Ultrasound features and preoperative accuracy of the fine needle aspiration biopsy in detection of thyroid carcinomas.

OBJECTIVE: To analyze the ultrasound (US) characteristics and fine needle biopsy (FNAB) of thyroid carcinomas (TCs) prior to surgery and compare with postoperative histopathology and to determine FNAB sensitivity and specificity. MATERIAL AND METHODS: Retrospective analysis of the US data during 1999-2015 was performed, as well as analysis of FNAB results and using histopathology report as "gold standard" the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this method was evaluated. RESULTS: Data revealed that tumors >51 mm were declining by 50% in the period 2011-2015 compared to 2005-2010 or by 18% 2011-2015 compared to 1999-2004 and significant increase was detected in diagnosis of multicentric tumors. The analysis revealed that FNAB has sensitivity = 65.7% CI (0.59% - 0.71%) and specificity = 50% CI (0.43%-0.56%), PPV = 56.9% and NPV = 59.2%. CONCLUSION: We found increasing detection of smaller TCs, as well as more frequent detection of multicentricity of the neoplastic foci. FNAB results in our study revealed low sensitivity and specificity. Major limitation of the study was inability to exactly separate US guided from non US guided FNAB in evaluation of the sensitivity and specificity, due to retrospective nature of the analysis. Further studies evaluating only US guided FNAB should be performed.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia.

OBJECTIVE: Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). METHODS: Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). RESULTS: Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypothyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). CONCLUSION: Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

OBJETIVO: As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). MéTODOS: Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). RESULTADOS: Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). CONCLUSãO: Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Thyroid Function of Pregnant Women and Perinatal Outcomes in North Macedonia / Função tireoidiana de mulheres grávidas e resultados perinatais na Macedônia do Norte

Abstract Objective Thyroid diseases are the second most common endocrine disorders in the reproductive period of women. They can be associated with intrauterine growth restriction (IUGR), preterm delivery, low Apgar score, low birthweight (LBW) or fetal death. The aim of the present study is to explore thyroid dysfunction and its relationship with some poor perinatal outcomes (Apgar Score, low birthweight, and preterm delivery). Methods Dried blood spot samples from 358 healthy pregnant women were analyzed for thyroid stimulating hormone (TSH), total thyroxine (TT4), and thyroglobulin (Tg). Neonatal data were collected upon delivery. Four groups were formed based on thyroid function tests (TFTs). Results Of the 358 tested women, 218 (60.72%) were euthyroid. Isolated hypo thyroxinemia was present in 132 women (36.76%), subclinical hyperthyroidism in 7 women (1.94%), and overt hypothyroidism in 1 (0.28%). The perinatal outcomes IUGR (p = 0.028) and Apgar score 1 minute (p = 0.015) were significantly different between thyroid function test [TFT]-distinct groups. In the multiple regression analysis, TT4 showed a statistically significant inverse predictive impact on LBW (p < 0.0001), but a positive impact of Tg on LBW (p = 0.0351). Conclusion Thyroid hormones alone do not have a direct impact on neonatal outcomes, but the percentage of their participation in the total process cannot be neglected. Based on the regression analysis, we can conclude that TT4 and Tg can be used as predictors of neonatal outcome, expressed through birthweight and Apgar score. The present study aims to contribute to determine whether a test for thyroid status should become routine screening during pregnancy.

Resumo Objetivo As doenças da tireoide são as segundas doenças endócrinas mais comuns no período reprodutivo das mulheres. Elas podem estar associadas à restrição de crescimento intrauterino (RCIU), parto prematuro, baixo índice de Apgar, baixo peso ao nascer (BPN) ou morte fetal. O objetivo do presente estudo é explorar a disfunção tireoidiana e sua relação com alguns resultados perinatais insatisfatórios (índice de Apgar, baixo peso ao nascer e parto prematuro). Métodos Amostras secas de sangue em 358 gestantes saudáveis foram analisadas para hormônio estimulador da tireoide (TSH), tiroxina total (TT4) e tireoglobulina (Tg). Os dados neonatais foram coletados no momento do parto. Quatro grupos foram formados com base em testes de função tireoidiana (TFT). Resultados Das 358 mulheres testadas, 218 (60,72%) eram eutireoidianas. Hipotiroxinemia isolada estava presente em 132 mulheres (36,76%), hipertireoidismo subclínico em 7 mulheres (1,94%) e hipotireoidismo evidente em 1 (0,28%). Os resultados perinatais RCIU (p = 0,028) e índice de Apgar de 1 minuto (p = 0,015) foram significativamente diferentes entre os grupos distintos de TFT. Na análise de regressão múltipla, TT4 mostrou impacto preditivo inverso estatisticamente significativo no BPN (p < 0,0001), mas impacto positivo da Tg no BPN (p = 0,0351). Conclusão Isoladamente, os hormônios tireoidianos não têm impacto direto no desfecho neonatal, mas o percentual de sua participação no processo total não pode ser desprezado. Com base na análise de regressão, podemos concluir que TT4 e Tg podem ser usados como preditores do resultado neonatal, expressos por meio do peso ao nascer e do índice de Apgar. O presente estudo tem como objetivo contribuir para que um teste para verificar o estado da tireoide deva se tornar um rastreamento de rotina durante a gravidez.

Prognostic factors in thyroid carcinomas: a 17-year outcome study

ABSTRACT Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Prognostic factors in thyroid carcinomas: a 17-year outcome study.

Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Genomic test ends a long diagnostic odyssey in a patient with resistance to thyroid hormones.

BACKGROUND: Resistance to thyroid hormones is a very rare condition, which is often misdiagnosed and mistreated. The cases where there is a concomitant autoimmune thyroid disorder are ultra-rare and particularly challenging to treat. Diagnostic and research-based genomic testing can sometimes identify pathogenic variants unrelated to the primary reason for testing (incidental findings). CASE PRESENTATION: We present a patient with thyroid resistance associated with hypothyroid Hashimoto thyroiditis. The long diagnostic odyssey spanning over 20-years included repeated misdiagnoses and mistreatments and was concluded by a research-based genomic testing, identifying a "de novo" THRB pathogenic variant. The varying sensitivity of various tissues to thyroid hormones accompanied by hypothyroid Hashimoto thyroiditis continues to pose a significant treatment challenge. CONCLUSIONS: Thyroid hormone resistance continues to be an un(der)- and misdiagnosed thyroid condition whose management is particularly challenging when associated with autoimmune thyroid disease. Whole exome sequencing has the potential to identify THRB pathogenic variants as incidental findings. Reporting such secondary findings from genomic testing may be particularly important in the context of the rarity of the condition and the potential clinical consequences of misdiagnosis and mistreatment.

The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism.

OBJECTIVE: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. SUBJECTS AND METHODS: Fifty-four patients with newly diagnosed mild ScH (4.2

The effect of levothyroxine treatment on left ventricular function in subclinical hypothyroidism

ABSTRACT Objective: Treatment of subclinical hypothyroidism (ScH), especially the mild form of ScH, is controversial because thyroid hormones influence cardiac function. We investigate left ventricular systolic and diastolic function in ScH and evaluate the effect of 5-month levothyroxine treatment. Subjects and methods: Fifty-four patients with newly diagnosed mild ScH (4.2 <TSH < 10.0 mU/L) and 30 euthyroid subjects matched by age were analysed. Laboratory analyses and an echocardiography study were done at the first visit and after 5 months in euthyroid stage in patients with ScH. Results: Compared to healthy controls, patients with ScH had a lower E/A ratio (1.03 ± 0.29 vs. 1.26 ± 0.36, p < 0.01), higher E/e' sep. ratio (762 ± 2.29 vs. 6.04 ± 1.64, p < 0.01), higher myocardial performance index (MPI) (0.47 ± 0.08 vs. 0.43 ± 0.07, p < 0.05), lower global longitudinal strain (GLS) (-19.5 ± 2.3 vs. −20.9 ± 1.7%, p < 0.05), and lower S wave derived by tissue Doppler imaging (0.077 ± 0.013 vs. 0.092 ± 0.011 m/s, p < 0.01). Levothyroxine treatment in patients with ScH contributed to higher EF (62.9 ± 3.9 vs. 61.6 ± 4.4%, p < 0.05), lower E/e' sep. ratio (6.60 ± 2.06 vs. 762 ± 2.29, p < 0.01), lower MPI (0.43 ± 0.07 vs. 0.47 ± 0.08%, p < 0.01), and improved GLS (-20.07 ± 2.7 vs. −19.55 ± 2.3%, p < 0.05) compared to values in ScH patients at baseline. Furthermore, in all study populations (ScH patients before and after levothyroxine therapy and controls), TSH levels significantly negatively correlated with EF (r = −0.15, p < 0.05), E/A (r = −0.14, p < 0.05), GLS (r = −0.26, p < 0.001), and S/TDI (r = −0.22, p < 0.01) and positively correlated with E/e' sep. (r = 0.14, p < 0.05). Conclusion: Patients with subclinical hypothyroidism versus healthy individuals had subtle changes in certain parameters that indicate involvement of systolic and diastolic function of the left ventricle. Although the values of the parameters were in normal range, they were significantly different compared to ScH and the control group at baseline, as well as to the ScH groups before and after treatment.The results of our study suggest that patients with ScH must be followed up during treatment to assess improvement of the disease. Some of the echocardiography obtained parameters were reversible after levothyroxine therapy.

Sentinel Lymph Node Detection in Colorectal Cancer - First Experience.

BACKGROUND: Colorectal cancer (CRC) is the second commonest cancer in women, the third in men, being the fourth commonest cause of cancer death. The most important factor for prognosis and staging in CRC patients is the status of the regional lymph nodes (LN). AIM: To implement the method for sentinel lymph node (SLN) detection in CRC patients using radiocolloid, and test its detection rate, sensitivity, accuracy, negative predictive value and the possibility for upstaging. MATERIAL AND METHODS: The study included 40 CRC patients, age 63 ± 14 years, without LNs detected on CT or MRI. SLN detection was performed after endoscopically peri- and intratumoral injection of 99mTc-SENTISCINT. All patients underwent resection with systemic lymphadenectomy, and the SLNs were detected ex vivo. Pathohistology was performed to all resected LNs. RESULTS: The identification rate was 95%, the accuracy of the procedure was 92.1%, the negative predictive value was 86.95%, the sensitivity was 83.3%, and the upstage was 22.5%. CONCLUSION: Identification of SLNs in CRC patients with this method is possible and the detection rate, negative predictive value, accuracy and sensitivity are reliable. We expect to contribute in the upstaging of stage II CRC patients and the selection of appropriate oncology treatment protocols.

Demographic and Clinical Features of Thyroid Carcinomas in Republic of Macedonia (1999-2010).

BACKGROUND: Thyroid carcinomas (TC) are the most common endocrine malignancies. In some parts of the world, the incidence of TCs has increased over the past few decades, especially in females according to some studies. AIM: We have set as the objective for our study to analyse the demographic, ultrasound features, thyroid hormonal status and frequency of thyroid carcinomas in the Republic of Macedonia according to histopathological type. MATERIALS AND METHODS: Retrospective analysis of medical data from all diagnosed and treated patients with TC at the Institute of Pathophysiology and Nuclear Medicine for the period 1999-2010 was performed. Demographic characteristics: age at diagnosis, gender, histopathological type of TC and from clinical features: US findings and thyroid hormonal state at initial examination and their distribution in eight state regions were evaluated. RESULTS: Total number of 204 patients with TC in the Republic of Macedonia was registered. Papillary thyroid carcinoma (PTC) was the most frequent with 131 pts (64.21%), follicular (FTC) with 13 pts (6.37%) was second thyroid malignoma, followed by medullary (MTC) with 12 pts (5.88%), anaplastic (ATC) 11 pts (5.39%) and the rarest types were Hurtle cell carcinoma and intrathyroid sarcoma with only 1 diagnosed case. Age varied widely from 7 yrs to 88 yrs age (average 47.9 ± 16.6 yrs). PTC was more prevalent in younger age groups, while ATC was diagnosed in elderly patients. In all of the eight-country regions, the prevalence rate was higher for females than males (3:1) or 15.21/105 female to 5.03/105 male prevalence rate. According to US appearance mostly TC was unilateral in 42.65% and multifocal in 7.84% with dimensions from 15 to 50 mm. CONCLUSION: There is an increase in incidence and prevalence rate of TCs in our country, mostly PTC, while reduction exists in the number of diagnosed cases of ATC and FTC, comparing with previous studies before iodine prophylaxis program. Different from described in the literature is female: male (4:1) ratio for ATC. According to US features, we can conclude that introduction of more detailed reporting system may improve diagnostic accuracy.

Etiopathogenesis of Differentiated Thyroid Carcinomas.

INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database. DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies.

Dementia and depression in older adults: a southeast European perspective: summary of a dementia psychogeriatric symposium held in Ohrid, Macedonia, 23 May 2013.

We present a report on the recent symposium on dementia and depression in older adults, held in Ohrid, Macedonia and discuss the urgent need for development of psychogeriatric and affiliated services in the Southeast European region. The limited epidemiological data from nine countries in this region suggest high variability of prevalence rates for mental health problems in older adults (>65 years of age). At the moment, there are over 520,000 older adults in the region living with dementia alone. The prevalence rates for dementia (%) are either similar to those of the developed countries (9-9.6% in build-up northern Greece and Albania, respectively) or substantially lower (3.6-4% in rural northern Greece and Montenegro, respectively). The latter may be due to either cultural diversity or lack of adequate medical health service provision and expertise to recognize and diagnose dementia. Indeed, there is a lack of organized specialized services for older adults with mental health problem in the region. The symposium raised the awareness of this problem in the region and called for networking between isolated individuals working in this field to improve the current situation and facilitate further development of adequate clinical services to meet the growing needs of the older adults in the countries of the Southeast Europe.

C-reactive protein in patients with normal perfusion and mild to moderate perfusion defects who have undergone myocardial perfusion imaging with 99m-Tc sestamibi gated spect.

High-sensitivity C-reactive protein (CRP) has been extensively used in recent years to assess cardiovascular risk more thoroughly. A significant association between elevated CRP, a prevalence of coronary artery disease (CAD) and adverse cardiac events has been found. Stress myocardial SPECT perfusion imaging (MPI) is an accurate noninvasive technique for detecting CAD. The aim of our study was to find out if there are any differences in the CRP levels between patients with normal myocardial perfusion and mild to moderate perfusion defects, detected with 99m-Tc sestamibi gated SPECT MPI. We prospectively studied 127 patients (79 men, 48 women) suspected of having CAD or with previously confirmed CAD, who were referred for MPI. According to the findings of the stress study, they were divided into two groups: with normal/ near normal myocardial perfusion (n = 85) and with a mild to moderate perfusion defect (n = 42). Levels of CRP in the former group were significantly lower (2.7 mg/L vs. 4.2 mg/L, p = 0.01). There were significantly more men (78.6% vs. 54%, p = 0.000*) and smokers (26% vs. 15%, p = 0.003), also the rates of PCI were significantly higher (36% vs. 15%, p = 0.006) in patients with mild to moderate perfusion defects. The two groups did not differ significantly in age, type of stress, presence of most risk factors for CAD, previous myocardial infarction and CABG. The results of our study have shown that patients with mild to moderate perfusion defects on stress myocardial perfusion SPECT imaging have significantly higher levels of C-reactive protein, compared to those with normal/near normal myocardial perfusion.

Gender differences in detecting coronary artery disease with dipyridamole stress myocardial perfusion imaging using 99m-Tc sestamibi gated SPECT.

There are some specifics in the presentation of coronary artery disease (CAD) in women compared with men that may cause diagnostic pitfalls. The accuracy of noninvasive diagnostic testing in women tends to be lower than that in men. Stress myocardial perfusion imaging with 99m-Tc sestamibi gated SPECT is an accurate technique for detecting CAD. Only a few studies have compared dipyridamole stress imaging according to gender. The aim of the study was to compare the diagnostic value of dipyridamole myocardial perfusion imaging with 99m-Tc sestamibi gated SPECT in detecting CAD among patients of both sexes. We studied 62 consecutive patients (38 men, 24 women) using 99m-Tc sestamibi gated SPECT and dipyridamole stress to detect CAD. All the patients also underwent coronary angiography. Overall regional sensitivity was significantly lower in women compared with men (71.4% vs. 92.7%, p=0.039). There were no significant differences for detecting CAD in individual coronary arteries, although regional sensitivity in all three vascular territories was higher in men compared to women. The lowest sensitivity in women was found in the LAD territory (66.6%). Overall regional specificity in men and women was similar and did not reach statistical significance (88.7% vs. 94.7%). Significantly lower specificity in men was found only in the RCA territory (79.1%), compared with that in women (100%). Our results confirmed that there are certain gender differences in the diagnostic performance of dipyridamole stress myocardial perfusion imaging with 99-Tc sestamibi gated SPECT which are assigned to the characteristics of the female population. However, the diagnostic accuracy is also quite high in women, which makes this technique efficient enough in detecting CAD among this population.