ACTA ENDOCRINOLOGICA (BUC)

Introduction. Irisin is a recently discovered novel adipomyokine that induces an increase in total body energy expenditure, improves insulin sensitivity and glucose tolerance. It has been shown that circulating levels of irisin are low in patients with obesity, diabetes mellitus and impaired glucose tolerance. However, the information about the level of circulating irisin in gestational diabetes mellitus (GDM) is controversial. Material and Methods. Serum irisin was measured by an ELISA in a longitudinal prospective cohort study in 221 women. There were 156 healthy pregnant and 65 women with GDM. Results. Circulating irisin levels were significantlly higher in the middle pregnancy compared with early pregnancy levels in healthy pregnant women and in women with GDM. Serum irisin levels were found to be lower in GDM compared to healthy pregnant women during first trimester but the difference was not observed throughout the pregnancy and it was comparable in middle pregnancy. There was a significant inverse correlation of BMI with serum irisin (r = -0.193, p = 0.004) and between HbA1c and mean glucose of OGTT with serum irisin (r =-0.377, p =0.0001) and (r = -0.147, p:0.03) in the early pregnancy of pregnant women repectively. Conclusions. The present study shows that serum irisin level increases throughout the gestational period from early to middle pregnancy in women with GDM, but there is no effect of irisin on the development of GDM.

Context. Nonalcoholic fatty liver disease is common in type 2 diabetes mellitus patients, being difficult to diagnose. Objective. To find a correlation between elastographic parameters and lab results, for facilitating the diagnosis of nonalcoholic fatty liver disease. Design. This is a cross sectional study, conducted at the Departments of Diabetes, Nutrition and Metabolic Diseases, and Gastroenterology and Hepatology, of the Clinical Emergency Hospital “Pius Brinzeu” Timisoara. Subjects and Methods. We included 190 type 2 diabetes mellitus patients, collected data regarding medical history, clinical and biological features and applied the Alcohol Use Disorders Identification Test. We excluded patients with other causes of liver disease. Liver steatosis and fibrosis were evaluated through transient elastography, yielding two parameters: liver stiffness as an indicator of liver fibrosis stage, expressed in kPa, and liver steatosis stage, assessed by controlled attenuation parameter, expressed in dB/m. Data were analyzed using SPSS 15. Results. The analyzed group comprised 113 patients. Elastographic measurements showed that 93.8% of the patients had steatosis (controlled attenuation parameter ≥232.5 dB/m) and 70.8% severe steatosis (controlled attenuation parameter ≥290 dB/m). Severe steatosis was more common in women (75.7%) than in men (68.1%) (p<0.0001). From the patients with steatosis, 47.2% had liver stiffness values suggestive for fibrosis and 19.8% for cirrhosis. Most patients with steatosis and severe fibrosis were obese (66.7%). Triglycerides/HDLc ratio >4 correlated with hepatic steatosis (p=0.04), being more common in patients with severe fibrosis/cirrhosis (58.3%) than in those with absent or mild fibrosis (36.2%). Conclusions. Our study found a clear correlation between type 2 diabetes mellitus and the presence of liver steatosis. It correlates with body mass index, waist circumference (in men) and triglycerides/HDLc ratio. Controlled attenuation parameter is a useful noninvasive method for detection and quantification of liver steatosis.

Background. Oncogenic osteomalacia (OOM) is a rare syndrome caused by a tumor that produces a phosphaturic factor: fibroblast growth factor 23 (FGF23). These tumors can be extremely difficult to localize because they are small, slow growing and cause no local symptoms.\r\nPatient and methods: Venous sampling for detection of a gradient of FGF23 has been used to limit the area of further\r\nimaging. We describe a case of OOM in a 73-year old woman, with two years of spontaneous fractures, severe musculoskeletal pain and phosphate wasting.\r\nResults: Her serum FGF23 level was increased and whole-body intravenous sampling (11 sites) revealed a FGF23 gradient\r\nfrom the right leg. The second sampling indicated that the source of FGF23 was below the knee, but imaging studies, including magnetic resonance imaging and octreotide scintigraphy, were not conclusive. A third sampling demonstrated increasing FGF23 the more distal one came in the lower leg. Imaging of the forefoot finally identified a 10 mm tumor that was removed. Histopathological examination showed a phosphaturic mesenchymal tumor of mixed connective\r\ntissue type. The phosphate level and symptoms improved in days after surgery.\r\nConclusion: Repeated determinations of a venous gradient of FGF23 may be used to localize tumors of OOM.

Background. The purpose of this study was to observe the effects of denosumab on bone mineral density (BMD), bone turnover markers and serum calcium in patients with primary hyperparathyroidism (PHPT) and osteoporosis. Methods. Seven consecutive patients with PHPT were administered a single subcutaneous injection of denosumab, 60 mg. The subjects were followed up to 6 months: serum calcium on days 1,3,7,14,30 and at 3 months and 6 months; serum intact parathyroid hormone (iPTH), C-telopeptide (CTX) and N-mid osteocalcin at baseline, 3 months and 6 months. BMD by DXA, at the femoral neck (FN) and lumbar spine (LS), were measured at baseline and at 6 months. Results. The patients (mean age= 69.8 yrs, range 62-81) had mild PHPT (mean total calcium = 10.8 mg/dL; mean PTH = 148.9 pg/mL); all had osteoporosis and four were currently treated with various bisphosphonates (BP). After 6 months mean LS BMD increased significantly by 4.5 % (p = 0.04) and mean FN BMD by 2.4% (p= 0.09 two-tailed; p = 0.047 one-tailed). Serum CTX decreased significantly by 90% at 3 months (p = 0.04), and by 48% at 6 months (p = 0.02); the similar changes for serum osteocalcin were 41% and 42% (p = 0.07, onetailed), respectively. In the first two weeks, serum total Ca variably decreased vs. baseline (0.5 to 2.8 mg/dL) in six out of seven patients. After 6 months mean total serum Ca nonsignificantly increased vs. baseline (11.4 mg/dL vs. 10.8 mg/dL, p = 0.1). Serum iPTH levels did not significantly change at both 3 and 6 months; after 6 months there was a trend toward decreased values (p = 0.03 onetailed). Conclusion. Denosumab increased BMD at both lumbar spine and femoral neck, and significantly decreased bone resorption in patients with PHPT. The effects on hypercalcemia were mild and transient, with a numerical increase after 6 months.

Context. Hyperparathyroidism-jaw tumour (HPTJT) syndrome is a rare autosomal dominant cause of familial hyperparathyroidism associated with ossifying fibromas (OF) of the maxillofacial bones and increased risk of parathyroid carcinoma, caused by inactivating germline mutation of the cell division cycle 73 (CDC73) gene. Objective. To report the first Romanian family with HPT-JT and genetic screening of CDC73 gene. Subjects and Methods. Mutational analysis of the CDC73 gene and genetic screening of the family of a proband with HPT-JT. Histological diagnosis of parathyroid tumors (WHO criteria) and immunohistochemistry (parafibromin) were performed. Results. Three of the six screened family members had evidence of PHPT and surgically proven parathyroid tumours. Two of the three affected members had parathyroid carcinomas and one had two parathyroid adenomas. Genetic screening of CDC73 gene revealed that 4 of 6 patients showed a heterozygous germline deletion of one nucleotide: c.128-IVS1+1 delG. All the three affected patients, resulted to be carriers of the CDC73 mutation, but each one bearing a different CDC73 polymorphism. Conclusions. We identified a new CDC73 germline mutation in a Romanian family of HPT-JT. Analysis of clinical phenotypes in the four mutated individuals confirmed the incomplete penetrance and the variable clinical expression of the disease.

Context. GnRHa treatment has been a standard of care in progressive early puberty (EP). Choice of the GnRHa formulation is dependent on the preference of the clinician. Objective. To compare the effects of triptorelin acetate (TA) and leuprolide acetate (LA) on anthropometry in girls with EP. Design. A descriptive observational study. Subjects and Methods. Girls diagnosed with central EP and treated with GnRHa at least for one year were included; treated with TA (n=46) and LA (n=35). First year anthropometric response and final height were evaluated. Results. The mean age at the initiation of GnRHa treatment of girls was 8.5±0.5 years. The ratio of obesity and of overweight was 7.4 and 25.9%, respectively. In both TA and LA groups, anthropometric data of the patients at initiation and at the first year of treatment were similar. Although growth velocity was similar in each group, in LA group height SDS at the first year of the treatment showed a significant decrease (p=0.045), but not in TA group (p=0.317). No significant ΔBMI was observed with treatment. The differences between FH – PAH at initiation (height gain) in TA and LA groups were 2.9±4.7 and 4.0±5.8 cm, respectively (p=.316). Height gain per treatment year was 1.7±3.0 cm. Conclusions. There was a significant decrease in height SDS at the first year of leuprolid treatment, but not in triptorelin. Although these two analogs show similar effects on treatment, a not significant but slightly better benefit in leuprolide was observed.

Adipocytokines involved in inflammation and the acute phase responders have been found to be increased in the metabolic syndrome (MS). The aim of the study was to compare the ‘normal’ weight women’s fibrinogen, hsCRP, adiponectin, TNF-α, vascular cell adhesion molecule (VCAM) with obese patients with MS, and to evaluate the association between fibrinogen, hsCRP, adiponectin, TNF-α, VCAM and insulin resistance. The study included 52 obese women who met the criteria for MS defined as in 2001, the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) ATP III and 24 normal women. Serum concentrations of glucose (FBG), triglyceride, total and HDL-Cholesterol were determined by enzymatic procedures, serum insulin was measured by chemiluminescence, plasma levels of adiponectin, TNF-α and VCAM by Elisa, hsCRP by immunoturbimetric assay and fibrinogen by coagulation method. Measurements of insulin resistance were obtained using the homeostasis model assessment. Mean plasma levels of adiponectin, TNF-α, VCAM, fibrinogen and hsCRP were found 6.11±2.39 mg/ml, 3.10±3.30 pg/ml, 14.21±4.00 ng/ml, 375.49±49.67 mg/dl, 0.33±0.10 mg/dl in the obese with MS; 6.20±2.48 mg/ml, 3.01±1.68 pg/ml, 12.63±2.54 ng/ml, 304.06±49.52 mg/dl, 0.30±0.19 mg/dl in the normal women, respectively. Mean fasting insulin level and HOMA-IR were measured 13.80±6.32 mU/ml and 3.69±1.90 mU/ml, respectively in obese with MS. In normal women, fasting insulin level and HOMA-IR were measured 8.30±3.08 mU/ml and 1.49±0.37, respectively. Mean levels of adiponectin were positively correlated with mean TNF-α levels in the obese with MS (r=0.472, p=0.001). VCAM was negatively correlated with TNF-α levels (r=-0.301, p=0.038) in the obese with MS. This study demonstrated that TNF-α showed a positive association with adiponectin and a negative association with VCAM in the obese women with MS.

Context. Despite the developments in strategies related to the iodization of salt, iodine deficiency is still a serious problem, particularly among pregnant women in certain regions of Turkey. Objective. We aimed to re-evaluate the efficiency of iodine prophylaxis in pregnant women and adults 13 years after iodized dietary salt became mandatory in Istanbul. Subjects and Methods. This study was performed with pregnant women (n = 200) and adults (n = 200, 100 nonpregnant women and 100 men). The participants were questioned about the iodization status of the salt they used. Urinary iodine concentration (UIC) was measured using the Sandell-Kolthoff method. Goiter size and UIC were determined according to Pan American Health Organization and World Health Organization recommendations, respectively. Results. Ratio of iodized table salt use was 91% in both groups. Although the median UICs were 162.5μg/L (95% CI = 162.5–186.1) in pregnant women and 167μg/L (95% CI = 153.7–172.7) in adults, 43% of pregnant women had a UIC < 150μg/L, and 23% of adults had a UIC < 100μg/L. The prevalence of goiter was significantly higher in pregnant women than that in adults (50% and 32%, respectively), but a small goiter was found in all cases. Conclusion. Iodine prophylaxis in Istanbul is sufficient and has progressed. However, iodine deficiency remains a problem for a considerable proportion of pregnant women, despite more than one decade of successful salt iodization in Istanbul Province. Iodine-containing preparations should be considered to supplement iodized salt for pregnant women.

Context. Adipokines secreted by fat cells are vital to the control of energy metabolism, communicating the nutrient status with the tissues responsible for controlling both energy intake and expenditure and insulin sensitivity. Objective. We aimed to prove in an experimental animal study that maternal obesity has long term adverse fetal metabolic consequences, which pass on even to the next generation of descendants. Design. The effects of maternal obesity have been studied on animal model using 50 obese female Wistar rats, in which we induced obesity by high-calorie high-fat diet administered by gavage. Subjects and Methods. Obese rat females were sacrificed at gestation term and we analyzed the secretion of adipokines from maternal venous blood: leptin and adiponectin, placental, pancreatic, liver and brain homogenates lipid peroxidation levels estimated by: MDA (malonyl-dialdehyde), total thiols and GSH – as antioxidant factors and routine biochemistry. Results. Low levels of adiponectin and increased levels of leptin positively correlated with the value of placental and fetal tissue lipid peroxidation (from the liver, pancreas and brain) measured by elevated MDA and total thiols and low levels of GSH. The lipid peroxidation in the organs examined generated consistent results, showing high levels of peroxidation expressed through high values of MDA in the groups with Omega 6 supplements respectively no supplementation, and low levels of antioxidants expressed through glutathione and thiols. Conclusions. Endocrine secretion of adipokines from the adipocytes and the recruited macrophages of obese mothers is positively correlated with placental and tissue lipid peroxidation level and routine biochemical parameters.

Aim. To evaluate the diagnostic performance of radiomics features of two-dimensional (2D) and threedimensional (3D) ultrasound (US) in predicting extrathyroidal extension (ETE) status in papillary thyroid carcinoma (PTC). Patients and Methods. 2D and 3D thyroid ultrasound images of 72 PTC patients confirmed by pathology were retrospectively analyzed. The patients were assigned to ETE and non-ETE. The regions of interest (ROIs) were obtained manually. From these images, a larger number of radiomic features were automatically extracted. Lastly, the diagnostic abilities of the radiomics models and a radiologist were evaluated using receiver operating characteristic (ROC) analysis. We extracted 1693 texture features firstly. Results. The area under the ROC curve (AUC) of the radiologist was 0.65. For 2D US, the mean AUC of the three classifiers separately were: 0.744 for logistic regression (LR), 0.694 for multilayer perceptron (MLP), 0.733 for support vector machines (SVM). For 3D US they were 0.876 for LR, 0.825 for MLP, 0.867 for SVM. The diagnostic efficiency of the radiomics was better than radiologist. The LR model had favorable discriminate performance with higher area under the curve. Conclusion. Radiomics based on US image had the potential to preoperatively predict ETE. Radiomics based on 3D US images presented more advantages over radiomics based on 2D US images and radiologist.