Taking into account the wide prevalence of cases of impaired thyroid function, in particular, thyrotoxicosis, and the high frequency of occurrence in practice, doctors of various specialties remain interested in this pathology.

Diseases accompanied by a violation of the function of the thyroid gland reduce the efficiency and worsen the quality of life of patients. There are about 200 million such patients in the world. The condition characterized as hyperfunction is represented by thyrotoxicosis syndrome.

Thyrotoxicosis (hyperthyroidism) is a syndrome, the presence of which is associated with an increased content of thyroid hormones in the blood, which occurs in various diseases or exogenous excess intake of thyroid hormones. Thyrotoxicosis is observed in diffuse toxic goiter, multi-node toxic goiter, thyrotoxic adenoma, subacute thyroiditis (the first 1-2 weeks), postpartum (mute) thyroiditis, autoimmune thyroiditis (its hyperthyroid phase – “hasitoxicosis”), thyroiditis that developed after exposure to ionizing radiation, thyrotropinoma, unregulated TSH secretion syndrome, follicular thyroid cancer and its metastases, with ectopic goiter (ovarian struma), excessive iodine intake (iodine-basedova disease), trophoblastic tumors secreting chorionic gonadotropin, iatrogenic and “artificial or conditional” thyrotoxicosis.

The most common cause of thyrotoxicosis is diffuse toxic goiter-it accounts for 80% of all cases of thyrotoxicosis.

At the same time, the incidence of diffuse toxic goiter is from 1 to 2 cases per 1000 people. 2.7% of women and 0.2% of men had or are suffering from diffuse toxic goiter.

The most common diffuse toxic goiter occurs in women aged 30 to 60 years, but people of both sexes (both infants and elderly people) are ill.

This disease was first described in 1825 by Caleb Parry, in 1835 – by Robert Graves, in 1840 – by Karl von Bazedov. Historically, the name of this pathology is common in English – speaking countries – “Graves ‘ disease”, in German – speaking countries – “Bazedov’s disease”. In Russia, the term “diffuse toxic goiter”is traditionally used.

Diffuse toxic goiter (DTZ) is a disease that develops in people with a certain hereditary predisposition. The pathogenesis of increased synthesis of thyroid hormones and thyroid hyperplasia in DTZ is due to autoimmune mechanisms.

The main role in the development of diffuse toxic goiter is played by genetic predisposition; the type of inheritance, according to modern concepts, is polygenic. The genes of the HLA system, as well as other genes located outside the histocompatibility locus, which are involved in the inheritance of autoimmune thyroid diseases, play a role in the inheritance of this disease.

Infiltration of lymphocytes stimulates the proliferation of thyrocytes, which leads to an increase in the size of the gland and the development of the goiter itself.

B-lymphocytes are involved in the formation of autoantibodies to various thyroid antigens, including thyroid-stimulating antibodies. The interaction of thyroid-stimulating antibodies with the thyroid-stimulating hormone receptor (TSH) leads to an increase in the synthesis and release of thyroid hormones into the blood, similar to the effects that occur when TSH and the TSH receptor are combined. These antibodies bind to the TSH receptor, bring it into an active state, triggering intracellular systems (cascades of cAMP and phosphoinositols), which stimulate the capture of iodine, the synthesis and release of thyroid hormones, as well as the proliferation of thyrocytes. There is a proliferation and growth of follicular cells.

Some other factors may contribute to the initiation of DTZ. These are stress, smoking (smoking increases the risk of developing diffuse toxic goiter by 1.9 times), as well as radiation, a previous infection caused by certain bacterial agents that can induce molecular mimicry.

Of course, based on the available modern data, the leading role in the development of DTZ is assigned to autoimmune mechanisms due to hereditary predisposition.

The role of mental trauma and emotional stress in the development of the disease has been repeatedly emphasized in the literature on DTZ. However, this assumption is currently disputed. Moreover, epidemiological studies conducted in various countries do not confirm that emotional stress can play an etiological role in the development of DTZ.

Nevertheless, it should be borne in mind that under stress, the secretion of adrenal medulla hormones (adrenaline and norepinephrine) increases, which, as is known, increase the rate of synthesis and secretion of thyroid hormones. On the other hand, stress activates the hypothalamic-pituitary system, increases the secretion of cortisol, TSH, which can serve as a trigger – a trigger moment in the mechanism of DTZ development. According to most researchers, emotional stress is involved in the development of DTZ by affecting the body’s immune system. It has been established that emotional stress leads to 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 frequency of autoimmune diseases and cancer.

The sympathetic nervous system, which has adrenergic receptors on capillaries that are closely in contact with the membranes of thyroid follicles, can participate in changing biogenic amines or change individual proteins that are components of the membrane. In an organism with a compromised immune system, such repeated changes can cause various autoimmune reactions. In the Russian literature, stress is given a place as a factor contributing to the realization of a genetic predisposition to the development of DTZ.

The clinical picture of thyrotoxicosis and, in particular, DTZ is very characteristic.

So, more than 170 years ago, Robert Graves vividly described the picture of thyrotoxicosis in his article. He presented a description of three cases of palpitations in women with an enlarged thyroid gland, linking these symptoms with each other. In particular, a 20-year-old woman developed symptoms similar to those of hysteria: after being in a nervous state, she noticed that her pulse became rapid, then weakness appeared, she became pale and thin. This pattern was observed during the year, the eyeballs increased, the whites of the eyes were visible to a considerable depth around the entire circumference of the iris.

Patients with DTZ complain of general weakness, increased irritability, nervousness and mild excitability, sleep disorders, sometimes insomnia, sweating, poor tolerance to elevated ambient temperature, tremor, palpitations, sometimes pain in the heart area of a stabbing or compressing nature, increased appetite and despite this-weight loss, diarrhea.

However, patients often present non-specific complaints: fatigue, sleep disorders, chest pain. Sometimes there is an atypical picture, there are symptoms that are not characteristic of thyrotoxicosis in its classical description. There may be an increase in body weight, anorexia, nausea, vomiting, urticaria, headache.

The clinical picture of DTZ is primarily characterized by the presence of symptoms of thyrotoxicosis: an increase in the size of the thyroid gland, as well as the development of ophthalmopathy in a large number of patients.
The thyroid gland is usually diffusely enlarged, but the degree of enlargement of the thyroid gland does not correspond to the severity of thyrotoxicosis. In most cases, the gland is diffusely enlarged, with palpation of a tight-elastic consistency, painless. The magnification may not be symmetrical. In men with a pronounced clinical picture of thyrotoxicosis, in some cases, there may not be a significant increase in the size of the gland, which is palpated with difficulty, the increase is mainly due to the lateral lobes tightly adjacent to the trachea.

The development of the clinical picture of thyrotoxicosis is associated with the influence of thyroid hormones circulating in the blood on various organs and tissues that cause violations of the functioning of the latter. In particular, there is a disconnection of oxidative phosphorylation, a violation of thermoregulation, and an increase in oxygen consumption by body tissues.

An important clinical, and in severe cases, a prognostic factor is the defeat of the cardiovascular system. Changes in the cardiovascular system are caused by an excess of the action of thyroid hormones on the heart muscle, which causes a violation of intracellular processes and leads to the formation of myocardiodystrophy syndrome. Disorders of the cardiovascular system are manifested in the form of constant sinus tachycardia, extrasystole, paroxysmal, possibly permanent form of atrial fibrillation, in an increase in systolic and a decrease in diastolic blood pressure (high pulse pressure), the development of heart failure is possible, especially in the elderly. At the same time, clinical manifestations of heart failure do not respond well to therapy with digitalis preparations.

The violation of thermoregulation that occurs with thyrotoxicosis due to an increase in metabolism leads to an increase in body temperature, patients note a constant feeling of heat, and also due to the increased and inefficient consumption of oxygen by tissues, there is a feeling of lack of fresh air.

The skin of the patients is warm to the touch, moist, the skin vessels are dilated. There may be the appearance of urticaria, hyperpigmentation of the folds, increased sweating, brittle nails, hair loss.
In patients with a typical course of thyrotoxicosis, there is an increased appetite, thirst, abdominal pain, unstable stools, a moderate increase in the liver (during the examination, an increase in the activity of aminotransferases, alkaline phosphatase is detected). Due to accelerated catabolism, patients lose weight. With the progression of the disease, muscle mass decreases, almost in all cases of the disease, weakness of the muscles of the proximal parts develops (thyrotoxic myopathy). This happens not only due to an increase in protein catabolism, but also due to damage to the peripheral nervous system. Deep tendon reflexes are increased.

Catabolic syndrome, in addition, is manifested by the loss of protein and a decrease in bone density.
With thyrotoxicosis, there is a violation of the function of the genital glands, oligo– and amenorrhea develops, gynecomastia appears in men. Libido and potency decrease.

In DTZ, in most cases, there are characteristic changes on the part of the visual organ. The eye slits are dilated, which gives the impression of an angry, surprised or frightened look. The expansion of the eye slit gives the impression of exophthalmos. The development of the above symptoms is associated with the influence of the sympathetic nervous system, under the influence of which there is an increase in the tone of smooth muscle fibers. Exophthalmos is also characteristic of ophthalmopathy, which is an independent autoimmune disease, the development of which is based on a complex lesion of the orbital tissues.

Most of the clinical effects are associated with the effect of an excessive amount of thyroid hormones on the sympathetic nervous system. As a result, tachycardia, tremor of the fingers of outstretched hands (the so-called Marie’s symptom) occur, tremor of the whole body, tongue, sweating, irritability, a feeling of anxiety and fear, hyperactivity, restlessness is possible.

Thyroid hormones stimulate the reticular formation and cortical processes in the central nervous system.

The toxic effect of thyroid hormones on the central nervous system causes the development of thyrotoxic encephalopathy, the manifestations of which are nervous excitability, irritability, anxiety, emotional lability, frequent mood changes, tearfulness, decreased ability to concentrate attention, chaotic unproductive activity, sleep disorders, sometimes depression, even mental reactions. True psychoses are rare, but there are descriptions of them in the literature for thyrotoxicosis. Cases of thyrotoxicosis manifestation as mania are described.

However, a number of patients may experience the so-called “apathetic” form of thyrotoxicosis, which is characterized by the presence of weight loss, atrial fibrillation, heart failure, sometimes paroxysmal myopathy in the absence of ophthalmopathy and psychomotor agitation. In some patients with this form of thyrotoxicosis, there is a pronounced mental retardation, apathy, adynamia.

Often, the first sign that attracts the attention of others, especially close people, is a change in the behavior of patients with thyrotoxicosis. Sometimes enough time passes from the onset of the disease and patients turn to the doctor only when symptoms from the cardiovascular system increase, and nervousness is attributed to an abundance of stress.

Disorders of the emotional sphere in thyrotoxicosis come to the fore. They are detected in almost all patients. There is an increased affective lability. Lability of mood is accompanied by constant internal tension, anxiety, anxiety. Patients can commit inconsistent and unmotivated actions. It should be emphasized that patients themselves often do not notice changes in their own personality and fix their attention on changes in the external world: everything around them seems fickle, fussy and extremely changeable.

Somatogenic mental disorder in thyrotoxicosis is an important part of the clinical picture and depends on the severity of the disease and the effectiveness of treatment. Asthenic symptoms and affective disorders in the form of emotional lability are very characteristic. There is an increased vulnerability and touchiness. Patients are tearful, prone to unmotivated mood swings, they easily have an irritation reaction, which can be replaced by crying. Patients complain of increased fatigue, which is expressed in both physical and mental asthenia. In such patients, hyperesthesia phenomena are often noted in the form of intolerance to loud sounds, bright light, and touch.

In many cases, there is a low mood, sometimes reaching a state of pronounced depression. Depression is usually accompanied by a state of anxiety, hypochondriac complaints. Phobias may occur.

Less often there are states of lethargy and apathy, as well as states of euphoria with a decrease in criticism.

Sleep disorders are very typical – difficulty falling asleep, frequent awakenings, disturbing dreams.

With a prolonged course of ineffectively treated thyrotoxicosis, intellectual and mnestic disorders are possible.

The chronic course of anxiety disorders may itself be associated with an increased risk of cardiovascular diseases.

There is evidence that with thyrotoxicosis, the frequency of panic disorders, simple phobias, obsessive–compulsive disorders, depressive disorders and cyclothymia is significantly higher than in the general population.

The diagnosis of pathology associated with thyrotoxicosis syndrome is based on the clinic and the results of laboratory and instrumental studies. The disease leading to the development of thyrotoxicosis syndrome is determined. For diagnostic purposes, the level of TSH, free T4 and T3 is determined. For etiological diagnosis, ultrasound examination of the thyroid gland, scintigraphic examination, as well as determination of the level of antibodies to the TSH receptor (AT–RTG), fine-needle biopsy of nodular formations suspected of a tumor are performed.

Since, as noted earlier, 80% of cases of thyrotoxicosis are based on diffuse toxic goiter, we will focus on its treatment.

Patients should receive a full-fledged diet with a sufficient amount of vitamins and trace elements.

For the treatment of thyrotoxicosis, drug therapy, therapy with radioactive iodine, as well as surgical treatment with previous preparation of thyrostatic drugs are used. In our country, as in Europe, conservative thyrostatic therapy has received the greatest use. In the USA, treatment with radioactive iodine prevails [10]. As a rule, thyrostatic therapy is combined with drugs from the group of b–blockers. b-blockers not only reduce the negative impact on the cardiovascular system in thyrotoxicosis: by reducing heart rate and lowering blood pressure, they reduce the peripheral conversion of thyroxine to triiodothyronine. When prescribing thyrostatic drugs, it is recommended to additionally prescribe thyroxine preparations to achieve an euthyroid state during the entire treatment period. This combination is called “block and replace”. The criterion of adequately selected treatment is the stable maintenance of normal levels of free T4 and TSH. The treatment lasts from 12 to 24 months.

Surgical treatment is carried out with severe thyrotoxicosis, a significant increase in the thyroid gland, ineffectiveness or intolerance to thyrostatic therapy. In order to exclude the possibility of a recurrence of thyrotoxicosis, it is recommended to perform an extremely subtotal resection of the thyroid gland with the remaining thyroid residue of no more than 2-3 ml.

A highly effective and safe method of treating diffuse toxic goiter and other diseases occurring with thyrotoxicosis is J131 iodine therapy. It should be noted, however, that such a widespread and having significant advantages (non-invasiveness, relative cheapness, lack of risk associated with surgical intervention) method is still poorly available in our country.

Therapy of diseases occurring with thyrotoxicosis syndrome is carried out in a complex. In addition to prescribing treatment aimed at reducing the excessive effect of thyroid hormones on the body, it is necessary to help the patient, taking into account the presence of mental disorders that are so characteristic of this pathology.

Sedatives are traditionally used to achieve a general soothing effect, as well as to normalize sleep. In addition to sedatives, the use of anxiolytics is advisable in the treatment of anxiety disorders against the background of asthenia.

For the treatment of mental changes, it is preferable to use modern psychopharmacological drugs, since they are effective and have fewer side effects.

Tranquilizers and anxiolytics are recommended as psychopharmacological agents with minimal effect on the functions of internal organs, body weight, low probability of interaction with somatotropic drugs and adequate for the treatment of mental disorders in somatically ill patients.
In this regard, a new drug with an anxiolytic effect, Zoloft, is of interest. Its influence on anxiety disorders of different structure was studied. It was established that its main effect is anxiolytic, combined with an activating one. Zoloft has the greatest effectiveness in” simple ” structure of anxiety disorders. In patients with acute anxiety-phobic disorders, the structure of which is dominated by sensory anxiety with episodes of generalization, the formation of mastering imaginative representations, sensually saturated phobias, with pronounced vegetative disorders, senestalgia, high treatment results are achieved.

When using Zoloft, there is a decrease or elimination of anxiety (anxiety, bad premonitions, fears, irritability), tension (timidity, tearfulness, anxiety, inability to relax, insomnia, fear), and consequently, somatic (muscle, sensory, cardiovascular, respiratory, gastrointestinal symptoms), vegetative (dry mouth, sweating, dizziness), cognitive (difficulty concentrating, impaired memory) disorders.

These symptoms are characteristic of mental disorders with thyrotoxicosis, which makes the use of Zoloft promising in the complex therapy of this pathology and can improve the quality of life of patients.