ACTA ENDOCRINOLOGICA (BUC)

Context. The metabolic syndrome is a profound, systemic impairment of the metabolism of lipids, carbohydrates and branched amino-acids, affecting specially obese people. Recently, many studies outlined the presence of the metabolic syndrome, also in non obese persons. Objective and design. To assess the relationship between insulin resistance and the cardiovascular component of the metabolic syndrome in a group of young, non obese subjects using a cross sectional study. Subjects and methods. We enrolled 103 subjects with body mass index < 30 Kg/m2, without metabolic syndrome to whom fasting glucose, triglycerides, high density lipoprotein cholesterol, insulinemia, waist circumference and arterial pressure were recorded in a crosssectional approach. Insulin resistance was evaluated using the homeostasis model assessment for insulin (HOMA-IR) index. Statistic data processing included Pearson relation and multiple regression (backward method), using the SPSS version 21 software. Results. A significant relationship between waist circumference, diastolic blood pressure and HOMA-IR is found. High value of HOMA-IR (>2.6) was more frequently in men (p=0.011). The incidence of the 2 metabolic components mentioned above was higher in the high value HOMA-IR group: 33% vs. 7% in women and 50% vs. 4% in men. Multiple regression showed a strong correlation between HOMA-IR and waist circumference (p<0.001) and diastolic blood pressure (p=0.008) that was maintained inside the women group (p=0.016 and p=0.032, respectively). In men, HOMA-IR correlated with waist circumference (p=0.031). Conclusion. We found a significant interdependence between waist circumference, diastolic blood pressure and HOMA-IR. Based on our results, we consider that lifestyle intervention should start as soon as abnormal waist circumference is recorded.

Background. Hip fractures are a major issue of public health as they are responsible for high morbidity, excess mortality and costs. There are differences in Europe and worldwide in the incidence rates of hip fractures and time trends, in the context of the population aging. Ten years ago, we characterized the incidence of hip fracture in Romania using data from the national hospital discharge register. Objective. This is the first Romanian study to assess the hip fracture incidence rates over a period of 11 years, between 2008 and 2018. Subjects and Methods. This analysis is a nationwide retrospective study on hospitals reporting primary DRG data on hip fracture, using a rigorous definition with both diagnostic and surgical procedure codes. The population aged 40+ was stratified in 5-year intervals and both the crude incidence rates and the adjusted incidence rates of hip fracture using standardization on age for the 2018 reference population were calculated in women and men. Results. From 2008 to 2018, the number of hip fractures rose by 53 % in women (from 7513 to 11512) and 22.4 % in men (from 4266 to 5220). Meanwhile, the Romanian population over 40 years increased by 12.5% in women and 14.2% in men. The crude incidence rate rose by 36.2% in women and 7.2% in men and the age-standardized incidence rates by 27.4% in women and 6% in men. These increases are mostly based on 85+ age populations’ changes. Conclusions. In Romania, the hip fractures incidence continues to grow throughout an 11-year-period, especially in women, representing an increasing burden for our society.

Background. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced cancers. Antibodies directed against programmed cell death receptor 1 (PD-1) interrupt the ability of the cancerous cell to depress the immune system. Methods and results. We report three patients who developed different endocrine abnormalities after treatment with nivolumab, a monoclonal antibody directed against PD-1. First, we report a 76-year-old male presenting with generalized fat loss after treatment with nivolumab which predominantly affected his face and trunk. Second, we described the development of thyroiditis that presented with thyrotoxicosis and the expression of thyroid-stimulating hormone receptor antibodies (TRAb). Finally, we observed the emergence of adrenal insufficiency due to hypophysitis in another case. Conclusion. Although immune checkpoint inhibitors are an effective anticancer treatment modality, adverse effects are evident that can affect the endocrine system. These adverse events may relate to different endocrine systems that include the thyroid and pituitary glands. Also, acquired generalized lipodystrophy should be suspected in patients developing unusual fat loss after treatment with ICIs.

Background. Glycogen synthase kinase.3β (GSK.3β) has an important role in several signaling pathway including Wnt signaling pathway. Recent evidence has shown that this pathway is involved in follicle development, ovulation and Corpus luteum formation. Aim. In this study we have investigated the effect of LiCl (as a GSK.3β inhibitor) on the ovulation and corpus luteum formation in rat. Materials and methods. Immature 23-day female rats were injected with PMSG (15 IU) to induce follicular development, followed 48h later by HCG (15IU) to induce ovulation. To inhibit GSK3β activity 250 mg/kg LiCl were administerted at the time of LiCl injection. The ovaries were removed at 1,4,8,12,24 h after LiCl treatment and prepared for histological studies. Results. Our results show that the number of preovulatory follicle in LiCl treatment rats was not increased compared with control group. The number of corpus luteum blood vessels were decreased in comparison with control group (p<0.05). Conclusions. These findings show that although LiCl does not inhibit ovulation, it disrupts blood vessel formation in the corpus luteum.

Context. Mealtime insulin bolus is traditionally administered before meals in children with type 1 diabetes (T1D). Controlled studies on the use of pre-and postprandial insulin bolus have shown variable results. There are no realworld studies on postprandial bolusing of insulin in young children with T1D. Methods. Children with T1D aged <7 years were grouped into preprandial (Group 1) or postprandial (Group 2) groups according to the practice of prandial insulin use. Their retrospective data on mean glycosylated hemoglobin (HbA1c), hypoglycemic events, and diabetic ketoacidosis (DKA) episodes were compared. Results. Forty-four children (mean age 4.1±1.3 years, range 2-7 years) with mean diabetes duration of 2.0±0.7 years (range, 1-4 years) were identified; 23 (52.3%) belonged to Group 1 and 21 (47.7%) to Group 2. There were no differences in the mean HbA1c levels, mean hypoglycemic events, and DKA episodes between the two groups during a mean follow-up duration of two years. Conclusion. Young children with T1D administered insulin bolus during or immediately after meals showed similar long-term glycemic control and diabetesrelated adverse event profile compared to the premeal timing of insulin bolus. Larger real-world studies are needed on flexible insulin bolus timing in young children with T1D.

Background. The involvement of IGF 1 in renal pathophysiology has been studied in many details in type 1 diabetes but the role of IGF 1 in early nephropathy in patients with type 2 diabetes is less well characteristic. Objective. To determine whether serum IGF1 and GFBP-1 levels were different between patients with and without diabetic nephropathy and also to investigate the association between them and insulin resistance. Subjects and methods. Insulin resistance (HOMA-IR), IGF 1 and IGFBP-1 were measured in 20 type 2 diabetic patients with nephropathy, 20 type 2 diabetic patients without nephropathy and 15 control subjects. Results. Serum IGF 1 in diabetic nephropathy (333.3 +/-16.44 ng/mL) was significantly higher than in both diabetic patients without nephropathy (133.16 +/- 3.43 ng/mL) and in control subjects (174.33+/-6.23) (P <0.001). A significant negative correlation was observed between IGF 1 and HOMA, (r = -0.72) in diabetic patients without nephropathy and a positive correlation in diabetic nephropathy patients (r = 0.49). Conclusion. High IGF 1 and insulin levels in diabetic nephropathy patients in addition to the significant positive association between IGF 1 and HOMA suggest that both IGF 1 and insulin resistance may play major role in early renal changes in type 2 diabetes.

Background. The modern management of phenylketonuria (PKU) consists of generalized newborn screening (NBS) for hyperphenylalaninemia (HPA), confirmation of HPA in children detected in the NBS, introduction of dietary treatment in the first weeks of life, followed by monitoring the treatment of PKU for decades to maintain phenylalaninemia within the limits that will not affect the brain. The present study aimed to evaluate the usefulness of two chromatographic methodologies for determination of plasma Phe level in the routine management of PKU: the two dimensional thin layer chromatography (2D - TLC) and the high performance liquid chromatography (HPLC) procedures, respectively. Material and Methods. Samples of blood from 23 children with HPA detected by neonatal screening or with confirmed PKU who received treatment by low-Phe diet were analyzed to estimate the plasma Phe level by the two chromatographic procedures. Results. In case of three subjects the very low concentrations of plasma Phe could not be detected by the 2D - TLC methodology, since the spot was not visible on the chromatogram. In four patients the differences between the values of plasma Phe determined by the two methodologies are not statistically significant, while in fifteen subjects the differences are highly statistically significant. This is due to the greater errors that appear in the case of 2D - TLC methodology. In the range of concentrations of plasma Phe higher than 360 μmol/L (which is the cut-off value for HPA), although in four cases there were statistically significant differences in the level of plasma Phe determined by the two methodologies, the value obtained by the 2D - TLC methodology was high enough to influence the decision of changing the diet so that HPA is kept under control. In addition, the intense spot of Phe on the 2D - TLC chromatogram may be detected even by un unexperienced laboratory specialist. Conclusion. The HPLC procedure for measurement of plasma Phe level is very suitable to be used in the routine management of PKU. The 2D - TLC procedure may be accompanied by relatively high errors; however, it detects patients with severe PKU.

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Background. Fine needle aspiration biopsy (FNAB) is an important tool in the diagnosis of thyroid nodules. Aim. Our aim was to investigate the malignancy criteria in thyroid nodules by gray-scale ultrasonography (US) and duplex Doppler ultrasonography (DDUS), and their usefulness in reducing the number of unnecessary FNAB’s. Study design. This was a prospective observational study. Subjects and methods. 181 benign and 18 malignant thyroid nodules were evaluated by US and DDUS before FNAB or thyroidectomy. US was used to note size, shape, internal structure, nodule echogenicity, marginal properties, peripheral hypoechogenic halo, and microcalcifications. DDUS studies were used to evaluate the maximum and minimum flow velocity (Vmax and Vmin), systolic/diastolic flow velocity ratio (S/D), pulsatility index (PI), resistive index (RI), acceleration time (AT) and acceleration value. Results. Contour irregularity, size and presence of microcalcifications (p<0.001, p=0.02 and p=0.002, respectively) and S/D, Vmin, PI, RI and AT were significantly different (p=0.004, p=0.007, p=0.032, p=0.003 and p=0.003, respectively) were significant for malignant nodules. Benign and malignant nodules with or without suspicious US findings had similar DDUS findings. Vmax, Vmin, PI, RI, and AT were significantly different in the presence of microcalcification (p=0.043, p=0.001, p=0.031, p=0.04, and p=0.019 respectively). AT was significantly different in the case of absence of microcalcification (p=0.019). Comparing the irregular margins, Vmin, PI and RI were significantly different (p=0.014, p=0.003, and p=0.014 respectively). Conclusion. Benign and malignant thyroid nodules can be differentiated using gray-scale US findings and DDUS based indices together to reduce the number of unnecessary FNAB’s.

Introduction. Vinegar is known with its positive impact on post-prandial dysmetabolism. The aim of this study was to\r\nelucidate the acute effects of high amount vinegar on blood glucose and lipid parameters.\r\nMaterial and Methods. Sixteen type 2 diabetic patients who had been treated with metformin only, were served a\r\nstandardized meal to which 50 g vinegar was added on the first day but not on the second day. Blood glucose, insulin and lipid levels were measured during fasting and at the second hour after intake of the meal.\r\nResults. Postprandial increase in the levels of venous blood glucose measurements was not different in the vinegar group when compared with the reference group (p=0.163). There was no significant difference on postprandial insulinemia (p=0.796). While investigating the effect of the vinegar on postprandial lipemia, no differences in triglyceride\r\nchanges was found between vinegar and reference group (p=0.816).\r\nConclusion. In this study in which we have tried to find an answer to the question about the effect of high amount grape\r\nvinegar on postprandial metabolism, no favorable or deleterious effect on postprandial changes of glycemia and\r\nlipemia was found.