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Öğe Association of MG53 with presence of type 2 diabetes mellitus, glycemic control, and diabetic complications(Public Library Science, 2023) Andac, Burak; Ozgun, Eray; Bulbul, Buket Yilmaz; Colak, Serpil Yanik; Okur, Mine; Yekdes, Ali Cem; Ocal, EftalObjectivesMitsugumin 53 (MG53) is a myokine that acts as a membrane repair protein in tissues. Data on the effect of MG53 on insulin signaling and type 2 diabetes mellitus (T2 DM) are still unknown; most are from preclinical studies. Nevertheless, some researchers have argued that it may be a new pathogenic factor, and therapies targeting MG53 may be a new avenue for T2 DM. Our study aims to evaluate the relationship of circulating MG53 levels with the presence of diabetes, diabetic complications, and glycemic control.MethodsWe conducted a case-control study with 107 patients with T2 DM and 105 subjects without insulin resistance-related disease. Concurrent blood samples were used for serum MG53 levels and other biochemical laboratory data. MG53 concentration was measured using Human-MG53, an enzyme-linked immunosorbent assay kit (Cat# CSB-EL024511HU).ResultsWe found no difference in MG53 levels between the diabetic and control groups (p = 0.914). Furthermore, when the subjects were divided into tertiles according to their MG53 levels, we did not find any difference between the groups in terms of the presence of diabetes (p = 0.981). Additionally, no correlation was observed between weight, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, albumin excretion in the urine, e-GFR levels, and MG53. Finally, MG53 levels were similar between the groups with and without microvascular and macrovascular complications of diabetes.ConclusionOur research finding provides insightful clinical evidence of lack of association between the levels of MG53 and T2 DM or glycemic control, at least in the studied population of Turkeys ethnicity. However, further clinical studies are warranted to establish solid evidence of the link between MG53, insulin resistance and glycemic control in a wider population elsewhere in the world.Öğe A Comprehensive Approach to the Thyroid Bethesda Category III (AUS) in the Transition Zone Between 2nd Edition and 3rd Edition of The Bethesda System for Reporting Thyroid Cytopathology: Subcategorization, Nuclear Scoring, and More(Humana Press Inc, 2024) Bagis, Merve; Can, Nuray; Sut, Necdet; Tastekin, Ebru; Erdogan, Ezgi Genc; Bulbul, Buket Yilmaz; Sezer, Yavuz AtakanSignificant interobserver variabilities exist for Bethesda category III: atypia of undetermined significance (AUS) of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Thus, subcategorization of AUS including AUS nuclear and AUS other is proposed in the recent 3rd edition of TBSRTC. This study investigated the impact of the nuclear features/architectural features/nuclear score (NS) (3-tiered)/subcategories and subgroups on risk of malignancy (ROM) in thyroid fine-needle aspirations (FNA). 6940 FNAs were evaluated. 1224 (17.6%) cases diagnosed as AUS were reviewed, and 240 patients (initial FNAs of 260 nodules and 240 thyroidectomies) were included. Subcategories and subgroups were defined according to TBSRTC 2nd and 3rd editions. Histological diagnostic groups included nonneoplastic disease, benign neoplasm, low-risk neoplasm, and malignant neoplasm. Overall, ROM was 30.7%. ROM was significantly higher in FNAs with nuclear overlapping (35.5%), nuclear molding (56.9%), irregular contours (42.1%), nuclear grooves (74.1%), chromatin clearing (49.4%), and chromatin margination (57.7%), and these features were independent significant predictors for malignancy. FNAs with NS3 had significantly higher ROM (64.2%). Three-dimensional groups were significantly more frequent in malignant neoplasms (35.7%). ROM was significantly higher in AUS-nuclear subcategory (48.2%) and in AUS-nuclear and architectural subcategory (38.3%). The highest ROM was detected in AUS-nuclear1 subgroup (65.2%). ROM was significantly higher in the group including AUS-nuclear and AUS-nuclear and architectural subcategories, namely high-risk group than the group including other subcategories, namely low-risk group (42.0%vs 13.9%). In conclusion, subcategorization may not be the end point, and nuclear scoring and evaluation of architectural patterns according to strict criteria may provide data for remodeling of TBSRTC categories.Öğe Falsely Elevated Thyroid Stimulating Hormone in Two Cases Requiring Special Follow-up(Galenos Publ House, 2023) Colak, Serpil Yanik; Ozgun, Eray; Andac, Burak; Okur, Mine; Bulbul, Buket Yilmaz; Celik, MehmetInappropriate thyroid stimulating hormone (TSH) refers to an elevation in TSH levels that does not match the clinical findings and free T3 and free T4 levels. Several conditions can cause this, such as pituitary tumors that produce TSH, resistance to thyroid hormones, macro-TSH, and antibody interference. Macro-TSH is a condition that causes TSH to be measured high in the blood for a long time by forming a complex with immunoglobulins, mostly IgG. However, patients are clinically euthyroid because macro-TSH is not a bioactive complex. It is essential to exclude the diagnosis of falsely elevated TSH to protect patients from unnecessary or high -dose levothyroxine therapy. In our first case, we presented a patient in whom subclinical hypothyroidism was detected during in vitro fertilization treatment, and levothyroxine was started. The other case was an operated papillary thyroid cancer patient. In both cases, although the dose of levothyroxine was increased, insufficient TSH response to increased fT4/fT3 levels suggested inappropriate TSH elevation. The polyethylene glycol (PEG) precipitation method was used to detect the assay variability. TSH recovery after PEG was 0.96016 and 21016, respectively, supporting the diagnosis of macro-TSH. In both cases, detecting Macro-TSH was crucial in preventing thyrotoxicosis caused by excessive levothyroxine dosage. In addition, delay in treatment for infertility was prevented in the first case.Öğe The Impact of Total Tumor Diameter on Lymph Node Metastasis and Tumor Recurrence in Papillary Thyroid Carcinomas(Mdpi, 2024) Can, Nuray; Bulbul, Buket Yilmaz; Ozyilmaz, Filiz; Sut, Necdet; Mercan, Meltem Ayyildiz; Andac, Burak; Celik, Mehmet(1) Introduction: The impact of multifocality/bilaterality on the prognosis of papillary thyroid carcinoma (PTC) is a matter of debate. In order to clarify this debate, several studies have attempted to identify additional parameters associated with poor prognosis, including total tumor diameter (TTD), in the context of multifocal PTCs. In this context, this study was carried out to investigate the impact of TTD on tumor recurrence and lymph node metastasis (LNM) in PTCs. (2) Materials and Methods: The sample of this single-center retrospective study consisted of 706 patients diagnosed with PTC. TTD was calculated as the sum of the largest diameters of tumor foci in multifocal tumors. The resulting TTDs were grouped into TTDs <= 10 mm, TTDs > 10 mm, TTDs <= 20 mm, and TTDs > 20 mm, using 10 mm and 20 mm as cutoff values. (3) Results: There was no significant difference between multifocal papillary microcarcinomas (PTMCs) with a TTD of >10 mm and unifocal PTCs with a primary tumor diameter (PTD) of >10 mm except for advanced age and lymphovascular invasion (LVI). In addition, perineural invasion (PNI) and TTD > 10 mm were found to be significant risk factors for LNM, and PNI, TTD > 10 mm, TTD > 20 mm, and bilaterality were found to be significant risk factors for recurrence. LVI, and TTD > 10 mm were found to be independent significant predictors for recurrence, and LVI and extrathyroidal extension (ETE) were found to be independent significant predictors for LNM. (4) Conclusions: Considering TTD > 10 mm in recurrence risk categorization models and adopting a clinical approach that takes into account multifocal PTMCs with TTD > 10 mm along with unifocal PTCs with PTD > 10 mm may be more useful in terms of clinical management of the disease.Öğe Relationship between lymphovascular invasion and clinicopathological features of papillary thyroid carcinoma(Assoc Basic Medical Sci Federation Bosnia & Herzegovina Sarajevo, 2017) Sezer, Atakan; Celik, Mehmet; Bulbul, Buket Yilmaz; Can, Nuray; Tastekin, Ebru; Ayturk, Semra; Ustun, FundaLymphovascular invasion (LVI) is an important prognostic factor in various solid tumors, however, data on the association between LVI and thyroid carcinomas are limited. In this study, we evaluated the relationship between LVI and clinicopathological features of papillary thyroid carcinoma (PTC). Six hundred seventy- eight patients diagnosed with PTC between 2012 and 2015 were included into the study. Patients were classified based on the presence or absence of LVI. Gender, age, ultrasonography (US), tumor size and multifocality, BRAFV600E mutation, perineural and capsular invasion, extrathyroid extension (ETE), nodal metastasis, and recurrences were evaluated, and risk analysis was performed for each parameter. The number of patients with LVI [LVI (+)] was 63, while the number of patients without LVI [LVI (-)] was 615. The female/male ratio was 564/114. LVI was present in 18.4% of male patients and in 7.4 % of female patients. In the age group between 17- 25 years LVI was detected in 6/13 patients, and this result was statistically significant compared to other age groups (p = 0.004). Suspicious lymph nodes upon US, perineural or capsular invasion, ETE, tumor size, and nodal metastasis were significantly more frequent in LVI (+) group (p < 0.001). The frequency of BRAFV600E mutation was also significantly higher in LVI (+) group (p < 0.001). Overall, the presence of LVI was associated with gender, tumor size, age, lymph node metastasis, pathological lymph nodes, perineural and capsular invasion, ETE, and BRAFV600E mutation. These results suggest that in PTC patients undergoing thyroidectomy, the presence of LVI should be considered as an indicator of aggressive clinicopathological features and those patients should be followed up carefully for recurrences and metastasis.Öğe RELATIONSHIP OF MAGNESIUM LEVEL WITH GLYCEMIC CONTROL AND LIPID PROFILE IN ADULT PATIENTS WITH TYPE 1 DIABETES MELLITUS(Polish Society Magnesium Research, 2021) Andac, Burak; Bulbul, Buket Yilmaz; Durak, Dudu Merve; Celik, MehmetType 1 diabetes mellitus (T1 DM) is a disease caused by the autoimmune destruction of pancreatic beta cells due to environmental factors in individuals with genetic predisposition. Magnesium (Mg) is one of the environmental factors suggested to be effective in the pathogenesis and progression of T1 DM. While studies link Mg deficiency with poor glycemic control and dyslipidemia, there are also findings suggesting no association. We aimed to assess the serum Mg levels in adults with T1 DM and evaluate its relationship with glycemic control and lipid profile. The study included 95 type 1 diabetic patients, who presented at the Endocrinology outpatient clinic, and 95 age- and gender-matched individuals without chronic disease. The comparison between the study groups was made using Student's t-test for qualitative data analysis and Mann-Whitney U test for quantitative data analysis without normal distribution. The Mg level of the diabetic patients was significantly lower than in the control group (p<0.001). In diabetic patients, the Mg level was significantly higher in the group with Hba1c <7% compared to the group with HbA1c >= 7%. The patients were divided into two groups according to the optimal Mg cut-off value (0.8 mmol L-1) determined by ROC analysis. The median (interquartile range (IQR)) values of HbA1c were 8.9% (10) in patients with Mg levels <0.8 mmol L-1; 7.6% (6) in patients with Mg levels >= 0.8 mmol L-1 (p<0.001). Although some studies have shown that Mg deficiency is associated with higher levels of LDL-cholesterol, triglyceride, and lower levels of HDL-cholesterol, there was no significant difference in the lipid profile parameters in our study. When the cut-off value of Mg level was taken as 0.8 mmol L-1, we did not find a significant relationship between the Mg level and lipid profile parameters. We conclude that Mg levels were lower in patients with T1 DM, and it was associated with poor glycemic control. However, Mg levels were not associated with dyslipidemia. Maintaining the Mg level above 0.8 mmol L-1 should be a supportive approach for glycemic control; however, more prospective studies are needed on this topic.Öğe TERT Expression in Pituitary Adenomas(De Gruyter Open Ltd, 2017) Can, Nuray; Celik, Mehmet; Bulbul, Buket Yilmaz; Sut, Necdet; Ozyilmaz, Filiz; Ayturk, Semra; Guldiken, SibelObjective: Although pituitary adenomas have benign histomorphological features, some of them may present in an aggressive manner. To predict the behaviour of these tumours, telomerase reverse transcriptase (TERT) activity in pituitary adenomas has been the subject of a few studies with contradictory results. This study aims to investigate whether immunohistochemical expression of TERT differs in neoplastic and nonneoplastic pituitary tissues and aims to investigate whether TERT expression is related to clinicopathological features of pituitary adenomas. Material and Method: The study included 48 patients who had been diagnosed with pituitary adenomas and had clinical follow-ups. Nonneoplastic pituitary tissues were obtained from autopsy specimens (n=20). Immunohistochemistry for TERT antibody was performed. Both the nuclear and cytoplasmic expression of TERT antibody was noted, and total combined TERT staining was evaluated according to nuclear and cytoplasmic stainings. Results: TERT expression did not differ between neoplastic and nonneoplastic pituitary tissues. Neither total (combined nuclear and cytoplasmic) TERT nor nuclear TERT expression revealed any statistically significant relationship with any of the clinicopathological features. Higher cytoplasmic TERT expression was observed in adenomas with recurrence than adenomas without recurrence (p=0.035). Conclusion: This study introduces the notion that immunohistochemical expression of TERT does not differ in neoplastic and nonneoplastic pituitary tissues. Pituitary adenomas with cytoplasmic immunohistochemical expression of TERT have significantly higher rates of recurrence. Further studies, including combined methods of immunohistochemistry and molecular analyses in larger groups, may reveal applicable results for the clinical significance of TERT in pituitary adenomas.Öğe URINE IODINE EXCRETION IN PATIENTS WITH PAPILLARY THYROID CANCER: EVALUATION OF THE RELATIONSHIP WITH THE PRESENCE OF A BRAF MUTATION(Polish Society Magnesium Research, 2020) Celik, Mehmet; Guldiken, Sibel; Salt, Semra Ayturk; Bulbul, Buket Yilmaz; Kucukarda, Ahmet; Can, Nuray; Tastekin, EbruIodine is an essential element for the production of thyroid hormones. In recent years, it has been suggested that excessive consumption of iodine may play a role in the pathogenesis of papillary thyroid cancer (PTC). In addition, studies have suggested that high iodine consumption is an important risk factor for the formation of a BRAF mutation in the thyroid gland. A prospectively designed study included 132 cases scheduled for thyroidectomy for various reasons. Urine iodine levels of all patients were examined before the operation. The iodine excretion levels of the patients were grouped according to the median urinary iodine concentration determined in community screenings (those with <100 mu g L-1 low iodine excretion, those with 100-199 mu g L-1 normal iodine excretion, those with 200-299 mu g L-1 high iodine excretion). Patients were divided into 3 groups according to the post-operative pathology results. As a result of thyroid histopathology, benign (n: 44), PTC (n: 88) (BRAF (+): 44 and BRAF (-): 44) cases were included in the study. BRAF mutations in patients diagnosed with PTC were evaluated using the Real Time PCR Melting Curve Analyzer method. The relationship between urinary iodine excretion levels and clinical, histopathological and BRAF positivity was examined. In our study, no difference was found in urinary iodine excretion between patients with and without PTC. Hashimoto's thyroiditis was observed more frequently in patients with PTC (p=0.023). In addition, Hashimoto's thyroiditis was statistically more frequently detected in the BRAF (-) group compared to the BRAF (+) and control group (p=0.034). Despite studies suggesting that high iodine consumption is important in PTC pathogenesis, we did not find a relationship between the mutation and iodine consumption, which plays an important role in the development of PTC.
