient begins to reduce the dose of thyreostatics and, after about 2-3 weeks, proceeds to receive a maintenance dose (10-15 mg per day). In parallel, starting from the moment of normalization of the level of St. T4, the patient is prescribed levothyroxine at a dose of 50-150 mcg per day. Such a scheme is called "block and replace". Thyrostatic completely blocks the work of the thyroid gland, levothyroxine replaces the emerging deficiency of thyroid hormones (compensated drug hypothyroidism). The "block and replace" scheme is easy to use because it allows you to completely block the production of thyroid hormones, which eliminates the possibility of recurrence of thyrotoxicosis. The criterion for the adequacy of therapy is the persistent maintenance of a normal level of St. T4 and TSH (the latter may return to normal for several months from the start of treatment). Contrary to popular belief, thyrostatics themselves do not have a "goitogenic" effect. An increase in the thyroid volume against the background of their intake naturally develops only with the development of medical hypothyroidism - a high level of TSH in this situation stimulates exclusively hyperplastic processes in the thyroid gland. Drug-induced hypothyroidism can be easily compensated by prescribing levothyroxine as part of the "block and replace" scheme.

Supportive therapy "block and replace" - 10-15 mg of thiamazole and 50-150 mcg of levothyroxine - lasts no more than 24 months. A further increase in the volume of the thyroid gland against the background of ongoing conservative therapy, even if stable maintenance of euthyroidism significantly reduces the chances of success of treatment. After the end of the course of treatment, the drugs are canceled. Most often relapse develops during the first year after cessation of therapy. In general, thyro-static therapy is fairly safe. Minor side effects, such as pruritus, urticaria, arthralgia, subfebrile, nausea, slight disturbances of taste and smell, are usually transient and expressed very moderately; when they are significant, you can transfer the patient to receive another drug. Throughout the treatment, the patient with an interval of not less than 1 time per month should carry out the determination of the level of white blood cells and platelets. Rare (0.06%), but a formidable complication of the use of thionamides (both tiamazol and almost the same frequency), PTU is agranulocytosis, casuistically rare - isolated thrombocytopenia. Other extremely rare severe side effects include acute liver necrosis (PTU), cholestatic hepatitis (carbimazole), autoimmune insulin syndrome with hypoglycemic conditions, lupus-like syndrome and vasculitis, which may be associated with antineutrophilic cytoplasmic antibodies.

Radioactive iodine therapy

It can be said without exaggeration that the majority of patients with HB, as well as with other forms of toxic goiter, receive therapy with radioactive iodine all over the world. This is due to the fact that the method is effective, non-invasive, relatively cheap, deprived of the complications that can develop during a thyroid surgery. Regardless of age, it has been proven that the risk of 1311 therapy is significantly lower than that of surgical treatment. The only contraindications to treatment with radioactive iodine are pregnancy and breastfeeding.

In significant quantities, 1311 accumulates only in the thyroid gland. After entering the gland, it begins to disintegrate with the release of r-cha-particles, which have a path length of about 1-1.5 mm, which provides local radiation destruction of thyrocytes. The safety of this method of treatment is demonstrated by the fact that in a number of countries, for example in the USA, therapy with radioactive iodine in the HB is carried out on an outpatient basis. A significant advantage is that treatment of 1311 can be performed without prior preparation with thionamides. Hypothyroidism usually develops within 6 months after administration of radioactive iodine.

A serious problem of domestic health care is the actual absence of a real possibility of treating patients with GD with radioactive iodine.

Surgical treatment

According to modern concepts, the goal of operative treatment, as well as the radioactive iodine therapy discussed above, is to remove the thyroid gland, on the one hand, ensuring the development of postoperative hypothyroidism, and on the other - most importantly - excluding any possibility of thyrotoxicosis recurrence. For this purpose, it is recommended to conduct thyroidectomy with the obligatory release of recurrent laryngeal nerves and near-thyroid glands. Conducting subtotal thyroid resections, on the one hand, carries a high risk of persisting or long-term relapse of thyrotoxicosis, and on the other, does not exclude the development of hypothyroidism. When performing subtotal resection of the thyroid gland, it should be understood that, while maintaining a part of the thyroid gland sufficient for the production of thyroid hormones, we leave the "target" in the body for autoimmune aggression.

Thus, at present, postoperative hypothyroidism has ceased to be considered as a complication of surgical treatment of HB, and is its goal. The prerequisite for this was the introduction into modern clinical practice of modern synthetic drugs levothyroxine, due to which postoperative hypothyroidism is quite easily compensated and does not lead to a decrease in the quality of life of patients. It should be noted that postoperative hypothyroidism itself does not actually develop, since the patient immediately after surgery (on day 1) begins to receive replacement therapy with levothyroxine. It can be said without exaggeration that today there is no hypothyroidism, the compensation of which, with the proper use of modern preparations of levothyroxine, would be impossible. The reasons for the failure to compensate for postoperative hypothyroidism should be sought either in the insufficient qualifications of the physician performing the replacement therapy, or in the patient's failure to follow fairly simple recommendations for taking the drug.

Absolute indications for surgical treatment exist in the following groups of patients:

Patients with Graves' disease and with suspicious or malignant thyroid nodes found in fine needle aspiration biopsy. According to some reports, 10–20% of thyroid nodules in patients with Graves disease are malignant.
Pregnant women who do not respond well to thyrostatic therapy or who develop serious allergic reactions to drug treatment. Surgery is usually done during the second trimester of pregnancy.
Patients who are planning a pregnancy shortly after treatment, since Most doctors do not recommend that patients become pregnant for at least 1 year after radioiodine therapy.
Patients with compression symptoms. These symptoms usually do not go away after treatment with radioactive iodine.
Patients with "radiophobia".

Relative indications for surgical treatment are:

The need for rapid elimination of thyrotoxicosis. After radioiodine therapy, there is a latent period lasting from 6 weeks to 6 months, during which patients receive thyrostatic drug therapy, while prompt treatment leads to a quick recovery.
Severe ophthalmopathy. Tire oidectomy stabilizes or reduces the manifestations of ophthalmopathy, whereas radioactive iodine tends to aggravate its course (if the treatment is not combined with the appointment of corticosteroids).
A significant increase in the thyroid gland (more than 100 ml) with a relatively low absorption of radioactive iodine.

Treatment of Graves Disease During Pregnancy, Neonatal Graves Disease, and Breastfeeding

Taking into account the difficulties that arise in the treatment of Graves' disease during pregnancy, the fact of its planning by a woman with this disease can significantly determine the choice of primary treatment. A radical cure, or at least a more or less prolonged remission after thyrostatic therapy, should be achieved before the onset of pregnancy, and the euthyroid state should be maintained until delivery. Other problems are the actual treatment of Graves disease during pregnancy, neonatal Graves disease and breastfeeding.

If Graves disease develops during pregnancy or when it comes to the development of pregnancy on the background of Graves disease, thyreostatic drugs should be prescribed in the minimum dose necessary to maintain the level of St. T4 at the upper limit of the norm or slightly above the norm. The use of the "block and replace" scheme during pregnancy is not indicated, since thyreostatics should be administered at a higher dose, which carries the risk of goiter and hypothyroidism in the fetus. PTU is the drug of first choice for the treatment of thyrotoxicosis during pregnancy, since there is no evidence that its use was combined with embryopathy. If a woman develops intolerance to vocational schools, she is prescribed carbim-ash or tiamazole. If it is impossible to control thyrotoxicosis in the second trimester of pregnancy, surgical treatment can be undertaken. The real need for this can be extremely rare, especially since by the middle of pregnancy and further along it the severity of thyrotoxicosis in Graves' disease significantly and progressively decreases.

It is believed that neonatal Graves disease develops in 0.1–0.2% of children born to women with this disease. The specific symptoms of the newborn are usually absent, and their appearance may be delayed. In utero, fetal thyrotoxicosis may be suspected on the basis of developmental delay, tachycardia. Of greater prognostic value is the detection of a high level of at-rTTG in a woman. The determination of the level of at-rTTG in the third trimester of pregnancy is indicated for women who, for the purpose of maintaining euthyroidism, received thyrostatic therapy throughout pregnancy, as well as for those women who in the past were operated on for Graves disease or received radioactive iodine treatment. In the last two cases, the production of at-rTTG may continue for quite a long time. The elimination of thyrotoxicosis after ablative therapy does not yet imply an immunological remission of Graves' disease, and the antibodies produced can penetrate the placenta and stimulate the thyroid gland. In practice, the definition of the TVІІ level is sufficient, although the TSAb level would be more informative.

Breastfeeding while taking ti-rheostatics is safe enough. Again, VET theoretically has advantages over Tiamazol, since it penetrates into milk to a lesser extent. Nevertheless, the risk of hypothyroidism in a child cannot be completely excluded. In this situation, the appointment of thyrostatics in the minimum dose and periodic (every 2-4 weeks) study of thyroid function in a child is shown. From a practical point of view, the temporary remission of Graves disease, which usually develops in the second half of pregnancy, or at least at its end, usually takes up to 3-6 months of the postpartum period, during which feeding is absolutely safe. After 6 months in modern conditions, only a small number of infants breast milk forms the basis of nutrition. In this regard, a more rational (compared with frequent monitoring of the thyroid function of the child) is the cessation of lactation or the fearless assignment to the woman of an adequate dose of thyreostatics, which is solved individually.

Treatment of Graves Disease in Children

The question of the optimal method of treating Graves disease in children also remains open due to the difficulties of organizing more or less large controlled studies, which are related, firstly, to the rarity of the development of the disease in children, and secondly, to the fact that The choice of treatment method is rendered by social factors (family, educational system, etc.). A review has recently been published in the United States that summarizes the pros and cons of various methods of treating Graves' disease in children, and although many endocrinologists do not yet refer to those in 1311, this treatment has already been successfully performed in several thousand children. Thus, like much in endocrinology, the treatment of Graves' disease in children is still more related to the field of art than to science with its inherent system of evidence.

Forecast

BG is one of the most frequent autoimmune diseases in humans. His clinical picture and prognosis in most cases are determined by persistent thyrotoxicosis, which, if not adequately treated, can lead to severely disabled patients. The current principles of treatment of benthic hypertension, although not without drawbacks, can completely relieve the patient of thyrotoxicosis and ensure an acceptable quality of life.

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