Causes and treatment of Graves' disease. Are there any side effects of radioactive iodine therapy? What is Graves' disease and what is its cause

In endocrinological practice, such a pathology as Graves' disease is often encountered. This term is synonymous with . There is another name - diffuse toxic goiter. The latter refers to hypertrophy thyroid gland, which is an important organ. The thyroid gland produces special hormones that are involved in metabolic processes. What are the causes of the development and manifestation of Basedow's disease are described below.

Graves' disease is chronic illness non-infectious nature, in which there is a persistent increase in the synthesis of thyroxine and triiodothyronine. Pathology has an autoimmune etiology. Toxic goiter is so called because due to the increased secretion of thyroxine and triiodothyronine, poisoning of the body (thyrotoxicosis) is observed. This pathology occurs mainly in adults. In women, goiter is diagnosed much more often than in men. Most high rate incidence occurs between the ages of 30 and 50 years.

Often, Graves' disease is diagnosed in adolescents, the elderly, and pregnant women. Exact reasons disease progression has not been established. To possible etiological factors there is a hereditary predisposition, immune disorders, infectious pathologies. The relationship between the incidence rate and smoking has been established. To predisposing factors of development toxic goiter include injuries, inflammation of the substance of the brain, damage to the pituitary gland, adrenal glands. In some cases, the deviation is formed against the background of viral infections and chronic type tonsillitis.

Classification

Graves' disease can be mild, moderate, or severe. This division is based on the severity of thyrotoxicosis. At initial stage come to the fore neurotic disorders. heart function and endocrine glands does not suffer. Thyrotoxicosis medium degree severity is characterized by weight loss and severe tachycardia (up to 110 beats per minute).

The most severe is the 3rd degree of thyrotoxicosis. With it, there is an exhaustion of the patient and signs of damage to the vital important organs(heart, lungs, kidneys). WHO divides diffuse toxic goiter into 3 types. The basis is the degree of organ enlargement. The state of the gland is assessed by palpation and visually. At stage 0, the state of the gland is not changed. Transformations are detected by a blood test. At grade 1, goiter is determined during palpation, but there are no signs of deviations on external examination. In stage 2, neck deformity is often observed. The goiter can be huge.

signs

The symptoms of Graves' disease are determined by the degree of disruption in hormone production. The following subjective signs of the disease are distinguished:

• weakness;
• malaise;
• shortness of breath
• restlessness;
• anxiety;
• mood lability;
• depression
• sleep disturbance;
• nausea;
• decrease in visual acuity.

With development, the appearance of hallucinations, the occurrence of delirium (impaired consciousness), and arousal are possible. Symptoms of the disease are due to the following pathological processes on the background high concentration in the blood of thyroid hormones:

• enhanced breakdown of fats;
• intensive breakdown of proteins;
• increased sensitivity to adrenaline and norepinephrine;
• excessive heat production;
• exacerbation nerve impulses in the brain.

With thyrotoxicosis against the background of Graves' disease, almost all systems (nervous, cardiovascular, endocrine, digestive) suffer.

The main symptom of this pathology is an enlarged thyroid gland. Sometimes the goiter is completely absent. Always with diffuse toxic formation suffers the cardiovascular system. The pathology is characterized by the following symptoms:

• increased heart rate;
• violation heart rate;
• arterial hypertension;
• the presence of edema in the lower extremities;
• cough.

Neurological symptoms are also very common. With Graves' disease, there is an increase in tendon reflexes, trembling, impaired sensitivity, and muscle wasting. Patients find it difficult to change position. The skin and its appendages also suffer: brittle nails, hyperhidrosis, redness, and swelling are observed. With diffuse toxic goiter, the organs of vision often suffer. Such patients can be recognized by pronounced exophthalmos - omission lower eyelids and raising the upper, lacrimation, swelling around the orbits.

With absence curative measures there is a possibility of loss of vision. Often detected positive symptom Grefe. It is characterized by incomplete closure of the patient's eyelids. Often suffers sexual function and reduced body weight. In women, there may be a violation of the normal course menstrual cycle. Less common organ dysfunction digestive tract, which is manifested by a violation of the stool by the type of diarrhea, vomiting.

Treatment is prescribed by a doctor only after a complete laboratory and instrumental research. Differential Diagnosis carried out with the following diseases:

• pituitary adenoma;
• myocarditis;
• Hashimoto's disease;
• glands;
• nodular goiter.

If a patient is suspected of having Graves' disease, the following studies are carried out:

• Ultrasound of the thyroid gland;
• physical examination (palpation);
• a blood test for the content of T3 and T4;
• determination of thyroid-stimulating hormone in the blood;
• detection of antibodies by ELISA.

With diffuse toxic goiter, a blood test reveals a decrease in the concentration of T3 and T4 and an increase in the content of TSH. If necessary, a radionuclide study and a test with thyrotropin-releasing hormone are performed. Of great importance in the formulation of the correct diagnosis are the symptoms of the disease.

Treatment

Treatment of this endocrine pathology can be conservative or surgical. The first method involves the use of drugs that suppress the synthesis of thyroid hormones (Mercazolil, Thiamazole, Methylthiouracil), and symptomatic remedies. Mercazolil should not be used during gestation and breastfeeding baby, leukopenia, granulocytopenia and individual intolerance to the drug. AT severe cases and with a developed crisis, beta-blockers and glucocorticoids are used.

If you have trouble sleeping, your doctor may prescribe sedatives. Treatment with Mercazolil and its analogues is carried out by a long course. You need to take medicines constantly according to the scheme indicated by the doctor. Self-medication is unacceptable. Modern method elimination of Graves' disease and other pathologies of this organ is radioisotope therapy. Similar treatment organized only within the walls of a specialized institution.

The patient takes capsules containing radioactive iodine. The latter contributes to the irradiation of the gland. After a course of therapy, the synthesis of hormones is normalized. This method is non-invasive, effective and harmless. Treatment radioactive iodine Not suitable for pregnant and lactating women. Therapy of the former is carried out with Propylthiouracil at a low dose.

If it is impossible to use drugs and a large goiter with neck deformity and dysfunction of the heart, surgical treatment is performed.

During the operation, the iron is removed. Surgery carried out only after the normalization of the patient's condition, otherwise there is a risk of developing a crisis as a result of the intervention.

Thus, diffuse toxic goiter is a very common endocrine disease.

Graves' disease (or diffuse toxic goiter) belongs to the group of endocrine autoimmune pathologies affecting the thyroid gland. For certain reasons, the thyroid tissue produces aggressive cells (antibodies), leading to diffuse damage to the tissue of the glandular organ, to the formation of seals and increased production of hormones.

This disease was studied and thoroughly described by the American George Graves (1835). In Russia this pathology more often called Basedova in honor of the German practitioner Karl Adolf von Basedow (1840).

The process of hypertrophy and hyperfunction of the thyroid gland leads to the development of thyrotoxicosis, that is, to hormone intoxication. Pathology ranks first among endocrine diseases.

According to statistical studies, women are more often ill than men. Age for this pathology also has great importance, apparently, this is due to puberty or with a decline in the hormones of the reproductive system.

It is the age from 18 to 43 years that is acceptable for the development of diffuse toxic goiter. The pushing factor is iodine deficiency in drinking water.

Thyrotoxicosis is common in Russia in iodine-deficient regions as North Caucasus, Ural, Altai, Volga region and Far East. Lack of iodine in water bodies exists in the northern part of the Russian Federation and Siberia.

Over the past 5 years, there has been a slight shift towards an increase in the incidence. This fact is explained as follows: elevated level toxic substances in air, ground or water, permanent stressful situations, the use of fast food and products containing a large number of preservatives and substances of group E, increased radiation background and frequent solar perturbations.

Etiopathogenesis of the disease

Graves' disease can be associated with a number of pathologies that cause genetic mutations in the form of clone or killer cells. Autoimmune aggression destroys one's own thyroid tissue, the main target of which is thyroid-stimulating hormone (TSH) receptors.

They function as recognizers of pituitary and hypothalamus hormones. It is they who affect the quantitative reproduction of TSH, and their antibodies disrupt the balance of production and contribute to excessive stimulation and an excessive increase in thyroxine and triiodothyronine.

As a result of these actions, intoxication begins in the body with damage to organs and systems. An autoimmune reaction leads to the development of goiter and ophthalmopathy. To start a pathological chain for the production of clones that destroy their own tissue, certain conditions are needed.

List of causes contributing to the development of toxic goiter:

• hereditary factor;
• Chronic infectious and viral diseases;
• Stress of any etiology;
• Traumatization of the skull;
• throat pathology;
• Neoplasms of benign and malignant etiology;
• Blood diseases;
• Radiation sickness;
• Poisoning with pesticides;
• Infectious and inflammatory processes in the body.

Risk factors for the development of autoimmune diffuse goiter are multiple sclerosis, leukemia, diabetes, hepatitis type B and C, as well as pregnancy, anemia and low background immune system. Medicinal substances (Insulin, Interferon Alpha, Leukeran) and procedures (radiation and radioisotope therapy) used in a schematic therapeutic tactic of these pathologies can provoke Basedow's disease.

As for the pregnant condition of a woman: during the gestation of the fetus, autoimmune reactions may occur, perceiving the fetus as a "foreign invasion", the primary reaction begins with the thyroid gland.

Symptomatic picture

Graves' disease, the symptoms of which begin with a change in the size of the gland and feeling foreign body in the throat, begins with complaints of unbearable irritability and cardiac arrhythmia.

Full list of symptoms:

HYPERTHYROISIS SYNDROME

At present, there is no generally accepted classification of various diseases of the thyroid gland (TG). The leading endocrinologists of the world, including Russia, lay the basis for various types of thyroid diseases on the syndromic principle, which reflects certain (quantitative and qualitative) disorders of the functioning of the thyroid gland, accompanied by a variety of metabolic, structural and functional changes. various levels organization of the body. Features of the location, structure, physiology, metabolism, effects of action and biological significance of thyroid hormones produced by the gland are presented in the previous chapter on the syndrome of hypothyroidism.

Hyperthyroidism syndrome (thyrotoxicosis) is a collective term that includes various clinical conditions of the body, characterized by excessive production (mainly by the thyroid gland) of thyroid hormones (thyroxine and triiodothyronine), an increase in their content in various biological media (including blood) and biological action.

Thyrotoxicosis is always accompanied by toxic changes in various cellular and tissue structures of the body, due to an excess of thyroid hormones.

Separate symptoms of thyrotoxicosis were described as early as 1802 in Italy by Flaiani, and in 1825 in England by Caleb Pari. The clinical signs of hyperthyroidism were described in more detail in 1835 in England by Robert Graves and in 1840 in Germany by Carl von Basedow. In Russia, the term "diffuse toxic goiter" has become entrenched and is widely used. However, this term has several disadvantages. Firstly, this term lacks the necessary word disease (general, systemic suffering of the body); secondly, the term "diffuse goiter" reflects only a macroscopic change ( diffuse magnification) thyroid (which is not always the case with this disease); thirdly, the term "toxic" reflects only a functional and biochemical change (which, together with a macroscopic diffuse change, is not obligate for Graves-Basedow-Flyani disease, but may also occur in other diseases).

Among the various forms of pathology, which are based on thyrotoxicosis, diffuse toxic goiter or Graves-Basedow-Flyani disease is the most common (about 80%).

This disease affects from 0.5 to 2% of the population of developed countries. Women get sick 8-10 times more often than men. The disease occurs at any age, but the peak incidence occurs between 30-50 years of age (i.e., young and mature age).

The disease is rare in children and the elderly. In regions with normal iodine intake, the disease develops in 2% of women. In representatives of the European and Asian races, the incidence of Graves-Basedow's disease is the same. In persons of the Negroid race, it is lower. Frequency of new cases this disease is 3 per 1000 women.

In Russia, due to the existing iodine deficiency, almost throughout the entire territory of the Russian Federation, multinodular toxic goiter and thyrotoxic adenoma are quite common.

Screening of a "healthy" population over the age of 60, conducted in the United States, revealed thyrotoxicosis in 2.3% of men and 5.9% of women.

Classification of thyrotoxicosis

Thyrotoxicosis syndrome is caused by a variety of reasons, has a variety of mechanisms of development and clinical forms.

Pathogenetic and clinical classification thyrotoxicosis syndrome.

Thyrotoxicosis due to increased production of thyroid hormones:

1. Graves' disease - Basedow.

2. Multinodular toxic goiter

3. Toxic adenoma (Palmer's disease).

4. Iodine-induced thyrotoxicosis.

5. TSH-conditioned thyrotoxicosis (TSH - thyroid-stimulating hormone):

TSH-producing pituitary adenoma;

Syndrome of resistance of thyrotrophs to thyroid hormones.

Thyrotoxicosis due to the production of thyroid hormones outside the thyroid gland:

1. Chorionepithelioma.

2. Functioning metastases follicular cancer thyroid.

3. Ectopic goiter (ovarian tumor producing thyroid hormones - struma ovarii).

Thyrotoxicosis, not associated with hyperproduction of thyroid hormones:

1. Medication (iatrogenic, due to an overdose of thyroid drugs).

2. Thyrotoxicosis in the form of the following types of thyroiditis:

Subacute de Quervain's thyroiditis, first 2 weeks;

Hyperthyroid stage autoimmune thyroiditis- Chasitoxicosis phase;

Painless and postpartum thyroiditis.

3. Due to radiation thyroiditis.

4. Caused by the intake of non-thyroid medications (amiodarone, a-interferon).

5. Due to the increased sensitivity of tissues to thyroid hormones.

According to the severity of the course, the following forms of thyrotoxicosis are distinguished:

(subclinical), medium (manifestant), severe (marantic).

The state of "subclinical (mild) thyrotoxicosis" is defined mainly as subnormal (below the lower limit of normal) or "oppressed" TSH content with normal or slightly elevated levels of triiodothyronine (T3) and thyroxine (T4) in the blood serum. It should also be borne in mind that a decrease in the content of TSH in the blood serum, determined by sensitive methods, may be caused by other reasons (for example, the use of glucocorticoids, various chronic diseases, dysfunction of the pituitary gland).

With a mild form of the disease (subclinical thyrotoxicosis), the following are noted:

1) a slight decrease in body weight (no more than 10% of the initial value), usually with increased appetite; 2) moderate tachycardia (up to 100 beats per minute); 3) the occurrence of minor neurovegetative disorders (increased emotional lability, sweating of the skin, especially the skin of the palms, sleep disturbance, etc.); 4) the appearance of periodic slight trembling of the fingers of outstretched hands; 5) no signs of circulatory failure; 6) no increase in pulse pressure; 7) absence of malfunctions.

With moderate severity of the disease (manifestant thyrotoxicosis), the following are found:

1) moderate weight loss (up to 20% of the initial value) against the background of increased appetite; 2) severe tachycardia (ranging from 100 to 120 beats / min, not only during the day, but also at night); 3) strengthening of neurovegetative disorders (manifested by significant emotional lability, sweating of the body, especially the skin of the palms, sleep disorders, etc.); 4) the development of a pronounced small-scale trembling of the fingers, especially high

hands stretched forward; 5) the occurrence of some signs of circulatory failure; 6) the presence of an increase in pulse pressure; 7) development of working capacity disorders.

With severe severity of the disease (marantic thyrotoxicosis), the following are observed:

1) a significant decrease in body weight (more than 20% of the initial value) with a pronounced increase in appetite; 2) pronounced tachycardia (exceeding 120 beats / min, not only during the day, but also at night); 3) significant and growing neurovegetative disorders (dramatically increased irritability, excitability, weakness of internal inhibition processes in the central nervous system, a pronounced violation of the duration and quality of sleep, hyperhidrosis of the body, especially the skin of the palms); 4) mental (psychopathic) disorders; 5) a pronounced and growing trembling not only of the fingers, but also of the head and the tongue protruding from the mouth, as well as the body; 6) increased circulatory failure; 7) Appearance atrial fibrillation hearts; 8) thyroid relative adrenal insufficiency; 9) the development of not only myopathy, but also ophthalmopathy, and even hepatopathy; 10) sharply pronounced violations both physical and mental performance.

2. Characteristics of Graves' disease - Basedow

Graves-Basedow's disease, or diffuse toxic goiter, according to modern concepts, is understood to be an organ-specific autoimmune disease that develops with a defect in the immunological control system and is caused by excessive secretion of thyroid hormones, usually by a diffusely enlarged thyroid gland.

Etiology of Graves-Basedow's disease. This disease is considered multifactorial. Of great importance in its etiology belongs to a variety of pathogenic (disturbing) physical, chemical and biological factors that have a strong and long-term effect on the body, and especially negative psychosocial and psychoemotional influences.

It is well known that when emotional stress, especially in distress, the secretion of the hormones of the adrenal medulla - adrenaline and norepinephrine, which increase the rate of synthesis and secretion of thyroid hormones, increases significantly. On the other hand, under stress, the hypothalamic-pituitary-corticoadrenal system is activated, which is accompanied by an increase in the secretion of adrenocorticotropic hormone, cortisol and TSH, which can serve as a starting point in the mechanism of the development of Graves-Basedow disease.

There is also evidence that emotional overstrain contributes to the development of the disease by negatively affecting the body's immune system. It has been established that intense emotional stress leads to hypo- and even atrophy of the thymus gland, reduces the formation of antibodies, reduces the concentration of interferon in the blood serum, increases the predisposition to infectious diseases, increases the incidence of autoimmune diseases and cancer.

Initiation of the formation of antibodies to the TSH receptor can also be facilitated by some viruses and bacteria, in particular Yersinia enterocolitica, which has the ability to specifically complex with TSH. In addition to Yersinia enterocolitica, other bacteria, such as mycoplasma, also have a protein structure (TTT-like receptor) that is able to complex with TSH, which initiates the formation of antibodies to the TSH receptor.

In the etiology of the onset of Graves-Basedow's disease, overstrain and disruption of higher nervous activity, disorders of various regulatory systems (including the immune system) can play a certain role. Recently, great importance has been given to the genetic predisposition to the development of this disease (in particular, the carriage of HLA-B8, HLA-DR3, HLA-DQA1 * 0501 in Europeans has been proven). The detection of circulating autoantibodies in 50% of relatives of patients with Graves-Basedow disease also indicates a genetic predisposition.

A very significant place in the development of this disease belongs to various risk factors. For example, according to I. I. Dedov, G. A. Melnichenko and V. V. Fadeev (2009), only smoking increases the risk of developing this disease by 1.9 times, and the risk of developing endocrine ophthalmopathy against the background of an already existing disease - 7.7 times.

Often, Graves-Basedow's disease is combined with other autoimmune forms of pathology (type 1 diabetes mellitus, primary hypocorticism, etc.), which is considered as type II autoimmune polyglandular syndrome.

In Graves-Basedow's disease, combined with endocrine ophthalmopathy, an increase in the frequency of the HLA-B8, HLA-DR3 and HLA-Cw3 ​​genes was revealed.

Clinical manifestations of Graves-Basedow disease. The clinical picture of this disease is very variable, depending on its severity. In particular, it varies from obliterated (monosymptomatic) variants to extremely well-defined forms with an obvious diagnosis at first glance (mainly due to the combination of exophthalmos with severe weight loss and tremor). The latter are especially common in the manifest and marantic forms of the disease, especially in adulthood and old age.

Patients with Graves-Basedow's disease complain of general weakness, increased irritability, nervousness, mild irritability, sleep disturbances (up to insomnia), sweating, poor tolerance for elevated ambient temperature, palpitations, sometimes pain in the region of the heart of a stabbing or squeezing nature, diarrhea, increased appetite and weight loss.

In Graves-Basedow's disease, in most cases there are characteristic eye symptoms that develop as a result of a violation of the autonomic innervation of the eyes. palpebral fissures widely dilated, which gives the impression of an angry, surprised or frightened look (Delrymple's symptom). Characterized by rare blinking (Stelwag's symptom) and increased pigmentation of exposed parts of the body, especially the eyelids (Jellinek's symptom), as a rule, are noted with a long and severe course of the disease. When looking down, the upper eyelid lags behind the iris, and therefore a portion of the sclera appears between the lower eyelid and the iris (Kocher's symptom). A violation of the convergence of the eyeballs is also detected, i.e., the ability of the eyes to fix the gaze at a close distance is lost (Mobius symptom). The development of these symptoms is associated with an increase in the tone of smooth muscle fibers involved in both lifting upper eyelid, and in the lowering of the lower eyelid, innervated by the sympathetic nervous system. There is also a lack of wrinkling of the forehead when looking up (Geoffroy's symptom).

In most cases, there is a protrusion of the eyeballs - exophthalmos, the degree of which can be determined using an ophthalmometer.

The protrusion of the eyeball from the level of the orbit in healthy people is 12-14 mm. In Graves' disease - Graves' disease, the protrusion (protrusion) of the eye increases by 2 or more times.

Often, this disease is accompanied by endocrine ophthalmopathy and pretibial myxedema (swelling, thickening and hypertrophy of the skin of the anterior surface of the lower leg). Very rarely, acropathy is detected (periosteal osteopathy of the feet and hands, radiographically resembling "soap foam").

The development of clinical signs of Graves-Basedow's disease is associated with excessive secretion of thyroid hormones and their effect on various metabolic processes and functions of various organs and tissues. In particular, such characteristic changes are noted in the body as an increase in oxygen consumption, basal metabolism, and heat generation (calorigenic action).

Most of the effects of excess thyroid hormone are mediated through activation of the sympathetic nervous system: tachycardia, tremor of fingers, tongue, entire body (symptom of "telegraph pole"), sweating, irritability, anxiety and fear.

Violations of the cardiovascular system are manifested in the form of tachycardia (the pulse even during the period of night sleep is more than 80 per minute), an increase in systolic and a decrease in diastolic blood pressure (accompanied by an increase in pulse pressure), attacks of atrial fibrillation, the appearance of its permanent form with the development of heart failure . The heart sounds are loud, a systolic murmur is heard at the apex of the heart.

The electrocardiogram reveals: different types sinus arrhythmia(especially sinus tachycardia), high voltage of the teeth, acceleration or deceleration of atrioventricular conduction, negative or biphasic T wave, attacks of atrial fibrillation (especially in the elderly). The presence of the latter presents a certain difficulty in diagnosing the disease. It should be noted that the clinical manifestations of heart failure that occur in Graves-Basedow disease are difficult to treat with digitalis preparations. It is important to emphasize that in the period between attacks, the general condition of patients can even be satisfactory, and the number of heartbeats is within the normal range.

Increased generation of heat in the body of patients occurs due to the activation of metabolic (mainly catabolic) processes due to an excess of thyroid hormones, usually leads to an increase in body temperature: patients feel a constant feeling of heat, sleep under one sheet at night (“sheet symptom”),

Most patients have increased appetite (in the elderly, appetite may be reduced), thirst, digestive tract dysfunction, diarrhea, moderate liver enlargement (in some cases, even slightly pronounced jaundice is detected), and an increase in aminotransferase activity in the blood.

Catabolic syndrome, manifested by progressive weight loss of patients (depending on the duration and severity of the disease), they lose weight either quickly or slowly by 5-10-15 or more kg, especially when they had initially overweight. In severe cases, not only the subcutaneous fat layer disappears, but also the volume of muscles decreases.

Muscle weakness develops due not only to protein catabolism, but also to damage to the peripheral nervous system. With this disease, weakness of the muscles, especially of the proximal extremities (thyrotoxic myopathy), is revealed.

Under the influence of an excess of thyroid hormones, significant changes are observed in bone tissue, manifested by the catabolism of its proteins. The result of the latter is the development of osteoporosis. An excess of thyroid hormones contributes to decompensation of the disturbed carbohydrate metabolism up to the development of diabetes mellitus. Deep tendon reflexes are increased. A tremor of outstretched fingers is detected, sometimes to such an extent that patients can hardly fasten buttons, handwriting changes and the “saucer” symptom is characteristic (when holding a saucer with an empty cup, a rattling sound is made as a result of a small tremor of the hands).

CNS dysfunction is characterized by irritability, anxiety, irritability, mood lability, loss of the ability to concentrate (the patient often switches from one thought to another), sleep disturbance, sometimes depression, and even mental reactions. True psychoses are rare.

Disorders of the function of the gonads are manifested in the form of oligo- or amenorrhea, reduced fertility. In men, gynecomastia is noted (as a result of a violation of the exchange of sex hormones in the liver and changes in the biological environment of the ratio of estrogens and androgens). Patients have reduced libido and potency.

With Graves-Basedow's disease, a thyrotoxic crisis can even develop, which is considered as an urgent clinical syndrome, which is a combination of severe thyrotoxicosis and thyroid adrenal insufficiency. The main reason for its occurrence is considered to be inadequate thyreostatic therapy. The provoking factors of this crisis are surgery, infectious and other diseases. Clinically, a thyrotoxic crisis is manifested by severe mental anxiety up to psychosis, motor hyperactivity, alternating apathy and disorientation, hyperthermia (up to 40 ° C), suffocation, pain in the heart, abdominal pain, nausea, vomiting, acute heart failure, hepatomegaly, thyrotoxic coma .

The pathogenesis of Graves-Basedow's disease. The pathogenesis of this disease is hereditary predisposition, autoimmune reactions, the formation of "thyroid-stimulating" globulins, causing thyroid hyperplasia with increased production of thyroid hormones (T3 and T4). The main link in the pathogenesis of Graves-Basedow's disease is determined by increased production of stimulating autoantibodies to TSH receptors (AT-rTTH), usually resulting from a congenital defect in the immune system (impaired immunological tolerance). According to R. Wolpe, the defect in specific T-suppressors plays a major role in the genesis of Graves-Basedow's disease. In this regard, the resulting autoreactive lymphocytes (CD4+ CD8+ T-lymphocytes and B-lymphocytes) with the participation of various adhesive molecules (ICAM-1, E-selectin, CD44, etc.) infiltrate the thyroid parenchyma. Here they recognize antigens formed as a result of damage to various structures of the thyroid gland, which are presented by different cells (macrophages, B-lymphocytes, T-lymphocytes). Subsequently, with the help of cytokines and signaling molecules, antigen-specific stimulation of B-lymphocytes is initiated, transforming into plasma cells responsible for the production of specific immunoglobulins against various pathologically altered components of thyrocytes.

However, unlike many other autoimmune diseases, in Graves-Basedow's disease, there is no oppression (destruction), but stimulation of the target organ. This is accompanied by increased production of autoantibodies to fragments of TSH receptors that are not located on the membranes of thyrocytes. After interacting with specific autoantibodies, these TSH receptors are activated and trigger a post-receptor cascade of mechanisms responsible for both increased synthesis of thyroid hormones in thyrocytes and hypertrophy of the latter.

Clinically most significant syndrome developing in Graves-Basedow's disease is thyrotoxicosis, manifested by an increase in metabolism, the development of dystrophic changes in many tissues and organs, especially in those structures in which there is high density thyroid receptors (myocardium, nervous tissue and etc.).

Pathological changes in the body. Morphological changes in Graves-Basedow disease are very diverse. The leading morphological features of this disease are: 1) diffuse hyperplastic processes in the thyroid epithelium (an indicator of its increased morphological and functional activity); 2) the formation of new follicles in the gland and the development of papillary outgrowths in some of them (different both in shape and size); 3) the presence of a "liquid" state of the colloid (an indicator of enhanced excretion of thyroid hormones from the thyroid gland).

Hyperplastic processes in the thyroid gland are not only diffuse, but also focal. Foci of increased proliferation in the gland can lead to the formation of nodes and the development of nodular toxic goiter. The structure of the node is determined by the nature of the proliferation of the epithelium and the degree of accumulation of the colloid. Allocate different kinds nodular toxic goiter: 1) papillary or cytopapillary adenoma, 2) follicular adenoma, 3) adenoma from Askanazi-Gurtle cells.

In Graves-Basedow's disease in the thyroid gland, along with hyperplastic processes in the parenchymal tissue, pronounced dystrophic processes in her stroma. The latter are accompanied by the appearance and growth of connective tissue, often combined with hyalinosis and calcification. In addition, lymphoid and plasmacytic infiltration with the formation of lymphoid follicles is noted in the thyroid stroma.

In parenchymal organs, dystrophic changes, areas of necrosis and sclerotic changes are found. A dystrophic process also develops in the heart muscle, which may end in the development of myocardiosclerosis. The phenomena of fatty degeneration of the liver with a clinic of toxic hepatitis are found. From the side of the central nervous system, pathomorphological changes develop mainly in the diencephalon and medulla oblongata. In severe cases, atrophic changes in the adrenal cortex and gonads are noted.

Graves' disease (or diffuse toxic goiter) belongs to the group of endocrine autoimmune pathologies that affect the thyroid gland. For certain reasons, the thyroid tissue produces aggressive cells (antibodies), leading to diffuse damage to the tissue of the glandular organ, to the formation of seals and increased production of hormones.

This disease was studied and thoroughly described by the American George Graves (1835). In Russia, this pathology is often called Basedova in honor of the German practitioner Karl Adolf von Basedow (1840).

The process of hypertrophy and hyperfunction of the thyroid gland leads to the development of thyrotoxicosis, that is, to hormone intoxication. Pathology ranks first among endocrine diseases.

According to statistical studies, women are more often ill than men. Age for this pathology is also of great importance, apparently, this is due to puberty or a decline in the hormones of the reproductive system.

It is the age from 18 to 43 years that is acceptable for the development of diffuse toxic goiter. The pushing factor is iodine deficiency in drinking water.

Thyrotoxicosis is common in Russia in iodine-deficient regions such as the North Caucasus, the Urals, Altai, the Volga region and the Far East. Lack of iodine in water bodies exists in the northern part of the Russian Federation and Siberia.

Over the past 5 years, there has been a slight shift towards an increase in the incidence. This fact is explained by the following: an increased level of toxic substances in the air, soil or water, constant stressful situations, the use of fast food and products containing a large amount of preservatives and group E substances, an increased background radiation and frequent solar perturbations.

Etiopathogenesis of the disease

Graves' disease can be associated with a number of pathologies that cause genetic mutations in the form of clone or killer cells. Autoimmune aggression destroys one's own thyroid tissue, the main target of which is thyroid-stimulating hormone (TSH) receptors.

They function as recognizers of pituitary and hypothalamus hormones. It is they who affect the quantitative reproduction of TSH, and their antibodies disrupt the balance of production and contribute to excessive stimulation and an excessive increase in thyroxine and triiodothyronine.

As a result of these actions, intoxication begins in the body with damage to organs and systems. An autoimmune reaction leads to the development of goiter and ophthalmopathy. To start a pathological chain for the production of clones that destroy their own tissue, certain conditions are needed.

List of causes contributing to the development of toxic goiter:

• hereditary factor;
• Chronic infectious and viral diseases;
• Stress of any etiology;
• Traumatization of the skull;
• throat pathology;
• Neoplasms of benign and malignant etiology;
• Blood diseases;
• Radiation sickness;
• Poisoning with pesticides;
• Infectious and inflammatory processes in the body.

Risk factors for the development of autoimmune diffuse goiter are multiple sclerosis, leukemia, diabetes mellitus, type B and C hepatitis, as well as pregnancy, anemia, and a reduced immune system. Medicinal substances (Insulin, Interferon Alpha, Leukeran) and procedures (radiation and radioisotope therapy) used in a schematic therapeutic tactic of these pathologies can provoke Basedow's disease.

As for the pregnant condition of a woman: during the gestation of the fetus, autoimmune reactions may occur, perceiving the fetus as a "foreign invasion", the primary reaction begins with the thyroid gland.

Symptomatic picture

Graves' disease, whose symptoms begin with a change in size of the gland and a feeling of a foreign body in the throat, begins with complaints of unbearable irritability and cardiac arrhythmia.

Full list of symptoms:

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

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

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

AT 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;
• changing living conditions;
• change in diet;
• professional hazard;
• increasing the influence of solar radiation.

Etiology and pathogenesis of the disease

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

Graves' disease is based on autoimmune inflammation. Aggression own defensive forces organism is directed against thyrocytes. The main target in diffuse toxic goiter is the TSH receptor. This structure is responsible for the perception by the cells of the thyroid gland of the influence of central endocrine organs(pituitary and hypothalamus). In Graves' disease, antibodies to the thyroid-stimulating hormone receptor are produced. They mimic the stimulating effect of the pituitary gland.

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

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

Clinical picture of Graves' disease

Complaints of patients 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 side circulatory system there may be an increase in heart rate, the development of atrial fibrillation, hypertension, shortness of breath, edema, chest pain.

Graves' disease affects appetite. Because of this, many patients increase daily calorie content food more than doubled. Metabolism and production of thermal energy 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 in Graves' disease is characterized by constant moisture. Patients sweat even in cold rooms.

The gastrointestinal tract with 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 violations menstrual function, infertility, decreased sexual desire.

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

Endocrine ophthalmopathy in Graves' disease

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

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

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

AT extreme cases endocrine ophthalmopathy can lead to damage to the optic nerve and blindness. Damage to the eyes and fiber of the orbit in diffuse toxic goiter is amenable to drug treatment (corticosteroids). cosmetic defect in the future, it can 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. AT rare cases additionally, radioisotope scanning should be carried out, cytological examination, x-ray or computed tomography.

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

Thyrotoxicosis in the analyzes confirms low level thyroid-stimulating hormone and a high titer of thyroxine and triiodothyronine.

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

On ultrasound, a large volume of thyroid tissue, heterogeneity of its structure and increased blood supply are usually observed.

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.

Efficiency conservative therapy 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 the operation or radioisotope treatment to be successful, the patient needs careful preparation(examination, correction hormonal background, treatment of concomitant diseases).

Hypothyroidism is the most common outcome of radical treatment. This condition requires constant replacement therapy synthetic thyroxine.