Treatment of diffuse toxic goiter

Currently, there are three main methods for treating diffuse toxic goiter: drug therapy, surgical intervention - subtotal resection of the thyroid, and treatment with radioactive iodine. All available methods of therapy for diffuse toxic goiter result in a decrease in the elevated level of circulating thyroid hormones to normal numbers. 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 patients, concomitant diseases.

Drug treatment of diffuse toxic goiter

For medicinal treatment of diffuse toxic goiter, thioureas are used - mercazolil (foreign analogs of methimazole and thiamazole), carbimazole and propylthiouracil, which block the synthesis of thyroid hormones at the level of the transition of monoiodotyrosine to diiodotyrosine. Recently, there have been data on the effect of thyreostatic drugs on the immune system of the body. Immunosuppressive action of Mercazolilum along with a direct effect on the synthesis of thyroid hormones, apparently, determines the advantage of Mercazolilum for the treatment of diffuse toxic goiter in front of 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 Mercazolilum can be performed for any severity of the disease. However, the condition for successful drug treatment is an increase in the gland to grade III. In more severe cases, patients after preliminary preparation with thyreostatic drugs are referred for surgical treatment or radioiodine therapy. Doses of Mercazolil vary from 20 to 40 mg / day, depending on the severity of the disease. Treatment is carried out under the control of pulse frequency, body weight, clinical blood test. After reducing the symptoms of thyrotoxicosis, maintenance doses of merka-zolil are prescribed (2.5-10 mg / day). The total duration of drug therapy for diffuse toxic goiter is 12-18 months. If it is not possible to remove mercazolil due to worsening of the condition at maintenance doses and the occurrence of relapses of the disease, patients should be referred for surgical treatment or radioiodine therapy. Patients with a tendency to relapse to treat with Mercazolilum for many years is not recommended, because there is a possibility against the background of intensifying the production of the thyroid-stimulating hormone of morphological changes in the thyroid gland. The probability of thyroid cancer as a result of a prolonged, for a number of years of ongoing thyreostatic therapy is indicated by many authors. There are still no reliable methods for determining the activity of immune changes during thyreostatic treatment. The determination of thyroid stimulating antibodies is expedient for the prognosis of remission or its absence. In those cases when the euthyroid state is reached, and the content of thyroid stimulating antibodies does not decrease, as a rule, relapses occur. According to recent data, it may be useful to determine the histocompatibility of the HLA system. In carriers of certain antigens (B8, DR3) after drug therapy, a significantly more frequent recurrent course was observed. When treating with thyreostatic drugs, complications can occur in the form of toxic-allergic reactions (pruritus, urticaria, agranulocytosis, etc.), zobogenic effect, drug hypothyroidism. 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. It is necessary to carefully monitor the number of leukocytes in the peripheral blood. Other side effects of Mercazolil include dermatitis, arthralgia, myalgia, fever. When symptoms of intolerance to thyroid medications appear, treatment with Mercazolil should be discontinued. The zobogenic effect is a consequence of excessive blockade of the synthesis of thyroid hormones with subsequent release of TSH, which in turn causes hypertrophy and hyperplasia of the thyroid gland. To prevent the zobogenic effect when euthyroidism is reached, a thyroxine of 25-50 μg is added to treatment with mercapolil.

Therapeutic use of iodine preparations is now strictly limited. In patients with diffuse toxic goiter (Graves' disease) as a result of prolonged therapy with these medicinal substances, the thyroid gland is enlarged and compacted in the absence of adequate compensation of thyrotoxicosis. The effect of the drug is transient, it is often observed a gradual return of symptoms of thyrotoxicosis with the development of refractoriness to iodine and antithyroid drugs. The use of the first does not affect the level of thyrostimulating activity of the blood of patients with diffuse toxic goiter. Iodine preparations can rarely be used as an independent treatment method in rare cases.

Diffuse toxic goiter is a medical indication for the artificial termination of pregnancy in terms of up to 12 weeks. At present, when combined pregnancy and diffuse toxic goiter of mild and moderate severity and a small increase in the thyroid gland, antithyroid drugs are prescribed. With more severe thyrotoxicosis, patients are referred for surgical treatment. During pregnancy, the dose of thyreostatic drugs should be reduced to a minimum (not more than 20 mg / day). Thyrostetics (excluding propitsila) are contraindicated in breastfeeding. The addition of thyroid preparations to thyreostatic drugs during pregnancy is contraindicated, since antithyroid substances, in contrast to thyroxine, pass through the placenta. Therefore, in order to achieve an euthyroid state, the mother needs an increase in the dosage of mercazolil, which is undesirable for the fetus.

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

As an independent therapy for mild to moderate thyrotoxicosis, lithium carbonate is used in some cases. There are two possible ways of influencing lithium on thyroid function: direct inhibition of the synthesis of hormones in the gland and the effect on peripheral metabolism of thyronins. Lithium carbonate in tablets of 300 mg is prescribed at a rate of 900-1500 mg / day, depending on the severity of the symptoms. In this case, the effective therapeutic concentration of lithium ion in the blood is 0.4-0.8 meq / l, which rarely leads to undesirable side reactions.

Given the pathogenetic mechanisms of the formation of cardiovascular disorders in diffuse toxic goiter, along with thyrotoxic drugs, beta-blockers (indial, obzidan, anaprilin) are used. According to our information, beta-blockers significantly expand the possibilities of therapeutic measures for diffuse toxic goiter (Graves' disease), and their rational use contributes to improving the effectiveness of the therapy. Indications for the appointment of these drugs are stable, not inferior to thyreostatic therapy, tachycardia, violation of the heart rhythm in the form of extrasystole, atrial fibrillation. The prescription of medicines is carried out taking into account individual sensitivity and with preliminary carrying out to patients of functional samples under the control of an electrocardiogram. Doses of drugs vary from 40 mg to 100-120 mg / day. Signs of the adequacy of the dose is a reduction in heart rate, pain in the heart, no side effects. Against the background of complex therapy with beta-blockers for 5-7 days, there is a clear positive effect, the general condition of the patients improves, the heart rate decreases, the extrasystoles decrease or disappear, the tachysystolic form of atrial fibrillation passes into normo- or bradysystolic form, and in some cases is restored heartbeat; pains in the heart area decrease or disappear. The appointment of beta-blockers has a positive effect on patients who were previously treated with thyreostatic drugs without much effect, and, in addition, allows in a number of cases to significantly reduce the dose of Mercazolil. Beta-blockers are successfully used in preoperative preparation of patients with intolerance of even small doses of thyreostatic drugs. Appointment in such cases obzidana or atenolol in combination with prednisolone (10-15 mg) or hydrocortisone (50-75 mg) allows to achieve clinical compensation of thyrotoxicosis. Beta-blockers affect the sympathetic nervous system (sympathetic action) and directly on the heart muscle, reducing its need for oxygen. In addition, these drugs affect the metabolism of thyroid hormones, promoting the conversion of thyroxin to an inactive form of triiodothyronine - a reversible ( _R T ₃ ) T ₃. A decrease in the T ₃ level , an increase in _R T ₃ is considered a specific effect of propranolol on the exchange of thyroid hormones at the periphery.

In the treatment of diffuse toxic goiter, corticosteroids are widely used. The positive effect of the use 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 action of glucocorticoids, thyroxine is converted into _R T ₃ ), as well as by immunosuppressive action. To compensate for adrenal insufficiency, depending on the severity of it, prednisolone is used in physiological doses of 10-15 mg / day. In more severe cases, parenteral administration of glucocorticoids is recommended: hydrocortisone 50-75 mg, intramuscularly or intravenously.

Endocrine ophthalmopathy is treated jointly by an endocrinologist and ophthalmologist, taking into account the severity of the disease, the activity of the immunoinflammatory process and the presence of clinical signs of thyroid dysfunction. An indispensable condition for the successful treatment of ophthalmopathy in diffuse toxic goiter (Graves' disease) is the achievement of an euthyroid state. Pathogenetic method of treatment of EOC is therapy with glucocorticoids, which have an immunosuppressive, anti-inflammatory, anti-edematous effect. The daily dose of 40-80 mg of prednisolone with a gradual decrease in 2-3 weeks and complete cancellation after 3-4 months. The retrobulbar injection of prednisolone is impractical in connection with the formation of scar tissue in the retrobulbar area, which hinders the outflow of blood and lymph. In addition, the effect of HA on EOC is related to their systemic, rather than local, action.

In the literature there are conflicting data on the effectiveness of treatment of exophthalmos and myopathy with immunosuppressants (cyclophosphamide, cyclosporine, azathiaprin). However, these drugs have a large number of side effects, there is no convincing evidence of their effectiveness to date. In this connection, they should not be recommended for wide application.

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

With steroid-resistant forms of ophthalmopathy, plasmapheresis or hemosorption is carried out. Plasmapheresis - selective removal of plasma from the body with subsequent replacement of its freshly frozen donor plasma. Hemosorption has a broad spectrum of action: immunoregulating, 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 congestion hyperemia, limitation of eyesight, weakening of convergence, appearance of diplopia, severe pain in the eyeballs, remote x-ray therapy is performed on the orbital area from the straight and side fields with the protection of the anterior segment of the eye. X-ray therapy has an antiproliferative, anti-inflammatory effect, leading to a decrease in the production of cytokines and the secretory activity of fibroblasts. The effectiveness and safety of small doses of radiotherapy (16-20 Gy per course, daily or every other day in a single dose of 75-200 R) was noted. The best therapeutic effect is observed when radiotherapy is combined with glucocorticoids. The effectiveness of X-ray therapy should be assessed within 2 months after the end of treatment.

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

1. Surgery on the eyelids in connection with the defeat of the cornea;
2. Correcting operations on the oculomotor muscles with diplopia;
3. Decompression of orbits.

Treatment of thyrotoxic crisis is primarily aimed at reducing the level of thyroid hormones in the blood, suppressing adrenal insufficiency, preventing dehydration and fighting with it, eliminating cardiovascular and neuro-vegetative disorders. With the development of thyrotoxic reactions in the form of fever, excitation, tachycardia, it is necessary to start measures to eliminate threatening symptoms.

Patients increase doses of thyreostatic drugs, prescribe corticosteroids. When the crisis develops, intravenously inject 1% solution of Lugol (replacing potassium iodide with sodium iodide).

To stop the symptoms of hypokorticism, 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, if necessary, can be increased.

Beta-adrenoblockers are used to reduce hemodynamic disorders and manifestations of sympathetic-adrenal hyperreactivity. Propranolol or inderal is administered intravenously - 1-5 mg of a 0.1% solution, but not more than 10 mg for 1 day. Then they switch to oral medications (obzidan, anaprilin). Beta-blockers should be used with caution, under the control of heart rate and blood pressure, they should be canceled gradually.

Barbiturates, sedatives are shown to reduce the symptoms of nervous excitement. It is necessary to take measures against the occurrence of heart failure. Introduction of moistened oxygen is shown. Dehydration and hyperthermia are being combated. When joining the infection, antibiotics of a wide spectrum of action are prescribed.

There were reports that for the treatment of patients with thyrotoxic crisis began to resort to plasmapheresis as a method that allows you to quickly remove large amounts of thyroid hormones and immunoglobulins circulating in the blood.

[1], [2], [3], [4], [5], [6], [7], [8]

Surgical treatment of diffuse toxic goiter

Indications for surgical treatment of DTZ are large sizes of goiter, compression or displacement of the trachea, esophagus and large vessels, congestive goitre, severe forms of thyrotoxicosis complicated by atrial fibrillation, lack of stable compensation against the background of ongoing medical 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. When allergic reactions and intolerance of Mercazolil appear, the necessary preoperative preparation is carried out with large doses of corticosteroids and beta-blockers. The main clinical indicators of patient readiness for surgery are a condition close to euthyroid, a decrease in tachycardia, normalization of blood pressure, an increase in body weight, normalization of the psychoemotional state.

In case of diffuse toxic goiter, subtotal subfascial resection of the thyroid gland is performed according to O. Nikolaev's technique. Complex pathogenetically justified preoperative preparation, observance of all details of operative intervention guarantee a favorable course of the postoperative period and a good result of the operation.

Therapeutic application ¹³¹ I

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

The use of ¹³¹ I with a therapeutic purpose was preceded by a large number of experimental studies. It was found 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. This selective concentration and the absence of a pronounced side effect on surrounding tissues depend on the physical properties of the isotope formed during the decay of beta and gamma particles behaving differently in tissues. The main part of ¹³¹ I consists of beta particles with a maximum energy of 0.612 MeV and a mean free path of no more than 2.2 mm. They are completely absorbed by the central parts of the thyroid tissue and destroy them, whereas the surrounding parathyroid glands, trachea, larynx, recurrent nerve are almost not exposed to the action of the rays. In contrast to the beta rays, gamma rays with energies from 0.089 to 0.367 MeV have a pronounced penetrating power. At the same time, the negative effect of the radioisotope on surrounding tissues increases in proportion to the increase in goiter. It is established that the initial treatment period 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 with mixed goiter is much lower and, according to our data, does not exceed 71%.

Indications for therapy ¹³¹ I: treatment should be performed at the age of at least 40 years; severe heart failure in patients in whom surgical treatment is risky; a combination of diffuse toxic goiter (Graves' disease) with tuberculosis, severe hypertension, 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 ¹³¹ I: pregnancy, lactation, children, youth and young age; a greater degree of enlargement of the thyroid gland or a squamous location of the goiter; diseases of the blood, kidney and peptic ulcer.

Preliminary preparation in a hospital includes carrying out measures against cardiovascular failure, leukopenia, nervous excitability. In the period of treatment associated with increased intake of hormones into the bloodstream, it is necessary to prescribe thyreostatic medications several days before and within 2-4 weeks after the administration of I. However, this combination naturally, to some extent, reduces the therapeutic effect of ¹³¹ I, but does not exert its pronounced side effects. Thus, LG Alekseev and co-workers, 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 increased to 7.4%.

In addition to this combination, it is possible to combine ¹³¹ I with beta-blockers, which are known to impair many of the symptoms of thyrotoxicosis. In the rational preparation of patients for treatment, ¹³¹ I attach considerable importance to vitamin therapy, especially the use of a complex of B vitamins and ascorbic acid.

When choosing a therapeutic dose, the severity of the disease is important. So, according to our data, the average dose in ballistic patients with moderate hyperthyroidism was from 4 to 7.33 mCi, and in severe patients - 11.38 mCi. Equally important is the mass of the gland, which is determined by the scanning method. A definite role in the selection of a dose is played by diagnostic indices of ¹³¹ I in iron. It is noted that the higher they are, the higher doses must be used. When calculating them, the effective half-life is taken into account. It significantly speeds up in severe patients with thyrotoxicosis. For proper selection of the dose, the age of the patients should also be taken into account. It is known that the sensitivity of the gland to radiation in the elderly increases. In connection with the variety of reasons that influence the choice of a therapeutic dose, a number of formulas are proposed that facilitate this task.

Equally important is the method of application. Some believe that it is possible to administer the entire dose once, while others - in divided doses - in 5-6 days and, finally, in a fractional-long way. Proponents of the first method believe that the application of ¹³¹ I thus makes it possible to quickly eliminate thyrotoxicosis and exclude the possibility of development of thyroid resistance to ¹³¹ I. Defenders of fractional and fractional-extended methods argue that such an introduction allows for the individual characteristics of the organism to be taken into account and thus the development of hypothyroidism can be prevented . The interval between the first and second courses - 2-3 months - allows to restore the function of the bone marrow and other organs after the radiation exposure of the initial dose of iodine, as well as to prevent 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 fractionally. In addition, patients with severe thyrotoxicosis are also advised to administer the drug courses for prevention and other complications (thyrotoxic crisis, toxic hepatitis, etc.).

In patients with a moderate course of the disease can be limited to a one-time introduction of ¹³¹ I. Repeated reception is best done after 2-3 months. The value of the repeated dose also has practical value. It should increase by 25-50% in comparison with the initial one with a fractional introduction and be halved for a single dose.

When calculating the therapeutic dose, according to our data, for 1 g of thyroid mass in patients with moderate-to-severe thyrotoxicosis it is necessary to inject it from 60-70 μCi, and in severe and younger patients to 100 μCi, the calculation of the initial dose for all forms the disease should not exceed 4-8 μCi. The results of treatment affect after 2-3 weeks: sweating, tachycardia decrease, temperature drops, weight loss ceases. After 2-3 months, heartbeat 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 often occurs in patients with mixed goiter, and in DTZ not more than 1% of patients.

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

The next complications after treatment may occur already in the first hours after the introduction of ¹³¹ I (headaches, palpitations, a feeling of heat throughout the body, dizziness, diarrhea and pain all over the body). They last not for long and do not leave consequences. Late complications occur on the 5th-6th day and are characterized by more pronounced symptoms: the appearance or strengthening of cardiovascular insufficiency, joint pain and swelling. There may be a slight increase in the volume of the neck, reddening in the thyroid gland and soreness - the so-called aseptic thyroiditis begins, which occurs in 2-6% of cases. There may also develop jaundice, indicating a toxic hepatitis. The most serious complication is the thyrotoxic crisis, but it is noted not 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 the treatment of this complication with substitution therapy - thyroxine - should be started if the level of TSH in the blood is doubled regardless of the clinical manifestations. Persistent hypothyroidism can develop with both large and small doses.

Prognosis and ability to work

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

The late diagnosis of diffuse toxic goiter, as well as inadequate treatment, contribute to the further development of the disease and disability. The appearance of severe symptoms of insufficiency of the adrenal cortex, liver damage, heart failure complicate the course and outcome of the disease, make a prediction regarding the ability to work and the life of patients unfavorable.

The prognosis of ophthalmopathy is complicated and not always parallel to the dynamics of thyrotoxicosis symptoms. Even with the achievement of an euthyroid state, ophthalmopathy often progresses.

Correct employment of patients with diffuse toxic goiter promotes the preservation of their working capacity. According to the decision of the Consultative-Expert Commission (CEC), patients should be freed from heavy physical labor, night shifts, overtime work. With severe forms of diffuse toxic goiter, their physical performance drops sharply. During this period they are disabled and, by the decision of the WTEC, can be transferred to a disability. When the condition improves, a return to mental or easy physical labor is possible. In each case, the issue of disability is decided individually.