ACTA ENDOCRINOLOGICA (BUC)

Background. Repeated implantation failure (RIF) is the most important problem in assisted reproductive technologies (ART). In the process of embryo implantation, accurate function of progesterone through progesterone receptors (PR) is crucial for establishment of a receptive endometrium. FKBP51 and FKBP52 are two co-chaperones acting as negative and positive regulators of PR function, respectively. Studies have shown that any deficiencies in expression of PR or its co-chaperones causes reproductive disorders. Materials and Methods. In this study we evaluated the PR protein expression by immunohistochemistry and expression of PR, FKBP51, FKBP52 genes by quantitative real-time PCR in endometrial tissue of normal and RIF women during the window of implantation. Results. Immunohistochemical studies showed that the PR protein expression in stromal cells is significantly higher in the endometrium of normal women than RIF women (P< 0.001). In addition, a significantly lower PR and FKBP52 gene expression was observed in endometrial tissue of RIF women compared to normal women (P< 0.001 and P< 0.001, respectively), whereas there was no significant difference in PR protein in epithelial cells (P= 0.3) and FKBP51 gene expression between the two groups (P= 0.6). Conclusion. The results indicate that altered expression of PR protein in stromal compartment and gene expression of PR and FKBP52 gene in endometrial tissue can be related to endometrial receptivity defects and occurrence of RIF.

Introduction. Considering the very important role of adiponectin and leptin in\r\natherogenesis, it is important to study their relationship with other important factors in\r\nestablishing the cardiometabolic risk: hyperglycemia and serum lipids.\r\nPatients and Methods. There were studied 79 subjects (s), aged 59? 9 years, divided\r\ninto 3 groups according to body mass index (BMI): group I with BMI<25 kg/m2 - 19 s,\r\ngroup II with BMI 25-30 kg/m2 - 30s, and group III with BMI >30 kg/m2 - 30 s. In all\r\nsubjects the plasmatic levels of adiponectin, leptin and other cardiometabolic risk factors:\r\nblood glucose, total cholesterol, triglycerides, high density cholesterol, low density\r\ncholesterol were measured.\r\nResults. Considering the values of adiponectin and leptin in the three groups,\r\nadiponectin was significantly increased (14355?9120.40 vs 5889.167?6278.963 ng/mL,\r\np=0.015) and leptin significantly decreased (7212?7428.45 vs 9235.81?10988.66 pg/mL,\r\np=0.03), in group I in comparison with group II+III. Adiponectin and leptin were not\r\nsignificantly different in subjects with fasting glucose less or more than 110 mg/dL and the\r\nsame insignificant difference was registered for both adipokines between diabetic and non\r\ndiabetic subjects. Considering the plasma lipid fractions, it was registered an inverse\r\nsignificant correlation between adiponectin and total cholesterol, respectively LDL\r\ncholesterol, and a positive correlation with HDL cholesterol; leptin was inversely correlated\r\nwith HDL cholesterol, but not with LDL cholesterol or total cholesterol.\r\nConclusion. In the present study, the plasmatic values of adipokines (adiponectin and\r\nleptin) were correlated only to the BMI values (obesity) and respectively to the lipidic\r\nfractions. No correlation was registered with diabetes or impaired fasting glucose.

Aims. To investigate the effect of sulphonylurea (SU) treatment on all-cause and cardiovascular mortality as compared with metformin (MET), when used in combination with insulin (INS) in type 2 diabetes. Methods. All type 2 diabetes patients aged ≥40 years were included at their first prescription of INS+MET or INS+SU, during 2001-2008. They were considered at risk until death or December 31st, 2011. Mortality rates were calculated per 1000 person-years. Crude and adjusted rate ratios (RR) were calculated using time dependent analysis with INS+MET as reference. Results. There were 7122 patients (60.8% women) included in the analysis, with a mean age at baseline of 62.0±9.9 years. During the 11 years of study, patients on INS+MET contributed 13620 person-years and 330 deaths (mortality rate 24, CI95% 22-27), while those on INS+SU contributed 8720 person-years and 393 deaths (mortality rate 45, CI95% 41-50). Adjusted all-cause mortality RR were: SU 1.6 (CI95% 1.21-2.11, p<0.001), glimepiride 1.18 (CI95% 0.73-1.91, p=0.51), gliclazide 1.78 (CI95% 1.07-2.95, p=0.024), glibenclamide 1.66 (CI95% 0.71-3.88, p=0.23), glipizide 1.24 (CI95% 0.68-2.27, p=0.49), and gliquidonum 2.32 (CI95% 1.54-3.50, p=0.001). Conclusions. When combined with insulin as dual therapy, patients treated with SU were at increased mortality risk as compared with insulin + MET.

ntroduction. Childhood obesity is a public health problem characterized by early insulin resistance (IR), inflammation, and oxidative stress. The presence of an uninterrupted low-grade inflammatory state impairs metabolic and cardiovascular health. The population is particularly susceptible to develop metabolic disorders related to increased body fat. Methods. Eighty-three adolescents were recruited and grouped according to HOMA-IR and BMI in either with or without IR and obese or normal-weight respectively. Anthropometric, biochemical, immunological and hormonal variables were determined. Transverse Analytical Study. Results. Obesity, dyslipidemia, IL-6, and C-reactive protein were significantly higher in the IR group than in the non-IR group. Obese adolescents showed increased insulin levels, HOMA-IR, inflammatory markers, and triglycerides; while having lower HDL-C, and adiponectin when compared to normal-weight adolescents. As expected, obesity-related anthropometric markers positively correlated with IR and inflammatory markers while negatively correlated with adiponectin levels. Conclusions. Early IR, subclinical inflammation, dyslipidemia, and hypoadiponectinemia characterize obesity in adolescents. These factors may increase the risk of future coronary heart disease (CHD) and diabetes mellitus development (DM) in early adulthood.

Context. Identification of CV risk factors from T2DM diagnosis allows optimization of treatment to prevent CV complications and death. Objective. The primary objective of the study was to describe the CV risk factors in patients with T2DM at the time of diagnosis and/or therapeutic specific measures taken. Design. This was a non-interventional, multicenter, retrospective chart review of newly diagnosed patients with T2DM in 49 study centers in Romania. Subjects and Methods. Adults with a diagnosis of T2DM between January - December 2014. Statistical analysis used appropriate descriptive methods. Results. 1218 patients were included, mean age (SD) at diagnosis was 59.16 (10.87) years. Half of the patients (54%) presented obesity and 47.7% of patients had arterial hypertension. Overall, 76.2% of subjects had LDLcholesterol ≥ 100 mg/dL, and 59.1% had triglycerides ≥ 150 mg/dL. The mean glycemia was 198.8 mg/dL (78.3) and 50.2% of patients had HbA1c ≥7%. Sedentary lifestyle in 73.8% of the cases, and 91.3% unhealthy eating habits reported. In addition to diet, 82.2% of patients received antidiabetes treatment, 62.6% lipid-lowering, and 66.6% antihypertensive medication. Conclusion. This retrospective study showed a high prevalence of CV risk factors and/or established CV disease at the time of T2DM diagnosis in Romania.

This review discusses current international recommendations for GDM diagnosis and management and argues whether it would be worth considering first, universal screening for GDM in our country, second, updating of management guidelines and third, organized follow-up of women diagnosed with GDM and adoption of lifestyle interventions after delivery that could reduce the onset and prevalence of type 2 DM.

Aim. To establish a nomogram combining preoperative ultrasonic and clinical features for predicting lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN) metastasis in papillary thyroid carcinoma (PTC) patients. Methods. Preoperative ultrasonic and clinical variables of patients with PTC from 2014 to 2021 were retrospectively analyzed. The risk factors associated with LN-prRLN metastasis were identified and validated through a developed nomogram model based on univariate and multivariate logistic regression analysis. Results. A total of 615 patients (690 lesions) were enrolled for the training dataset and 207 patients (226 lesions) for the validation dataset with 54 (6.57%) patients developing LN-prRLN metastasis. Multivariate logistic regression analysis demonstrated that the preoperative ultrasound measurement of larger tumors (≥20 mm), higher TI-RADS category (category 5), and higher thyroglobulin level (9.86 ng/mL) in patients with PTC were predictive factors for LN-prRLN metastasis. The nomogram model was established and verified yielding a relatively good predictive performance in the training and validation dataset (AUC: 0.868 vs. 0.851). Conclusions. The nomogram combining preoperative ultrasonography with clinical features in this study is highly predictive of LN-prRLN metastasis in patients with PTC, which may provide more personalized recommendations for clinicians in preoperative decisionmaking for complete dissection of LN-prRLN.

Context. Thyroid hormones have metabolic effects such as relationship between hypothyroidism and atherosclerosis. Objective. Evaluate the effects of hypothyroidism on Non-Alcoholic Fatty Liver Disease and atherosclerosis by using AIP, APRI score, FIB-4 indices. Material and Methods. 1370 patients with hypothyroidism who applied to the Endocrinology and Metabolism outpatient clinic between 01.01.2017-30.12.2021 were included the study. Pregnants, patients with a history of thyroid carcinoma, cardiovascular and liver diseases were excluded. TSH, fT4, Anti TPO, Anti TG, thrombocyte, ALT, AST, HDL, Triglyceride values of the cases were analyzed and atherogenic index of plasma (AIP), AST to Platelet Ratio Index (APRI) and Fibrosis-4 (FIB-4) indices were calculated. Results. 1170 (85.4%) of the cases were female.The age of those who had high risk of AIP was found to be higher than those with low and moderate risk (p=0.001; p=0.003; p<0.01). The ages of those who had low-risk FIB-4 Index were found to be lower than those with moderate risk and high risk (p=0.001; p=0.001; p<0.01). A positive relationship was detected between APRI and FIB-4 (r=0.681; p=0.001; p<0.01).AIP increased as TSH increased in hypothyroid patients. No significant correlations were detected between TSH, APRI, and the FIB-4 Index. No significant differences were detected between AIP, APRI, FIB-4, and thyroid autoantibodies. Conclusion. In hypothyroid patients, the AIP index increased with age and the increase in TSH. A strong relationship was detected between AIP and TSH . For this reason, we think that keeping TSH within the normal range with regular follow-ups and treatment in patients with hypothyroidism will reduce the risk of atherosclerosis.

Paget's disease of bone is a metabolic skeleton disorder with different epidemiological patterns: increased incidence up to 3% of the Northern Caucasian population over the age of 55 or a very rare occurrence as in Asia. We present a case of a 69 years old female patient with diffuse bone pain, suspected of osteoporosis after a DXA investigation of bones. She has developed progressive skull deformation over the last 17 years and bilateral sensoneural deafness. On admission in our hospital, she had alkaline phosphatase serum levels five times higher than the upper normal value and low values of 25 hydroxy vitamin D. Parathormone and calcium levels were in normal range. Radiologic findings confirmed the monostotic type of Paget's disease. Other biomarkers of bone remodeling: serum osteocalcin for bone formation and serum beta Cross Laps for bone resorption, showed moderately increased levels. High dose therapy with alendronate and alphacalcidol were given with the normalization of bone markers after 9 months of sustained treatment. The vitamin D deficiency of this patient is an independent, associated disease, producing a decrease of bone mineral density as shown by DXA measurement. The case presentation and the review of the medical literature on this subject are intended to remind clinicians of the importance of appropriate diagnosis and therapy in this disease, as well as the importance of establishing the prevalence of Paget's disease of bone in Romania.

Objective. Thyroid fine-needle aspiration (FNA) and cytology is a reliable diagnostic method used in the assessment of malignancy when evaluating thyroid nodules, in conjunction with clinical and ultrasonographic findings. The aim of this study is to compare clinical, ultrasonographic, cytological and histopathological findings in children who underwent thyroid FNA. Methods. Subjects comprised 80 patients (52 female) aged 13.7±2.8 years at the time of FNA who where evaluated for thyroid nodules. Clinical, ultrasonographic and cytological findings of patients were evaluated retrospectively. Results. Autoimmune thyroiditis was present in 30% and history of radiotherapy to the head or neck in 10%. The cytological diagnosis of patients included: inadequate or hemorrhagic sample in 10%; benign in 42.5%; atypia or follicular lesion of undetermined significance (AUS/FLUS) in 15%; suspicion of follicular neoplasia (SFN) in 7.5%; suspicion of malignancy (SM) in 8.8%; and malignant in 16.3%. Thirty-seven patients underwent thyroidectomy. Malignancy rates for histopathologic follow-up were 75%, 85.7% and 100% for SFN, SM and malignant categories, respectively. Only one benign and two AUS/FLUS FNAs were found to be malignant on histopathological examination. Among patients who had received radioiodinetherapy, 87.5% had malignancy. In this study, the sensitivity of FNA was 96%, specificity 50%, positive predictive value 90.9%, negative predictive value 75%, and diagnostic value of FNA was 89.2%. Conclusion. Thyroid FNA results were highly compatible with histopathological examination. Sensitivity, positive predictive value and diagnostic value of FNA were high.