The activity of proliferation and apoptosis of thyrocytes in the thyroid tissue of patients of nodular goiter with autoimmune thyroiditis considering the polymorphism of the BCL-2 (RS17759659), CTLA-4 (RS231775), APO-1/FAS (RS2234767) genes

Nodular goiter with autoimmune thyroiditis is one of the most important problems of modern endocrinology, with inadequately studied etiological and pathogenic mechanisms of development. It is characterized by the lack of objective and reliable diagnostic methods, effective treatment methods, uncertain therapy or indications for the choice of treatment methods. A total we have examined 125 patients who were operated for a nodular endemic goiter with autoimmune thyroiditis. Investigated the activity of proliferation and apoptosis of thyrocytes in the thyroid tissue of patients of nodular goiter with autoimmune thyroiditis considering the polymorphism of the bcl-2 (rs17759659), ctla-4 (rs231775), apo-1/fas (rs2234767) genes. The expression/density markers - Fas/ FasL, Bcl-2, p53 and Ki-67 on the thyrocytes in the lymphoid infiltration and destruction areas, as well as in normal thyroid tissue (as a control) were studied. The number of immunoreactive cells, which expressed the above-mentioned regulating apoptosis and proliferation markers in NGAIT patients, depending on the genes polymorphism BCL-2 (rs17759659), CTLA-4 (rs231775) and APO-1/Fas (rs2234767) were counted. It was found that in NGAIT patients a few links of programmable thyroid cell killing of Fas-induced apoptosis were activated, and associated with the polymorphic cite of BCL-2 (rs17759659) gene and almost 6 times weaker with CTLA-4 (rs231775) gene, through enhanced expression of Fas and Fas L on the cells surface in lymphoid infiltration and destruction areas (stronger in GG genotype carriers of BCL2 gene)

Changes in the vulnerability of clinical manifestations of thyrotoxic cardiomyopathy as indicators of remote results of surgical treatment in patients with toxic goiter

The aim of the work – improvement of the evaluation method of remote results of surgical treatment in patients with toxic goiter, taking into account the changes in the severity of clinical manifestations of thyrotoxic cardiomyopathy Materials and methods. The research was conducted in 150 patients operated for toxic goiter of moderate severity (48) and severe (102). The method of estimation of remote results of surgical treatment, taking into account the regression of signs of thyrotoxic cardiomyopathy and gradation and division into good, satisfactory, unsatisfactory and ineffective treatment, was developed. Results and discussion. A good remote outcome of surgical treatment of thyrotoxicosis was achieved in 26 (54.2 %) patients with moderate thyrotoxicosis and in 9 (8.8%) patients with severe thyrotoxicosis, satisfactory in 21 (43.7 %) and 36 (35, 3%) cases respectively and unsatisfactory – in 1 (2.0 %) and 33 (32.4 %). Ineffective surgical treatment was recognized in 24 (23.5 %) patients. Unsuccessful results and ineffective surgical treatment of toxic goiter were found in patients with severe heart rate rhythm disorders, structural and functional changes in the cardiac muscle and functional classes II and III. Conclusions. Long-term results of surgical treatment of patients with toxic goiter are determined by the severity of thyrotoxic cardiomyopathy. In cases of severe thyrotoxicosis, the question of the need for surgical treatment should be put in the development of severe heart rhythm disorders and structural and functional changes in the heart muscle

Drug therapy in autoimmune thyroiditis

Background. Autoimmune thyroiditis (AIT) is one of the unsolved problems of modern endocrinology, the etiology and pathogenesis being still insufficiently known. Objectives. To study the effects of substitution, antioxidant and lymph-drainage ther­apy on the structure and function of the thyroid gland in patients with AIT and hypothyroidism. Methods. We have identified 2 groups of patients with AIT and subclinical hypothyroid­ism. The first group – control group – included 20 patients who received substitution therapy with thyroxine. The second group included 33 patients who received a comprehensive treatment with thyroxine, alpha lipoic acid and Lymphomyosot. Results. The use of substitution therapy with thyroxine and the proposed an­tioxidant and lymph drainage therapy in patients with AIT led to the improve­ment of the structure of the gland, reduced the activity of peroxide oxidation pro­cesses and the activity of pro-inflammatory cytokines, increased the level of anti­oxidant defense enzymes, normalized the number of aniline-positive lymphocytes, improved the lymphatic drainage function of the gland. Our results sustain the effectiveness of the proposed method of complex treatment in patients with autoimmune thy­roiditis

Evaluation of remote results of surgical treatment of nodular endemic goiter with autoimmune thyroiditis

Introduction. Autoimmune thyroiditis is one of the most important problems of modern endocrinology, with inadequately studied etiological and pathogenic mechanisms of development. It is characterized by the lack of objective and reliable diagnostic methods, effective treatment methods, uncertain therapy or indications for the choice of treatment methods. The aim of the study. Determination of markers for prediction of clinical course and choice of surgery’ volume in patients with nodular goiter and autoimmune thyroiditis, taking into account the oxidative, autoimmune and apoptotic processes. Material and methods. A total of 95 patients who were operated for a nodular endemic goiter on the background of autoimmune thyroiditis were examined. The status of pro- and antioxidant systems, the activity of proinflammatory cytokines, hormonal function of thyroid gland, the level of antibodies to thyroperoxidase, thyroglobulin antibodies and ultrasound structural changes in the thyroid gland have been evaluated in all patients, before and after surgery. Results. In patients with nodular endemic goiter and autoimmune thyroiditis, in the remote period after surgical treatment, there is a significant increase in the peroxide oxidation index and a decrease in the activity of antioxidant defense systems, against the suppression of apoptotic processes and the activation of pro-inflammatory cytokines. These processes lead to functional failure, hyperplasia and the progression of structural thyroid abnormalities, with progression of the functional incapacity of the thyroid gland and inadequate long-term outcome of treatment. Conclusions. The study allowed to clarify the indications and contraindications of different methods of treatment in patients with NGAIT, taking into account the parameters of severity of peroxide oxidation processes, the activity of apoptosis and functional capacity of the gland

MOLECULAR-GENETIC MECHANISMS IN DEVELOPMENT OF DEGREE OF FUNCTION AND HYPERPLASIA OF THYROID GLAND OF PATIENTS WITH NODULAR GOITER WITH AUTOIMMUNE THYROIDITIS AND THYROID ADENOMA

Introduction. Autoimmune thyroiditis affects in average 2% to 5% of the general population, with young adult females and the elderly being the most vul-nerable patients. Hashimoto's thyroiditis causing hypothyroidism is the most prevalent etiology. Although genetics is well known to cause and influence the progression of autoimmune diseases in approximately 79%, other environmental factors are known to be involved in the development of autoimmune thyroid dis-eases: quantity of ingested iodine, stress, drugs, pregnancy, and changes in sexual hormones. Autoimmune thyroiditis, as a background disease of nodular goiter, in which hypothyroidism usually develops, has been insufficiently studied. Material and methods. The BCL-2 (rs17759659), CTLA-4 (rs231775), Fas (rs2234767) genes' polymorphism were studied by Real-Time Polymerase Chain Reaction in 95 patients with NGAIT, 30 patients with thyroid adenoma (TA) and 25 healthy individuals. The thyroid gland (TG) functional activity changes (nor-mal function, subclinical and clinical hypothyroidism) and TG hyperplasia degrees (IB, II and III) were analyzed. Results. TA and NGAIT are more common in the minor G-allele carriers (GА- and GG-genotypes) of the BCL-2 gene and in homozygous G allele patients (GG-genotype) of the Fas gene by 11.5 and 4.34 times (р<0.01), with no signifi-cant interdependence between the CTLA4 gene's genotypes. TG hyperplasia in patients' general cohort as well as in those with NGAIT is associated with the wild A alleles of the CTLA-4 gene (АА- and AG-genotypes): the І and ІІІ degree hy-perplasia occurred reliably more frequently in the AA genotype carriers, and ІІ degree of the TG enlargement in the AG genotype patients. Conclusions. Pathology of the thyroid gland has unreliable chances to be inherited depending on the polymorphism of BCL-2 (rs17759659), CTLA-4 (rs231775) and Fas (rs2234767) genes in Bukovina region (Western Ukraine). We did not find any difference between the relative incidences of the genotypes of the analyzed genes in the patients with NGAIT and those with TA or depending on the TG function (euthyroid goiter, subclinical and clinical hypothyroidism).

CHARACTERISTICS AND FEATURES OF CLINICAL MANIFESTATIONS OF PRIMARY HYPERALDOSTERONISM (LITERATURE REVIEW)

Introduction. Primary hyperaldosteronism as a cause of secondary arterial hypertension ranges from 4.6 to 13.0%, and among patients with refractory hypertension to medication therapy is about 20%. Meanwhile, its detectability among patients with arterial hypertension in centers of primary health care is from 6 to 13%, and in secondary care centers – from 23 to 30%. The high frequency of life-threatening cardiovascular complications dictates the need for early and timely diagnosis of primary hyperaldosteronism in the stages of the primary and secondary units of medical care. In addition, studies conducted in German and Italian hospitals among general practitioners showed a low level of knowledge about primary hyperaldosteronism. Objective. To promote the knowledge of general practitioners about clinical symptoms and clinical features of primary hyperaldosteronism. Results. Therefore, the main task of the work is the systematization and dissemination of knowledge for general practitioners about the symptoms and peculiarities of the clinical course of primary hyperaldosteronism. Such signs as an inadequate response to hypotensive therapy of a combination of three drugs, a manifestation of arterial hypertension under the age of 30, a rapid increase in blood pressure even in the elderly and/or the loss of efficacy of antihypertensive therapy, apnea in dream are distinguished in its non-specific clinical picture, without indicating priority. In the literature, there are recommendations to separate classical and secondary clinical manifestations. Classical include arterial hypertension, hypokalemia, hypervolemia, metabolic alkalosis, and minor ones such as headache, retinopathy, neuromuscular symptoms (paresthesia’s, convulsions, general weakness), carbohydrate metabolism disorders, arrhythmias, early onset of hypertrophy and fibrosis of the heart muscle and smooth muscle vessels, hypokalemia and moderate hypernatremia. Conclusions. In the clinical course of the disease, the cardiovascular, neuromuscular, renal and metabolic syndromes are distinguished, or in combination of several of them, in each particular case, the primary hyperaldosteronism may appeared (or manifested)

INFLUENCE OF THE CTLA-4 (RS231775) GENE POLYMORPHISM ON THE DEGREE OF THE THYROID GLAND ENLARGEMENT IN PATIENTS OPERATED FOR NODULAR GOITER SECONDARY TO AUTOIMMUNE THYROIDITIS

Objectives: To analyze the influence of the CTLA-4(+49G/A)rs231775 gene polymorphism on the degree of thyroid gland enlargement in patients operated for nodular goiter secondary to autoimmune thyroiditis (NGAIT) and thyroid adenomas (TA). Also, to analyze the clinical course of the disease, depending on the genotype of this gene. Methods: The CTLA-4 (rs231775) genes' polymorphism were studied by Real-Time Polymerase Chain Reaction in 95 patients with NGAIT, 30 patients with TA and 25 healthy individuals. Results: It has been found that, in patients with nodular goiter secondary to autoimmune thyroiditis, hyperplasia of the thyroid gland is associated with the wild A allele of the CTLA-4 gene (AA- and AG-genotypes): IB and III levels of hyperplasia are more likely to occur in carriers of the AA genotype by 30.13% and 26.35%, and the second degree of the thyroid gland enlargement- in patients with the AG-genotype by 33.52% and 34.04%, respectively. Conclusions: The incidence of the hypertrophic form of autoimmune thyroiditis is associated with AA- and AG-genotypes of the CTLA-4 gene, characterized by a particular severity, with the rapid development of an "aggressive" proliferative process in the thyroid tissue, according to sonographic findings. The carrier of the GG genotype is associated with an atrophic origin of autoimmune thyroiditis; the tissue is characterized by a high content of cells in which there are atypical or follicular changes of an unclear genesis

Electrophysiological identification of nerves of the larynx among the tissuesof operative wound in goiter surgeries

The objective of the study was to analyze the technology of electrophysiological identification of laryngeal nerves in goîter surgeries. Methods: The technology of electrophysiological identification of laryngeal nerves in goiter surgeries was developed. It is based on the recording of changes in the sound vibrations generated by the passage of air through the voice gap, the area of which changes in the event of a change in the tension of vocal cords from electrostimulation of the laryngeal nerves. The greatest changes in the frequency and amplitude of sound vibrations occur when electrostimulation of tissues near the nerve and the nerve itself. This phenomenon allows to determine the location of the nerve and prevent its injury. Results: The method was tested in 173 patients who had been operated for goiter. There were no cases of temporary or permanent disorders of phonation. Conclusions: The developed technology of electrophysiological identification of laryngeal nerves in goiter surgeries is reliable, easy to apply, and is not expensive. The influence of other factors on its results was not noted

Remote results of hemithyroidectomy and their prognostication in patients with unilateral nodular goiter combined with autoimmune thyroiditis

As a result of the histological examination of the removed thyroid tissue, autoimmune thyroiditis has been diagnosed in 10.4% of patients. During the surgical treatment and while choosing the surgery volume, the pathogenetic mechanisms of the onset and progression of autoimmune processes in the thyroid tissue are not taken into account