Treatment of hypothyroidism

The main method of treating all forms of hypothyroidism is replacement therapy with thyroid preparations. TSH preparations have allergenic properties and are not used as a treatment for secondary (pituitary) hypothyroidism. Recently, studies have appeared on the effectiveness of intranasal (400-800-1000 mg) or intravenous (200-400 mg) administration of TRH for 25-30 days in patients with secondary hypothyroidism caused by a defect in endogenous stimulation and secretion of biologically inactive TSH.

The most common domestic drug is thyroidin, obtained from dried thyroid gland of cattle in the form of 0.1 or 0.05 g dragees. The amount and ratio of iodothyronines in thyroidin varies significantly in different batches of the drug. Approximately 0.1 g of thyroidin contains 8-10 mcg T ₃ and 30-40 mcg T ₄. The unstable composition of the drug complicates its use and assessment of its effectiveness, especially in the early stages of treatment, when precise minimum doses are needed. The effectiveness of the drug is reduced, and sometimes completely leveled, also due to its poor absorption by the mucous membrane of the gastrointestinal tract.

In addition to thyroidin, the pharmacy network has thyroxine tablets of 100 mcg T4 _, triiodothyronine - 20 and 50 mcg (Germany), as well as combination drugs: thyreocomb (70 mcg T4, 10 mcg T3 _and 150 mg potassium iodide), thyreotom (40 mcg T4 _, 10 mcg T3 ₎ and thyreotom forte (120 mcg T4 _, 30 mcg T3 ₎. Combination drugs suppress TSH secretion more effectively. Replacement therapy for hypothyroidism is carried out throughout life, excluding transient forms of the disease, for example, in case of an overdose of antithyroid drugs during the treatment of toxic goiter or in the early postoperative period after surgical removal of the thyroid gland. Currently, thyroid drugs are used in the treatment of toxic goiter in combination with antithyroid drugs to eliminate their goitrogenic effect and overdose, but the latter is not always done thoughtfully enough; thyroid hormones are often prescribed before the elimination of toxic effects and in unjustifiably large doses.

The main principle of treating hypothyroidism is based on careful and gradual, especially at the beginning of treatment, selection of the dose taking into account the age of patients, the severity of hypothyroidism, the presence of concomitant diseases and the characteristics of the drug. It is a mistake to think that the young age of patients allows for the active use of thyroid drugs at the very beginning of treatment. The determining and limiting factor in medical tactics is not so much age (although it is also important), but the severity and duration of the disease without treatment. The more severe the hypothyroidism and the longer patients of any age have been without replacement therapy, the higher their overall sensitivity, especially the susceptibility of the myocardium to thyroid drugs, and the more gradual the adaptation process should be. An exception is comatose states, when urgent measures are needed.

Triiodothyronine has 5-10 times greater biological activity than thyroxine. The first signs of its action appear after 4-8 hours, maximum on the 2-3rd day, complete elimination - after 10 days. When taken orally, 80-100% of the dose taken is absorbed. The speed of the effect allows using the drug in such critical situations as hypothyroid coma or the threat of its development. On the contrary, triiodothyronine is not suitable for monotherapy, since frequent and fractional doses are necessary to create a stable level in the blood. In this case, the risk of negative cardiotropic effects increases, especially in elderly patients. It is more advisable to use thyroxine, and in its absence - combination drugs or small doses of T ₃ in combination with thyroidin. Since 80% of circulating T3 _is formed as a result of peripheral metabolism of thyroxine and only 20% is of thyroid origin, treatment with thyroxine provides a high probability of approaching truly physiological ratios. The drug, like triiodothyronine, is well absorbed in the gastrointestinal tract, but, acting more slowly (half-life is 6-7 days), is devoid of many of the negative properties of T3 _both when administered orally and intravenously. Initial doses of T3 _should be within 2-5 mcg, thyroidine - 0.025-0.05 g. Doses of T3 _are initially increased every 3-5 days by 2-5 mcg and thyroidine by 0.025-0.05 g every 7-10 days. When using combination drugs, the initial dose is 1/4-1/8 of a tablet. Further increase is carried out even more slowly - once every 1-2 weeks until the optimal dose is reached.

Foreign researchers recommend using thyroxine, starting with 10-25 mcg, increasing the dose by 25 mcg every 4 weeks (up to 100-200 mcg). In comparative studies, 25 mcg of T3 turns out to be equivalent to 100 mcg of T4 mainly in terms of its effect on visceral organs (myocardium), but not on the level of TSH secretion, which is less dependent on T3 _. Elimination of lipid disorders under the influence of T4 goes in parallel with the normalization of the TSH level, and often even ahead of it. The proposed schemes are purely indicative. In the case of a combination of hypothyroidism and pregnancy, it is necessary to conduct full-fledged replacement therapy to prevent abortion and congenital malformations in the fetus.

As already mentioned, tachycardia and/or arterial hypertension should not prevent the administration of hormones, however, with the onset of thyroid therapy, the sensitivity of beta-adrenergic receptors in the myocardium to endogenous catecholamines increases, which causes or intensifies tachycardia. In this regard, the use of beta-blockers in small doses (10-40 mg/day) along with thyroid hormones is necessary. Such a combination of drugs reduces the sensitivity of the cardiovascular system to thyroid therapy and shortens the adaptation time. Beta-blockers in patients with hypothyroidism are used only in combination with thyroid hormones.

In secondary hypothyroidism, often combined with hypocorticism, a rapid increase in the dose of thyroid hormones can cause acute adrenal insufficiency. In this regard, replacement therapy with corticosteroids should be prescribed simultaneously with thyroid therapy or slightly precede it. Small doses of glucocorticoids (25-50 mg cortisone, 4 mg polcortolone, 5-10 mg prednisolone) can be useful in adapting to thyroid hormones in the first 2-4 weeks in patients with severe hypothyroidism. A particularly favorable effect of corticosteroids on the general condition and immunobiochemical indices was noted in patients with spontaneous hypothyroidism. Intercurrent diseases do not require interruption of thyroid therapy. In the case of a "fresh" myocardial infarction, thyroid hormones are discontinued several days before and re-prescribed in a lower dose. It is more appropriate to use thyroxine or thyroidin rather than triiodothyronine. In this case, the ability of thyroid hormones to enhance the effect of anticoagulants should be taken into account.

The complexity of treating hypothyroid coma is determined not only by the critical severity of the patient and the need for complex therapeutic measures, but also by the often elderly age of patients, in whom high sensitivity of the myocardium to thyroid drugs limits their use in large doses. With a low metabolic balance, overdoses of cardiac glycosides, diuretics, tranquilizers, etc. easily occur. Treatment of hypothyroid coma is based on the combined use of large doses of thyroid hormones and glucocorticoids. It is recommended to begin treatment with intravenous thyroxine at 250 mcg every 6 hours, which leads to an increase and saturation of the hormone level in peripheral tissues within 24 hours. Then switch to maintenance doses (50-100 mcg / day). However, since the effect of thyroxine appears later and is more extended in time, most authors recommend starting treatment with triiodothyronine, which significantly faster shows its general metabolic effect and more quickly penetrates the central nervous system through the blood-brain barrier. The initial dose of T3 _- 100 mcg is administered through a gastric tube, then adding 100-50-25 mcg every 12 hours, varying the dose depending on the increase in body temperature and the dynamics of clinical symptoms. Slow absorption through the mucous membrane of the gastrointestinal tract dictates the need for intravenous administration of triiodothyronine. In the absence of ready-made drugs, they are combined from tablets. A. S. Efimov et al. in a detailed description of hypothyroid coma, based on an analysis of the literature, provide specific recommendations for the preparation of triiodothyronine for parenteral administration.

Simultaneously with thyroid hormones, 10-15 mg of prednisolone or 25 mg of water-soluble hydrocortisone are administered by drip or through a gastric tube every 2-3 hours, and 50 mg of hydrocortisone intramuscularly 3-4 times a day. After 2-4 days, the dose is gradually reduced.

The anti-shock measures include the introduction of 5% glucose, plasma substitutes, and angiotensin. Norepinephrine should not be used, as it increases coronary insufficiency in combination with thyroid drugs. Fluid administration should be limited (no more than 1000 ml/day) to prevent cardiac overload and due to worsening hyponatremia. However, the latter is corrected with a sufficient dose of glucocorticoids. Cardiac glycosides are indicated, but due to the increased sensitivity of the myocardium, symptoms of their overdose easily occur. Oxygenation is indicated to eliminate acidosis and improve pulmonary ventilation, and in severe cases, controlled breathing. To prevent further heat loss, passive insulation is recommended by wrapping with blankets, slowly increasing room temperature (by 1 °C per hour) to no higher than 25 °C. Active surface heating (heating pads, reflectors) is not recommended, since peripheral vasodilation worsens the hemodynamics of internal organs. After consciousness is restored, the general condition improves, and heart rate and respiration return to normal, the required dose of thyroid drugs is maintained, and glucocorticoids are gradually discontinued.

In patients with atherosclerosis, hypertension, angina and myocardial infarction, full compensation of thyroid insufficiency should not be achieved: maintaining mild hypothyroidism will to a certain extent guarantee against drug overdose. Normalization of the level of thyroid-stimulating and thyroid hormones in the blood is also not an end in itself, although the speed and degree of TSH reduction may indicate the rate of compensation and the adequacy of the dose.

A number of studies indicate that myocardial receptors are much more sensitive to thyroid hormones, especially T3 _, than pituitary receptors. Therefore, symptoms of clinical overdose occur much earlier than normalization of TSH levels in the blood. When selecting an adequate dose and evaluating the effectiveness, one should focus on the dynamics of clinical symptoms, ECG, improvement of the lipid spectrum, and normalization of the Achilles reflex time. Until the dose is stabilized, ECG monitoring is performed after each increase. When indicated, coronary vasodilators and cardiac glycosides are used. However, it should be remembered that thyroid hormones reduce the sensitivity of the myocardium to cardiac glycosides and that in hypothyroidism, due to slow metabolism, symptoms of their overdose easily occur. Reassessment of compensation should be performed at least once a year, especially in elderly patients. A number of factors that change the stability of compensation should be taken into account. Thus, in winter the need for thyroid medications increases, but with age (over 60 years), on the contrary, it decreases. To achieve compensation, 3-6 months are required. The daily dose of thyroxine is 1-2 tablets, thyro-comb - 1.5-2.5 tablets, thyrotom - 2-4 tablets. In patients with peripheral resistance to thyroid hormones, the daily dose is significantly higher than usual.

The prognosis for life is favorable. The first symptoms of the effectiveness of thyroid therapy appear already at the end of the first week in the form of a decrease in chilliness, sometimes an increase in diuresis. However, fluid retention may persist even after the restoration of the euthyroid state and indicate inadequate production of vasopressin. Restoration of 50% of working capacity and lipolytic effects on physical activity and intravenous administration of norepinephrine occurs in the first 6-9 weeks with a thyroxine dose of 80-110 mcg, most often not the final one.

These data should be taken into account when assessing the working capacity of patients and not forcing a return to work in severe cases. With compensated hypothyroidism, working capacity is usually preserved.