ACTA ENDOCRINOLOGICA (BUC)

Objective. Osteoporosis is a complex disease and its development is influenced by genetic, epigenetic, metabolic, and environmental factors. However, specific genetic factors associated with osteoporosis are not fully understood. The aim of this study was to identify genetic risk factors for osteoporosis. Methods. This study included 86 females with osteoporosis and 47 healthy females. We analyzed rs1800587, rs16944, rs1799814, rs4988321, rs2228570, and rs35211496 variations in IL1A, IL1B, CYP1A1, LRP5, VDR, and RANK, respectively, using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) analysis. Results. Our analysis revealed that the CT and TT genotype for rs1800587 in IL1A was associated with higher bone mineral density in the lumbar spine, trochanter, Ward's triangle, and femoral neck (p=0.020, p=0.021, p=0.015, and p=0.013, respectively). The rs1800587 variation in IL1A was associated with a reduced risk of osteoporosis in both dominant and codominant inheritance models (CC vs. CT, p=0.016 and CC vs. CT/TT, p=0.035, respectively). However, we did not identify any statistically significant differences in either genotype or allele frequencies between the control group and the patients with osteoporosis for the other genetic variations examined. Conclusion. Our findings suggest that the rs1800587 variation in IL1A gene is associated with a significantly decreased risk of osteoporosis in the Turkish population.

Background. Retinopathy is a common complication of diabetes and strongly related to the duration of the disease and the quality of its management. Despite this relationship, some studies have reported the prevalence of diabetic retinopathy at diagnosis to be 5-30%.\r\nAim. To investigate the prevalence of retinopathy in patients with newly diagnosed type 2 diabetes and its relation to some association factors in Isfahan, Iran.\r\nMethods. During 2001-2004, all newly diagnosed type 2 diabetics (n= 710) attending Isfahan Endocrine and Metabolism Research Center, were enrolled, by consecutive patient selection. Everybody accepted our invitation. The patients were examined by an internist and then by an ophthalmologist for retinopathy. Fasting plasma glucose, glycosylated hemoglobin, lipid profile, and 24-hour urinary albumin and creatinine concentrations were measured.\r\nResults. Of 710 patients, 286 were male. Mean age of the patients was 48.8(9.8) years (31-72 years) and median of diabetes duration was 6 months (0.5-12 months), respectively. Nine percent of patients (CI95%: 7-11) [(9.8% of men (CI95%: 6-13) and 8.5% of women (CI95%: 6-11)] had retinopathy (Odds ratio= 0.85, CI95%: 0.51-1.43, P= 0.5). In the final analysis using logistic regression test, body mass index (OR= 0.9, CI 95%: 0.8-1, P= 0.01), diastolic hypertension (OR= 3.9, CI 95%: 1.33-11.7, P= 0.01) and 24-hour urinary albumin concentration (OR= 1.005, CI 95%: 1-1.01, P= 0.01) were identified as association factors\r\nfor retinopathy.\r\nConclusions. Retinopathy was moderately prevalent in our patients.

Introduction. Diagnosing Cushing Syndrome (CS) remains challenging due to its diverse symptoms and the complexity of its subtypes. This study aimed to optimize diagnostic cut-off values for differentiating CS subtypes using the 1 mg dexamethasone suppression test (DST) in a cohort of 237 patients. Materials and Methods. Retrospective data from patients diagnosed with non-functional adrenal adenomas (NFA), mild autonomous cortisol secretion (MACS), adrenal CS, and pituitary CS at the Dokuz Eylül University Endocrinology and Metabolism Clinic (2005–2016) were analyzed. Sensitivity and specificity of morning cortisol levels after DST were evaluated using receiver operating characteristic (ROC) curve analysis. Results. The analysis identified optimal morning cortisol cut-off levels: 2.14 μg/dL (59.04 nmol/L) for MACS, 2.3 μg/dL (63.4 nmol/L) for adrenal CS, and 2.33 μg/dL (64.28 nmol/L) for pituitary CS. Conclusion. These optimized thresholds demonstrated high sensitivity and specificity, significantly improving diagnostic precision over the conventional threshold of 1.8 μg/dL (50 nmol/L). The findings underscore the importance of tailored cut-off values to address subtype-specific diagnostic challenges, reducing delays and mitigating long-term complications. Personalized diagnostic approaches, incorporating patient demographics and disease-specific characteristics, are essential for enhancing diagnostic accuracy and facilitating timely interventions.

The aim of this study is to analyze and identify the main predictors that may indicate multifocal growth of PTC. Materials and methods. The main and control groups included patients with the category of malignant multifocal process T1-3mN0Mx (n=109) and unifocal T1- T3N0Mx (n=50) respectively, who underwent thyroidectomy with lymphadenectomy. Ultrasound characteristics of the nodes, tissue changes of the thyroid gland were taken into account. Results. Fibrous changes can be considered as one of the risk factors of the presence of additional PTC lesion. Discussion. There is no unambiguity in the definition of predictors of multifocal PTC growth. Conclusions. No clear predictors of multifocal PTC have been identified. It is advisable to improve the quality of ultrasound, to focus on single-focus PTC in patients with fibrinous changes in the thyroid gland at normal levels of TSH.

Context. Some adrenal tumors, such as pheochromocytoma, can be life-threatening. Therefore it is crucial to distinguish them from other lesions, especially prior to surgery. Chromogranin A (CgA) seems to potentially be a good marker for tumors of chromaffin origin. Objective. To assess the differentiating value of CgA in the diagnostic work-up of pheochromocytoma. Design. Retrospective study of operated patients with adrenal incidentaloma with lesions > 10 Hounsfield’s units (HU) on CT. Subjects and Methods. Thirty patients (11 males, 19 females; aged 61.5±21 years) were enrolled in the study. Patients using medications interfering with the assessment of CgA and metanephrines were excluded. Two groups were formed: those with pheochromocytoma (Ph, n=16) and those with non-pheochromocytoma (N-Ph, n=14) lesions. Data included radiological features of masses, serum CgA and 24-hour urine metanephrines (24 - HUM) concentrations. Results. No difference in 24-HUM level nor tumor size or density was found between groups Ph and N-Ph. Median serum CgA concentration was higher in Ph group compared to the N-Ph: 99.35 (68.12-172.73) vs. 52.92 (34.37-101.26) ng/mL, respectively (P=0.04). In Ph group, the size of the lesion correlated negatively with density (r= -0.53, P=0.042). No significant correlation in CgA, 24-HUM, density or size of the lesion was found. Performed curve receiver operating characteristic (ROC) showed AUC=0.7232 for CgA. Taking into account CgA serum value of ≤ 50 ng/mL (sensitivity: 93.75%, specificity: 50.00%, P=0.012), we proposed an algorithm for management of lesions > 10 HU on CT. Conclusion. CgA level ≤ 50 ng/mL might be useful in initial screening evidence for the exclusion of pheochromocytoma. It is crucial to eliminate factors interfering with the measurements.

Objective. To evaluate the effect of multiple daily injection (MDI) treatment replaced by Exenatide BID as compared with continuation of MDI. Patients and Methods. A total of 140 patients with type 2 diabetes, taking metformin and multiple daily insulin injections, were randomized to exenatide or insulin group that continued their insulin treatment. Patients were followed-up for 16 weeks. Blood glucose profiles, BMI, waist circumference, HbA1C, serum lipids and side effects were assesssed at weeks 0,12 and 16. Results. There were no significant differences between the two groups with respect to baseline parameters. Glycemic control was similar between the two groups. The mean changes in HbA1C in exenatide group were -0.66±0.63% and in insulin group -0.74±0.92 % (p=0.594). In exenatide group, 59.6 % of patients and in insulin group 85.71 % of patients had maintained or improved glycemic control at the end of the study. In insulin group, insulin requirement increased 5.86 ± 4.46 units/day. Body weight and waist circumference decreased significantly in exenatide treatment group with respect to insulin group (p<0.001). Conclusions. Substituting exenatide for insulin might be an option in insulin-treated, type 2 diabetic patients having obesity, and poor glycemic control. However, patients with longer duration of diabetes and insulin treatment and with lower C-peptide levels might not benefit from exenatide therapy.

Background. It is important to protect recurrent laryngeal nerve (RLN) during thyroid surgery. Thus, intraoperative neuromonitoring (IONM) has got popularity. But, the half life of neuromuscular blocking agents used has a reverse correlation with reliability and effectiveness of IONM. This study aimed to research the effect of Sugammadex Sodium, a specific nemuromuscular blocking agent antagonist, on nerve conduction and IONM. Materials and methods. Twenty patients who underwent thyroidectomy under IONM followed an enhanced NMB recovery protocol-rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at the beginning of operation. To prevent laryngeal nerve injury during the surgical procedures, all patients underwent intraoperative monitoring. At the same time, the measurement of TOFWatch acceleromyograph of the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio ≥ 0.9. Age, sex, recurrent laryngeal nerve transmission speeds prior to and after operation, BMI, duration of surgery, the change in nerve transmission after drug administration and complications were analyzed. Results. The mean age and the mean BMI were 47.6±11.82 years and 28.74±3.20, respectively. The mean operation duration was 52.65±5.51 minutes. There was no difference in either right or left RLN monitoring values before and after surgery. Following the drug injection, the TOF guard measurements on the 1st, 2nd, 3rd and 4th minutes were 23.5±4.90; 69.5±6.86; 88±4.1 and 135.9±10.62, respectively. Conclusion. Neuromuscular blocking antagonist use and monitoring nerve transmission speed with TOFguard can provide a safer resection.

Context. Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective. In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design. In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods. In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results. When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion. Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Objective. This study aims to investigate the factors affecting development of acute kidney injury (AKI) in patients with severe hypothyroidism. Methods. This retrospective observational study involved patients with primary hypothyroidism and thyroid stimulating hormone (TSH) levels of more than 50 mIU/L at their review in the endocrinology outpatient clinic, between January 2015 and April 2021. Factors affecting the development of AKI were examined by logistic regression analysis. Results. A total of 100 patients, 20 (11 male (M), 9 female (F)) in the AKI (case) group and 80 (23 M, 57 F) patients in control group, were included in our study. The median age of the case group (56 years, interquartile range (IQR) 44.3–68.5) was significantly higher than the control group (49 years, IQR 32.3–60; p = 0.027), and the ratio of males to females was significantly higher in the case group (p = 0.001). Multivariate logistic regression analyses showed that hypothyroidism diagnosed after the age of 60 years (odds ratio (OR) 59.674, 95% confidence intervals (CI) 5.955–598.031; p = 0.001), free triiodothyronine (FT3) < 1.3 pg/mL (OR 17.151, 95% CI 2.491–118.089; p = 0.004) and creatine kinase (CK) > 1000 U/L (OR 1.522, 95% CI 1.602– 82.848; p = 0.015) were predictors for the development of AKI in patients with severe hypothyroidism. Conclusion. We recommend close follow-up and monitoring of patients with AKI caused by severe hypothyroidism if patients who are diagnosed at age > 60 years, CK > 1000 U/L or FT3 < 1.3 pg/mL.

Background. There have been a number of reports on the relationship between the PPARγ2 Pro12Ala genotype and the development of obesity. Objective. A case-control survey was designed to investigate the potential association between a Pro12Ala polymorphism in the PPARγ2 gene and obesity and/or obesity-related phenotypes in a population from Turkey. Materials and methods. The polymerase chain reaction and restriction enzyme digestion were used to genotype the Pro12Ala polymorphism of the PPARγ2 gene in 149 unrelated obese and 105 non-obese control subjects from Turkey. The data were analyzed statistically. Results. We found that the overall minor allele frequency was 0.12 in cases and 0.095 in controls. In terms of genotype distribution and allele frequencies among the cases versus controls in the population studied, only the genderstratified analysis revealed a significantly higher frequency of Pro/Ala genotype within males. The polymorphism was associated with significantly higher weight, height, waist circumference, central adiposity (waist-to-hip ratio, WHR), lean body weight as well as dry body weight, but not overall adiposity (total body fat percentage, TBF) in cases carrying Ala allele (Pro/Ala or Ala/Ala). However, in the subjects carrying Ala allele of the control group, WHR values were found significantly lower. Conclusion. Our results showed that the Pro12Ala polymorphism in the PPARγ2 gene is associated with obesity in the studied adult population from Turkey. These data suggest that the Pro12Ala polymorphism in PPARγ2 may be a potential genetic risk factor for central obesity.