Browsing by Author "Beleslin, Biljana Nedeljković (6701355427)"

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[No abstract available]

Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Purpose: Graves’ orbitopathy (GO) is an inflammatory autoimmune disorder of the orbit and while the antiphospholipid antibodies (aPL) Abs were associated with the markers of inflammation in the antiphospholipid syndrome (APS), there is no literature that investigate the presence of aPL Abs in GO. We analyzed the prevalence of aPL Abs and the differences between aPL (+) and aPL (−) subgroups of GO patients. Methods: Study included consecutive patients with GO (66 with Graves’ (GD), 10 with Hashimoto (HD), and 8 were euthyroid). Anticardiolipin (aCL) and anti-beta 2glycoprotein I (aβ2gpI) Abs were measured by ELISA. Results: aPL Abs were present in 9/84 (10.71%) patients. The IgM aβ2gpI Abs were present in 8/66 and in 1/10 patients with GD and HD. The IgG aCL Abs were present in one GD patient, and IgM aCL were present in 3/66 GD and in 1/10 patients with HD. In GD group, anti-Tg Abs were in positive correlation with aβ2gpI IgG (p = 0.000) and with anti-TPO Abs (p = 0.016). In HD group, anti-Tg Abs were in positive correlation with IgM aCL (p = 0.042), while anti-TPO Abs were in positive correlation with aβ2gpI IgM (p = 0.014). Conclusion: This study is the first report of the aPL Abs presence in GO patients. The anti-thyroid Abs were linked to aPL suggesting that their presence is not the sole consequence of hyperstimulation of autoreactive B-lymphocytes. Larger studies are necessary to confirm potential cause-effect relations. © 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Background: Despite commercially improved, standardised routine methods used in medical laboratories, precision laboratory medicine lacks harmonisation of results to make the laboratory result useful for its intended purpose. Furthermore, to obtain reliable laboratory results and precise diagnoses, it is important and recommended that each laboratory confirms the analytical and clinical characteristics of the method used. This study aimed to evaluate the analytical and clinical performance of the IMMULITE®2000 TSI bridge immunoassay to determine autoreactive thyroid stimulating hormone receptor antibodies (SH-R-Ab). Methods: A total of 86 patients with clinically present Graves’ orbitopathy and 23 healthy volunteers as a control group were included in the study. The total TSH-R-Ab concentration was determined using an ECLIA (Elecsys Anti-TSHR Immunoassay Roche Diagnostics, GmbH, Mannheim, Germany) on the Cobas e411 analyser (Roche, Diagnostics, GmbH). The TSH-R-Ab concentration was measured using a CLIA method (IMMULITE TSI 2000, Siemens Healthcare Diagnostics, UK). The inaccuracy of the method was investigated using two levels of commercial control samples (low and high analyte concentration). Results: The results obtained meet the general minimum requirements for the analytical performance of laboratory methods (CV<5%). The overall laboratory inaccuracy was acceptable according to FDA guidelines (CV<20%). The results showed a statistically significant correlation between the analysed methods (r=0.9041, p < 0.0001) but with a relative bias of 24.5%. The best ratio of sensitivity and specificity determined by the ROC analysis (93.3% and 100%, respectively) was obtained for a cut-off value of 0.1215 IU/L, which is significantly lower compared to the cut-off value specified by the manufacturer (0.55 IU/L). Conclusions: The IMMULITE 2000 TSI bridge immunoassay for TSH-R-Ab quantification confirmed adequate precision, which is essential for routine use. However, further studies are required to evaluate its analytical specificity. © 2025 Society of Medical Biochemists of Serbia. All rights reserved.

More than a half century of experience with aspiration punch of nodal changes in the thyroid gland has confirmed this procedure as a golden standard in the examination of thyroid nodal disease. Although sensitivity, specificity, reliability and reproducibility are incontestably high, this procedure cannot give a simple answer on whether the change examined is benign or malignant. Numerous attempts to improve the procedure resulted in considerably advanced findings. Besides refining the cytopathologic examination techniques, confirmation or determination of hormones, proteins and other substances in the material obtained by fine-needle aspiration are actually the greatest contribution to improvement the of procedure's diagnostic value. These markers are actually followed, in most medical centers, in aspirates of thyroid nodal changes but also surrounding lymph nodes in order to evaluate with greater certainty the type, volume and spread; this is important to establish treatment procedures and to evaluate the residual disease after accomplishing the treatment.

More than a half century of experience with aspiration punch of nodal changes in the thyroid gland has confirmed this procedure as a golden standard in the examination of thyroid nodal disease. Although sensitivity, specificity, reliability and reproducibility are incontestably high, this procedure cannot give a simple answer on whether the change examined is benign or malignant. Numerous attempts to improve the procedure resulted in considerably advanced findings. Besides refining the cytopathologic examination techniques, confirmation or determination of hormones, proteins and other substances in the material obtained by fine-needle aspiration are actually the greatest contribution to improvement the of procedure's diagnostic value. These markers are actually followed, in most medical centers, in aspirates of thyroid nodal changes but also surrounding lymph nodes in order to evaluate with greater certainty the type, volume and spread; this is important to establish treatment procedures and to evaluate the residual disease after accomplishing the treatment.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation. Copyright 2024, Mary Ann Liebert, Inc., publishers.

Background: Hypothyroidism is common, however, aspects of its treatment remain controversial. Our survey aimed at documenting treatment choices of European thyroid specialists and exploring how patients' persistent symptoms, clinician demographics, and geo-economic factors relate to treatment choices. Methods: Seventeen thousand two hundred forty-seven thyroid specialists from 28 countries were invited to participate in an online questionnaire survey. The survey included respondent demographic data and treatment choices for hypothyroid patients with persistent symptoms. Geo-economic data for each country were included in the analyses. Results: The response rate was 32.9% (6058 respondents out of 17,247 invitees). Levothyroxine (LT4) was the initial treatment preferred by the majority (98.3%). Persistent symptoms despite normal serum thyrotropin (TSH) while receiving LT4 treatment were reported to affect up to 10.0% of patients by 75.4% of respondents, while 28.4% reported an increasing such trend in the past 5 years. The principal explanations offered for patients' persistent symptoms were psychosocial factors (77.1%), comorbidities (69.2%), and unrealistic patient expectations (61.0%). Combination treatment with LT4+liothyronine (LT3) was chosen by 40.0% of respondents for patients who complained of persistent symptoms despite a normal TSH. This option was selected more frequently by female thyroid specialists, with high-volume practice, working in countries with high gross national income per capita. Conclusions: The perception of patients' dissatisfaction reported by physicians seems lower than that described by hypothyroid patients in previous surveys. LT4+LT3 treatment is used frequently by thyroid specialists in Europe for persistent hypothyroid-like symptoms even if they generally attribute such symptoms to nonendocrine causes and despite the evidence of nonsuperiority of the combined over the LT4 therapy. Pressure by dissatisfied patients on their physicians for LT3-containing treatments is a likely explanation. The association of the therapeutic choices with the clinician demographic characteristics and geo-economic factors in Europe is a novel information and requires further investigation. Copyright 2024, Mary Ann Liebert, Inc., publishers.

Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays. © 2022 Sciendo. All rights reserved.

Background: Thyrotropin receptor autoantibodies (TSH-R-Ab) are indispensable biomarkers in the laboratory assessment of thyroid-associated orbitopathy (TAO). Clinical sensitivity of three different assays for TSH-R-Ab determination was evaluated in patients with TAO. Methods: 87 consecutive TAO patients were enrolled and their serum samples analyzed in parallel with three assays. An ECLIA competitive binding and a chemiluminescent bridge immunoassay were used to measure total and binding TSH-R-Ab concentration, while their functional activity was determined using a stimulatory TSH-R-Ab (TSAb) cell-based bioassay. Results: Compared to the two binding assays (ECLIA p<0.001, bridge p=0.003), the TSAb bioassay was more sensitive pertaining to the positive detection of TSH-R-Ab in TAO patients. No difference (p=0.057) was noted between the ECLIA and bridge assays regarding sensitivity rate. All patients with active and/or moderate-to-severe TAO tested positive in the TSAb bioassay (100% and 100%, respectively), while the positivity rates for bridge and ECLIA binding assays were 89.7% and 82.1% for active TAO, and 90.2% and 86.3% for severe TAO, respectively. Negative predictive values of the bioassay, bridge, and ECLIA assays were 100%, 75%, and 71%, respectively for active TAO, and 100%, 86%, and 71%, respectively for moderate-to-severe TAO. The superiority of the bioassay was most prominent in euthyroid (ET) TAO. Positivity rates of the TSAb bioassay, bridge and ECLIA binding assays were 89.6%, 75%, and 64.6%, respectively for inactive TAO; 86.1%, 69.4%, and 52.8%, respectively for mild TAO; 87.5%, 62.5%, and 12.5%, respectively for euthyroid TAO. The bridge assay correlated better with the ECLIA binding assay (r=0.893, p<0.001), compared to the bioassay (r=0.669, p<0.001). Conclusions: In patients with TAO of various activity and severity, the TSAb bioassay demonstrates a superior clinical performance compared to both ECLIA and bridge binding assays. © 2022 Sciendo. All rights reserved.

Background: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. Purpose: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. Methods: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. Results: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41–50, 51–60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03–1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33–0.48), Northern Europe (OR 0.28, 95% CI 0.22–0.36) and Western Asia (OR 0.16, 95% CI 0.11–0.24) compared to Western Europe. Associations with respondents’ sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. Conclusions: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Background: Treatment of simple goiter (SG) growing over time with thyroid hormone (TH) therapy is discouraged by international guidelines. Purpose: To ascertain views of European thyroid specialists about TH treatment for euthyroid patients with growing SG and explore associations with management choice. Methods: Online survey on the use of TH for growing SG among thyroid experts from 28 European countries. Results: The response rate was 31.5% (5430/17,247). Most respondents were endocrinologists. Twenty-eight percent asserted that TH therapy may be indicated in euthyroid patients with a growing SG. National and regional differences were noted, from 7% of positive responses in The Netherlands to 78% in Czech Republic (p < 0.0001). TH was more frequently prescribed by respondents over 40 years old (OR 1.77, 2.13, 2.41 if 41–50, 51–60, >60, respectively), and working in areas of former iodine insufficiency (OR 1.24, 95% CI 1.03–1.50). TH was less frequently prescribed by endocrinologists (OR 0.77, 95% CI 0.62-0.94) and respondents working in Southern Europe (OR 0.40, 95% CI 0.33–0.48), Northern Europe (OR 0.28, 95% CI 0.22–0.36) and Western Asia (OR 0.16, 95% CI 0.11–0.24) compared to Western Europe. Associations with respondents’ sex, country, availability of national thyroid guidelines, and gross national income per capita were absent or weak. Conclusions: Almost a third of European thyroid specialists support treating SG with TH, contrary to current guidelines and recommendations. This calls for urgent attention. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%–83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7–0.9) and respondents >60 years (OR: 0.7; 0.6–0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients (“weekly” [OR: 1.4; CI: 1.0–1.9], “daily” [OR: 1.8; CI: 1.3–2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3–1.9) were most likely to consider LT4. Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment. © 2024 John Wiley & Sons Ltd.

Objectives: The use of levothyroxine (LT4) treatment aiming to improve fertility in euthyroid women with positive thyroid peroxidase antibodies (TPOAb) is not supported by the available evidence. The aim of the study was to document the use of LT4 by European thyroid specialists in such patients. Design: The data presented derive from Treatment of Hypothyroidism in Europe by Specialists, an International Survey (THESIS), a questionnaire conducted between 2019 and 2021 to document the management of hypothyroidism by European thyroid specialists. Here, we report the aggregate results on the use of LT4 in infertile, euthyroid women with positive TPOAb. Results: A total of 2316/5406 (42.8%) respondents stated that LT4 may be indicated in TPOAb positive euthyroid women with infertility. The proportion of those replying positively to this question varied widely across different countries (median 39.4, range 22.9%–83.7%). In multivariate analyses males (OR: 0.8; CI: 0.7–0.9) and respondents >60 years (OR: 0.7; 0.6–0.8) were the least inclined to consider LT4 for this indication. Conversely, respondents managing many thyroid patients (“weekly” [OR: 1.4; CI: 1.0–1.9], “daily” [OR: 1.8; CI: 1.3–2.4]) and practicing in Eastern Europe (OR: 1.5; CI: 1.3–1.9) were most likely to consider LT4. Conclusions: A remarkably high number of respondents surveyed between 2019 and 2021, would consider LT4 treatment in TPOAb positive euthyroid women with infertility. This view varied widely across countries and correlated with sex, age and workload, potentially influencing patient management. These results raise concerns about potential risks of overtreatment. © 2024 John Wiley & Sons Ltd.