Analysis of visual evoked potentials in patients with neurofibromatosis type 1: new concepts.

Introduction: Neurofibromatosis type 1 (NF type 1) is an autosomal dominant disease with typical clinical manifestations, such as skin lesions, Lisch nodules, optic pathway gliomas, and neurofibromas, caused by the mutation of the NF1 gene. Visual evoked potentials (VEP) present a measure of the electrophysiological response of visual cortex to a visual stimulus. The role of VEP in the pathophysiology of NF type 1 is very complex and requires additional research. The Aim: We examined the differences between NF type 1 patients with normal and altered VEP and analyzed the correlation between the prolongation of P100 latency and disease severity. Materials and methods: Two groups were formed: a control group and a study group with NF type 1 patients. Based on the control group analysis, a threshold value for a normal VEP finding of 116 ms was obtained, and it was used to divide the study group into subgroups with normal and altered VEP. We proceeded with examining the differences in clinical manifestations of the disease between the subgroups, after which we checked if there is a correlation between the prolongation of the P100 latency and the severity of the clinical picture according to the Riccardi scale. Statistical analysis was performed using the Pearson chi-square test and the Spearman correlation test in the program SPSS 28.0, with levels of statistical significance p = 0.05 and p = 0.001. Results: In the group with the abnormal VEP we found a statistically significant more frequent occurrence of optic tract glioma (p = 0.008), tumors (p = 0.032), epilepsy (p = 0.043), and cognitive disorders (p = 0.028), while the other clinical signs had an equal prevalence in both groups. A moderately strong correlation (r s = 0.665) was observed between the prolongation of P100 latency and the severity of the clinical picture. Conclusion: Our results showed the important role of VEP in the description of clinical phenotypes of NF type 1. The authors of the study propose VEP to be included in the diagnostic algorithms designed for patients with NF type 1.

Effects of successful parathyroidectomy on neuropsychological and cognitive status in patients with asymptomatic primary hyperparathyroidism.

PURPOSE: Besides typical clinical symptoms, primary hyperparathyroidism (pHPT) is associated with impaired quality of life and cognitive status. The aim of this study was to evaluate the quality of life and cognitive impairment in patients with pHPT, before and after parathyroidectomy. METHODS: We conducted a panel study, which included asymptomatic pHPT patients scheduled for parathyroidectomy. Besides demographic and clinical data, patients' quality of life and cognitive capacity were recorded before, 1 month, and 6 months following parathyroidectomy using the Short Form 36 questionnaire (RAND-36), Beck Depression Inventory (BDI), Depression Anxiety Stress Scales (DASS), Mini-Mental State Examination (MMSE), and Symptom Check List 90-revised version (SCL90R). RESULTS: During a 2-year follow-up, 101 patients entered the study (88 women), with an average age of 60.7 years. The Global score of RAND-36 test ameliorated by almost 50% 6 months after parathyroidectomy. The most sustained subscores of the RAND-36 test were role functioning/physical and health change, with an improvement of more than 125%. According to the BDI, DASS depression subscore, and SCL90R depression subscore, the extent of depressive symptoms reduction was approximately 60% 6 months postoperatively. The level of anxiety was reduced by 62.4%, measured by both the DASS and SCL90R anxiety subscores. The stress level was almost halved according to the DASS stress subscore (from 10.7 to 5.6 points). The results of the MMSE test showed a significant improvement postoperatively, for 1.2 points (4.4%). A worse preoperative score of each tool was related to the higher magnitude of improvement 6 months after parathyroidectomy. CONCLUSION: A considerable number of pHPT patients, even without other typical symptoms, show signs of impaired quality of life and neurocognitive status preoperatively. After a successful parathyroidectomy, there is an improvement in quality of life, declined levels of depression, anxiety, and stress, as well as amelioration of cognitive status. Patients with more impaired quality of life and pronounced neurocognitive symptoms may expect more benefits from the surgery.

Redox metabolism correlates with cellular turnover and clinical phenotype of papillary thyroid carcinoma and colloid goiter.

Introduction: Papillary thyroid carcinoma (PTC) and colloid goiter (CG) represent the most common thyroid malignant and benign diseases, respectively. Oxidative stress is considered to have an important role in the pathogenesis of both diseases, but without sufficient and comprehensive data. The aim was to evaluate the redox profile, its influence on cell survival of PTC, comparing it with CG as a control and its relation with demographic, pathological and clinical parameters. Material and methods: We evaluated for the first time the PTC and CG tissue profile of advanced oxidation protein products (AOPP) and total thiols as parameters of redox metabolism and deoxyribonuclease I (DNase I) and deoxyribonuclease II (DNase II) activity as biomarkers of cell turnover and apoptosis. Tissue levels of biochemical parameters were quantified in PTC and CG tissue using spectrophotometric methods. Study parameters were evaluated in light of different demographic, clinical and pathological features of PTC and CG. Results: Papillary thyroid carcinoma tissue is characterized by increased antioxidant activity and a normal prooxidation level. Biochemical parameters show numerous correlations with demographic and clinical characteristics of PTC and CG patients. DNase I and II activities are dependent upon the AOPP concentration in PTC tissue. The size of CG can be predicted with combined use of AOPP, DNase I and DNase II. AOPP is the most powerful predictor of PTC capsular invasion, multicentric intrathyroid dissemination and lymph node metastasis phenotype. Conclusions: Evaluated parameters can be used for assessment of tumor redox and survival status and the clinical course of PTC and CG.

Profiling of Circulatory Elements Reveals Alteration of Essential and Toxic Trace Metals in Crohn's Disease.

The status of essential and toxic trace metals in the blood of Crohn's disease (CD) patients is unexplained. This study aimed to provide the first elemental profiling of the most recognized essential elements (Mn, Cu, Zn, Se) and selected toxic trace elements (As, Cd, Pb, and U) in sera and cell lysate (CL) samples of CD patients (n = 84). The results were compared with sex- and age-matched samples from the control group (CG). CD sera contained significantly higher levels of Mn, As, Cd, Pb, and U than did CG sera. An identical pattern, with the added inclusion of Cu (also higher in CD patients than in the CG), was obtained for CL samples. However, the most important finding was hypermanganesemia, which indicates that Mn could act as a toxic trace metal in CD. As, Cd, and U were the most significant toxic elements that showed antagonistic effects on the extrusion of essential Mn and Cu. Circulatory system screening markers for CD are hereby proposed (Mn/Cu, Mn/As, and Mn/Pb ratios). These three metal ratios were strongly and significantly correlated with F-Calprotectin levels, and deserve consideration as new markers of CD. The target metals and metal ratios should be taken into consideration as novel initiating and/or modifying factors for CD.

Elemental Composition of Pheochromocytoma Resolved on Solid/Adrenal Tissue and Whole Blood Level.

Pheochromocytoma (PCC) is an unusual benign adrenal tumor with an unexamined status of the elements. This study delivers the first insight into the levels of microelements (Mn, Co, Cu, Zn, As, Se, Th), toxic elements (Cd, Pb, U), and macroelements (Na, K, Mg, Ca) in both adrenal tissue and whole blood samples collected from PCC patients. The results were strengthened by comparing recorded findings with the patients' healthy adrenal tissue (HAT) and with whole blood samples from the healthy individuals. PCCs had significantly higher levels of Zn, Se, Na, K, and Mg and lower levels of Mn, Co, Pb, and As than that of HATs. Compared to healthy blood samples, the patients' blood exhibited considerably higher levels of Na, K, and Ca but significantly lower levels of Mn, Cu, Zn, Se, and Mg. Females had significantly higher levels of essential Se and toxic Pb and Cd in their PCC tissue samples compared to males. PCC tissue levels of Mn and Cu were significantly elevated in smokers over levels in nonsmokers and in PCC patients with tumor sizes below 5 cm compared to PCC diameters above 5 cm. The data presented in this study provide a new insight into the pathophysiology of PCC. Thus, recorded elements should be considered as initiators/modifiers of PCC and potential inductors of malignant transformation. The findings of this research deepen scientific understanding of this rare adrenal disease, which, in turn, could highlight the pathogenesis of PCC.

Evaluation of Genetic Damage in Persons Occupationally Exposed to Antineoplastic Drugs in Serbian Hospitals.

INTRODUCTION: Although useful in the treatment of malignant cells, antineoplastic drugs (ANPDs) as chemical genotoxic agents, can interfere with normal cell physiology causing genetic damage and unfavourable health effects, especially in occupationally exposed persons. The Cytokinesis-block Micronucleus (CBMN) Cytome assay has been widely used in human biomonitoring studies as a reliable biomarker of chemical genotoxic exposure. OBJECTIVES: Our comprehensive research was conducted in order to evaluate micronuclei as a marker for preventive medical screening purposes for persons occupationally exposed to ANPDs. METHODS: Using the CBMN Cytome test, peripheral blood lymphocytes of 201 control and 222 exposed subjects were screened for genetic damage. RESULTS: Age and gender influenced micronucleus (MN) frequency, but smoking habit did not. The mean micronuclei frequencies and other parameters of the CBMN Cytome test [numbers of binuclear lymphocytes with one (MN1) or two (MN2) micronuclei] were significantly higher in the group of exposed persons. Positive correlation between duration of occupational exposure and MN frequency was revealed. CONCLUSIONS: The results of our study performed on a large sample confirmed the capacity of the CBMN Cytome assay to serve as a reliable biomarker of long-term ANPD exposure.

Alteration of Trace Elements in Multinodular Goiter, Thyroid Adenoma, and Thyroid Cancer.

Modest progress has been made in understanding the role of trace elements as endocrine disruptors. The aim of this study was to examine whether there is a change in the content of trace elements in thyroid disease, as well as whether the ratio of elements could be considered a blood marker for thyroid disease. In addition, this study examined the influence of biological and clinical/pathological parameters on the elemental profile. Blood samples from patients diagnosed with multinodular goiter (MNG), thyroid adenoma (TA), and thyroid cancer (TC) were examined and compared with control samples using chemometric analysis. The concentrations of essential (Mn, Co, Cu, Zn, Se) and toxic elements (Ni, As, Cd, Pb, U) were determined by ICP-MS. This study showed for the first time that the content of Mn, Co, Ni, Cu, Zn, Se, and Pb in pathological blood samples was significantly lower compared to the control, while opposite results were obtained for As, Cd, and U. Based on the classification model, the most important trace metals for discrimination of MNG and TC from the control group (CG) were Co and Zn, while Co, Zn, and Mn influenced the distinction of CG from TA. Moreover, it was found that Cu/Zn and U/Se ratios had significantly increased values in pathological blood samples leading to the possibility of establishing new circulating screening markers. These findings can represent significant translational information since these diseases are widespread and the diagnostic procedure is still difficult in many cases.

The first insight into the trace element status of human adrenal gland accompanied by elemental alterations in adrenal adenomas.

BACKGROUND: The baseline status of trace metals in adrenal tissue is unresolved, while the elemental profile for any adrenal pathology has not been examined so far. This study aimed to determine the baseline status of important toxic (Ni, As, Cd, Pb, Th, U) and essential trace elements (Mn, Co, Cu, Zn, Se) in healthy adrenal tissues (HATs) as well as to examine whether there are alterations in the elemental composition of adenomatous adrenal tissues (AATs). Furthermore, this study aimed to find potential trace metals that could play a role in the pathogenesis of adrenal adenoma (AA). METHODS: The study included 45 patients diagnosed with AA. Impacts of relevant parameters such as gender, age, smoking habits and nodular sizes were considered. All samples were subjected to microwave digestion and the trace elements were determined by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: This is the first study that provided an insight into the elemental status of HATs. It was also shown that AATs had altered trace metal contents. Compared to HATs, the most significant findings were related to the high content of essential (Cu, Mn, Se, Zn) and Pb as a non-essential metal. Although gender, age and smoking habits had a modest effect on metal profiles, the most significant alterations were related to the nodular diameter above 4 cm, indicating that the growth of benign tumor could influence changes in elemental composition. CONCLUSION: For the first time the baseline contents of essential and toxic trace metals in HATs were determined. The results of this study may highlight the role of toxic and essential trace metals in AAs and could provide new insights into the molecular basis of pathophysiological changes caused by the hazardous effects of trace metals on adrenal structure and function.

Oxidative Stress Profile in Genetically Confirmed Cases of Leber's Hereditary Optic Neuropathy.

The mechanisms of the complex pathophysiology of Leber's hereditary optic neuropathy (LHON) are still insufficiently clarified. The role of oxidative stress as an etiological factor has been proposed and demonstrated in vitro, but without conclusive data that rely on clinical samples. The aim of the study was to evaluate and characterize the existence of oxidative stress in the plasma of LHON patients and healthy individuals. Whole mitochondrial genome sequencing has been performed in order to identify primary LHON mutations. For the assessment of oxidative stress, the following biomarkers were determined in plasma: total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI), while oxidative damage of cellular proteins was estimated by quantifying advanced oxidation protein products (AOPP). All three primary LHON mutations (m.3460G > A, m.11778G > A and m.14484 T > C) were identified as a genetic cause of the disease, where the most prevalent one was m.11778G > A. LHON patients have a highly significant increase of TOS and a marked decrease of TAS levels, which suggests the existence of substantial oxidative stress. OSI is high in LHON patients, which definitely implies the presence of redox imbalance. Elevated level of AOPP in LHON patients refers to the significant deleterious effects of oxidative stress on cellular proteins. Oxidative stress parameters do not significantly differ between LHON individuals with different primary mutations. Both symptomatic and asymptomatic LHON patients have an augmented level of oxidative stress which suggests that primary mutations exhibit a pro-oxidative phenotype. Gender and smoking habit significantly influence examined biochemical parameters when LHON patients are compared with the control group. Different mitochondrial haplogroups are characterized by altered levels of OSI in LHON group. The absence of physiological correlations between redox parameters reflects the deregulation of homeostatic oxidative/antioxidative balance in LHON patients. This is the greatest series of LHON patients that were evaluated for oxidative stress and the first case-controlled study that evaluated TOS, TAS, OSI, and AOPP and their influence on disease phenotype. It is evident that the presence of oxidative stress represents an important pathophysiological event in LHON and that it could potentially serve as a circulatory biomarker for a therapy efficacy understanding.

The Role of MIF in Hepatic Function, Oxidative Stress, and Inflammation in Thioacetamide-induced Liver Injury in Mice: Protective Effects of Betaine.

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on the etiology and stage of liver disease. OBJECTIVE: Our study aimed to investigate the role of MIF in oxidative stress and inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice. METHODS: The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into the following groups: control; Bet-group that received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group that received TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received the same doses. After eight weeks of treatment, blood samples were collected for biochemical analysis, and liver specimens were prepared for the assessment of parameters of oxidative stress and inflammation. RESULTS: In MIF-/-mice, TAA reduced transaminases, γ-glutamyltranspeptidase, bilirubin, malondialdehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN-γ, and increased thiols and total antioxidant status (TAS). Betaine attenuated the mechanism of MIF and mediated effects in TAA-induced liver injury, reducing transaminases, γ-glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g, and increasing thiols. CONCLUSION: MIF is a mediator in hepatotoxic, pro-oxidative, and proinflammatoryeffects of TAA-induced liver injury. MIF-targeted therapy can potentially mitigate oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases anti-oxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.

Ectopic thyroid tissue in adrenal gland, case report and review of literature.

Ectopic thyroid tissue is a rare pathological finding bellow the diaphragm and extremely rare finding is ectopic thyroid tissue in the adrenal gland (ETTAG). Thyroid tissue can be located anywhere along the way of embryological migration pathway of thyroglossal duct. In most cases of ectopic thyroid tissue, it is located in the neck. Here we present a case of 29 years old patient that was laparoscopically operated because of adrenal incidentaloma which showed 28 mm in maximal diameter on MRI. The patient had normal adrenal function. Pathohistological finding confirmed ETTAG. Follicular cells express TTF-1, Thyroglobulin, PAX8, and cytokeratin 7, and lack expression of calretinin. This is the 15th such case described in literature. Women are much more affected than men (14:1), and it usually presents in the fifth decade (mean age 49). In all cases ETTAG was composed of normal follicular cells, and C cells were not found. Review of the literature reveals that adrenal ectopic thyroid tissue is almost always cystic, and has distinctive pathologic features. The most important thing is that ETTAG must be distinguished from metastatic deposits from thyroid gland carcinoma. Our patient had normal thyroid function, without any nodules in thyroid gland. We report the youngest patient with ectopic thyroid tissue located in the adrenal gland.

Correction to: Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter.

The original version of this article unfortunately contained a mistake.

Assessment of trace metal alterations in the blood, cerebrospinal fluid and tissue samples of patients with malignant brain tumors.

The pathogenesis of malignant brain tumors (MBTs) should be better understood due to the evident association between prolonged exposure to metals and increased risk of MBTs. The present research aimed to find trace metals that could contribute to the pathogenesis of MBTs. Essential trace elements (Mn, Co, Zn, Cu, Se) and relevant toxic metals (Al, Ni, As, Sr, Cd, Ce, Pt, Pb, U) in the serum, cell fraction (CF), cerebrospinal fluid (CSF) and cancerous tissue (CT) samples of MBT patients were analyzed. The results were compared with sex- and age-matched control groups. For the first time, this research showed that elemental profiles of serum, CF, CSF and CT samples in MBT patients were significantly altered compared to the appropriate controls, as well as that higher contents of trace elements (particularly Mn, Se, and Pb) could be involved in the pathogenesis of MBTs. However, the most noticeable change found was the elevated U content, indicating its considerable role as a major cerebral discriminator of the presence/absence of MBTs. The U/Se ratio could be considered as an appropriate blood marker in diagnostic MBT evaluation. The reported results could contribute to better understanding of the poorly understood pathogenesis of MBTs. Furthermore, the reported results could highlight a molecular basis for the pathophysiological changes caused by the hazardous effects of trace metals on brain homeostasis.

Case-control study of primary hyperparathyroidism in juvenile vs. adult patients.

OBJECTIVES: Primary hyperparathyroidism in juveniles is extremely rare condition, but in the last few decades the incidence is increasing. The aim of this study was to compare biochemical and clinical characteristics of juvenile and adult primary hyperparathyroidism patients. METHODS: A retrospective case-control study was conducted from 2004 until 2017 in high volume endocrine surgery center. Juvenile group consisted of all primary hyperparathyroidism patients younger than 20 who have undergone parathyroidectomy, and two-fold more patients older than 20 were classified in control (adult) group. RESULTS: A total of 14 patients with the age ≤20 years were included in the juvenile group, while 28 patients older than 20 were selected for the control group. Female-to-male ratio in juveniles was 1:1, and in adults 8:1 (p = 0.005). The most common form of the disease in juveniles was bone disease (42.9%) and most of adults were asymptomatic (39.3%). Mean preoperative serum calcium level was significantly higher in juveniles than in adults, 3.47 ± 0.74 mmol/L vs. 2.96 ± 0.25 mmol/L, p = 0.025. Mean preoperative PTH level was higher in juveniles than in control group, 572.6 ± 533.3 ng/L vs. 331.8 ± 347.5 ng/L, p = 0.089. CONCLUSION: Clinical manifestations of primary hyperparathyroidism significantly differ in juvenile and adult patients. Juvenile primary hyperparathyroidism represents more severe form of the disease, often with end-organ damages, and it should be considered in patients with unspecific symptoms.

Redox Status and Antioxidative Cofactor Metals Influence Clinical and Pathological Characteristics of Papillary Thyroid Carcinoma and Colloid Goiter.

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.

Evaluation of trace metals in thyroid tissues: Comparative analysis with benign and malignant thyroid diseases.

Evaluation of trace metals at level of solid tissue can provide better information than blood or urine and, therefore, could highlight the role of metals in the etiology of organ-specific disease. The current study aimed to establish the baseline content of four essential (Mn, Cu, Zn, Se) and four toxic metals (As, Cd, Pb, U) in the healthy thyroid tissues (HTTs) by considering sex, age and smoking habits. A further aim was to examine whether differences in the content of metals exist in regard to the thyroid diseases, such as benign tumor (BT), Hashimoto's thyroiditis (HT), multinodular goiter (MNG) and thyroid cancer (TC). A total number of investigated tissue samples were 423. All metals were quantified by inductively coupled plasma-mass spectrometry (ICP-MS). It was found that the content of Cu and U was higher in HTTs of women, while the content of Zn was higher in HTTs of men. Increased content of Zn and decreased content of U was found in the group of HTTs above 50 years compared to a younger group (<50 years). Increased content of Cd, Pb and U distinguish smokers from the non-smokers. In comparison with other population groups worldwide, investigated Serbian population had up to 15 times reduced content of Se. Despite the difference in metal's profile according to biological variables, this study also demonstrated, for the first time, that each thyroid disease has its unique metal's profile. The most altered metal's content was found in tissues with HT. Contrarily, the greatest similarity in metal's content with HTTs was found in BT tissues. Based on the increased content, metal's that dominantly discriminated HTTs from the HT, MNG and TC was As, Pb and Cd, respectively. Reported results could highlight the role of toxic and essential trace metals in the not very well clarified etiology of thyroid diseases and, moreover, could provide a molecular basis for pathophysiological changes of metal's hazardous effects on thyroid health at the tissue level.

Cadmium as main endocrine disruptor in papillary thyroid carcinoma and the significance of Cd/Se ratio for thyroid tissue pathophysiology.

BACKGROUND: The etiology of papillary thyroid carcinoma (PTC) is unknown and some literature data support the hypothesis that heavy metals, as endocrine disrupters, could play a major role in the pathogenesis of thyroid cancer. This study aimed to estimate the content of selected toxic and essential trace metals (Mn, Co, Ni, Cu, Zn, As, Se, Cd, Pb, Th, and U), as well as the selected ratio's (Cu/Zn and Cd/Se) in the malignant thyroid tissues according to sex, age, smoking habits, familial history of any thyroid disease, pathohistological (PH) types of PTC, tumor size, the existence of a thyroid capsular invasion, intrathyroid tumor dissemination, retrosternal thyroid growth, and TNM progress of PTC. METHODS: The study included 66 patients with PTC (women/men ratio = 46/20, mean age: 54 ± 14 years). A comparative analysis was made by collecting the healthy thyroid tissues (HTTs) of the same patients, making the total number of samples 132. All trace metals were quantified by inductively coupled plasma-mass spectrometry (ICP-MS). RESULTS: Metals that significantly separated papillary thyroid tissues (PTTs) from the HTTs were Cd, U and Se (p < 0.05). The obtained negative correlation between Cd and Se in the PTTs could explain extrusion of essential Se caused by increased content of Cd. Only Cd had an influence on the retrosternal thyroid growth, while the essential metals (Mn, Co, and Zn) had an influence on thyroid capsular invasion. CONCLUSION: It was found that Cd act as the main endocrine disrupter, which could highlight its role in the etiology of PTC. Considering that the Cd/Se ratio significantly separated two studied groups and had an influence on the retrosternal thyroid growth, its altered content could contribute to the better understanding of the molecular basis for pathophysiological changes in the PTC.

The influence of redox status on inter-individual variability in the response of human peripheral blood lymphocytes to ionizing radiation.

PURPOSE: Ionizing radiation (IR) can act on atomic structures, producing damage to biomolecules. Earlier investigations evaluating individual radiosensitivity in vitro were focused on cytogenetic biomarkers (chromosomal aberrations - CA and micronuclei - MN). Since IR can also cause oxidative damage by producing reactive oxygen species, the main goal of this investigation was to establish the influence of redox status on CA and MN frequency in human peripheral blood lymphocytes. MATERIALS AND METHODS: Blood samples from 56 healthy donors were irradiated at doses of 0, 0.75, 1.5 and 3 Gy and then analyzed cytogenetically and biochemically. RESULTS: The results showed inter-individual variability in all analyzed parameters, as well as dose-dependent increases in almost all of them. Correlation analysis indicated no association between CA, MN and oxidative stress parameters. However, findings for overall response (HRR) parameters showed that donors with lower values for parameters of antioxidant status had increased levels of cytogenetic damage and higher responses to irradiation and vice versa. CONCLUSION: Besides well-established cytogenetic biomarkers of radiation exposure, our results indicated promising future use for biochemical oxidative status parameters in routine radiation protection practice, since together they can provide a complete radiation response profile in cases of continuous low-dose exposure, as well as in a radiation emergency.

Survival and prognostic factors for survival, cancer specific survival and disease free interval in 239 patients with Hurthle cell carcinoma: a single center experience.

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.

Surgical treatment of concomitant thyroid and parathyroid disorders: analysis of 4882 cases.

The thyroid gland disease incidence in hyperparathyroidism (HPT) is higher than the incidence of thyroid disease in general population. Likewise, HPT is more frequent in patients primary admitted due to thyroid disease, than in general population. The aim of this study was to determine the incidence and clinical characteristics of concomitant HPT and thyroid disease, based on a single center experience. From 2009 to 2014, a total of 4882 patients underwent thyroidectomy and/or parathyroidectomy at the Center for Endocrine Surgery, Belgrade. We reviewed the database to find out indications for surgery, clinical characteristics, operative and histopathological findings. Out of 4033 patients, who underwent thyroidectomy, in 114 cases (2.8 %) parathyroidectomy was simultaneously performed. Out of these 114 patients, 42 patients (37 %) had normocalcemic HPT. Among 849 patients primary operated due to HPT, thyroid gland disease that required surgery was found in 224 (26.4 %). In patients primary seen for HPT, thyroid cancer was found in 22 (9.8 %), Hashimoto's thyroiditis in 41 (18.3 %) and micropapillary carcinoma in 36 cases (16.1 %). Due to residual or recidivant HPT, 16 patients (15 who primary underwent parathyroidectomy and 1 primary seen for thyroid disease) needed a reoperation. There are a considerable number of patients with concomitant thyroid and parathyroid disease; this justifies the routine analyses of calcemia and PTH level in patients preparing for thyroidectomy, and sets up the ground for the thyroid investigations in HPT.