Exercises to help treat Graves' disease. Diagnosis of Graves' disease

Among the numerous diseases thyroid gland one of the most famous among the masses is the so-called Graves' disease, named after the American R. J. Graves, who discovered it in 1835. This is not the only name for this pathology; it is also called Flajani’s disease, Graves’ disease, and in Russia you can most often find the name “diffuse toxic goiter.” Let's figure out what the essence of this thyroid pathology is and how it can be dealt with.

Diffuse toxic goiter is a disease autoimmune type which arises due to excess production thyroid hormones. They are produced by diffuse thyroid tissue, hence one of the names. This phenomenon leads to poisoning of the body with hormones, that is, thyrotoxicosis. The immune system begins to function incorrectly, antibodies begin to be produced that act not on some external elements, but on the thyroid gland itself. Although the gland is not destroyed, it begins to work especially actively, as a result of which hormones begin to “accumulate” in huge quantities.

How to determine?

There are certain symptoms that help identify manifestations of this disease. Each of them may relate to some other pathology, but if several symptoms are observed at the same time, then you need to pay close attention to this. The most striking sign of a probable manifestation of the problem is bulging eyes, which is formed due to the process of scarring of soft tissues. Graves' disease, also known as Graves' disease, causes the muscles responsible for eye movement to permanent basis swell. But this is not the only possible symptom. The following can also be highlighted:

Unnecessarily quick loss weight.
Diarrhea.
Changes in pulse, manifestations of arrhythmia.
Swelling, sweating.
Problems with nail plates (thinning).
Trembling in hands.
Fatigue, increased weakness.
Hypertension or tachycardia.
Irritability, attacks for no reason, increased excitability.

Graves' disease (Bazedow's disease, diffuse toxic goiter)- a systemic autoimmune disease that develops as a result of the production of antibodies to the thyroid hormone receptor, clinically manifested by damage to the thyroid gland with the development of thyrotoxicosis syndrome in combination with extrathyroid pathology: endocrine ophthalmopathy, pretibial myxedema, acropathy. The disease was first described in 1825 by Caleb Parry, in 1835 by Robert Graves, and in 1840 by Karl von Basedow.

Etiology

Diffuse toxic goiter is a multifactorial disease in which genetic features immune response are realized against the background of the action of factors environment. Along with ethnically associated genetic predisposition (carriage of HLA-B8, -DR3 and -DQA1*0501 haplotypes in Europeans), psychosocial factors play a certain role in the pathogenesis of diffuse toxic goiter. Emotional stress and exogenous factors, such as smoking, can contribute to the implementation of a genetic predisposition to diffuse toxic goiter. Smoking increases the risk of developing diffuse toxic goiter by 1.9 times. Diffuse toxic goiter in some cases is combined with other autoimmune endocrine diseases (type 1 diabetes mellitus, primary hypocortisolism).

As a result of impaired immunological tolerance, autoreactive lymphocytes (CD4+ and CD8+ T lymphocytes, B lymphocytes) with the participation of adhesion molecules (ICAM-1, ICAM-2, E-selectin, VCAM-1, LFA-1, LFA-3, CD44 ) infiltrate the parenchyma of the thyroid gland, where they recognize a number of antigens that are presented by dendritic cells, macrophages and B lymphocytes. Subsequently, cytokines and signaling molecules initiate antigen-specific stimulation of B lymphocytes, resulting in the production of specific immunoglobulins against various components of thyrocytes. In the pathogenesis of diffuse toxic goiter, the main importance is given to the formation stimulating antibodies to TSH receptor (AT-rTSH).

Unlike others autoimmune diseases with diffuse toxic goiter, it is not destruction that occurs, but stimulation of the target organ. In this case, autoantibodies are produced to a fragment of the TSH receptor, which is located on the membrane of thyrocytes. As a result of interaction with the antibody, this receptor comes into an active state, triggering a post-receptor cascade of thyroid hormone synthesis (thyrotoxicosis) and, in addition, stimulating hypertrophy of thyrocytes (enlargement of the thyroid gland). For reasons that are not entirely clear, T lymphocytes sensitized to thyroid antigens infiltrate and cause immune inflammation in a number of other structures, such as retrobulbar fat ( endocrine ophthalmopathy), tissue of the anterior surface of the leg (pretibial myxedema).

Pathogenesis

Clinically, the most significant syndrome that develops with diffuse toxic goiter due to hyperstimulation of the thyroid gland by antibodies to the TSH receptor is thyrotoxicosis. The pathogenesis of changes in organs and systems that develop during thyrotoxicosis is a significant increase in the level of basal metabolism, which over time leads to dystrophic changes. The structures most sensitive to thyrotoxicosis, in which the density of receptors for thyroid hormones is highest, are the cardiovascular (especially the atrial myocardium) and nervous systems.

Epidemiology

In regions with normal iodine intake, diffuse toxic goiter is the most frequent illness in nosological structure thyrotoxicosis syndrome (if you do not take into account diseases that occur with transient thyrotoxicosis, such as postpartum thyroiditis, etc.). Women get sick 8-10 times more often, in most cases between 30 and 50 years. The incidence of diffuse toxic goiter is the same among representatives of the European and Asian races, but lower among the Negroid race. The disease is quite rare in children and the elderly.

Clinical manifestations

Diffuse toxic goiter, in most cases, is characterized by a relatively short history: the first symptoms usually appear 4-6 months before visiting a doctor and making a diagnosis. As a rule, the key complaints are associated with changes in the cardiovascular system, the so-called catabolic syndrome and endocrine ophthalmopathy.

The main symptom from of cardio-vascular system is tachycardia and quite pronounced sensations of heartbeat. Patients can feel heartbeats not only in the chest, but also in the head, arms, and stomach. Heart rate at rest with sinus tachycardia caused by thyrotoxicosis can reach 120-130 beats per minute.

With long-term thyrotoxicosis, especially in elderly patients, severe dystrophic changes in the myocardium, a common manifestation of which is supraventricular rhythm disturbances, namely atrial fibrillation (atrial fibrillation). This complication of thyrotoxicosis rarely develops in patients under 50 years of age. Further progression of myocardial dystrophy leads to the development of changes in the ventricular myocardium and congestive heart failure.

Typically expressed catabolic syndrome, manifested by progressive weight loss (sometimes by 10-15 kg or more, especially in persons with initial excess weight) against the background of increasing weakness and increased appetite. The skin of patients is hot, sometimes there is severe hyperhidrosis. A feeling of heat is typical; patients do not freeze at a sufficiently low temperature in the room. Some patients (especially the elderly) may experience evening low-grade fever.

Changes from the side nervous system are characterized by mental lability: episodes of aggressiveness, agitation, chaotic unproductive activity are replaced by tearfulness, asthenia (irritable weakness). Many patients are not critical of their condition and try to maintain an active lifestyle against the backdrop of a rather severe somatic condition. Long-term thyrotoxicosis is accompanied by persistent changes in the patient’s psyche and personality. A frequent but nonspecific symptom of thyrotoxicosis is fine tremor: slight trembling fingers of outstretched arms is detected in most patients. In severe thyretoxicosis, tremors can be detected throughout the body and even make it difficult for the patient to speak.

Tyrotoxicosis is characterized by muscle weakness and a decrease in muscle volume, especially the proximal muscles of the arms and legs. Sometimes quite pronounced myopathy develops. Very rare complication is thyrotoxic hypokalemic periodic paralysis, which manifests itself periodically sudden attacks muscle weakness. Laboratory tests reveal hypokalemia and increased CPK levels. It is more common among representatives of the Asian race.

Intensification of bone resorption leads to the development osteopenia syndrome, and thyrotoxicosis itself is considered one of the most important factors risk of osteoporosis. Frequent complaints patients are hair loss, brittle nails.

Changes from the side gastrointestinal tract develop quite rarely. Elderly patients may have diarrhea in some cases. With long-term severe thyrotoxicosis, degenerative changes in the liver (thyrotoxic hepatosis) can develop.

Violations menstrual cycle are quite rare. Unlike hypothyroidism, moderate thyrotoxicosis may not be accompanied by a decrease in fertility and does not exclude the possibility of pregnancy. Antibodies to the TSH receptor penetrate the placenta, and therefore in children born (1%) to women with diffuse toxic goiter (sometimes years after radical treatment), transient neonatal thyrotoxicosis may develop. In men, thyrotoxicosis is often accompanied by erectile dysfunction.

In severe thyrotoxicosis, a number of patients exhibit symptoms of thyroidogenic (relative) adrenal insufficiency, which must be differentiated from the true one. Hyperpigmentation of the skin and exposed parts of the body is added to the symptoms already listed. (Jellinek's sign), arterial hypotension.

In most cases, diffuse toxic goiter occurs enlargement of the thyroid gland, which, as a rule, is diffuse in nature. Often the gland is significantly enlarged. In some cases, a systolic murmur can be heard over the thyroid gland. However, goiter is not an obligate symptom of diffuse toxic goiter, since it is absent in at least 25-30% of patients.

Of key importance in the diagnosis of diffuse toxic goiter are changes in the eyes, which are a kind of “calling card” of diffuse toxic goiter, i.e. their detection in a patient with thyrotoxicosis almost unambiguously indicates diffuse toxic goiter, and not another disease. Very often, due to the presence of severe ophthalmopathy in combination with symptoms of thyrotoxicosis, the diagnosis of diffuse toxic goiter is obvious already upon examination of the patient.

Another rare (less than 1% of cases) disease associated with diffuse toxic goiter is pretibial myxedema. The skin of the anterior surface of the leg becomes swollen, thickened, and purple-red in color (“ Orange peel"), often accompanied by erythema and itching.

The clinical picture of thyrotoxicosis may differ from the classic version. So, if young people Diffuse toxic goiter is characterized by a detailed clinical picture; in elderly patients, its course is often oligo- or even monosymptomatic (heart rhythm disturbance, low-grade fever). In the “apathetic” version of the course of diffuse toxic goiter, which occurs in elderly patients, clinical manifestations include loss of appetite, depression, physical inactivity.

A very rare complication of diffuse toxic goiter is a thyrotoxic crisis, the pathogenesis of which is not entirely clear, since a crisis can develop without an extreme increase in the level of thyroid hormones in the blood. Reason thyrotoxic crisis There may be acute infectious diseases accompanying diffuse toxic goiter, surgical intervention or radioactive iodine therapy against the background of severe thyrotoxicosis, withdrawal of thyreostatic therapy, and administration of a contrast iodine-containing drug to the patient.

Clinical manifestations of a thyrotoxic crisis include a sharp worsening of the symptoms of thyrotoxicosis, hyperthermia, confusion, nausea, vomiting, and sometimes diarrhea. Registered sinus tachycardia over 120 beats/min. Atrial fibrillation, high pulse pressure followed by severe hypotension are often observed. The clinical picture may be dominated by heart failure, respiratory distress syndrome. Manifestations of relative adrenal insufficiency are often expressed in the form of skin hyperpigmentation. The skin may be jaundiced due to the development of toxic hepatosis. Laboratory tests may reveal leukocytosis (even in the absence of concomitant infection), moderate hypercalcemia, and increased alkaline phosphatase levels. Mortality during thyrotoxic crisis reaches 30-50%.

Diagnostics

TO diagnostic criteria Diffuse toxic goiter includes:

Laboratory confirmed thyrotoxicosis (decrease in TSH, increase in T4 and/or T3).

Endocrine ophthalmopathy (60-80% of cases).

Diffuse increase in the volume of the thyroid gland (60-70%).

Diffuse enhancement of 99m Tc uptake according to thyroid scintigraphy.

Increased level of antibodies to the TSH receptor.

At the first stage of diagnosing diffuse toxic goiter, it is necessary to confirm that the patient has clinical symptoms(tachycardia, weight loss, tremor) is caused by thyrotoxicosis syndrome. For this purpose, they carry out hormonal study, which reveals a decrease or even complete suppression of TSH levels and an increase in T4 and/or T3 levels. Further diagnosis is aimed at differentiating diffuse toxic goiter from other diseases occurring with thyrotoxicosis. In the presence of clinically pronounced endocrine ophthalmopathy, the diagnosis of diffuse toxic goiter is almost obvious. In some cases, in the absence of obvious endocrine ophthalmopathy, it makes sense to actively search for it using instrumental methods(Ultrasound and MRI of the orbits).

Ultrasound for diffuse toxic goiter, as a rule, reveals diffuse enlargement of the thyroid gland and hypoechogenicity, characteristic of all its autoimmune diseases. Determining the volume of the thyroid gland is, in addition, necessary for choosing a treatment method, since the prognosis of conservative thyreostatic therapy for goiter big size bad enough. Thyroid scintigraphy is not necessary in typical cases (thyrotoxicosis, endocrine ophthalmopathy, diffuse goiter, young age of the patient). In less obvious situations, this method makes it possible to differentiate diffuse toxic goiter from diseases occurring with destructive thyrotoxicosis (postpartum, subacute thyroiditis etc.) or from the functional autonomy of the thyroid gland (multinodular toxic goiter with “hot” nodes).

In diffuse toxic goiter, at least 70-80% of patients have circulating antibodies to thyroid peroxidase (AT-TPO) and thyroglobulin (AT-TG), however, they are nonspecific for this disease and occur in any other autoimmune pathology thyroid gland (autoimmune thyroiditis, postpartum thyroiditis). In some cases, an increase in the level of AT-TPO can be regarded as indirect diagnostic sign diffuse toxic goiter, when we're talking about about its differential diagnosis from non-autoimmune diseases occurring with thyrotoxicosis (functional autonomy of the thyroid gland). A fairly specific test for the diagnosis and differential diagnosis of diffuse toxic goiter is to determine the level antibodies to TSH receptor which in this disease are given the main pathogenetic significance. However, it should be taken into account that in some cases these antibodies are not detected in patients with obvious diffuse toxic goiter, which is due to the imperfection of relatively recently developed test systems.

Treatment

There are three methods of treating diffuse toxic goiter ( conservative treatment thyreostatic drugs, surgery and therapy 131 I), while none of them is etiotropic. IN different countries specific gravity The use of these treatment methods is traditionally different. Thus, in European countries, conservative therapy with thyreostatics is most accepted as the primary method of treatment; in the USA, the vast majority of patients receive 131 I therapy.

Conservative therapy carried out using thiourea preparations, which include thiamazole(mercazolyl, tyrosol, methizol) and propylthiouracil(PTU, propitsil). The mechanism of action of both drugs is that they actively accumulate in the thyroid gland and block the synthesis of thyroid hormones due to inhibition of thyroid peroxidase, which adds iodine to tyrosine residues in thyroglobulin.

Purpose surgical treatment, as well as therapy 131 I is the removal of almost the entire thyroid gland, on the one hand, ensuring the development of postoperative hypothyroidism (which is quite easily compensated), and on the other, eliminating any possibility of relapse of thyrotoxicosis.

In most countries of the world, the majority of patients with diffuse toxic goiter, as well as with other forms of toxic goiter, receive radioactive 131 I therapy as the main method of radical treatment. This is due to the fact that the method is effective, non-invasive, relatively inexpensive, and devoid of those complications which can develop during thyroid surgery. The only contraindications to treatment with 131 I are pregnancy and breast-feeding. IN significant quantities 131 I accumulates only in the thyroid gland; after entering it, it begins to disintegrate with the release of beta particles, which have a path length of about 1-1.5 mm, which ensures local radiation destruction of thyrocytes. A significant advantage is that 131 I treatment can be carried out without preliminary preparation thyreostatics. In diffuse toxic goiter, when the goal of treatment is destruction of the thyroid gland, therapeutic activity, taking into account the volume of the thyroid gland, the maximum uptake and half-life of 131 I from the thyroid gland, is calculated based on an estimated absorbed dose of 200-300 Gray. With an empirical approach, a patient without preliminary dosimetric studies is prescribed about 10 mCi for a small goiter, and 15-30 mCi for a larger goiter. Hypothyroidism usually develops within 4-6 months after administration of 131 I.

Peculiarity treatment of diffuse toxic goiter during pregnancy is that a thyreostatic agent (preference is given to PTU, which penetrates the placenta worse) is prescribed in a minimal amount required dose(only according to the “block” scheme), which is necessary to maintain the level of free T4 at upper limit norm or slightly above it. Usually, as the duration of pregnancy increases, the need for thyrostatic drugs decreases and most women after 25-30 weeks do not take the drug at all. However, most of them develop a relapse of the disease after childbirth (usually 3-6 months).

Treatment thyrotoxic crisis involves intensive activities with the administration of large doses of thyreostatics. Preference is given Vocational school at a dose of 200-300 mg every 6 hours, if not possible self-administration by the patient - through a nasogastric tube. In addition, beta-blockers are prescribed (propranolol: 160-480 mg per day per os or intravenously at a rate of 2-5 m g/hour), glucocorticoids (hydrocortisone: 50-100 mg every 4 hours or prednisolone (60 mg/day), detoxification therapy (saline, 10% glucose solution) under hemodynamic control . Effective method The treatment for thyrotoxic crisis is plasmapheresis.

Forecast

In the absence of treatment, it is unfavorable and is determined by the gradual development of atrial fibrillation, heart failure, and exhaustion (marantic thyrotoxicosis). In the case of normalization of thyroid function, the prognosis of thyrotoxic cardiomyopathy is favorable - in most patients, cardiomegaly regresses and is restored sinus rhythm. The probability of relapse of thyrotoxicosis after a 12-18-month course of thyreostatic therapy is 70-75% of patients.

The description of a disease unknown in the 19th century belongs to the American doctor Robert Graves. Inappropriate behavior, depressed state, groundless inquiries and suspicions he called (later received the name or Graves' disease).

The thyroid gland becomes ill due to the increased activity of its cells, producing the necessary normal life hormones. She suffers from negative impact of its cells, mistakenly mistaking them for foreign, and fights against them. This process turns into thyroiditis, which leads to the same enlargement of the thyroid gland.

The body produces antibodies that influence the changes that occur in increasing the active activity of the thyroid gland, which have a negative effect on it with thyroid hormones. Antibodies arise in the body for various reasons.

In patients, the existence of receptors is observed, the thyroid-stimulating hormone of the pituitary gland recognizes them as erroneous, and a determination occurs immune system, How foreign bodies. Or the immune system is susceptible to a defect that does not protect its own cells. After suffering any disease, in some cases the body reacts with the appearance of antibodies.

Factors provoking thyrotoxicosis

Various factors trigger Graves' disease. They are like this:

heredity;
stress;
lack of iodine in the body;
environmental pollution;
ENT diseases;
head injuries;
infections of various nature, affecting the body.

The onset of Graves' disease often occurs in areas where there is severe iodine deficiency.

Degrees of thyrotoxicosis

Signs that determine the degree of the disease:

I degree - the thyroid gland is palpable, although outwardly not noticeable.
II degree - an enlarged thyroid gland is noticeable when swallowing.
III degree - deformation of the thyroid gland affects the change in the appearance of the neck.
IV degree – the goiter is noticeably prominent.
V degree - a severe goiter protrudes, other tissues are pressed by the thyroid gland.

Very often, women under 50 years old suffer from Graves' disease. Female body because of physiological characteristics has loads: pregnancy, childbirth, lactation period. Graves' disease is inherited, and identifying the onset of the disease is important. Treatment of thyrotoxicosis in a woman will occur by leading to normal state special hormone levels medicines. These drugs do not penetrate the placenta, and the baby will develop a thyroid gland without disturbances.

Symptoms of thyrotoxicosis

Symptoms of Graves' disease are determined through the autoimmune reaction and the functional activity of the thyroid gland. Part of the special hormones, when necessary, fills the follicle consisting of thyroid cells. At negative manifestations there is a release of a hormone that provokes. Treatment is prescribed comprehensively. The inflamed thyroid gland releases thyroxine into the blood; when it reaches a high concentration, it causes the onset of the disease -.

Sometimes a toxic adenoma is observed - this is an independent node, the action of which is produced by the hormones T3, T4. Rapid saturation of the body with iodine after a long-term deficiency of this trace element is the cause of this disease.

Description of thyrotoxicosis by Adolf von Basedow

Graves' disease was studied and new signs were identified by the doctor Adolf von Basedow, after which it also became known as: . Symptoms of the disease appear as follows:

The neck thickens, the goiter is visible as a complete formation or having separate nodes;
Intense palpitations, insomnia, tachycardia and rapid pulse occur.
There is shortness of breath, which is diagnosed as asthma.
Eyelids swell, double vision, frequent lacrimation.
Protruding eyeballs– exophthalmos. Can be seen in half of patients with this disease. The patient has pronounced bulging eyes, accompanied by moisture and redness, and the eyelids are characterized by swelling.
The liver becomes enlarged, stool becomes more frequent, frequent pain in a stomach.
Noticeable pigmentation appears around the eyes and on the palms of the hands.
Sweating increases, it becomes hot even in cold weather.
The skin is moist and hot on contact;
appear mental changes– aggressiveness, restlessness, nervousness. Changes in mood are noticed: from cheerfulness to depression. With such severe symptoms, it is necessary emergency help doctors.
A tremor is noticeable, a fractional tremor is clearly visible on the outstretched fingers.
Osteoporosis develops and the risk of fractures increases - this refers to an excess of hormones that affect the decrease in calcium and phosphorus in the bones.
Appetite increases, but significant weight loss is noticed.
Constantly thirsty, frequent diarrhea and urination.
Hair becomes brittle and brittle and actively falls out.

Graves' disease did not spare Nadezhda Konstantinovna Krupskaya, affecting her immune system. Her bulging eyes were clearly expressed in her appearance, and she was unable to become a mother.

Stages of Graves' disease

The main causes of Graves' disease or Graves' disease are: heredity and polluted ecological environment; there are 3 stages of the disease:

Mild stage - increased heart rate up to 100 beats per minute, decreased performance, absent-mindedness, increased fatigue, weight loss, tachycardia.
The middle stage is 20% weight loss, increased heart rate per minute to 100-120 beats, increased nervousness.
Severe stage - failures in the cardiovascular system and liver, loss of performance, mental problems, weight decreases by more than 20%, pulse beats per minute increase to 200.

Diagnostic methods

An endocrinologist diagnoses Graves' disease. The onset of the disease is determined in the area of the thyroid gland, and then an ultrasound is prescribed. A blood test is also necessary to determine thyroxine levels, thyroid-stimulating hormone, triiodothyronine. To detect cardiac pathologies, it is necessary to do an electrocardiogram.

An important factor for diagnosing the body is hormonal examination, which helps determine the degree of accumulation of thyroid hormones. You can get enough information about the disease by performing a test that detects changes in the volume of the thyroid gland. If urgently necessary, a radioisotope study is carried out.

Treatment of Graves' disease is long and complex because all body systems are affected, the chance of complete remission is 50%.

Features of treatment of Graves' disease

Medication. It is used in two cases: as an independent treatment for Graves' disease, and as a preparation for more complex methods of therapy. Thyreostatic drugs are used. Correct Application dose helps relieve symptoms of the disease. Drug overdose will lead to worsening hyperthyroidism. Along with these drugs for treatment, it is necessary to take sedatives that promote good sleep and relieving nervous excitability, and beta-blockers, reducing the negative effects of excess hormones.
Thyroidectomy. If the size of the thyroid gland is enlarged and it compresses the tissue around it, a part of it is cut out. This treatment method is used when symptoms return after stopping the pills. Surgery is performed after normalizing hormones through medication therapy.
. This method, which affects Graves' disease, consists in the fact that the thyroid gland, which can store iodine, takes a radioactive drug that takes away the ability to produce excess hormones. This treatment method is used for patients with contraindications to surgical interventions and elderly people who have not been helped by medications. Therapy for Graves' disease is carried out in two ways: one-time and fractionally extended. First, the patient is brought to a state of iodine deficiency - this facilitates the rapid penetration of radioisotope iodine; it is dosed depending on the condition of the thyroid gland. This method of treatment should not be used in case of severe bulging eyes, pregnancy or lactation. The advantage of this method of treatment is that there are no scars, there is almost no bleeding, and the recurrent nerves are not injured.

Thyrotoxicosis in children

Graves' disease occurs in children, the real causes are still unknown. Doctors have suggested that the disease occurs due to various infections or chronic ENT diseases.

Prolonged uncontrolled exposure to the sun, parental alcohol addiction, mental or physical injuries, hereditary predisposition– can lead to thyrotoxicosis. Children become tearful with mood swings and are subject to uncontrollable twitching of the arms, head and facial muscles. Early signs Graves' disease occurs accelerated heartbeat, pulse rate per minute up to 90 beats. Some adolescents with Graves' disease may experience a delay in sexual development.

The duration of treatment for thyrotoxicosis in children is up to 3 years; they have to constantly take medications to help the thyroid gland normalize its function.

During the treatment of Graves' disease, a constant diet enriched with proteins is required and the intake of salty foods and sugary drinks is reduced. Surgical operations carried out only with a very enlarged goiter and with advanced disease. Radioiodine therapy is not used for children.

Prevention measures

To prevent Graves' disease, you should follow simple steps:

eat foods containing iodine;
undergo a thyroid examination with a doctor twice a year for prevention using ultrasound;
exclude excessive physical activity for the body;
support the body with intake;
strive to create favorable relationships in the team and family.

At the first slight sign of Graves' disease, you should immediately contact medical institution. Self-treating Graves' disease is increased danger, the consequences may be irreversible.

B Graves' disease (Bazedow's disease, diffuse toxic goiter, GD) is a systemic autoimmune disease that develops as a result of the production of antibodies to the thyroid stimulating hormone receptor (TSH), clinically manifested by damage to the thyroid gland (TG) with the development of thyrotoxicosis syndrome in combination with extrathyroidal pathology (endocrine ophthalmopathy, pretibial myxedema, acropathy). 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 with HD, the thyroid gland is affected.

In the USA and England, the frequency of new cases of HD varies from 30 to 200 cases per 100 thousand population per year. Women develop GD 10-20 times more often. In regions with normal iodine supply Graves' disease is the most common cause persistent thyrotoxicosis , and in iodine-deficient regions in the etiological structure of toxic goiter, HD competes with the functional autonomy of the thyroid gland (nodular and multinodular toxic goiter). In Russia, the term Graves' disease (Bazedow's disease) is traditionally used as a synonym for diffuse toxic goiter , which is not without a number of significant drawbacks. Firstly, it characterizes only macroscopic (diffuse goiter) and functional (toxic) changes in the thyroid gland, which are not obligatory for Graves’ disease: on the one hand, there may be no enlargement of the gland, on the other hand, it may not be diffuse. At the same time, diffuse enlargement of 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” (rather than just toxic goiter) in relation to the disease under discussion is likely more justified, since it better emphasizes the systemic nature of the autoimmune process. In addition, throughout the world, the term Graves' disease is traditionally most often used and thus recognized, and in German-speaking countries, Graves' disease.

Pathogenesis

HD is a multifactorial disease in which the genetic characteristics of the immune response are realized against the background of environmental factors. Along with ethnically associated genetic predisposition (carriage of HLA-B8, -DR3 and -DQA1*0501 haplotypes in Europeans), psychosocial and environmental factors are of particular importance in the pathogenesis of HD. Thus, the importance of infectious and stress factors has been discussed for quite some time, in particular, a number of works put forward the theory of “molecular mimicry” between antigens of the thyroid gland, retrobulbar tissue and a number of stress proteins and antigens of bacteria (Yersinia enterocolitica). Emotional stressors and exogenous factors, such as smoking, can contribute to the implementation of a genetic predisposition to HD. Thus, a temporal relationship was discovered between the manifestation of HD and the loss of a spouse (partner). Smoking increases the risk of developing HD by 1.9 times.

GD in some cases is combined with other autoimmune endocrine diseases (type 1 diabetes mellitus, primary hypocortisolism); This combination is usually denoted as autoimmune polyglandular syndrome type II .

As a result of impaired immunological tolerance, autoreactive lymphocytes (CD4 + - and CD8 + -T lymphocytes, B lymphocytes) are mediated by adhesion molecules (ICAM-1, ICAM-2, E-selectin, VCAM-1, LFA-1, LFA- 3, CD44) infiltrate the thyroid parenchyma, where they recognize a number of antigens that are presented by dendritic cells, macrophages, B lymphocytes and HLA-DR-expressing follicular cells. Subsequently, cytokines and signaling molecules initiate antigen-specific stimulation of B lymphocytes, resulting in the production of specific immunoglobulins against various components of thyrocytes. In the pathogenesis of HD, education is of primary importance stimulating antibodies to the TSH receptor (AT-rTSH). These antibodies bind to the TSH receptor, bring it into an active state, triggering intracellular systems (cascades of cAMP and phosphoinositols), which stimulate the uptake of iodine by the thyroid gland, the synthesis and release of thyroid hormones, as well as the proliferation of thyrocytes. As a result, thyrotoxicosis syndrome develops, which dominates the clinical picture of HD.

Clinical picture

Classical Merseburg triad (goiter, tachycardia, exophthalmos), described by Karl Basedov, occurs in approximately 50% of patients. In approximately 2/3 of cases, HD develops after the age of 30, at least 5 times more often in women. In certain populations (Japan, Sweden), HD manifests itself in almost half of the cases during the first year after birth.

As stated, clinical picture BG is determined thyrotoxicosis syndrome , which is characterized by: weight loss (often against the background of increased appetite), sweating, tachycardia and palpitations, internal anxiety, nervousness, trembling of the hands (and sometimes the whole body), general and muscle weakness, fatigue and a number of other symptoms described in detail in literature. Unlike multinodular toxic goiter, which is associated with the functional autonomy of the thyroid gland, with GD, as a rule, there is 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 origin often occurs oligo- or monosymptomatically (evening low-grade fever, arrhythmias) or even atypically (anorexia, neurological symptoms). Palpation examination reveals in approximately 80% of patients thyroid enlargement , sometimes quite significant: palpation of the gland is dense, painless.

In some cases, with HD, manifestations may come first endocrine ophthalmopathy (severe exophthalmos, often asymmetrical in nature, diplopia when looking to one side or up, lacrimation, a feeling of “sand in the eyes,” swelling of the eyelids). Here it should be noted that the presence of severe endocrine ophthalmopathy (EOP) in a patient allows one to almost accurately determine etiological diagnosis already according to the clinical picture, since among the diseases occurring with thyrotoxicosis, EOP is combined only with GD.

Diagnostics

Diagnosis in typical cases does not cause significant difficulties (Table 1). If a patient is suspected of having thyrotoxicosis, he is shown TSH level determination highly sensitive method (functional sensitivity of at least 0.01 mU/l). When found reduced level TSH is performed on the patient determination of the level of free T 4 and T 3 : if at least one of them is elevated, we are talking about manifest thyrotoxicosis, if they are both normal, we are talking about subclinical.

After confirming that the patient has thyrotoxicosis, etiological diagnosis , aimed at identifying the specific disease that caused it. Ultrasound reveals diffuse enlargement of the thyroid gland in approximately 80% of cases of HD; In addition, this method can reveal the hypoechogenicity of the thyroid gland, which is characteristic of most autoimmune diseases. According to scintigraphy data in HD, a diffuse increase in the uptake of the isotope by the gland is detected. As with all other autoimmune thyroid diseases, GD can be characterized by high levels of classical antibodies to the thyroid gland (antibodies to thyroid peroxidase - AT-TPO and antibodies to thyroglobulin - AT-TG). This is observed in at least 70-80% of HD cases. Thus, the detection of classical antibodies does not allow distinguishing GD from chronic autoimmune, postpartum and “painless” (“silent”) thyroiditis, but can, in combination with other signs, significantly help in differential diagnosis GD and functional autonomy of the thyroid gland. It should be remembered that classical antibodies can be detected in healthy people without any thyroid disease. Has greater diagnostic value determination of the level of antibodies to the TSH receptor (AT-rTSH), which, alas, is not yet absolute due to the imperfections of the available test systems. Table 2 shows a brief description of other diseases occurring with thyrotoxicosis, with which HD must be differentiated.

Treatment

First of all, when planning treatment, you need to clearly understand that with HD we are talking about an autoimmune disease, the cause of which is the production of antibodies to the thyroid gland by the immune system. Contrary to this, unfortunately, very often one has to deal with the idea that surgical removal parts of the thyroid gland in itself can cause remission of the disease (i.e., essentially, an autoimmune process), although both surgery for HD and therapy with radioactive iodine-131 should ideologically be perceived only as the removal of the “target organ” for antibodies from the body , eliminating thyrotoxicosis. Currently, there are 3 methods of treating HD, each of which has significant drawbacks.

First of all, when planning treatment, you need to clearly understand that with HD we are talking about an autoimmune disease, the cause of which is the production of antibodies to the thyroid gland by the immune system. Contrary to this, unfortunately, very often one has to deal with the idea that surgical removal of part of the thyroid gland in itself is capable of causing remission of the disease (i.e., essentially an autoimmune process), although both GD surgery and radioactive iodine therapy -131 should be ideologically perceived only as the removal of the “target organ” for antibodies from the body, eliminating thyrotoxicosis. Currently, there are 3 methods of treating HD, each of which has significant drawbacks.

Conservative treatment of Graves' disease

It is prescribed to achieve euthyroidism before surgical treatment, as well as in certain groups of patients as a basic long-term course of treatment, which in some cases leads to stable remission. It makes sense to plan long-term conservative therapy not in all patients. First of all, we are talking about patients with a moderate increase in thyroid volume (up to 40 ml); with a large goiter, thyrotoxicosis will inevitably develop after discontinuation of thyreostatics. In addition, it is not advisable to plan conservative therapy in patients with large (more than 1-1.5 cm) nodular formations in the thyroid gland and in the presence of severe complications of thyrotoxicosis (atrial fibrillation, severe osteoporosis, etc.). Practically meaningless (and most importantly - unsafe for the patient) prescription repeat courses treatment for the development of relapse of thyrotoxicosis after 12-24 months of thyreostatic therapy. An important condition planning long-term thyrostatic therapy is the patient’s willingness to follow the doctor’s recommendations (compliance) and the availability of qualified endocrinological care.

Drugs from the group have been used as the main thyreostatics for many decades in clinical practice around the world. thionamides: thiamazole (Metizol) and propylthiouracil. The key mechanism of action of thionamides is that, once in the thyroid gland, they suppress the action of thyroid peroxidase, inhibit iodine oxidation, iodination of thyroglobulin and condensation of iodotyrosines. As a result, the synthesis of thyroid hormones stops and thyrotoxicosis is stopped. Along with this, a not universally supported hypothesis has been put forward that thionamides, primarily thiamazole, have effects on the immunological changes that develop in HD. In particular, it is assumed that thionamides affect the activity and number of certain subpopulations of lymphocytes, reduce the immunogenicity of thyroglobulin by reducing its iodization, reduce the production of prostaglandins E 2, IL-1, IL-6 and the production of heat shock proteins by thyrocytes. This is precisely what is associated with the fact that in a properly selected group of patients with HD , against the background of maintaining euthyrosis with thionamides for approximately 12-24 months in 30% of cases, stable remission of the disease can be expected .

If the patient is planning a course of thyrostatic therapy, thionamides are initially prescribed in relatively large doses: 30-40 mg of thiamazole (for 2 doses) or propylthiouracil - 300 mg (for 3-4 doses). With this therapy, after 4-6 weeks, 90% of patients with moderate thyrotoxicosis manage to achieve a euthyroid state, the first sign of which is normalization of the level of free T4. TSH level may remain reduced for a long time. For the period until euthyroidism is achieved (often for a longer period), it is advisable for most patients to prescribe b-blockers (propranolol - 120 mg/day for 3-4 doses or long-acting drugs, for example, atenolol - 100 mg/day once). In the last decade, most guidelines have moved away from the “fascination” with small starting doses of thiamazole, when it was initially proposed to prescribe 10-15 mg of the drug per day, since with this treatment option the achievement of euthyroidism is extended over too long a period of time, which is clinically unprofitable, often unsafe and does not exclude the risk of leukopenic reactions. At the same time, the unsafe prescription of megadoses of thiamazole as initial therapy (80-120 mg) was also abandoned, except in cases of severe thyrotoxicosis.

After normalization of the free T4 level, the patient begins to reduce the dose of the thyreostatic agent and after about 2-3 weeks switches to taking a maintenance dose (10-15 mg per day). In parallel, starting from the moment of normalization of T level 4 or slightly later, the patient is prescribed levothyroxine at a dose of 50-100 mcg per day. This scheme is called “block and replace”: one drug blocks the gland, the other replaces the emerging deficiency of thyroid hormones. The “block and replace” regimen 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 persistent maintenance normal level T 4 and TSH (the latter may return to normal within several months from the start of treatment). Contrary to popular belief, thiamazole and propylthiouracil themselves do not have a so-called “goitrogenic” effect. An increase in the size of the thyroid gland naturally develops against the background of taking them only with the development of drug-induced hypothyroidism , which can be easily avoided by prescribing levothyroxine as part of a block-and-replace regimen.

Maintenance block-and-replace therapy (10–15 mg thiamazole and 50–100 mcg levothyroxine) lasts from 12 to a maximum of 24 months (Table 1). A further increase in the volume of the thyroid gland during therapy, even under the condition of stable maintenance of euthyroidism (this will naturally occur with drug-induced hypothyroidism or, conversely, with insufficient blockade of the thyroid gland) significantly reduces the chances of treatment success. Throughout treatment, the patient must have the level of leukocytes and platelets determined at intervals of at least 1 time per month. A rare (0.06%) but dangerous complication of thionamides (both thiamazole and, with almost the same frequency, propylthiouracil) is agranulocytosis, and, incidentally, isolated thrombocytopenia is rare. After completing the course of treatment, the drugs are discontinued; Most often, relapse develops during the first year after cessation of therapy.

Surgical treatment

By modern ideas, the purpose of surgical treatment, as well as the iodine-131 therapy discussed below, is to remove most of the thyroid gland, on the one hand, ensuring the development of postoperative hypothyroidism, and on the other (which is most important) - eliminating any possibility of relapse of thyrotoxicosis. For this purpose, it is recommended to carry out extremely subtotal resection of the thyroid gland leaving no more than 2-3 ml of thyroid residue . Carrying out subtotal resections, on the one hand, carries high risk persistence or distant relapse of thyrotoxicosis, and on the other hand, does not at all exclude the development of hypothyroidism. When performing so-called “economical resections”, the volume of which is regarded as inadequate throughout the world, it should be understood that by leaving during the operation a part of the thyroid gland sufficient for the production of thyroid hormones, the body, in fact, remains a “target” for antithyroid antibodies, produced by cells of the immune system.

Thus, postoperative hypothyroidism has now ceased to be considered as a complication of surgical treatment of HD, and is his goal . The prerequisite for this was the introduction into widespread clinical practice modern drugs of levothyroxine, against the background of adequate intake of which the patient maintains persistent euthyroidism and a quality of life that does not differ from normal. Today we can say without exaggeration that there is no such hypothyroidism, compensation for which would be impossible with the proper use of modern thyroid hormone preparations. Failures in the treatment of postoperative and any other hypothyroidism should be sought either in the insufficient qualifications of the person conducting replacement therapy, or in the patient’s failure to comply with sufficient simple recommendations on taking the drug.

Radioactive iodine therapy

It can be said without exaggeration that throughout the world the majority of patients with GD, as well as with other forms of toxic goiter, receive exactly radioactive iodine-131 therapy . This is due to the fact that the method is effective, non-invasive, relatively cheap, and free of the complications that can develop during thyroid surgery. The only contraindications to treatment with iodine-131 are pregnancy and breastfeeding.

If in our country to this day there continues to be an opinion that therapy with iodine-131 is indicated only for elderly patients who, for one reason or another, cannot undergo surgery, then in fact, there is no longer a lower age limit for prescribing iodine-131, and in many countries, iodine-131 is successfully used to treat HD in children. It has been proven that, regardless of age, the risk of iodine-131 therapy is significantly lower than that of surgical treatment.

Iodine-131 accumulates in significant quantities only in the thyroid gland; after entering it, it begins to disintegrate with the release of b-particles, which have a path length of about 1-1.5 mm, which ensures local radiation destruction of thyrocytes. The safety of this treatment method is demonstrated by the fact that in a number of countries, for example, in the USA, where 99% of patients with GD receive iodine-131 as a first-line treatment, iodine-131 therapy for GD is carried out on an outpatient basis. A significant advantage is that treatment with iodine-131 can be carried out without prior preparation with thionamides. In HD disease, when the goal of treatment is destruction of the thyroid gland, therapeutic activity, taking into account the volume of the thyroid gland, the maximum uptake and half-life of iodine-131 from the thyroid gland, is calculated based on the estimated absorbed dose of 200-300 Gy. Hypothyroidism usually develops within 6 months after administration of iodine-131.

A serious problem in domestic endocrinology is the virtual absence at the disposal of endocrinologists of such an excellent method of treating HD as iodine-131 therapy.

Conclusion

GD is one of the most common human autoimmune diseases. Its clinical picture and prognosis in most cases are determined by persistent thyrotoxicosis, which, in the absence of adequate treatment, can lead to severe disability of the patient. The current principles of treatment of HD, although not without shortcomings, can completely relieve the patient of thyrotoxicosis and ensure an acceptable quality of life.

Graves' disease is one of the most known diseases thyroid gland. In 1835, it was described by the American R. J. Graves. Other names for this thyroid pathology: Basedow's disease, diffuse toxic goiter, Flajani's disease.

In English-language medical literature, the term Graves' disease is most often used, in German sources - Graves' disease.

The average prevalence of diffuse toxic goiter in Russia is 0.1–0.2%. It is higher among residents of iodine-deficient regions. The peak incidence occurs between the ages of 20 and 40 years. Women suffer Graves' disease 7–8 times more often than men.

IN last years There is a persistent trend towards an increase in the incidence of diffuse toxic goiter.

This fact can be explained by several reasons:

accumulation of unfavorable genetic factors in the population;
changes in living conditions;
change in diet;
occupational hazard;
increased influence of solar radiation.

Etiology and pathogenesis of the disease

Diffuse toxic goiter is associated with certain genetic mutations. The initial pathology manifests itself under the influence of adverse effects ( viral infections, redundant sunlight, stress).

Graves' disease is caused by autoimmune inflammation. The aggression of the body's own defenses is directed against thyrocytes. The main target for diffuse toxic goiter is the TSH receptor. This structure is responsible for the perception by thyroid cells of the influence of the central endocrine organs (pituitary gland and hypothalamus). In Graves' disease, antibodies to the thyroid-stimulating hormone receptor are produced. They imitate the stimulating effects of the pituitary gland.

The result of this is an excessive increase hormonal function thyroid tissue. Thyroxine and triiodothyronine begin to be produced in obvious excess. High level of these hormones leads to the development of thyrotoxicosis.

Autoimmune inflammation in the thyroid gland is often combined with similar processes in other tissues. The most common combination is endocrine ophthalmopathy and Graves' disease.

Clinical picture of Graves' disease

Patient complaints are usually associated with changes in the psychological status and activity of the heart. Patients are concerned about sleep disturbance (insomnia), anxiety, tearfulness, aggressiveness, irritability, nervousness. From the outside circulatory system There may be an increase in heart rate, the development of atrial fibrillation, hypertension, shortness of breath, edema, and chest pain.

Graves' disease affects appetite. Because of this, many patients increase daily calorie content food more than doubled. Metabolism and thermal energy production are also increased, so patients with diffuse toxic goiter gradually lose weight. In severe cases, weight loss reaches 10–20%.

A characteristic symptom of diffuse toxic goiter is trembling in the hands. The tremor may be subtle. It intensifies if the patient closes his eyes.

The skin with Graves' disease is characterized by constant moisture. Patients sweat even in cold rooms.

The gastrointestinal tract in diffuse toxic goiter is unstable. Patients suffer from digestion: there may be heartburn, diarrhea, pain along the intestines.

The reproductive system is also affected by thyrotoxicosis. Symptoms of Graves' disease in this area can be considered disorders menstrual function, infertility, decreased sexual desire.

Long-term thyrotoxicosis affects mineral metabolism and provokes multiple caries and bone fractures.

Endocrine ophthalmopathy in Graves' disease

Eye damage with diffuse toxic goiter occurs in more than 50–70% of cases. Endocrine ophthalmopathy is associated with autoimmune damage to the retrobulbar (orbital) fatty tissue. Swelling in this anatomical area is extremely dangerous. It causes bulging eyes, that is, exophthalmos. The eye moves forward from the orbit, the closure of the eyelids, the activity of the muscular system, and the blood supply to the tissues are disrupted.

Specific symptoms of endocrine ophthalmopathy can be seen when examining the patient. Doctors pay attention to:

Dalrymple's sign (excessive opening of the palpebral fissure);
Stellwag's sign (rare blinking);
Graefe's sign (delayed upper eyelid when looking down);
Moebius symptom (no gaze fixation on a close object), etc.

In extreme cases, endocrine ophthalmopathy can lead to optic nerve damage and blindness. Damage to the eyes and orbital tissue in diffuse toxic goiter can be treated with medication (corticosteroids). Cosmetic defect can later be eliminated by a plastic surgeon.

Confirmation of Graves' disease

To diagnose the disease, a medical examination, blood tests, and ultrasound of the thyroid gland are used. In rare cases, it is additionally necessary to carry out radioisotope scanning, cytological examination, x-ray or computed tomography.

The main diagnostic criterion for Graves' disease is persistent thyrotoxicosis against the background of an enlarged thyroid gland.

Tests confirm thyrotoxicosis low level thyroid-stimulating hormone and high titers of thyroxine and triiodothyronine.

The autoimmune nature of the disease can be proven using tests for antibodies to the TSH receptor. The higher the antibody titer, the greater the severity of inflammation.

Ultrasound usually reveals a large volume of thyroid tissue, heterogeneity of its structure and increased blood supply.

Treatment of the disease

Treatment of Graves' disease begins with thyreostatics. These drugs block the synthesis of hormones in the thyroid gland. Their dose is gradually reduced to maintenance. Duration full course drug treatment is 12–30 months.

The effectiveness of conservative therapy for diffuse toxic goiter is about 30–35%. In other cases, dose reduction and drug withdrawal provoke a relapse of thyrotoxicosis. Such an unfavorable course of Graves' disease is an indication for radical treatment.

In order for surgery or radioisotope treatment to be successful, the patient needs careful preparation (examination, correction hormonal levels, therapy of concomitant diseases).

The outcome of radical treatment is most often hypothyroidism. This condition requires constant replacement therapy synthetic thyroxine.