Search

The present research aimed to determine the clinical and pathohistological characteristics of thyroid gland diseases in adolescents who were previously surgically treated at the Endocrine Surgery Center of the University Medical Center of Serbia from 01/01/2001 to 01/01/2011. The study covered 170 patients of both sexes from the population of adolescents (aged 16 to 20 years) with various malignant and benign thyroid gland diseases. The data for this study were extracted from the medical histories of patients and the electronic database of the Center for Endocrine Surgery. Detailed data analysis included diagnosis, symptomatology, surgical intervention type, and disease stage. The following thyroid status parameters were analyzed from preoperative data: thyroxine (T4), thyroxine free fraction (FT4), triiodothyronine (T3), triiodothyronine free fraction (FT3), and thyroid stimulating hormone (TSH). In addition, the pathohistological features of diagnosed thyroid diseases were also determined, with a special focus on the presence of well-differentiated cancers. Papillary carcinomas were the most common of well-differentiated cancers in adolescents over the ten-year follow-up period. Based on the assessed data, total thyroidectomy was the most commonly used type of surgical intervention in these patients. The conducted research provides essential information related to both the biological characteristics and diagnostics of these cancers and their surgical treatment in such a sensitive population. Moreover, research showed that the clinical presentation of thyroid cancer in adolescents is almost identical to that in adults., Competing Interests: The authors declare no conflicts of interest.

Objective: Medullary thyroid carcinoma (MTC) can be very aggressive, and early diagnosis is based on routine measurement of serum calcitonin (CT) and RET genetic testing for hereditary forms. Basal serum CT (bCT) concentrations are useful in the early detection of MTC, although it is still unclear whether they can also be used for the differential diagnosis between MTC and C-cell hyperplasia (CCH). Since false-positive results can be obtained with the basal measurement of CT, a provocative test to evaluate stimulated CT (sCT) is often needed. The objective of this study was to investigate the utility of a calcium gluconate test for CT in distinguishing MTC from CCH, a precancerous condition in hereditary forms of MTCs but with unclear significance in sporadic MTCs., Methods: A total of 74 patients underwent the calcium loading test before thyroidectomy, and bCT and sCT levels were compared with histologic results by receiver operating characteristic plot analyses., Results: A peak CT level of 388.4 pg/mL after stimulation with calcium gluconate was able to significantly distinguish patients with MTC from those with CCH and those without C-cell pathology, with 81.8% sensitivity and 36.5% specificity. A bCT level of 16.1 pg/mL was able to distinguish between these 2 groups of patients with a sensitivity of 90%., Conclusion: High-dose calcium test is an effective procedure that can be applied for differential diagnosis of MTC and CCH. Reference ranges for calcium sCT levels and CT thresholds in different groups of patients have been identified., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Papillary thyroid carcinoma (PTC) is the endocrine neoplasm that occurs the most often worldwide, and its molecular pathophysiology is still not well characterized. Redox status is recognized as an important factor of carcinogenesis, but its influence on the PTC's clinical course needs to be better elucidated. The aim of this research was to determine the tissue redox status of 65 PTC and 45 colloid goiter (CG) patients together with antioxidative cofactor metal profiling. The malondialdehyde (MDA) concentration was used to access the prooxidation level, while antioxidant mechanisms were estimated by assaying the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). The antioxidative cofactor metals included quantification of Se, Cu, Zn, and Mn concentration. PTC tissues had normal prooxidation levels and increased GPx and GR activity. The activity of SOD has been significantly reduced in multicentric PTC dissemination and increased in smokers. SOD activity was directly dependent on MDA levels in CG tissues. CG patients with retrosternal goiter had reduced MDA concentration and SOD activity. Numerous correlations between redox parameters in PTC tissues reveal good co-activation of antioxidative mechanisms and cooperative response on prooxidation. PTC tissues had decreased Se levels and increased concentration of Cu and Mn in comparison to other tissues. MDA concentration and SOD activity were significant predictors of PTC's multicentric dissemination and for the existence of lymph node metastases, respectively. Particularly, the concentration of Cu predicted the retrosternal localization in CG patients. Significant findings presented in this study provide a possibility for development of novel prognostic molecular biomarkers of PTC and CG.

Purpose: The aims of this study were to investigate the rate of intrathyroid extension of papillary thyroid microcarcinoma (PTMC) in patients operated for benign thyroid disease and to identify independent risk factors associated with it., Methods: A retrospective study of 301 patients operated for benign thyroid diseases (hyperthyroid diseases, multinodular goitre, Hashimoto thyroiditis and benign thyroid tumours) was performed at a high-volume endocrine surgery unit of a tertiary referral academic hospital, in a 5-year period. These patients had a PTMC incidentally discovered on definite histopathological findings following total or near-total thyroidectomy. Since distinguishing between intrathyroid extension of PTMC as the result of intrathyroid dissemination or as the result of multicentricity is challenging, we observed them together as multifocality. In statistical analysis, we used standard descriptive statistics and univariate and multivariate logistic regression analysis to determine independent risk factors associated with multifocality., Results: In our study, there were 85.4% females and 14.6% males with a median age of 54 years. A multinodular goitre (32.5%) was the most common indication for an operation. Most patients (68.4%) had a PTMC that was 5 mm or smaller. The most frequent histological variants of PTMC were the follicular variant (52.8%), followed by the papillary variant (22.6%) and the mixed follicular-papillary variant (18.6%). A multifocal PTMC was present in 26.6% of cases. An independent protective factor for multifocality of PTMC was a thyroid gland that weighed more than 38 g (OR 0.55, 95% CI 0.31-0.97, p = 0.039). Size of PTMC greater than 5 mm was an independent risk factor for a multifocal PTMC (OR 3.26, 95% CI 1.85-5.75, p = 0.000). Finally, the mixed follicular-papillary variant of PTMC represents an independent risk factor for a multifocal PTMC (OR 2.42, 95% CI 1.09-5.36, p = 0.030)., Conclusions: Intrathyroid extension is present in more than a quarter of PTMCs found in patients operated for benign thyroid disease. Independent risk factors for intrathyroid extension are size of PTMC greater than 5 mm and the mixed follicular-papillary variant of PTMC, while a large thyroid gland is an independent protective factor.

Background: Hurthle cell carcinoma makes up 3 to 5% of all thyroid cancers and is considered to be a true rarity. The aim of our study was to analyze clinical characteristics and survival rates of patients with Hurthle cell carcinoma., Methods: Clinical data regarding basic demographic characteristics, tumor grade, type of surgical treatment and vital status were collected. Methods of descriptive statistics and Kaplan-Meier survival curves were used for statistical analysis. Cox proportional hazards regression was used to identify independent predictors., Results: During the period from 1995 to 2014, 239 patients with Hurthle cell carcinoma were treated at our Institution. The average age of the patients was 54.3, with female to male ratio of 3.6:1 and average tumor size was 41.8 mm. The overall recurrence rate was 12.1%, with average time for relapse of 90.74 months and average time without any signs of the disease of 222.4 months. Overall 5-year, 10-year and 20-year survival rates were 89.4%, 77.2%, 61.9% respectively. The 5-year, 10-year and 20-year cancer specific survival rates were 94.6%, 92.5%, 87.4%, respectively. When disease free interval was observed, 5-year, 10-year and 20-year rates were 91.1%, 86.2%, 68.5%, respectively. The affection of both thyroid lobes and the need for reoperation due to local relapse were unfavorable independent prognostic factors, while total thyroidectomy as primary procedure was favorable predictive factor for cancer specific survival., Conclusion: Hurthle cell carcinoma is a rare tumor with an encouraging prognosis and after adequate surgical treatment recurrences are rare.

Purpose: In contrast to other thyroid carcinomas it is difficult to establish a correct preoperative diagnosis for oxyphile carcinoma of the thyroid. In this study we looked for predictive malignancy factors in order to enable surgeons to choose operative treatment and to perform an adequate operation for each patient with an oxyphile neoplasm of the thyroid., Methods: In this retrospective study we have analyzed the medical files of all patients with oxyphile tumors of the thyroid operated between 1999 and 2008 in our institution. A total of 256 patients were included and divided into oxyphile adenomas (142) and carcinomas (114) on the basis of their definite histopathological diagnosis. The most important demographic and clinical characteristics were analyzed by univariate and multivariate logistic regression analysis., Results: Univariate analysis showed that male gender, thyroglobulin concentrations ≥300 ng/ml and tumor diameter >30 mm were significantly more frequent in patients with oxyphile carcinoma compared to patients with oxyphile adenoma, while coexisting Hashimoto thyreoiditis and positive AntiTPO antibodies appeared significantly less frequent in the carcinoma group. All variables with a p value <0.1 in the univariate test were subjected to multivariate regression analysis in which elevated preoperative thyroglobulin concentrations (≥300 ng/ml) was shown as the only independent predictive factor for oxyphile thyroid carcinomas (OR=5.88, 95% CI 2.78-12.05, p=0.001)., Conclusions: Preoperative thyroglobulin concentration is an independent predictor of malignancy for oxyphile thyroid carcinomas.

Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy worldwide for which the radiation exposure is the most influential risk factor. The levels of oxidative stress in PTC are not well characterized on the tissue level. The objective of this study was to evaluate total oxidant status (TOS) and total antioxidant status (TAS) in PTC and benign goiter (BG) tissues and to examine their association with clinicopathological characteristics. Tumor and normal thyroid tissue samples were collected from 59 PTC patients, and goiter tissues were collected from 50 BG patients. TOS and TAS were quantified in the tissue homogenates by spectrophotometric assays. TOS values in tumor tissues did not differ significantly from normal and goiter tissues; however, PTC tissues have significantly higher TAS values than normal and goiter tissues. TOS values correlated with retrosternal growth in BG patients. The significant correlations were found between TOS and TAS values and thyroid function parameters. In 17 PTC patients with multiple tumor foci (multicentric phenotype), TAS values were significantly lower, compared to 42 patients with unicentric PTC. TAS and TOS are the most useful predictors of thyroid capsular invasion by PTC. The age, sex, body mass index, smoking, familial history of thyroid disease and nodule size did not influence TOS and TAS in PTC or BG patients. In conclusion, we show the profiles of TOS and TAS in PTC and BG tissues. Importantly, PTC tissues possess increased antioxidant capacity. The redox status influences the parameters of the thyroid function and tumor's biological behavior.

As a key component of the transforming growth factor beta (TGFB) pathway, which regulates the expression of thyroid-specific genes, tumor suppressor SMAD4 is crucial for thyroid development and function. Aberrant expression of SMAD4 in thyroid tumor tissue was reported and mutations affecting the coding region have been detected, but a potential role of mutations in SMAD4 gene regulatory regions remains unexplored. The aim of this study was to analyze SMAD4 gene promoters in thyroid tumors. A total of 76 thyroidectomy specimens were studied, including 42 malignant and 34 benign tumors. The presence of mutations in four SMAD4 gene promoters was analyzed in thyroid tumor tissue and peripheral blood by PCR and DNA sequencing. The expression and intracellular localization of endogenous SMAD4 protein in selected tumor samples was studied by immunostaining and confocal microscopy. Of three novel variants detected, two were within promoter A (-204T/C and -5C/T) and one in promoter D (-180delA). Unlike somatic mutations previously detected in the nearby region, germline mutation -180delA in promoter D doesn't appear to affect SMAD4 expression in the thyroid tumor tissue. However, all newly detected SMAD4 promoter variants affect predicted binding sites of transcription factors involved in cell cycle regulation and should be further characterized functionally. Although not directly involved in carcinogenesis, detected variants may alter SMAD4 transcriptional regulation to some extent. Considering that dosage dependence is of great importance for the role of SMAD4 protein as a tumor suppressor, potential clinical significance of SMAD4 gene promoter mutations is worth further investigation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Thyroid cancer comprises a heterogeneous group of lesions with great diversity of biological behaviour. Markers which could help clinicians to identify high-risk patients for tailored optimization of clinical management are of crucial importance. HBME-1 protein level was analysed immunohistochemically using routinely prepared archival tissue sections of a broad range of papillary thyroid carcinoma (PTC) variants and in corresponding lymph node metastases (LNM). The results were evaluated in comparison with clinicopathological features of PTC. Positive immunoreaction was noticed in most classical (83/92; 90.2 %), follicular (60/71; 84.5 %) and trabecular (4/5; 80.0 %) variants of PTC. All cases of macrofollicular, Warthin-like and diffuse sclerosing PTC variants were HBME-1 positive (4/4, 3/3, 2/2; 100 % respectively). Tall cell and solid PTC variants showed diversity of staining (2/3; 66.67 % and 13/23; 56.52 % respectively), while PTCs with mixed histological pattern containing insular areas were mainly weakly positive (2/5; 40.0 %). A single case of clear cell PTC variant showed no reaction. Moreover, all matched metastatic PTC into lymph nodes (LNM) were HBME-1 positive (17/17; 100 %) and expressed HBME-1 in a similar pattern to the matched primary tumour. We also found a statistically significant association between high HBME-1 expression and the presence of lymph node metastasis, advanced pT status and pTNM stage (P < 0.05), but only a tendency for association with extrathyroidal invasion of the tumour (P = 0.058). Therefore, we recommend using immunoexpression of HBME-1 as useful mean to increase the likelihood of detecting most PTC variants and to predict some unfavourable clinical parameters in these patients.

Background: The aim of our study was to investigate the incidence of papillary thyroid microcarcinoma (PTMC) in patients operated for benign thyroid diseases (BTD) and its relation to age, sex, extent of surgery and type of BTD., Methods: Retrospective study of 2466 patients who underwent thyroid surgery for BTD from 2008 to 2013. To determine independent predictors for PTMC we used three separate multivariate logistic regression models (MLR)., Results: There were 2128 (86.3%) females and 338 (13.7%) males. PTMC was diagnosed in 345 (16.2%) females and 58 (17.2%) males. Age ranged from 14 to 85 years (mean 54 years). Sex and age were not related to the incidence of PTMC. The overall incidence of PTMC was 16.3%. The highest incidence was in Hashimoto thyroiditis (22.7%, χ(2) = 10.80, p < 0.001); and in patients with total/near-total thyroidectomy (17.7%, χ(2) = 7.05, p < 0.008). The lowest incidence (6.6%, χ(2) = 9.96, p < 0.001) was in a solitary hyperfunctional thyroid nodule (SHTN). According to MLR, Hashimoto thyroiditis (OR 1.54, 95% CI 1.15-2.05, p < 0.003) and SHTN (OR 0.43, 95% CI 0.21-0.87, p < 0.019) are independent predictors. Since the extent of surgery was an independent predictor (OR 1.45, 95% CI 1.10-1.92, p = 0.009) for all BTD, and sex and age were not; when the MLR model was adjusted for them, Graves disease (OR 0.72, 95% CI 0.53-0.99, p < 0.041) also proved to be an independent predictor., Conclusions: Sex and age are not statistically related to the incidence of PTMC in BTD. The incidence of PTMC is higher in Hashimoto thyroiditis and patients with total/near-total thyroidectomy; and lower in patients with a SHTN and Graves disease.

Alterations of the von Hippel-Lindau (VHL) tumor suppressor gene can cause different hereditary tumors associated with VHL syndrome, but the potential role of the VHL gene in papillary thyroid carcinoma (PTC) has not been characterized. This study set out to investigate the relationship of VHL expression level with clinicopathological features of PTC in an ethnically and geographically homogenous group of 264 patients from Serbia, for the first time. Multivariate logistic regression analysis showed a strong correlation between low level of VHL expression and advanced clinical stage (OR = 5.78, 95% CI 3.17-10.53, P<0.0001), classical papillary morphology of the tumor (OR = 2.92, 95% CI 1.33-6.44, P = 0.008) and multifocality (OR = 1.96, 95% CI 1.06-3.62, P = 0.031). In disease-free survival analysis, low VHL expression had marginal significance (P = 0.0502 by the log-rank test) but did not appear to be an independent predictor of the risk for chance of faster recurrence in a proportion hazards model. No somatic mutations or evidence of VHL downregulation via promoter hypermethylation in PTC were found. The results indicate that the decrease of VHL expression associates with tumor progression but the mechanism of downregulation remains to be elucidated.

Thyroid carcinomas in children and adolescents are rare tumors and the most common among them is papillary thyroid cancer (PTC). Its etiology is still under research and has not been clearly defined thus far, especially in young individuals. The aim of this case-control study was to determine potential risk factors for the development of PTC in children and adolescents. This type of study has not been carried out previously in this age group. A case-control study was carried out during a 15-year period, between 1995 and 2009. The case group included 75 patients with PTC younger than 20 years of age, with the youngest patient being 6.5 years old; 45 patients were female and 30 were male. The control group included the same number of participants, and the cases were individually matched by sex, age, and place of residence. Conditional univariate and multivariate logistic regression methods were applied in data analysis. According to univariate logistic regression analysis, PTC in children and adolescents was significantly related to the following factors: family history of thyroid cancer, family history of residence in an endemic-goiter area, family history of benign thyroid disease, and family history of nonthyroid malignant tumors. According to the multivariate logistic regression method, PTC in children and adolescents was independently related to a family history of thyroid cancer (odds ratio=4.5, 95% confidence interval=1.2-19.8) and a family history of nonthyroid malignant tumors (odds ratio=3.8, 95% confidence interval=1.4-8.7). In conclusion, all of the factors associated with the development of PTC in children and adolescents were related to their family history.

Aims and Background: Thyroid cancers are relatively rare tumors that appear more frequently in women than in men. Accordingly, most studies focus on studying risk factors for thyroid cancer in women and consequently on various hormonal or reproductive factors that are specific for women. The aim of our study was to examine risk factors for developing well-differentiated thyroid cancer in men. Heretofore, we did not encounter in the literature a study that was solely focused on studying risk factors for well-differentiated thyroid cancer in men., Methods: A case-control study was performed from 2005 to 2010. The case group included 204 consecutive well-differentiated thyroid cancers in male patients (180 papillary and 24 follicular including Hürthle cell). The control group comprised the same number of cases. Patients were individually matched by gender, age and place of residence. Statistical analysis included conditional univariate and multivariate logistic regression methods., Results: According to univariate logistic regression, well-differentiated thyroid cancer in men was significantly related to smoking status, duration of smoking, number of cigarettes smoked per day, history of goiter or thyroid nodules, history of non-thyroid cancer, diabetes mellitus, radiotherapy of the head and neck, and history of malignant tumors. According to multivariate logistic regression, it was independently related to smoking status (OR = 0.36; 95% CI, 0.19-0.69), history of goiter or thyroid nodules (OR = 9.19; 95% CI, 1.25-64.58), and a history of malignant tumors (OR = 2.11; 95% CI, 1.19-7.33)., Conclusions: Risk factors for well-differentiated thyroid cancer in men were goiter or thyroid nodules and family history of malignant tumors. Cigarette smoking was negatively associated with the disease.

Medullary thyroid cancer is a rare tumour that appears in two distinct forms. The rarer familial form is genetically determined. The sporadic form is more common, but its aetiology has not been defined clearly so far. The aim of this study was to examine the risk factors for development of sporadic medullary thyroid cancer (sMTC). A case-control study was carried out during the period 2000-2009. The case group included 98 consecutive patients with sMTC. The control group comprised twice as many cases (196), who were neighbours of the patients from the case group. Patients were individually matched by sex, age and place of residence. Conditional univariate and multivariate logistic regression methods were applied in data analyses. According to the univariate logistic regression method, sMTC was significantly related to smoking status, duration of smoking, number of cigarettes smoked per day, personal history of goitre or thyroid nodules, personal history of nonthyroid cancer, menarche after 14 years of age, first full-term pregnancy before 20 years of age and usage of oral contraceptives. According to the multivariate logistic regression method, sMTC was independently related to smoking status [odds ratio (OR)=0.46, 95% confidence interval (CI)=0.20-0.90], personal history of goitre or thyroid nodules (OR=11.29, 95% CI=1.16-73.45) and menarche after 14 years of age (OR=2.77, 95% CI=1.33-6.28). Risk factors for sMTC were goitre or thyroid nodules and late menarche; cigarette smoking appeared to be a protective factor.

Anaplastic thyroid cancer is very serious disease with bad prognosis and unknown etiology. The aim of the study was to test some hypotheses about other factors in addition to goiter related to anaplastic thyroid cancer occurrence. A case-control study was performed during the period 1993-2005. The case group comprised 126 patients with newly diagnosed anaplastic thyroid cancer. The control group comprised 252 patients who had for the first time goiter operation, and had no malignancy of thyroid gland. Cases and controls were individually matched by age, sex and place of residence (urban/rural). According to conditional multivariate logistic regression analysis, anaplastic thyroid cancer was significantly related to lower education (odds ratio=1.85, 95% confidence interval=1.21-2.82), other malignant tumors in personal history (odds ratio=4.37, 95% confidence interval=1.11-17.31), blood group B (odds ratio=3.69, 95% confidence interval=1.10-12.49), menarche at >or=15 years of age (odds ratio=2.63, 95% confidence interval=1.15-5.88), and first full-term pregnancy before 19 years of age (odds ratio=2.96, 95% confidence interval=1.26-6.96). On the basis of the results obtained, risk factors for anaplastic thyroid cancer are similar to risk factors for differentiated thyroid cancers.

Aims and Background: Thyroid cancer, whose etiology is largely uncertain, has been negatively associated with cigarette smoking in a several studies. We examined the association between cigarette smoking and risk for female thyroid cancer., Methods: A case-control study including 204 histologically verified female thyroid cancer patients and an equal number of hospital controls individually matched with cases by sex, age (+/- 2 years), place of residence and time of hospitalization was carried out during the period 1996-2000. In the analysis of data, univariate and multivariate conditional logistic regression methods were applied., Results: According to univariate analysis, female thyroid cancer was negatively associated with the initiation of smoking at a younger age, before the age of 20 (OR = 0.66, 95% CI = 0.50-0.90). None of the smoking habits remained independently related to female thyroid cancer after adjustment for other factors which were significantly associated with thyroid cancer in the present study., Conclusions: The results of the study do not suggest a role of cigarette smoking in the development of thyroid cancer in women.

Aims and Background: The aim of the present study was to test some hypothetical risk factors for anaplastic thyroid cancer., Study Design: A case-control study comprised 110 patients with histologically or cytologically verified anaplastic thyroid cancer and 110 hospital controls individually matched with cases by sex, age, place of residence and time of hospitalization. Univariate and multivariate logistic regressions were used for data analysis., Results: According to the conditional logistic regression analysis, the following factors were significantly and independently related to anaplastic thyroid cancer: history of goiter or thyroid nodules (odds ratio, OR, 37.55; 95% confidence interval, CI, 4.86-290.11), history of residence in endemic goiter area (OR, 2.56; 95% CI, 1.05-6.22), history of previous malignant non-thyroid tumor (OR, 5.51; 95% CI, 1.04-29.25), diabetes mellitus (OR, 4.06; 95% CI, 1.29-12.81) and low educational level (OR, 2.44; 95% CI, 1.17-5.06)., Conclusions: The results are in line with the current knowledge on factors related to thyroid cancer, except for the association between thyroid cancer and diabetes mellitus, which as far as we know has not yet been reported.