Treatment of diffuse toxic goiter

Currently, there are three main methods of treating diffuse toxic goiter: drug therapy, surgical intervention - subtotal resection of the thyroid gland, and treatment with radioactive iodine. All available methods of treating diffuse toxic goiter lead to a decrease in the elevated level of circulating thyroid hormones to normal values. Each of these methods has its own indications and contraindications and should be determined for patients individually. The choice of method depends on the severity of the disease, the size of the thyroid gland, the age of the patient, and concomitant diseases.

Drug treatment of diffuse toxic goiter

For drug treatment of diffuse toxic goiter, thiourea preparations are used - mercazolil (foreign analogues methimazole and thiamazole), carbimazole and propylthiouracil, blocking the synthesis of thyroid hormones at the level of conversion of monoiodotyrosine to diiodotyrosine. Recently, data have appeared on the effect of antithyroid drugs on the body's immune system. The immunosuppressant effect of mercazolil, along with the direct effect on the synthesis of thyroid hormones, apparently determines the advantage of mercazolil for the treatment of diffuse toxic goiter over other immunosuppressants, since none of them has the ability to disrupt the synthesis of thyroid hormones and selectively accumulate in the thyroid gland. Treatment with mercazolil can be carried out at any severity of the disease. However, a condition for successful drug treatment is an increase in the gland to grade III. In more severe cases, patients are referred for surgical treatment or radioiodine therapy after preliminary preparation with thyreostatic drugs. Doses of mercazolil range from 20 to 40 mg/day depending on the severity of the disease.

Treatment is carried out under control of pulse rate, body weight, clinical blood test. After the symptoms of thyrotoxicosis have reduced, maintenance doses of mercazolil (2.5-10 mg/day) are prescribed. The total duration of drug therapy for diffuse toxic goiter is 12-18 months. If mercazolil cannot be discontinued due to deterioration of the condition at maintenance doses and relapses of the disease, patients should be referred for surgical treatment or radioiodine therapy. It is not recommended to treat patients with a tendency to relapse with mercazolil for many years, since there is a possibility of morphological changes in the thyroid gland against the background of increased production of thyroid-stimulating hormone. Many authors point out the likelihood of thyroid cancer as a result of long-term thyreostatic therapy conducted over a number of years.

There are still no reliable methods for determining the activity of immune changes during antithyroid treatment. Determination of thyroid-stimulating antibodies is advisable for predicting remission or its absence. In cases where a euthyroid state is achieved and the content of thyroid-stimulating antibodies does not decrease, relapses usually occur. According to the latest data, determination of histocompatibility by the HLA system may be useful. In carriers of certain antigens (B8, DR3), a significantly more frequent relapse was observed after drug therapy. Complications in the form of toxic-allergic reactions ( itching, urticaria, agranulocytosis, etc.), goitrogenic effect, drug-induced hypothyroidism may be observed during therapy with antithyroid drugs. The most serious complication is agranulocytosis, which occurs in 0.4-0.7% of patients. One of the first signs of this condition is pharyngitis, so the patient's complaints about the appearance of pain or discomfort in the throat should not be ignored. Careful monitoring of the number of leukocytes in the peripheral blood is necessary. Other side effects of mercazolil include dermatitis, arthralgia, myalgia, fever. If symptoms of intolerance to antithyroid drugs appear, treatment with mercazolil should be discontinued. The goitrogenic effect is a consequence of excessive blockade of the synthesis of thyroid hormones with the subsequent release of TSH, which in turn causes hypertrophy and hyperplasia of the thyroid gland. To prevent the goitrogenic effect when euthyroidism is achieved, thyroxine 25-50 mcg is added to the treatment with mercazolil.

The therapeutic use of iodine preparations is currently strictly limited. In patients with diffuse toxic goiter (Graves' disease), as a result of long-term therapy with these drugs, the thyroid gland increases in size and hardens in the absence of sufficient compensation for thyrotoxicosis. The effect of the drug is transient, and a gradual return of thyrotoxicosis symptoms with the development of refractoriness to iodine and antithyroid drugs is often observed. The use of the former does not affect the level of thyroid-stimulating activity in the blood of patients with diffuse toxic goiter. Iodine preparations can only rarely be used as an independent treatment method.

Diffuse toxic goiter is a medical indication for artificial termination of pregnancy up to 12 weeks. Currently, in case of a combination of pregnancy and mild to moderate diffuse toxic goiter and a slight enlargement of the thyroid gland, antithyroid drugs are prescribed. In case of more severe thyrotoxicosis, patients are referred for surgical treatment. During pregnancy, the dose of antithyroid drugs should be reduced to a minimum (no more than 20 mg/day). Antithyroid drugs (except propicil) are contraindicated during breastfeeding. The addition of thyroid drugs to antithyroid agents during pregnancy is contraindicated, since antithyroid substances, in contrast to thyroxine, pass through the placenta. Therefore, to achieve a euthyroid state in the mother, it is necessary to increase the dosage of mercazolil, which is undesirable for the fetus.

Antithyroid drugs used to treat diffuse toxic goiter include potassium perchlorate, which blocks iodine penetration into the thyroid gland. Doses of potassium perchlorate are selected depending on the uptake of ¹³¹ I by the thyroid gland. For mild forms, 0.5-0.75 g/day is prescribed, for moderate forms - 1-1.5 g/day. The use of potassium perchlorate sometimes causes dyspeptic symptoms and skin allergic reactions. Rare complications when taking this drug include aplastic anemia and agranulocytosis. Therefore, a mandatory condition for its use is systematic monitoring of the peripheral blood picture.

Lithium carbonate is used as an independent therapy for mild to moderate thyrotoxicosis in some cases. There are two possible ways lithium can affect thyroid function: direct inhibition of hormone synthesis in the gland and influence on peripheral thyronine metabolism. Lithium carbonate in 300 mg tablets is prescribed at a rate of 900-1500 mg/day depending on the severity of symptoms. The effective therapeutic concentration of lithium ion in the blood is 0.4-0.8 mEq/l, which rarely leads to undesirable side effects.

Taking into account the pathogenetic mechanisms of formation of cardiovascular disorders in diffuse toxic goiter, beta-blockers (inderal, obzidan, anaprilin) are used along with thyrotoxic drugs. According to our data, beta-blockers significantly expand the possibilities of therapeutic measures in diffuse toxic goiter (Graves' disease), and their rational use helps to increase the effectiveness of the therapy. Indications for prescribing these drugs are persistent tachycardia that is not inferior to therapy with thyreostatics, heart rhythm disturbances in the form of extrasystole, atrial fibrillation. Prescription of drugs is carried out taking into account individual sensitivity and with preliminary functional tests of the patient under ECG control. Doses of drugs vary from 40 mg to 100-120 mg / day. Signs of an adequate dose are a decrease in heart rate, pain in the heart, and the absence of side effects. Against the background of complex therapy with beta-blockers for 5-7 days, a distinct positive effect occurs, the general condition of patients improves, the heart rate slows down, extrasystoles decrease or disappear, the tachystolic form of atrial fibrillation turns into a normo- or bradystolic form, and in some cases the heart rhythm is restored; pain in the heart area decreases or disappears. The administration of beta-blockers has a positive effect on patients who were previously treated with thyreostatic drugs without much effect, and, in addition, in some cases allows to significantly reduce the dose of mercazolil. Beta-blockers are successfully used in preoperative preparation of patients with intolerance to even small doses of thyreostatic drugs. In such cases, the administration of obzidan or atenolol in combination with prednisolone (10-15 mg) or hydrocortisone (50-75 mg) allows to achieve clinical compensation of thyrotoxicosis. Beta blockers act on the sympathetic nervous system (sympatholytic action) and directly on the heart muscle, reducing its oxygen demand. In addition, these drugs affect the metabolism of thyroid hormones, promoting the conversion of thyroxine into an inactive form of triiodothyronine - reverse ( RT ₃₎ T ₃. A decrease in the level of T ₃, an increase in _RT3 is considered a specific effect of propranolol on the metabolism of thyroid hormones in the periphery.

Corticosteroids are widely used in the treatment of diffuse toxic goiter. The positive effect of corticosteroids is due to the compensation of relative adrenal insufficiency in diffuse toxic goiter, the effect on the metabolism of thyroid hormones (under the influence of glucocorticoids, thyroxine is converted into RT ₃₎, and an immunosuppressive effect. To compensate for adrenal insufficiency, depending on its severity, prednisolone is used in physiological doses - 10-15 mg / day. In more severe cases, parenteral administration of glucocorticoids is recommended: hydrocortisone 50-75 mg, intramuscularly or intravenously.

Treatment of endocrine ophthalmopathy is performed jointly by an endocrinologist and an ophthalmologist, taking into account the severity of the disease, the activity of the immune-inflammatory process and the presence of clinical signs of thyroid dysfunction. A prerequisite for successful treatment of ophthalmopathy in diffuse toxic goiter (Graves' disease) is achieving a euthyroid state. The pathogenetic method of treating EOP is glucocorticoid therapy, which has an immunosuppressive, anti-inflammatory, anti-edematous effect. The daily dose is 40-80 mg of prednisolone with a gradual decrease after 2-3 weeks and complete cancellation after 3-4 months. Retrobulbar administration of prednisolone is inappropriate due to the formation of scar tissue in the retrobulbar region, which impedes the outflow of blood and lymph. In addition, the effect of GCs in EOP is associated with their systemic, not local action.

There are contradictory data in the literature on the effectiveness of treating exophthalmos and myopathy with immunosuppressants ( cyclophosphamide, cyclosporine, azathiaprine). However, these drugs have a large number of side effects, and convincing evidence of their effectiveness has not yet been obtained. Therefore, they should not be recommended for widespread use.

One of the possible mediators of the pathological process in the orbits is insulin-like growth factor I, therefore, a long-acting somatostatin analogue, octreotide, has been proposed as a treatment for ophthalmopathy. Octreotide, by suppressing the secretion of growth hormone, reduces the activity of insulin-like growth factor I and inhibits its action on the periphery.

In steroid-resistant forms of ophthalmopathy, plasmapheresis or hemosorption is performed. Plasmapheresis is the selective removal of plasma from the body with subsequent replacement with freshly frozen donor plasma. Hemosorption has a wide range of effects: immunoregulatory, detoxifying, increasing the sensitivity of cells to glucocorticoids. As a rule, hemosorption is combined with steroid therapy. The course of treatment consists of 2-3 sessions with an interval of 1 week.

In severe forms of ophthalmopathy, manifested by pronounced exophthalmos, edema and hyperemia of the conjunctiva, limitation of gaze, weakening of convergence, occurrence of diplopia, severe pain in the eyeballs, remote radiotherapy is performed on the orbital area from direct and lateral fields with protection of the anterior segment of the eye. Radiotherapy has an antiproliferative, anti-inflammatory effect, leading to a decrease in the production of cytokines and secretory activity of fibroblasts. The effectiveness and safety of small doses of radiation therapy (16-20 Gy per course, daily or every other day in a single dose of 75-200 R) have been noted. The best therapeutic effect is observed with a combination of radiation therapy and glucocorticoids. The effectiveness of radiotherapy should be assessed within 2 months after the end of treatment.

Surgical treatment of ophthalmopathy is performed at the fibrosis stage. There are 3 categories of surgical interventions:

1. Eyelid surgery due to corneal damage;
2. Corrective operations on the oculomotor muscles in the presence of diplopia;
3. Orbital decompression.

Treatment of thyrotoxic crisis is aimed primarily at reducing the level of thyroid hormones in the blood, relieving adrenal insufficiency, preventing and combating dehydration, eliminating cardiovascular and neurovegetative disorders. With the development of thyrotoxic reactions in the form of increased temperature, agitation, tachycardia, it is necessary to begin measures to eliminate threatening symptoms.

Patients are given increased doses of antithyroid drugs and corticosteroids. When a crisis develops, 1% Lugol's solution is administered intravenously (replacing potassium iodide with sodium iodide).

To relieve the symptoms of hypocorticism, large doses of corticosteroids (hydrocortisone 400-600 mg/day, prednisolone 200-300 mg), DOXA preparations are used. The daily dose of hydrocortisone is determined by the severity of the patient's condition and can be increased if necessary.

Beta-blockers are used to reduce hemodynamic disturbances and manifestations of sympathetic-adrenal hyperreactivity. Propranolol or inderal is administered intravenously - 1-5 mg of 0.1% solution, but not more than 10 mg during 24 hours. Then they switch to oral medications (obzidan, anaprilin). Beta-blockers should be used with caution, under the control of pulse and blood pressure, they should be discontinued gradually.

Barbiturates and sedatives are indicated to reduce the symptoms of nervous excitement. It is necessary to take measures against the development of heart failure. The introduction of humidified oxygen is indicated. Dehydration and hyperthermia are treated. If an infection occurs, broad-spectrum antibiotics are prescribed.

There have been reports that plasmapheresis has been used to treat patients with thyrotoxic crisis as a method that allows for the faster removal of large amounts of thyroid hormones and immunoglobulins circulating in the blood.

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Surgical treatment of diffuse toxic goiter

Indications for surgical treatment of DTG are large goiter sizes, compression or displacement of the trachea, esophagus and large vessels, retrosternal goiter, severe forms of thyrotoxicosis complicated by atrial fibrillation, lack of stable compensation against the background of drug therapy and a tendency to relapse, intolerance to thyrotoxic drugs.

Patients are referred for surgical treatment after preliminary preparation with thyrotoxic drugs in combination with corticosteroids and beta-blockers. In case of allergic reactions and intolerance to mercazolil, the necessary preoperative preparation is carried out with large doses of corticosteroids and beta-blockers. The main clinical indicators of the patient's readiness for surgery are a state close to euthyroid, a decrease in tachycardia, normalization of arterial pressure, an increase in body weight, and normalization of the psychoemotional state.

In diffuse toxic goiter, subtotal subfascial resection of the thyroid gland is performed using the method of O. V. Nikolaev. Comprehensive pathogenetically substantiated preoperative preparation, compliance with all details of the surgical intervention guarantee a favorable course of the postoperative period and a good result of the operation.

Medicinal use ¹³¹ I

The use of radioactive ¹³¹ I for therapeutic purposes has received wide recognition in both domestic and foreign medical practice.

The use of ¹³¹ I for therapeutic purposes was preceded by a large number of experimental works. It was established that the introduction of extremely wide doses ^{of 131} I to animals causes complete destruction of the thyroid gland, but does not damage other organs and tissues. Radioactive iodine, entering the thyroid gland, is distributed unevenly in it, and the therapeutic effect primarily affects the central areas, and the peripheral zones of the epithelium retain the ability to produce hormones. Such selective concentration and the absence of pronounced side effects on the surrounding tissues depend on the physical properties of the isotope formed during the decay of beta and gamma particles, which behave differently in tissues. The main part of ¹³¹ I is beta particles with a maximum energy of 0.612 MeV and a range of no more than 2.2 mm. They are completely absorbed by the central areas of thyroid tissue and destroy them, while the surrounding parathyroid glands, trachea, larynx, and recurrent nerve are almost not exposed to the rays. In contrast to beta rays, gamma rays with energies from 0.089 to 0.367 MeV have a pronounced penetrating ability. In this case, the negative effect of the radioisotope on the surrounding tissues increases proportionally to the increase in goiter. It has been established that the initial period of treatment is characterized by a more active concentration of the radioisotope in the diffuse part of the gland in areas of pronounced hyperplasia, then it accumulates in the remaining node. Therefore, the effect of treatment for mixed goiters is significantly lower and, according to our data, does not exceed 71%.

Indications for therapy ¹³¹ I: treatment should be carried out at the age of not younger than 40 years; severe heart failure in patients, in which surgical treatment is risky; a combination of diffuse toxic goiter (Graves' disease) with tuberculosis, severe hypertension, previous myocardial infarction, neuropsychiatric disorders, hemorrhagic syndrome; relapse of thyrotoxicosis after subtotal thyroidectomy, categorical refusal of the patient from surgical intervention on the gland.

Contraindications to treatment ^{with 131} I: pregnancy, lactation, childhood, adolescence and young age; large enlargement of the thyroid gland or retrosternal location of the goiter; blood diseases, kidney diseases and peptic ulcer disease.

Preliminary preparation in the hospital includes measures against cardiovascular insufficiency, leukopenia, nervous overexcitability. During the period of treatment associated with increased hormone intake into the bloodstream, it is necessary to prescribe antithyroid drugs several days before and for 2-4 weeks after the introduction of I. However, this combination naturally reduces the therapeutic effect ^{of 131} I to some extent, but does not have its pronounced side effects. Thus, L. G. Alekseev et al., using combined treatment, noted hypothyroidism in only 0.5-2.1% of patients, whereas with the introduction of only ¹³¹ I, the percentage of hypothyroidism increases to 7.4%.

In addition to such a combination, ¹³¹ I can be combined with beta-blockers, which are known to alleviate many symptoms of thyrotoxicosis. In the rational preparation of patients for treatment ^{with 131} I, considerable importance is attached to vitamin therapy, especially the use of a complex of B vitamins and ascorbic acid.

The severity of the disease is important when choosing a therapeutic dose. Thus, according to our data, in patients with moderate thyrotoxicosis, the average dose was from 4 to 7.33 mCi, and in severe patients - 11.38 mCi. No less important is the mass of the gland, which is determined by scanning. A certain role in selecting a dose is played by diagnostic indicators of the content of ¹³¹ I in the gland. It has been noted that the higher they are, the greater the doses that must be used. When calculating them, the effective half-life is also taken into account. It is significantly accelerated in severe patients with thyrotoxicosis. To correctly select a dose, one should also take into account the age of the patients. It is known that the sensitivity of the gland to radiation increases in the elderly. Due to the variety of reasons affecting the choice of a therapeutic dose, a number of formulas are proposed to facilitate this task.

The method of administration is no less important. Some believe that the entire dose can be administered at once, others - in fractions - after 5-6 days, and finally, in fractional and prolonged doses. Supporters of the first method believe that using ¹³¹ I in this way allows for the rapid elimination of thyrotoxicosis and the elimination of the possibility of the thyroid gland developing resistance to ¹³¹ I. Supporters of the fractional and fractional and prolonged methods argue that such administration allows for the individual characteristics of the body to be taken into account and thus can prevent the development of hypothyroidism. The interval between the first and second courses - 2-3 months - allows for the restoration of bone marrow function and other organs after the initial dose of iodine exposure, as well as preventing rapid destruction of the thyroid gland and maximum flooding of the body with thyroid hormones. To prevent hypothyroidism, it is better to administer the drug in fractions. In addition, patients with severe thyrotoxicosis are also recommended to administer the drug in courses to prevent other complications (thyrotoxic crisis, toxic hepatitis, etc.).

In patients with moderate disease, a single administration ^{of 131} I may be sufficient. Repeated administration is best done in 2-3 months. The size of the repeat dose is also of practical importance. It should be increased by 25-50% compared to the initial dose with fractional administration and halved with a single administration.

When calculating the therapeutic dose, according to our data, it is necessary to administer 60-70 μCi per 1 g of thyroid gland mass in patients with moderate thyrotoxicosis, and up to 100 μCi in severe cases and in younger individuals, and the initial dose for all forms of the disease should not exceed 4-8 μCi. The results of treatment are felt in 2-3 weeks: sweating and tachycardia decrease, the temperature drops, and weight loss stops. After 2-3 months, palpitations and weakness completely disappear, and work capacity is restored. Complete remission after treatment occurs in 90-95% of cases. Relapse of thyrotoxicosis is possible in no more than 2-5% of cases. It occurs more often in patients with mixed goiter, and in no more than 1% of patients with DTG.

The criterion for assessing the therapeutic effect of I is the functional state of the thyroid gland, determined by the content of thyroxine, triiodothyronine, thyroid-stimulating hormone, the test with thyroliberin or the inclusion of 99mTc in the thyroid gland.

The earliest complications after treatment may occur in the first hours after the introduction of ¹³¹ I (headaches, palpitations, feeling of heat throughout the body, dizziness, diarrhea and pain throughout the body ). They do not last long and do not leave consequences. Late complications occur on the 5th-6th day and are characterized by more pronounced symptoms: the appearance or intensification of cardiovascular insufficiency, joint pain and swelling. The neck may increase slightly in size, redness in the thyroid gland and soreness may occur - the so-called aseptic thyroiditis begins, which is observed in 2-6% of cases. Jaundice may also develop, indicating toxic hepatitis. The most serious complication is thyrotoxic crisis, but it is observed in no more than 0.88%. One of the frequent complications is hypothyroidism, which is observed in 1-10% of cases.

E. Eriksson et al. believe that treatment of this complication with replacement therapy - thyroxine - should be started if the TSH level in the blood doubles regardless of clinical manifestations. Persistent hypothyroidism can develop with both large and small doses of I.

Prognosis and working capacity

The prognosis of patients with diffuse toxic goiter is determined by the timeliness of diagnosis and the adequacy of the therapy. At the early stage of the disease, patients, as a rule, respond well to adequately selected therapy, and practical recovery is possible.

Late diagnosis of diffuse toxic goiter, as well as inadequate treatment, contribute to further development of the disease and loss of ability to work. The appearance of pronounced symptoms of adrenal cortex insufficiency, liver damage, heart failure complicate the course and outcome of the disease, make the prognosis for the ability to work and life of patients unfavorable.

The prognosis of ophthalmopathy is complex and does not always parallel the dynamics of thyrotoxicosis symptoms. Even when a euthyroid state is achieved, ophthalmopathy often progresses.

Proper employment of patients with diffuse toxic goiter helps to maintain their ability to work. By decision of the advisory and expert commission (AEC), patients should be exempted from heavy physical labor, night shifts, and overtime work. In severe forms of diffuse toxic goiter, their physical performance drops sharply. During this period, they are incapacitated and, by decision of the VTEK, can be transferred to disability. If the condition improves, it is possible to return to mental or light physical labor. In each specific case, the issue of ability to work is decided individually.