Treatment of hypothyroidism

The main method of treating all forms of hypothyroidism is substitution therapy with thyroid medications. TSH preparations have allergic properties and are not used as a remedy for secondary (hypophysial) hypothyroidism. Recently, there have been studies on the efficacy 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 the secretion of biologically inactive TSH.

The most common domestic drug is thyroidin, obtained from the dried thyroid gland of cattle in the form of pills of 0.1 or 0.05 g. The amount and ratio of iodothyronines in thyroidin varies considerably in different batches of the drug. Approximately 0.1 g of thyroidin contains 8-10 μg of T ₃ and 30-40 μg of T ₄. Unstable composition of the drug makes it difficult to use and evaluate its effectiveness, especially at the first stages of treatment, when exact minimum doses are needed. The efficacy of the drug is reduced, and sometimes completely eliminated, because of its poor absorption of the mucosa of the gastrointestinal tract.

Besides thyroidin in pharmacy network available thyroxine tablets of 100 g T ₄, triiodothyronine - 20 and 50 micrograms (Germany), as well as combination preparations: Thyreocombum (70 ug T4, 10 g of T ₃ and 150 mg of potassium iodide) tireotom ( 40 μg T ₄, 10 μg T ₃ ) and thyrotomized forte (120 μg T ₄, 30 μg T ₃ ). Combined drugs effectively suppress the secretion of TSH. Substitution therapy for hypothyroidism is carried out throughout life, excluding transient forms of the disease, for example, with an overdose of thyreostatic drugs during treatment of toxic goiter or in the early postoperative period after surgical removal of the thyroid gland. Currently, thyroid preparations are used in the treatment of toxic goiter in combination with thyreostatics to eliminate their zobogenic effect and overdose, but the latter is not always carried out reasonably well, often thyroid hormones are prescribed until the elimination of toxic phenomena and in unjustifiably large dosages.

The main principle of the treatment of 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 imagine that the young age of patients allows active use of thyroid preparations at the very beginning of treatment. Defining and limiting the medical tactics is not so much age (although he, too), how much the severity and duration of the disease without treatment. The heavier the hypothyrosis and the longer the patients of any age without substitution therapy, the higher their overall sensitivity, especially the susceptibility of the myocardium to thyroid preparations, and the more gradual the adaptation process should be. The exception is comatose states, when urgent measures are needed.

Triiodothyronine has 5-10 times more biological activity than thyroxine. The first signs of its action appear in 4-8 hours, a maximum of 2-3 days, complete elimination - after 10 days. When administered orally, 80-100% of the dose is absorbed. The rapidity of the effect makes it possible to use the drug in such critical situations as the hypothyroid coma or the threat of its development. On the contrary, triiodothyronine is not suitable for monotherapy, since frequent and fractional techniques are required to create a stable level in the blood. This increases the risk of negative cardiotropic effects, especially in elderly patients. It is more expedient to use thyroxine, and in its absence - combined drugs or small doses of T ₃ in combination with thyroidin. Since 80% of circulating T _{3 is} formed as a result of peripheral metabolism of thyroxine and only 20% is of thyroid origin, treatment with thyroxin gives a greater likelihood of approaching truly physiological relationships. A formulation as well as triiodothyronine, is well absorbed in the gastrointestinal tract but, acting slowly (half-life - 6-7 days), devoid of many negative properties of T ₃ and after oral and intravenous administration. The initial dose of T ₃ should be in the range of 2-5 mcg thyroidin - 0.025-0.05 doses of T ₃ is increased initially every 3-5 days to 2-5 ug and thyroidin at 0.025-0.05 g every 7-10 days. When using combination drugs, the initial dose is 1 / 4-1 / 8 tablets. Further increase is even slower - 1 every 1-2 weeks until the optimal dose is reached.

Foreign researchers recommend using thyroxine, starting at 10-25 μg, increasing the dose by 25 μg every 4 weeks (up to 100-200 μg). In comparative studies, 25 μg of T3 is equivalent to 100 μg of T4, mainly on the effect on visceral organs (myocardium), but not on the secretion level of TSH, less dependent on T ₃. Elimination of lipid disorders under the influence of T4 goes in parallel with the normalization of the level of TSH, and often outstrips it. The proposed schemes are purely indicative. When combined with hypothyroidism and pregnancy, a full replacement therapy should be used to prevent abortion and congenital malformations in the fetus.

As already indicated, tachycardia and / or hypertension should not interfere with the administration of hormones, but with the onset of thyroid therapy, the sensitivity of beta-adrenergic receptors in the myocardium to endogenous catecholamines increases, which causes or enhances tachycardia. In this regard, the use along with thyroid hormones beta-blockers in small doses (10-40 mg / day) is necessary. This 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 associated with hypokorticism, a rapid increase in thyroid hormone dose can cause acute adrenal insufficiency. In this regard, substitution therapy with corticosteroids should be given concomitantly with thyroid or somewhat precede it. Small doses of glucocorticoids (25-50 mg cortisone, 4 mg polcortolone, 5-10 mg prednisolone) may 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 parameters was observed in patients with spontaneous hypothyroidism. Intercurrent diseases do not require the interruption of thyroid therapy. In the case of a "fresh" myocardial infarction, thyroid hormones are canceled in a few days and reassigned in a smaller dose. It is more expedient to use thyroxine or thyroidin, and not triiodothyronine. In this case, the ability of thyroid hormones to enhance the action of anticoagulants should be considered.

The complexity of the treatment of hypothyroid coma is determined not only by the critical severity of the patient and the need for complex therapeutic measures, but also often by the elderly age of patients in whom high sensitivity of the myocardium to thyroid drugs limits their use in large dosages. With a low metabolic balance, there are easily overdoses of cardiac glycosides, diuretics, tranquilizers, etc. 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 administration of thyroxin at 250 μg every 6 hours, which leads to an increase and saturation of the level of the hormone in the peripheral tissues within 24 hours. Then switch to maintenance doses (50-100 μg / day). However, since the action of thyroxin appears later and is more prolonged in time, most authors recommend starting treatment with triiodothyronine, which significantly manifests its overall metabolic effect and quickly penetrates the central nervous system through the blood-brain barrier. The initial dose of T ₃ is 100 μg administered through the gastric tube, then adding 100-50-25 μg every 12 hours, varying the dose depending on the rise in body temperature and the dynamics of clinical symptoms. Delayed absorption through the mucous membrane of the gastrointestinal tract dictates the need for intravenous administration of triiodothyronine. In the absence of finished preparations, they are combined from tableted. A. S. Efimov et al. In a detailed description of the hypothyroid coma, based on an analysis of the literature, give 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 injected every 2-3 hours, or intramuscularly - 50 mg of hydrocortisone 3-4 times a day at the same time as thyroid hormones. After 2-4 days the dose is gradually reduced.

The complex of anti-shock measures includes the introduction of 5% glucose, plasma substitutes, angiotensin. Do not use norepinephrine, which in combination with thyroid medications increases coronary insufficiency. The introduction of fluid should be limited (not more than 1000 ml / day) to prevent cardiac congestion and the aggravation of hyponatremia. However, the latter is corrected by a sufficient dose of glucocorticoids. Cardiac glycosides are shown, but because of the increased sensitivity of the myocardium, the symptoms of their overdose easily appear. To eliminate acidosis and improve pulmonary ventilation, oxygenation is indicated, and in severe cases, controlled breathing. To prevent further loss of heat, passive warming is recommended by wrapping with blankets, a slow increase in room temperature (by 1 ° C per hour) is not higher than 25 ° C. Active surface heating (warmers, reflectors) is not recommended, as peripheral vasodilation worsens the hemodynamics of internal organs. After restoration of consciousness, improvement of general condition, normalization of heart rate and respiration, the necessary dose of thyroid preparations is left, and glucocorticoids are gradually canceled.

In patients with atherosclerosis, hypertension, angina pectoris and those who underwent myocardial infarction, full compensation for thyroid insufficiency should not be sought: the maintenance of mild hypothyroidism will to some extent be a guarantee against drug overdose. Also, the normalization of the level of thyroid-stimulating and thyroid hormones in the blood is not an end in itself, although the speed and degree of decrease in TSH may indicate the rate of compensation and the adequacy of the dose.

A number of studies indicate that myocardial receptors are significantly more sensitive to thyroid hormones, especially to T ₃, than the pituitary receptors. Hence the symptoms of a clinical overdose occur much earlier than the normalization of the level of TSH in the blood. When selecting an adequate dose and evaluating the effectiveness should focus on the dynamics of clinical symptoms, ECG, improving the lipid spectrum, the normalization of the time of the Achilles reflex. Prior to the stabilization of the ECG dose, monitoring is performed after each increase. At the testimony, coronary dilatation drugs, cardiac glycosides are used. However, it should be remembered that thyroid hormones reduce the sensitivity of the myocardium to cardiac glycosides and that hypothyroidism due to delayed metabolism easily causes symptoms of their overdose. Revaluation of compensation should be conducted at least once a year, especially in elderly patients. It should take into account a number of points that change the stability of compensation. So, in winter, the need for thyroid drugs increases, but with age (over 60 years), on the contrary, decreases. To achieve compensation, it takes 3-6 months. The daily dose of thyroxine is 1-2 tablets, thyreo-comba - 1.5-2.5 tablets, thyreotomy - 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 as a decrease in chilliness, sometimes an increase in diuresis. However, fluid retention can persist even after the restoration of the euthyroid state and indicate an inadequate production of vasopressin. Recovery of 50% efficiency and lipolytic effects on physical activity and intravenous norepinephrine is carried out in the first 6-9 weeks with a dose of 80-110 μg thyroxine, most often not definitive.

These data should be taken into account when assessing the patients' ability to work and not forcing them to return to work in difficult cases. With compensated hypothyroidism, work capacity, as a rule, is preserved.