Vol 12, No 2 (2016)

De Gustibus
Science can handle many gitiks
Gerasimov G.A.

In my previous column I have statred discussion about validity and trustfulness of sciebtific publications. In this publication I want to talk more about original articles that are kind of fodder for the science industry.

Clinical and experimental thyroidology. 2016;12(2):6-11
News of the world thyroidology
World thyroidology news
Manuylova Y.A., Moshenina S., Amosova M.V.

Abstracts of articles devoted to the most topical issues of thyroid pathology are provided. Influence of various associated diseases on thyroid function is considered, and the probability of emergence pathology various systems in case of the available thyroid diseases is studied. A part of articles is devoted to researches of such important subjects as quality of life patients with thyroid pathology  and cost efficiency of different types therapy. The works studying pathogenesis of thyroid diseases  are also included.

Clinical and experimental thyroidology. 2016;12(2):12-18
Original Studies
The study of galectin-3, Ki-67, ubiquitin, HMGA-2 by polymerase chain reaction in real time (RT-PCR) in the puncture specimens of nodular goiter
Berjozkina I.S., Saprina T.V., Zima A.P., Isaeva A.V., Latipova V.N., Muhamedov M.R., Bazilevich L.R., Popov O.S., Skuratovskaja D.A., Jurova K.A., Litvinova L.C.

Actuality. The differential diagnosis of follicular adenoma, follicular variant of papillary thyroid cancer and follicular thyroid cancer (TC) is one of the main topics of research. For this purpose several molecular markers were approbated, however their diagnostic effectiveness differs.

Aim. Quantification of candidate mRNA markers for differentiated thyroid cancer (galectin-3, Ki-67, ubiquitin, HMGA2) using polymerase chain reaction in real time (RT-PCR) of thyroid nodules pre-operative material. To evaluate the efficiency of this method for thyroid malignancy diagnostics.

Materials and methods. The study included 55 patients with a clinical diagnosis of nodular / multinodular goiter. A quantitative analysis of mRNA of galectin-3, Ki-67, ubiquitin, HMGA2 was performed on material puncture by reverse transcription and RT-PCR. The Second Derivative Maximum Method was used to analyze the results.

Results. The study included 46 women (83.6%) and 8 men (14.5%). The average age of the patients was 52.1 (from 23 to 82) years old. According to the results of histological examination, there were 35 (63.6%) benign tumors, 20 (36.4%) – cancer tumors (papillary carcinoma). There were no cases of follicular cancer in the histological findings. We found significant differences in the expression of mRNA of the ubiquitin gene between malignant and benign thyroid nodules.

Conclusion. The method of ubiquitin gene 8.24 mRNA estimation has a sensitivity of 68.4% and a specificity of 68.6% in the well-differentiated cancer diagnostics. The estimation of mRNA of gene Ki-67, galectin-3, HMGA by RT-PCR did not show itself as a reliable method for the differential diagnosis of thyroid nodules in the preoperative stage.

Clinical and experimental thyroidology. 2016;12(2):19-27
Quality of compensation and well-being of patients with primary hypothyroidism and obesity
Fadeyev V.V., Morgunova T.B., Manuylova Y.A., Madiyarova M.S.

Aim. The aim of the study was to compare quality of hypothyroidism compensation and well-being of patients with hypothyroidism with normal weight, overweight and obesity.

Methods. 306 patients with hypothyroidism on replacement therapy with L-T4 were included; of those 218 patients with compensated hypothyroidism. All patients were divided into groups depending on their body mass index: with normal body weight, overweight, obesity I and obesity II - III degree. We calculated the ideal body weight (IdBW) by Devine formula. Evaluation at baseline included: height, weight, BMI, quality of life (SF-36), TSQ, TSH, freeT3 (fT3), freeT4 (fT4) levels.


There were no difference in the quality of compensation between groups of normal-weight, overweight and obese patients (p > 0,05). L-T4 dose in patients with obesity and overweight was significantly higher compared to normal-weight patients (p < 0,05). The L-T4 dose per 1 kg of actual body weight was significantly higher (p <0,001) in the normal-weight and overweight euthyroid patients compared to patients with obesity. In contrast, L-T4 dose per 1 kg of ideal body weight was significantly higher (p <0,001) in overweight (1.78 [1.52, 2.06]) and obese patients (1 9 [1.71, 2.4] 1.99 [1.72, 2.4]), as compared with normal-weight patients (1.49 [1.27, 1.78]). There were no correlation between the fT3, fT4 levels and weight, and also between the L-T4 dose and weight. QOL and TSQ levels were the same in the groups of normal-weight, overweight and obese patients (p>0,05).


The compensation of hypothyroidism in patients with overweight/obesity is not worse than that of normal-weight patients. The achievement of euthyroidism requires less L-T4 dose per 1 kg of the actual weight and significantly higher dose for 1 kg of ideal weight in obesity/overweight patients. 

Clinical and experimental thyroidology. 2016;12(2):28-32
Medium to severe iodine deficiency still exists in Abkhazia
Gerasimov G.A., Tulisov A.V., Belyaeva A.I., Tuzhba A.V., Petrenko S.V.

Background. Due to historical reasons, Abkhazia is one of the few regions of the former Soviet Union where status of iodine nutrition of the population is still unknown and activities for the prevention of iodine deficiency are not carried out.

Aim. To assess the status of iodine nutrtition of Abkhazian population (schoolchildren and pregnant women).

Materials and methods. In total, 222 subjects were surveyed in Abkhazia, including 151 schoolchildren (age 8–12 years) and 61 pregnant women (aged 19–39 years). The content of iodine has been studied in the urine, and the use of iodized salt has been assesses at the household level.

Results. The results of the survey revealed medium to severe iodine deficiency in Abkhazia. In schoolchildren median urinary iodine concentration was 29.1 mcg/l, and in pregnant women – 26.5 mcg/l. In some clusters the median urinary iodine concentration was below 20 mcg/l indicating the possibility of severe iodine deficiency.

Conclusion. Results of the study point to a critical situation with regard to status of iodine nutrition of the population in Abkhazia. To eliminate iodine deficiency, based on experience of other Transcaucasian states (Armenia, Azerbaijan, Georgia), Abkhazia should take urgent measures to introduce partial or complete ban on the import, sale and use of common (non-iodized) salt.

Clinical and experimental thyroidology. 2016;12(2):33-37
Arterial-ventricular coupling and tolerance to physical exertion in patients with primary hypothyroidism
Mazur E.S., Mazur V.V., Kileynikov D.V., Semenichev D.G., Orlov Y.A.

Aim. To study the influence of medicamentous compensation of primary hypothyroidism on tolerance to physical exertion and arterial-ventricular coupling.

Material and methods. Thirty-one women with primary hypothyroidism underwent stress-echocardiography before and after medicamentous achievement of euthyroid state. Subclinical hypothyroidism was diagnosed in 15 patients. Overt hypothyroidism was diagnosed in 16 patients. Results are presented with 95% confidence interval.

Results. In patients with subclinical hypothyroidism reaching of euthyroid state was associated with an increase of physical capacity from 72.2 (55.9–88.5) to 95.5 (82.1–108.9) Wt (p < 0.001), a decrease in arterial stiffness index from 4.80 (4.45–5.15) to 3.87 (3.56–4.18) mm Hg × ml-1 × m-2 (p < 0.001), a decrease in left ventricular stiffness index from 6.67 (6.03–7.31) to 5.87 (5.30–6.44) mm Hg × ml-1× m-2 (p < 0.005). In patients with overt hypothyroidism reaching of euthyroid state was associated with an increase of physical capacity from 75.4 (64.1–86.6) to 98.2 (88.6–107.7) Wt (p < 0.001), a decrease in arterial stiffness index from 4.56 (4.18–4.94) to 4.00 (3.73–4.27) mm Hg × ml-1 × m-2 (p < 0.001), a decrease in left ventricular stiffness index from 6.47 (5.86–7.08) to 6.13 (5.69–6.57) mm Hg × ml-1 × m-2 (p > 0.05). In patients with subclinical hypothyroidism cardiovascular arterial-ventricular coupling index decreased from 0.72 (0.69–0.75) to 0.66 (0.62–0.71) units. In patients with overt hypothyroidism cardiovascular arterial-ventricular coupling index decreased from 0.71 (0.67–0.74) to 0.66 (0.63–0.69) units. In the whole group gain of left ventricular stiffness index after physical exertion increased from 4.13 (3.67–4.59) to 6.05 (5.60–6.50) mm Hg × ml-1 × m-2 (p < 0.01), cardiovascular arterial-ventricular coupling index increased from 0.07 (0.03–0.10) to 0.14 (0.11–0.17) units (p< 0.01).

Clinical and experimental thyroidology. 2016;12(2):38-45
Association of candidate gene polymorphisms for autoimmune thyroid diseases in patients with familial diffuse toxic goiter and autoimmune thyroiditis
Rymar O.D., Mikitinskaya A.K., Maksivov V.N., Shahmatov S.G., Schepina Y.V., Ryabikov A.N., Mustafina S.V.

Aim: to study the relation polymorphism of some genes of the immune response with familial autoimmune thyroid disease.

Materials and methods. 100 patients from 49 families were examined. At least 2 first-degree affected relatives with autoimmune thyroiditis or diffuse toxic goiter were included from each family. 76 persons were included to control group without thyroid pathology and negative history of any thyroid disease in families. Clinical, hormonal, ultra-sound data was collected for each subject. Genotyping ofCTLA4 A49G and PTPN22 C1858T polymorphisms was performed for 70 patients (35 families) with familial autoimmune thyroid disease and for all subjects from the control group.

Results. Autoimmune thyroid disease was observed among one generation (siblings) in 11 families (22.5%) and among two generations (parent-child) in 38 families (75.5%). Patients with chronic autoimmune thyroiditis with hypothyroidism in the outcome were dominated – 66%, 34% experienced diffuse toxic goiter. Autoimmune thyroiditis was observed in parent and offspring from 21 families (55%). In the group of siblings autoimmune thyroiditis was diagnosed for both relatives in 6 families (54%). Frequency of genotypes of CTLA4 A49G polymorphism is not differ between patients with familial autoimmune thyroid disease and control group. Carriage of T allele of PTPN22 C1858T polymorphism is associated with the risk of autoimmune thyroid disease developing in a group of female offspring: OR = 3.175; 95% CI 1,423–7,262. These results allow us to recommend to test this polymorphism to identify patients with the risk of autoimmune thyroid diseases in families.

Conclusion. Taking into account that DNA testing is one of the most important part of personalized approach in medicine, the current results of molecular genetic study for familial cases of autoimmune thyroid disease creates prerequisites for optimizing the diagnostic pathway of these patients.

Clinical and experimental thyroidology. 2016;12(2):46-54
Review of literature
Molecular genetics of follicular cell thyroid carcinoma
Yakushina V.D., Lerner L.V., Kazubskaya T.P., Kondrat'ieva T.T., Subramanian S.-., Lavrov A.V.

Thyroid cancer is the most frequent endocrine malignancy. In the most cases thyroid cancer arises from follicular cells. Diagnosis of the cancer is based on the cytological analysis of fine needle aspiration biopsy of thyroid nodes. But the accuracy of the cytological diagnosis is about 80% that leads to the false positive and false negative cases and wrong strategy of treatment. Identification of genetic and epigenetic markers in the biopsies will allow to improve diagnostic accuracy. This article describes mutations, aberrant DNA methylation and abnormal microRNA expression constituting the core of molecular genetics of follicular cell thyroid cancer. The mutations given in the article includes point mutations, fusions and copy number variation. Besides frequent and well described driver mutations in genes of МАРK, PI3K/Akt and Wnt signaling pathways, as well as TP53 and TERT genes, we introduce here less frequent mutations appeared in the literature during the past two years. In addition the article contains examples of diagnostic panels applying these markers.

Clinical and experimental thyroidology. 2016;12(2):55-64

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