ACTA ENDOCRINOLOGICA (BUC)

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.

Introduction. Bone formation takes place through a continuous remodeling process, which involves the resorption of old bone by osteoclasts and the formation of new bone tissue by osteoblasts, melatonin contributing to the hormonal modulation of the action of osteoblasts and osteoclasts. Aim. The aim of this study is to evidence the influence of melatonin administered in combination with estrogen on bone turnover markers in female Wistar rats with bilateral surgical ovariectomy. Material and method. The study was performed on 40 female Wistar rats with a weight of 160-200 g, which underwent bilateral surgical ovariectomy. At 14 days postovariectomy, hormone replacement therapy (estradiol benzoate – E2b – 10 μg/day) and combined estrogen (estradiol benzoate – E2b – 10 μg/day) and melatonin (added to the drinking water in a concentration of 25 μg/mL or 50 μg/mL – ethanol concentration 0.01%) – treatment were initiated over a period of 12 consecutive weeks. Subsequently, venous blood was collected for the determination of serum osteocalcin and C-terminal telopeptide of collagen type I levels. Results. Melatonin administered in combination with estrogen to ovariectomized female rats induces an increase in serum osteoalcin levels (statistically significant differences between all four groups p=0.001) and a decrease in serum C-terminal telopeptide of collagen type I levels (statistically significant differences between group I and the other three groups p=0.005; p=0.001; p=0.001 and between group II and group IV p=0.007). The influence on bone formation and resorption markers depends on the administered melatonin dose and on the post-ovariectomy estradiol level. Conclusions. Melatonin potentiates the effects of estradiol on bone in ovariectomized rats.

Context. Polycystic ovary syndrome (PCOS) is associated with increased prevalence of preeclampsia (PE); microRNAs (miRs) could play an important role in the pathogenesis of PE and PCOS. Objective. To investigate the expression levels of miRs 155-5p and 518b in blood leukocytes of patients with PE and PCOS. Design. Using real-time quantitative PCR method, miR-155-5p and miR-518b were examined from PE, PCOS, PE+PCOS, and controls. Subjects and Methods. The relative expression of the target miRs in patient samples was compared to control samples. The results were calculated as relative quantification values. Results. Confounding variables were controlled using analyses for covariance. Significant differences were observed in miR-155-5p (p=0.008) and miRNA-518 (p=0.016) expression levels among the groups. miR-155- 5p (p=0.014) and miR-518b (p=0.036) were upregulated in PCOS patients and miR-518b (p=0.028) were increased in cases with PCOS+PE. Near significant difference was found (p=0.06) in miR-518b expression levels in cases with PE, compared to controls. miR-518b was observed to be positively correlated with alanine transaminase in cases with PE (r=0.80; P=0.017) and PE+PCOS (r=0.80, p=0.017). Conclusions. Our preliminary findings suggested that expression profiling of miR-155-5p and miR-518b in blood leukocytes were upregulated in pregnant women with PCOS. Moreover, miR-518b was found to be related to PE in cases with PCOS

Background. This study aimed to assess the impact of oral iron replacement treatment on glucose metabolism and anthropometric measures in premenopausal women with iron deficiency anemia. Material and methods. This was a prospective study recruiting 30 premenopausal women diagnosed with iron deficiency anemia. The participants received standard oral iron (ferrous gluconate) at a dose of 567.7 mg/day for three months. After three months of iron treatment, the participants' height, weight, and waist circumference were measured again, and fasting blood tests and oral glucose tolerance tests were repeated. Results. The study included 30 premenopausal women with a median age of 24 years and a median BMI of 21.9 kg/m2. After three months of oral iron treatment, there was a significant increase in serum ferritin, hemoglobin, transferrin saturation, body weight, BMI, and waist circumference (p<0.001 for all). Fasting glucose levels decreased, and first-hour glucose at 75g OGTT increased significantly after treatment. Notably, HOMA-IR decreased significantly (1.46 vs. 1.15, p = 0.039). Conclusions. The findings indicate that after three months of treatment, there was a significant improvement in glucose metabolism as evidenced by the decrease in HOMAIR scores, despite an increase in weight, BMI, and waist circumference.

Context. It is unclear whether treatment is necessary for transient moderate hypocalcaemia occurring after total thyroidectomy; if it is present, it is unclear which treatment modality should be preferred. Objective. To investigate both the necessity and effectiveness of different treatment approaches of oral and/ or intravenous calcium treatment in patients with transient, postoperative, moderate hypocalcaemia. Design. This is a case control study made between June 2014 and June 2015. Subjects and Methods. Forty-five patients who had serum calcium levels 6 hours after total thyroidectomy between 7.5-8 mg/dL were divided into three equal groups: an oral calcium administration group, an intravenous calcium administration group and a no-treatment group. Serum calcium and parathyroid hormone levels were measured preoperatively and on postoperative days 1, 2, 5 and 10. Results. For post-thyroidectomy patients with serum calcium 7.5-8 mg/dL in the early postoperative period, no significant difference in serum calcium or parathyroid hormone was detected between groups. Conclusions. Follow-up without treatment seems to be the most effective approach for moderate hypocalcaemia occurring in the early period following total thyroidectomy; this suggests that intravenous treatment should be avoided.

Context. Different polymorphisms of the endothelial nitric oxide synthase gene (NOS3) have been related to diabetic kidney disease. Objective. To evaluate the association between advanced diabetic chronic kidney disease (ACKD) and the rs1799983 and rs2070744 poymorphisms of NOS3 in a population from the Gran Canaria island. Design. Cross-sectional case-control study. Subjects and methods. Polymorphisms were genotyped in 152 subjects with ACKD secondary to type 2 diabetes [estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2], 110 subjects with type 2 diabetes for 20 or more years since diagnosis without ACKD (eGFR ≥45 mL/ min/1.73m2 and albumin/creatinine ratio <300 mg/g and/or 24-h urinary albumin excretion <300 mg) and 292 healthy controls. Association between both polymorphisms and established coronary heart disease (CHD) was also analyzed in both groups with diabetes. Results. A greater proportion of homozygous individuals for the risk allele C of rs2070744 was found among subjects with ACKD. Association between ACKD and rs2070744 was observed in a recessive genetic model, both for comparison to subjects with diabetes but no ACKD [OR 2.17 (95% CI: 1.17-4.00), p=0.014] and for comparison to healthy controls [OR 1.61 (1.03-2.52), p=0.036]. The frequency of the C allele was significantly higher among subjects with CHD, but only in the group with ACKD. No associations were found for rs1799983. Conclusions. NOS3 rs2070744 is associated with ACKD in population with type 2 diabetes from Gran Canaria. A link between this genetic variant and CHD in Canarian subjects with type 2 diabetes could be restricted to cases with ACKD.

Context. Changes in the secretion of signaling molecules that originates from adipose tissue and inflammation draw attention in the pathogenesis of type 2 DM. Chemerin, one of the signaling molecules of adipose origin, and irisin, defined as the Renaissance of the metabolism, are among these molecules. Objectives. This cross-sectional study was planned in order to compare the values of serum irisin and chemerin levels in patients newly diagnosed with T2DM and in healthy subjects. Subjects and Methods. The study included 41 patients newly diagnosed with T2DM and 49 healthy individuals. The chemistry parameters were analyzed with a biochemistry autoanalyzer, and hormonal parameters were analyzed with an immunoassay analyzer. Plasma irisin and chemerin levels were measured using the enzyme-linked immunosorbent assay method. Results. There was a significant difference between the groups in terms of glucose, HbA1C, Insulin, HOMA-IR and lipid panel results. Irisin levels in the group of patients newly diagnosed with T2DM were lower than in the control group. Chemerin levels in the group of patients newly diagnosed with T2DM were higher than in the control group. Conclusion. Consequently, diabetes-dependent changes in chemerin and irisin concentrations suggest that these two hormones have a role in the pathophysiology of DM. Further studies are required to understand the complex structure of the signaling pathways of chemerin and irisin molecules as well as the physiological importance of these molecules as metabolism regulators especially in humans.

Objective. This study has two objectives. The first was to determine the cancer incidence in MNG cases, and to compare this with the thyroid cancer incidence in endemic goiter regions in our country and the rest of the world. The second objective was to evaluate the relationship between the dominant nodule diameter and the cancer incidence. Method. One hundred seventy-six patients who had presented to the Erzurum Oltu State Hospital General Surgery Clinic between October 2009 and March 2012 with the diagnosis of MNG, and who had undergone total thyroidectomy, were evaluated retrospectively. Findings. Papillary carcinoma was determined in 14 (8%) cases; medullary, anaplastic and follicular carcinoma were determined in 1 case each (0.6%). In 31 patients, the dominant nodule diameter was > 4cm, and malignancy was determined in 7 (22.6%) of them. Conclusion. The increase in the malignancy incidence was statistically significant in cases in which the dominant nodule diameter was > 4 cm. However, the frequency of thyroid papillary carcinoma was determined as 12.9% in MNG patients in whom the DND was > 4 cm.

Context. Anethum graveolens L. is used in the treatment of numerous diseases. But there is limited data about the Anethum graveolens efficiency in thyroid tissue. Objective. The aim of this study is to assess the functional and histopathological changes in thyroid tissues from rats treated with Anethum graveolens L. extract. Design. This is an experimental animal study and duration of the study was 30 days. Subjects and Methods. Twenty-eight female Wistar Albino rats were divided into four equal groups. A gavage of Anethum graveolens L. extract at 0, 50, 150 and 300 mg/kg/day doses were given to the rats with 1 mL 0.9% NaCl, respectively, for 30 days. Blood was taken at day 0, 15 and 30. fT3, fT4, TSH values and antioxidant efficiency were observed. Also the thyroidectomy tissue was assessed histopathologically. Results. There is no difference observed in the fT3, fT4 and TSH values of groups 1, 2 and 3 at day 1, 15 and 30 (p>0.05); however, in group 4, TSH value decreased on days 15 and 30 when compared to day 1 and the other groups (p<0.05). Also the hypertrophy and thyroid follicular cell hyperplasia were significantly increased in group 4 (p<0.05). There is no difference in antioxidant efficiency in any of the groups (p>0.05). Conclusion. Anethum graveolens L. extract is effective on both the function and the histology of thyroid tissue but it has no effect on antioxidant status.

Context. Human zonulin is a protein that regulates the intercellular tight junctions in various tissues and organs of the human body. Hashimoto’s thyroiditis (HT) is one of the most common endocrine autoimmune disorder, but the role of increased intestinal permeability in its pathogenesis is still being studied. Objective and design. This pilot cross-sectional study investigates serum zonulin concentration in adults with Hashimoto’s thyroiditis and assesses the relationship between zonulin levels, clinical hormonal and immunological characteristics. Subjects and methods. A group of 62 adults with HT participated in this study and were divided into three groups: hypothyroid (n=33) euthyroid (n=25) and hyperthyroid (n=4). Serum zonulin was determined using an ELISA method. Results. Age, gender and BMI were different between groups (hypothyroid and euthyroid ones). Serum zonulin values ranged from 2.6 to 198.0 ng/mL in participants. A direct positive correlation was found between serum zonulin levels and weight and BMI (r = 0.351, p = 0.008 and r = 0.236, p = 0.05, respectively). Conclusions. There is no correlation between zonulin and thyroid hormones or autoantibodies in Hashimoto thyroiditis patients. There is a difference in zonulin levels between the studied groups, but they are not statistically significant.