Nodular Thyroid Pathology Research Articles

Uni- and Multivariate Analyses of Cancer Risk in Cytologically Indeterminate Thyroid Nodules: A Single-Center Experience.

Every year in Italy, about 60,000 new cases of nodular thyroid pathology are diagnosed, of which almost 30% are cytologically indeterminate (TIR3A/3B). The risk of malignancy reported in the literature on thyroid nodules ranges from 5% to 15% for TIR3A and from 15% to 30% for TIR3B. It is suspected that these percentages are higher in practice. We performed univariate and multivariate analyses of clinical risk factors. The medical records of 291 patients who underwent surgery for cytologically indeterminate nodular thyroid disease were retrospectively reviewed. Clinical parameters and preoperative serum markers were then compared between the benign nodular thyroid disease and thyroid cancer groups. For each patient, clinical characteristics, comorbidities, neck ultrasonographic features, and histological reports were statistically analyzed using Chi-squared and Fisher's exact tests. A total of 134 malignant neoplasms were found (46%), divided into 55 cases (35%) in the TIR3A group and 79 cases (59%) in the TIR3B group. Statistical analysis was not significant in both populations for both sex and age (TIR3A p-value = 0.5097 and p-value = 0.1430, TIR3B p-value = 0.5191 p-value = 0.3384), while it was statistically significant in patients with TIR3A nodules associated with thyroiditis (p-value = 0.0009). In addition, the patients with TIR3A and 3B nodules were stratified by ultrasound risk for the prediction of malignancy and it was significant (p = 0.0004 and p < 0.0001). In light of these results, it emerges that surgical treatment of nodular thyroid pathology with indeterminate cytology TIR3A should always be considered, and surgery for TIR3B is mandatory.

ULTRASOUND SIGN «CALCIFICATION» OF NODULAR THYROID NEOPLASMS WHEN USING THE TI-RADS SYSTEM (CASE REPORT)

The problem of improving the quality of early differential diagnosis of thyroid nodules remains relevant, since the number of patients with this pathology is steadily increasing. Obtaining reliable criteria for node malignancy is clinically significant for carrying out further therapeutic and diagnostic measures. In the case of detecting calcifications during ultrasound examination of the thyroid gland, the choice of tactics becomes more complicated, since today there is no unified understanding of the value of calcifications, and contradictions in their assessments persist. The aim is to demonstrate the complexity of differential diagnosis of nodular thyroid pathology using the clinical example. Results. The article presents a clinical case which is complex from a diagnostic point of view; it is a clinical case of nodular thyroid pathology in a patient aged 71 years. To make the diagnosis, a multiparametric ultrasound examination was performed in В-mode. Based on the results of multiparametric ultrasound examination, indications for a fine needle aspiration biopsy were determined and further management for the patient with nodular thyroid formation was determined. The results of the multiparametric ultrasound examination were ambiguous. In B-mode, the nodes were characterized by a hypoechogenic heterogeneous structure with multiple cystic cavities with intersections and microcalcifications. Taking into account these signs, the nodes were assessed as malignant (TI-RADS4). The patient underwent a fine needle aspiration biopsy, the results of which indicated goiter with signs of regressive changes (Bethesda II). The conclusion of the pathomorphological study indicated stromal calcinosis. Conclusions. Taking into account the ultrasound sign of "calicificates" made it possible to more accurately assess the nature of pathomorphological changes in the nodes in the right (TI-RADS4) and left (TI-RADS4) lobes of the thyroid gland, which was then confirmed by a pathomorphological study. Thus, multiparametric ultrasound remains the leading method in the diagnosis of nodular thyroid pathology.

Structural and morphologic characteristics of nodular goiter in chronic iodine deficiency status

OBJECTIVES. Diffuse and nodular goiter are the most common thyroid gland (thyroid) diseases in children and adults living in iodine-deficient regions. Thyroid hormone potentiates progressive hypertrophy and hyperplasia of thyrocytes, with uneven proliferation of thyroid cells leading to nodule formation. Iodine deficiency, which promotes replication of thyroid follicular cells, also increases the incidence of TSH Receptor mutations, leading to receptor activation and autonomous functioning of follicles.AIM. To evaluate and describe ultrasound and cytologic thyroid nodes in the regions in Russia with proven iodine deficiency.MATERIALS AND METHODS. The study was conducted in regions with proven iodine deficiency in the Central and North Caucasian Federal Districts. Population of conditionally healthy adult volunteers (mean age — 47.5 years) was recruited as part of visiting events to screen for the occurrence of thyroid nodes.RESULTS. The results obtained indicate a high prevalence of multinodular colloid goiter in adult patients living in conditions of chronic iodine deficiency. In the Chechen Republic, the prevalence of nodular thyroid pathology was found in 64.5% (205/318) of cases, and in the Tula region — in 40.6% (116/286). In the studied sample the results of cytologic examination confirmed the presence of colloid thyroid masses in 97% (60/62) — Bethesda category II; in 3% (2/62) of patients nodular masses had Bethesda IV. Diffuse goiter prevalence in the examined population was 20.8%.CONCLUSIONS. A study indicates a high prevalence of iodine-deficient thyroid disease — multinodular colloid goiter in regions with proven chronic iodine deficiency. The wide prevalence of goiter with colloid and cystic components is confirmed by the cytologic examination with different ultrasound characteristics according to the EU-TIRADS classification. The obtained data correspond to the official statistics demonstrating high prevalence of nontoxic goiter in adults in the examined regions, which is an important argument confirming the need for systemic iodine prophylaxis.

The problem of iodine deficiency in the Chechen republic: assessment of the current state and ways of solution

To conduct a comprehensive study to assess the current iodine security of the population of the Chechen Republic, to analyze the prevalence of thyroid pathology and compare it with official statistics, to formulate conclusions about the necessary preventive measures. In the Chechen Republic, a total of 1239 people were examined, of which 921 were schoolchildren of pre-pubertal age (8-10 years) and 318 were adults. The survey of the adult population was carried out at medical organizations in four districts of the republic (Nadterechny, Shalinsky, Vedensky, Grozny) and included a questionnaire survey, a clinical examination by an endocrinologist with palpation of the thyroid gland, thyroid ultrasound, and a study by a qualitative method of samples of table salt used in households for the presence of iodine.Children's examinations were carried out by the cluster method on the basis of secondary schools in 9 out of 15 districts of the republic and included an examination by an endocrinologist and measurement of anthropometric parameters (height, weight), thyroid ultrasound to evaluate volume, determination of iodine concentration in single portions of urine and qualitative analysis of samples of table salt used in children's nutrition in families for the presence of iodine.The incidence and prevalence of thyroid disease among the population of the Chechen Republic were analyzed using data from official state statistics - form No. 12 «Information on the number of diseases registered in patients living in the area served by the medical institution» (ROSSTAT data as of 01.01.2021). According to the results of a survey of 921 pre-pubertal children, the median urinary iodine concentration was 71.3 µg/L (frequency of values below 50μg/L - 17,7%) and varies from 48.9 to 179.2 µg/L in the surveyed areas. According to thyroid ultrasound data, diffuse goiter was detected in 16.4% of the examined children, with goiter frequency ranging from 11.3% to 23.5%. The proportion of iodized salt consumed in schoolchildren's families was 4.2% in all study areas (range of values from 1.3% to 8%), which indicates an extremely low level of using iodized salt by household.According to the results of the examination of the adult population (n=318), structural changes in thyroid tissue were detected in 79.9% (n=254), while the proportion of nodular thyroid pathology being 83% (n=205), with a range of values across different districts of 52.5-80%. Based on the obtained data, according to WHO criteria, it can be stated that, overall, the degree of severity of iodine deficiency disorders in the Chechen Republic corresponds to mild severity with a tendency towards moderate severity in several districts of the foothills. The results of the examination of the adult population indicate a high prevalence of thyroid pathology, predominantly nodular, in the Chechen Republic. The data obtained in the course of large-scale research made it possible to initiate the development of necessary medical and organizational measures in the region - a program for the prevention of IDD.

Real-Time Evaluation of Thyroid Cytology Using New Digital Microscopy Allows for Sample Adequacy Assessment, Morphological Classification, and Supports Molecular Analysis.

Thyroid cytological examination, a key tool in preoperative thyroid nodule evaluation, is specific and accurate; some drawbacks are due to inadequate or indeterminate cytological reports and there is a need for an innovative approach overcoming the limits of traditional cytological diagnostics. Fluorescence laser confocal microscopes (FCM) is a new optical technique for allowing immediate digital imaging of fresh unfixed tissues and real-time assessment of sample adequacy and diagnostic evaluation for small biopsies and cytological samples. Currently, there are no data about the use of FCMs in the field of thyroid nodular pathology. The aims of this study were to test FCM technology for evaluating the adequacy of FNA samples at the time of the procedure and to assess the level of concordance between FCM cytological evaluations, paired conventional cytology, and final surgical histology. The secondary aim was to define the integrity of nucleic acids after FCM evaluation through NGS molecular analysis. Sample adequacy was correctly stated. Comparing FCM evaluation with the final histology, all cases resulting in malignant or suspicious for malignancy at FCM, were confirmed to be carcinomas (PPV 100%). In conclusion, we describe a successful application of FCM in thyroid preoperative cytological evaluation, with advantages in immediate adequacy assessment and diagnostic information, while preserving cellular specimens for permanent morphology and molecular analysis, thus improving timely and accurate patient management.

Post-transcriptional micro-RNAs in diagnostics and personalization of treatment in patients with thyroid tumors: literary review

Among the unsolved problems in the treatment of patients with nodular thyroid pathology, there is a large number of diagnostic operations associated with difficulties in cytological diagnostics of follicular neoplasia, limited by opportunities in preoperative assessment of the malignant potential of thyroid cancer. A decrease in the effectiveness of targeted therapy in patients with radioiodresistant thyroid cancer occurs due to the ability of the tumor to activate parallel proliferative signaling pathways. It is assumed that the key to solving these problems lies in understanding various genetic changes in the tumor cell, such as point mutations, insertions and deletions, gene merges, rearrangements or gene translocations. A special place in this list is occupied by microRNAs. It is a class of small non-coding RNAs, which regulate post-transcriptional gene expression and thereby participate in cell differentiation, proliferation, angiogenesis, apoptosis resistance and activation of thyroid cancer metastasis. This review contains information about microRNAs detected in various types of thyroid tumors of diagnostic, prognostic and therapeutic interest. While some of them have been introduced into routine practice, others are new and require additional research before clinical use.

Personalized immunohistochemical particulars of thyroid cancer in children

The idea of the paper from the state scientific program under the name „Modern personalized surgery in the diagnosis and complex treatment of tumors in children”. In the first stage, the executors conducted statistical research on the incidence of thyroid cancer in children. During 40 years from 18549 cases of nodular thyroid pathology, 1078 cases were detected at children: 105 - (9.7%) with cancer, adenomas 534 (49.5%), toxic nodular goiter 213 (19.7%) , struma Hashimoto 226 (21%),: ratio girl : boys 6: 1. The most affected age is 9-16 years. The highest morbidity is in children aged from 12 to 15 years.The morphological structure of thyroid cancer in children (105 patients) was as follows: first - papillary cancer - 68.6%, the second follicular cancer 23.8%, the third medullary cancer - 5.7% and the fourth anaplastic cancer - 1.9%.The priority goal of the authors was personalized medicine, which involves selecting an appropriate treatment for the patient, depending on the volume of the primary tumor, the morphological type and the biological evolution of the tumor. In the diagnostic plan for the assessment of tumor aggression, the authors will propose immunohistochemical research in assessing the angioinvasive aggression of thyroid carcinomas in children. It is proposed to investigate the expression of thyroiglobulin, keratin and vimentin, peroxidase. Peroxidase expression was studied in 22 children. Thyroglobulin expression was studied in 31 children. And the expression of keratin and vimentin was studied in 16 children [2, 4-6].

Scintigraphy in Thyroid Nodular Pathology

Thyroid scintigraphy is a method that formed more than 60 years ago and retains its importance for the diagnosis and assessment of the risk of nodular malignancy. The review examines the use of the scintigraphic method in functional and metabolic assessment of nodular goiter. Prerequisites for functional thyroid nodes screening with short-lived 99mTc-pertechnetate are outlined. Information is provided on the principles of its preparation and pharmacokinetics, as well as variants of the thyroid nodes functional activity, their possible malignant potential and indications for metabolic screening. The characteristic of metabolic activity allows to assess the risk of functionally “cold” thyroid nodes malignancy. The main stages of the use of nonspecific tumorotropic radiopharmaceuticals, the mechanism of their accumulation and metabolism in the thyroid tumors, the possibilities of the differential diagnosis of various types of nodular formations are presented. Modern views on the diagnostic capabilities of two-phase scintigraphy with 99mTс-methylisobutylisonitrile are reflected taking into account the relationship of radiopharmaceuticals accumulation with factors of proliferative activity and ultrastructural cell types, a variant of oncocytic pathology and multidrug-resistant protein expression.

The Role of CEUS in the Evaluation of Thyroid Cancer: From Diagnosis to Local Staging.

Ultrasound often represents the first diagnostic step for thyroid nodule evaluation in clinical practice, but baseline US alone is not always effective enough to achieve thyroid nodule characterization. In the last decades new ultrasound techniques, such as CEUS, have been introduced to evaluate thyroid parenchyma as recommended by EFSUMB guidelines, for use in clinical research field, although its role is not yet clear. Several papers show the potential utility of CEUS in the differential diagnosis of benign and malignant thyroid nodules and in the analysis of lymph node involvement in neoplastic pathology. Therefore, we carried out an evaluation of the literature concerning the role of CEUS in three specific areas: the characterization of the thyroid nodule, the evaluation of minimally invasive treatment and loco-regional staging of the lymph node in proven thyroid cancer. According to evidence reported, CEUS can also play an operative role in nodular thyroid pathology as it is able to guide ablation procedures on thyroid nodule and metastatic lymph nodes, to assess the radicality of surgery, to evaluate disease relapse at the level of the margins of ablated regions and to monitor the clinical evolution of necrotic areas in immediate post-treatment setting.

Optimization Of Diagnostics Of Nodular Thyroid Diseases Based On TI-RADS And TBSRTC Systems

To evaluate the effectiveness of the integrated use of TI-RADS and TBSRTC systems and their significance in the formation of therapeutic tactics in patients with nodular thyroid pathology.

BRAF status in сito-morphological diagnosis of thyroid nodules

The aim of study – to determine the significance of the BRAF V600E mutation presence in the cytomorphological diagnosis of thyroid nodules.Materials and methods. The study included 65 patients requiring surgical treatment for thyroid nodular pathology. Material to determine the BRAF V600E mutation was taken by means of a fine needle aspiration biopsy before surgery. The BRAF V600E mutation was detected by real-time PCR analysis.Results. A pathomorphological study of the removed thyroid nodules showed that all 22 benign nodules were BRAF-negative. Among the 43 papillary thyroid cancer only 20 were BRAF-positive (46.5 %). BRAF mutations were found more often (P < 0.001) in patients with classical and oxyphilic cell papillary thyroid cancer (60 % and 100 %, respectively) than in patients with follicular variant of PTC (6.7 %). Locally invasive tumors were more often BRAF-negative cases (P < 0.05) than non-invasive tumors and amounted to 75.0 % and 37.5 %, respectively. But, when comparing the morphological variant and invasive properties of the tumor, it was found that all cases of the follicular variant of the PC had signs of invasion and were significantly more often observed (P < 0.01) compared with the classical and oxyphilic cell variants. The BRAF V600E mutation was observed both in tumors with metastasis to the regional lymph nodes (55.0 %) and in tumors without metastases (37.5 %), with no significant difference.Conclusions. The presence of the BRAF V600E mutation is a diagnostic marker for papillary thyroid carcinoma, and its detection confirms the presence of malignancy. BRAF positive carcinomas were in 46.5 % of cases. The combination of BRAF-negative and the cytology of groups V and VI by Bethesda may indicate about a follicular variant of PTC. An increase in the number of molecular genetic markers in the preoperative diagnosis of thyroid cancer can significantly improve the quality of diagnosis and surgical treatment.

Thyroid scintigraphy in diagnosis of nodular and diffuse thyroid pathology

Diagnosis of the causes of thyrotoxicosis (destruction or increased functional activity of the thyroid tissue in nodular and diffuse thyroid pathology) is a key point in determining the management of patients with this pathology. Scintigraphy is the method of choice in differential diagnosis of the causes of thyrotoxicosis assessing the functional state of the thyroid gland. According to variable medical interest, thyroid scintigraphy can be performed using 99mTc-pertechnetate or radioactive iodine isotopes (123I, 124I, 131I). For thyroid uptake evaluation used scintigraphy with 99mTc-pertechnetate radiopharmaceutical, which is not organificates and quickly excretes from thyroid tissue. In case of thyroid iodine pharmacokinetics investigation radiopharmaceuticals labeled by iodine isotopes (123I,131I, 124I) are used. The review includes original scintigrams, tables and diagrams. Article shows thyroid scintigraphy informativity analysis, evaluates the place and role of the thyroid scintigraphy examinations in modern diagnostic algorithms taking into account the history of the disease, laboratory tests, ultrasound (TIRADS) and result ofFNA (Bethesda). Additionally authors focused on existing clinical guidelines analysis. An optimized algorithm for the diagnosis and treatment of diffuse and/or nodular thyroid pathology associated with thyrotoxicosis is proposed.

Thyroid and Pseudothyroid Dysfunction as a Cause That is Promoting the Relapse of Benign Focal Thyroid Pathology.

Several studies deal with learning causes stipulating nodular formations in the thyroid tissue, including those occurring against the ground of metabolic disorders of thyroid hormones. Our study’s objective was to determine the peculiarities of thyroid homeostasis disorders in patients suffering from benign nodular thyroid pathology with relapses of the disease and its relapse-free course. For this purpose, 96 female patients suffering from nodular thyroid pathology and 20 without thyroid pathology were examined. In the course of the study, the following were found in patients with benign focal thyroid pathology: disorders of the peripheral conversion of the thyroid hormones, compensatory activation of the hypothalamic-pituitary system evident in increased levels of the thyroid-stimulating hormone, ТSH/fT3 and ТSH/fT4 ratios, increasing titers of the anti-thyroid antibodies which can be hazardous for the risk of development of nodules or reflects the process of thyroid tissue damage; high level of thyroglobulin caused by an increased probability of relapse and rate of nodule growth, an increase of the thyroid gland volume associated with activation of the hypothalamic-pituitary system, increased antibodies titer and thyroid gland damage. Thus, changes of the examined indices in the blood can be used as prognostic markers concerning the relapse of nodule formation in the thyroid tissue.

A Rationale for Using Sonoelastography in Thyroid Nodular Pathology

Objective. To provide a rationale for using sonoelastography (SEG) in the differential diagnosis of thyroid cancer (TC).Material and methods. Thirty patients with thyroid nodules of various morphological structures were examined. The authors studied the data of SEG and immunohistochemistry (IHC) with monoclonal antibodies against types III and IV collagen (they evaluated the degree of the expressed collagen fibers). Analysis of variance, ROC analysis, and logistic regression were used (by comparing with the expression of collagens) to assess the predictive ability of ultrasound.Results. The study showed that irregular and uneven contours, microcalcifications, and “the height greater than the width” were most significant among the ultrasound signs in the diagnosis of TC. Cool colors prevailed when performing SEG in the pattern of thyroid cancer. Purple-blue hues were predominantly recorded (p&lt;0.05 with regard to benign nodules), green ones were less frequently. ROC analysis of compression elastography showed that the area under the curve was 0.785 (95% CI 0.740-0.826), sensitivity 78.1%, specificity 79.0%. Comparison of the data of IHC and SEG revealed a direct correlation of tissue elasticity with the degree of a stromal component and with the presence of collagen-containing structures.Conclusion. SEG may suppose the probable nature of thyroid nodules on the basis of their morphological features. The low degree of the stromal component and the low content of types III and IV collagen make follicular colloid goiter and adenoma soft, which is recorded at SEG. TC is characterized by a high collagen level attributable to the characteristics of the metabolism of cancer cells, which makes them solid in the mode of SEG.

Corrigendum: Medullary thyroid cancer. Returning to the need to determine the preoperative basal calcitonin level in patients with thyroid nodular pathology (Endocrine surgery. 2018;12(4). doi: 10.14341/serg10044)

A corrigendum on «Medullary thyroid cancer. Returning to the need to determine the preoperative basal calcitonin level in patients with thyroid nodular pathology»&#x0D; by Elena E. Stanyakina, Ilia S. Romanov, Tatiana T. Kondratieva, Alexander S. Krylov, Alexey D. Ryzhkov, Sergey V. Shiryaev (2018). Endocrine Surgery. 12(4). doi: 10.14341/serg10044&#x0D; There is an error on the page 189: "Blood test for hormones: thyroid stimulating hormone (TSH) — 52.6 mIU/l (reference values 0.25–4.0), adrenocorticotropic hormone (ACTH) &lt;20 IU/ml (0–30), thyreoglobulin (TG) &lt;0.2 ng/ml (0–30)". Instead of "antibodies to thyroglobulin (ATTG)" was published "adrenocorticotropic hormone (ACTH)".&#x0D; The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way.&#x0D; The original article has been updated.

Coexistent papillary thyroid carcinoma diagnosed in surgically treated patients for primary versus secondary hyperparathyroidism: same incidence, different characteristics

BackgroundThe coexistence of hyperparathyroidism and thyroid cancer presents important diagnostic and management challenges. With minimally invasive parathyroid surgery trending, preoperative thyroid imaging becomes more important as concomitant thyroid and parathyroid lesions are reported. The aim of the study was to evaluate the rate of thyroid cancer in patients operated for either primary (PHPT) or secondary hyperparathyroidism (SHPT).MethodsOur retrospective study included PHPT and SHPT patients submitted to parathyroidectomy and, when indicated, concomitant thyroid surgery between 2010 and 2017.ResultsParathyroidectomy was performed in 217 patients: 140 (64.5%) for PHPT and 77 (35.5%) for SHPT. Concomitant thyroid surgery was performed in 75 patients with PHPT (53.6%), and 19 papillary thyroid carcinomas (PTC) were found, accounting for 13.6% from all cases with PHPT and 25.3% from PHPT cases with concomitant thyroid surgery. Thirty-one of operated SHPT patients (40.3%) also underwent thyroid surgery and 9 PTC cases were diagnosed (11.7% of all SHPT patients and 29% of patients with concomitant thyroid surgery).We found differences between PHPT and SHPT patients (p < 0.001) with respect to age (54.6 ± 13y versus 48.8 ± 12y), female-to-male ratio (8:1 versus ~ 1:1), surgical technique (single gland parathyroidectomy in 82.8% PHPT cases; versus subtotal parathyroidectomy in 85.7% SHPT cases) and presurgical PTH (357.51 ± 38.11 pg/ml versus 1020 ± 161.38 pg/ml).Morphopathological particularities, TNM classification and multifocality incidence of PTC were similar in the two groups. All PTC from patients with SHPT were thyroid microcarcinomas (TMC, i.e. tumors with a diameter smaller than 1 cm), whereas seven out of the 19 cases with PTC and PHPT were larger than 1 cm.ConclusionsPTC was frequently and similarly associated with both PHPT and SHPT irrespective of presurgical PTH levels. Thyroid tumors above 1 cm were found only in patients with PHPT. Investigators should focus also on associated thyroid nodular pathology in patients with PHPT.

Medullary thyroid cancer. Returning to the need to determine the preoperative basal calcitonin level in patients with thyroid nodular pathology

There are International and Russian guidelines for the diagnosis and treatment of medullary thyroid carcinoma. There is a recommendation to determine the basal level of calcitonin for all patients with nodular thyroid disease at the all of these documents. However, this test is not performed for this category of patients routinely even in large clinics for a number of reasons, the main one, which seems to be an economic issue. Six months ago a patient addressed to our clinic who underwent surgical treatment for a papillary carcinoma (follicular variant) of the thyroid gland in the volume of thyroidectomy with pre-tracheal lymphodissection and subsequent course of radioiodine therapy at the place of residence. A relapse of the disease was suspected on the control examination at the place of residence and the patient was sent for consultation to the polyclinic of the N.N. Blokhin National Medical Research Center of Oncology. In our clinic, diagnostic studies were carried out, including a revision of the finished cytological and histological preparations and a conclusion was obtained – medullary carcinoma of the thyroid. Determination of basal level of calcitonin in serum showed a value of 1292 pg/ml. The level of basal calcitonin significantly decreased after repeated surgical treatment. This case shows that in order to avoid such mistake, which is described in our clinical case, it seems necessary to follow the national recommendations, international standards to determine the level of basal calcitonin for all patients with thyroid nodal pathology who consulted and treated in medical institutions.

ЧАСТОТА ПОЛІМОРФНИХ ВАРІАНТІВ ГЕНІВ У ХВОРИХ НА АВТО-ІМУННИЙ ТИРЕОЇДИТ І АДЕНОМУ ЩИТОПОДІБНОЇ ЗАЛОЗИ

На сьогодні питання етіології, патогенезу, діагностики та хірургічного лікування такої поєднаної патології як вузловий зоб і автоімунний тиреоїдит (АІТ) зберігають свою актуальність. Автоімунний тиреоїдит, як фонове захворювання вузлового зоба, при якому практично завжди розвивається гіпотиреоз, на даний час ще вивчено недостатньо. Очевидна роль генетичних факторів у їх розвитку. Своєчасна і точна діагностика вузлових утворень щитоподібної залози (ЩЗ) на фоні АІТ має важливе значення у виборі методу лікування вузлової тиреоїдної патології, показань, обсягу і характеру операційного лікування. Наявність сімейних форм захворювання і дані генеалогічних досліджень є доказом важливої ролі генетичного фактора в патогенезі АІТ. Підтверджують їх думку відомості про те, що в результаті повного генетичного сканування були виявлені деякі локуси, асоційовані з АІТ, при цьому ключову роль у схильності відіграють гени HLA (human leukocyte antigen) системи і протеїн-4, асоційований із цитотоксичними Т-лімфоцитами (Cytotoxic T lymphocyte-associated-protein 4, CTLA4). Але вплив цих генів на загальну генетичну схильність до АІТ становить лише близько 5 %.Мета дослідження – провести аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у хворих з патологією ЩЗ із урахуванням її виду (вузловий колоїдний зоб на фоні автоімунного тиреоїдиту (ВКЗАІТ), аденоми щитоподібної залози (АЩЗ)), змін функціональної активності ЩЗ (еутиреоз, субклінічний та клінічний гіпотиреоз) та ступеня збільшення ЩЗ (ІБ, ІІ і ІІІ ст.).Матеріали і методи. Проведено аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/ Fas (rs2234767) у 125 хворих, оперованих з приводу вузлової патології ЩЗ із урахуванням її виду – ВКЗАІТ, АЩЗ, змін функціональної активності ЩЗ (еутиреоз, субклінічний та клінічний гіпотиреоз) та ступеня збільшення ЩЗ (ІБ, ІІ і ІІІ ст.). Також обстежено 25 практично здорових донорів. Дослідження поліморфізму генів проводили методом полімеразної ланцюгової реакції у режимі реального часу.Результати досліджень та їх обговорення. Гіперплазія ЩЗ у хворих загалом, а також у таких із ВКЗАІТ асоціює з диким А-алелем гена CTLA-4 (АА- і AG-генотипи): ІБ та ІІІ ступені гіперплазії вірогідно частіше були у носіїв АА-генотипу на 30,13 і 26,35 % (χ2=9,26; р=0,01), а ІІ ступінь збільшення ЩЗ – у хворих із AG-генотипом на 33,52 і 34,04 % (χ2=12,34; р=0,002) відповідно. Патологія ЩЗ загалом має невірогідні шанси на успадкування залежно від поліморфізму генів BCL-2 (rs17759659), CTLA-4 (rs231775) та APO-1/Fas (rs2234767).Висновки. Наявність у геномі хворого AG поліморфного варіанта гена CTLA-4 підвищує ризик гіперплазії ЩЗ ІІ ступеня удвічі (OR=4,69; 95 % СІ OR: 1,60–13,69; p=0,004), тоді як носійство основного алеля у гомозиготному стані (АА-генотип) навпаки є протективним і робить шанси на гіперплазію ЩЗ ІІ ступеня найнижчими в обстеженій популяції (OR=0,46; 95 % СІ OR:0,09– 0,73; p=0,009). Решта поліморфізмів аналізованих генів не асоціюють із ризиком ні АЩЗ, ВКЗАІТ, ні функції ЩЗ, чи ступеня її збільшення.

Поліморфізм генів apo-1 / fas, ctla-4 та bcl-2 у пацієнтів, оперованих із приводу вузлової патології щитоподібної залози

Мета роботи: провести аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у хворих, оперованих із приводу вузлової патології щитоподібної залози із урахуванням її виду вузловий зоб на фоні автоімунного тиреоїдиту, аденома щитоподібної залози. Матеріали і методи. Проведено аналіз частоти поліморфних варіантів генів BCL-2 (rs17759659), CTLA-4 (rs231775), APO-1/Fas (rs2234767) у 125 хворих, оперованих з приводу вузлової патології щитоподібної залози із урахуванням її виду – вузлового зоба на фоні автоімунного тиреоїдиту, аденома щитоподібної залози. Також обстежено 25 практично здорових донорів. Дослідження поліморфізму генів проводили методом полімеразної ланцюгової реакції в режимі реального часу.Результати досліджень та їх обговорення. Мутація генів BCL-2 (rs17759659) та CTLA-4 (rs231775) у гомозиготному стані у хворих, оперованих з приводу вузлової патології щитоподібної залози, зустрічається із частотою 3,2–4,0 % без вірогідної різниці між хворими на патологію щитоподібної залози та здоровими. Мутація гена APO-1/Fas (rs2234767) у гомозиготному стані серед обстежених не траплялася взагалі.

Iodine deficiency a persisting problem: assessment of iodine nutrition and evaluation of thyroid nodular pathology in Portugal

The goal of eliminating iodine deficiency (ID) by the year 2000 has still not been achieved in several countries. More than 2 billion people worldwide (over 260 million school age children) remain ID. In Europe, there are still countries, such as Portugal, without national general population data on iodine nutrition (IN). This study aims at evaluating combined complementary data of the IN of the general population through urinary iodine concentration (UIC) and the thyroid histology profile from the inland region of Beira Interior (BI), in Portugal. UIC from a population sample of 214 volunteers (131 females and 83 males), with ages ranging from 8 to 97years (mean 51.5years±SD 20.74years), from BI was determined; the thyroid histology pattern in BI (6-year period) was evaluated; and the iodine content of the largest surface water reservoir of BI, never previously reported, was measured. Median UIC of 62.6μg/L was measured. Over 92% of the population had UIC less than 100μg/L. From 279 histology reports evaluated, the incidence of the different types of thyroid nodular pathology in BI was established. There were 60 histologic diagnoses of malignancy. The observed ratio of papillary to follicular carcinoma relatively close to 1 and the fairly high percentage of anaplastic carcinomas are characteristic of ID areas. The findings of this first general population study on IN from the inland region of BI, Portugal, document significant ID. This problem, with its serious public health implications, could be corrected by having affordable iodised salt widely and generally available and by promoting a proactive population attitude generated by ample public information and educational programs as to the negative consequences of ID.