ACTA ENDOCRINOLOGICA (BUC)

Context. Thyroid eye disease (TED), an orbital inflammatory status, generally occurred in Graves’ disease. Objective. This study aimed to acquire further insight into molecular mechanisms of TED, especially several key involved genes and pathways. Design. The microarray dataset GSE58331 including expression data for orbital adipose tissue samples, isolated from TED patients and normal controls, was downloaded from a publicly accessible Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified from 23 adipose tissues of TED patients versus 20 samples from normal controls. Subjects and Methods. A protein-protein interaction network of DEGs was constructed by using Search Tool for the Retrieval of Interacting Genes and Cytoscape 3.6.0. Several hub genes/proteins were extracted from the proteinprotein interaction network based on connectivity degree. Furthermore, we used the iRegulon plugin of Cytoscape3.6.0 to predict the transcription factors (TFs). Results. A total of 678 DEGs (538 up- and 140 down-regulated genes) were identified in TED patients. Proopiomelanocortin (POMC), interleukin 2 (IL-2), G protein subunit gamma 3 (GNG3), CXC motif chemokine receptor 4 (CXCR4), toll like receptor 4 (TLR4), colony stimulating factor 1 receptor (CSF1R), lysophosphatidic acid receptor 3 (LPAR3), CXC motif chemokine ligand-8 (CXCL8), etc., were considered as the hub genes among the DEGs. There were 6 TFs predicted to be differentially expressed in regulating the DEGs related to TED. A total of 71 DEGs had been reported to be associated with TED in the Comparative Toxicogenomics Database. Conclusions. Through this analysis, we have identified plenty of potential biomarkers and pathways which may have an important role in the pathogenesis of TED. However, these findings require verification by more detailed future experimental studies.

Context. Recent evidence has stressed that many proinflammatory factors are particularly conducive to the progression of diabetic nephropathy, but the mechanisms underlying the changes are poorly understood. Objective. The purpose of this study was to investigate if up-regulated expression of both phospholipase A2 (PLA2) and cyclooxygenase-2 (COX-2) is involved in renal damage and micro-inflammatory state in streptozotocin-induced diabetic rats. Animals and methods. Sixteen Sprague Dawley rats were randomly divided into 2 groups: control group and diabetes group. Animals in diabetes group were treated with intraperitoneal injection of streptozotocin. Eight weeks later, rat renal tissue was studied with light and transmission electron microscopes, and PLA2 and COX-2 and their mRNA expression were examined by immunohistochemistry and reverse transcription polymerase chain reaction, respectively. Results. The renal pathological lesions in diabetes group were obvious, including increased amounts of mesangial matrix, thickening of the glomerular and tubular basement membranes and fusion and effacement of the adjacent podocyte foot processes. Infiltrating inflammatory cells were observed in the tubules. Compared with control group, the expression of cytosolic PLA2 and COX-2 was significantly increased in diabetes group. Conclusions. It uncovers that the PLA2-COX-2 pathway may lead to renal inflammation associated with renal damage in streptozotocin- induced diabetic rats.

Aims. Resistin has been reported to impair the pancreatic beta cells and associated with insulin resistance. MicroRNAs (miRNAs) are short, endogenously produced non-coding ribonucleotides that bind mRNAs and function mainly as negative regulators in mammals. MiRNAs have been implicated in many diseases, including insulin resistance and diabetes. A considerable body of evidence has indicated an important function for miRNAs in insulin secretion. The current study was designed to investigate the effects of miR-494 in the reductions in insulin secretion attributable to resistin. Methods. Insulin secretion was determined by ELISA, and expressions of genes were identified using quantitative RT-PCR (qRT-PCR) or Western blot analysis. Results. Insulin secretion was significantly reduced by resistin. Overexpression of miR-494 inhibited insulin secretion both in diet culture and high glucose medium in MIN6 cell lines. MiR-494 down-regulated the protein level of STXBP5 by pairing with sites in the 3′UTR. Conclusion. miR-494 is involved in the insulin secretion regulated by resistin via its effects on STXBP5 in MIN6 cells.

Objective. This study aims to determine the frequency and prognostic significance of lactic acidosis in children with diabetic ketoacidosis (DKA) admitted to the pediatric intensive care unit. Methods. The study was carried out retrospectively by examining the patients admitted to the pediatric intensive care unit for the treatment of DKA. The ages of the patients ranged from 2 to 18 years. The patients with the following parameters were enrolled in the study: serum blood glucose>200 mg/dL, ketonuria presence, venous blood gas pH ≤7.1, bicarbonate <15. Results. A total of 56 patients were included in the study with a mean age of 111.07 ± 51.13 months. The recovery time from DKA was 16.05 ± 6.25 h in the group with low lactate level and it was 13.57 ± 8.34 h in the group with high lactate level with no statistically significant difference. There was a negative correlation between lactate levels and the recovery time from DKA. Conclusion. Lactic acidosis is common in DKA, and unlike other conditions, such as sepsis, it is not always a finding of poor prognosis that predicts the severity of the disease or mortality. We think that high lactate may even protect against possible brain edema-cerebral damage in DKA.

Introduction. With the introduction of iodized salt, more and more people are exposed to iodine sufficiency in some regions. The purpose of this study was to investigate the prevalence of nontoxic nodular goiter (NTNG) in the littoral region with high iodine supply after a nearly twodecade universal salt iodization. Subjects and Methods. Eight hundred and thirtyfive participants (from 25~65 years; males 421 and females 414) were invited for the study from Huan-cui District of Weihai City, Shandong Province from January 2013 to September 2014. All participants were inspected and diagnosed by endocrinologists according to the thyroid function tests and the thyroid gland imaging. After the normal diet of three days, the urine samples of the participants were collected between 8:00AM and 9:00AM and the urinary iodine (UI) concentrations were analyzed using Urinary Iodide Test Kit. Results. The overall prevalence of NTNG in the region was 40.1%, and different prevalence occurred in the different age ranges (p<0.01). The prevalence of NTNG was 32.51%, 37.44%, 49.70%, 58.57 and 74.77% in the age group of ≤ 30, 31-40, 41-50, 51-60 and >60 years, respectively. Meanwhile, the prevalence of NTNG in women (42.08%) was higher than that in men (34.29%, p<0.05). The median of UI concentrations were 139.4μg/L and 101.5μg/L for the group with NTNG and without NTNG, respectively (p<0.01). However, there was no significant difference in UI concentrations among the groups with different age ranges (p>0.05), and statistical difference was not observed for UI concentrations between women and men (p>0.05). Intriguingly, higher UI concentrations were found in the group with larger thyroid size (p<0.01). Conclusion. The iodine excess can lead to the high occurrence of nodular goiter in the littoral region, and individual UI concentration detection is recommended for the iodine nutritional status analysis among normal people when Universal Salt Iodization (USI) continues to be implemented in the region.

Background. Metformin is the first-line oral antidiabetic agent used in the treatment of diabetes mellitus. One of the adverse reactions of the long term use of metformin is cobalamin malabsorption. Clinical and laboratory findings are important in the diagnosis of cobalamin deficiency. Objective. This study aimed to evaluate the risk of cobalamin deficiency symptoms related to long-term use of metformin in type 2 diabetes mellitus patients at Pasar Rebo General Hospital in Jakarta. Setting. This quantitative, observational study with retrospective cohort design was conducted in outpatient department Pasar Rebo General Hospital November 2015 until January 2016. Methods. 200 subjects were recruited and divided into two groups, patients who had been taking metformin for 1-3 years and patients who had been taking metformin for more than 3 years. Each patient was assessed for the presence of cobalamin deficiency symptoms. Main outcome measure. Cobalamin deficiency symptoms evaluated were symptoms of neuropathy (measured by DN4 questionnaire) and hematologic abnormalities associated to cobalamin deficiency, i.e. macrocytic erythrocyte, hypersegmented neutrophils, and giant bands. Results. There are significant differences in the proportions of neuropathy symptoms (RR 2.36, 95%, p=0.000) and hematologic abnormalities (RR 1.5, 95%, p=0.007) between the two groups. Conclusions. Long-term use of metformin (≥3 years) may increase the risk of cobalamin deficiency symptoms in type 2 diabetes mellitus patients.

Context. Clinical studies demonstrated erythrocyte deformability (ED) is impaired in diabetic patients and described the correlations between HbA1c and ED. Few studies further investigated what an exact elevated HbA1c level linked to the impairment of ED in diabetes. Objective. This study was to determine a cut-off point of HbA1c level leading to the impairment of ED in patients with diabetes. Design. This was a retrospective observational study. ROC curve analysis was used to determine an optimal cut-off value of HbA1c for the increasing HSRV. Subjects and Methods. In this study, 300 type 2 diabetic patients were enrolled. The whole blood viscosity was measured. High shear reductive viscosity (HSRV) was used to indirectly estimate ED. Based on the obtained cut-off value and glycemic control criteria for HbA1c, we divided all the cases into different groups to further confirm the accuracy of the cut-off value. Results. In 300 patients, ROC curve illustrated that 9.05% was the optimal cut-off value as a predictor of the increasing HSRV. And higher odds ratio (OR) for significant decrease in ED was seen in the patients with HbA1c >9.05% compared to those with HbA1c≤9.05% (OR: 3.78, 95% CI: 2.08-6.87). HSRV increased significantly in patients with HbA1c level >9.05% in comparison to patients with HbA1c levels <6.5% between 6.5 and 8.0% and between 8.0 and 9.05%. Conclusion. ED decreased significantly in diabetic patients as soon as HbA1c level was higher than 9.05%.

Context. On naked eye examination adrenal myelolipoma (AML) tissue appears to be an ectopic adrenal or renal tissue, based on the similarity to their external texture. This necessitates a histo-pathological study for confirming the origin of the tissue. Objective. To establish the origin and histological features of the incidental AML tissue found during cadaveric dissection and review the literature for similar findings with clinical picture and treatment description. Subjects and Methods. Unilateral adrenal gland obtained from cadaveric dissection was subjected to histological study by H & E staining of the slides prepared. The literature review was done from articles published in PubMed indexed journals. Case report. A case of an incidental finding of AML during cadaveric dissection is presented which on naked eye examination was appearing to be an ectopic adrenal or renal tissue, based on the similarity to their external texture. On histological examination, a thin rim of adrenocortical tissue, surrounding the mature adipose tissue, and attenuated by islets of myeloid, erythroid and megakaryocytic cell lines in varying proportions, resembling the mature bone marrow morphology, was observed. The literature review on PubMed explains similar incidental post-mortem autopsy findings due to the asymptomatic nature of the tumor. The incidence of AML varied between 0.08% and 0.2% in the last decade of the 20th century, which increased up to 10 – 15% of incidental adrenal masses due to the widespread use of non-invasive imaging modalities leading to an increase in the diagnosis of the pathology. Conclusion. Before considering the ectopic incidence of tissue during cadaveric dissection, a histopathological examination is mandatory for confirmation. Adreno-myelolipoma is an asymptomatic post-mortem finding in 10-15% of cases of adrenal tissue which mimics ectopic adrenal gland or renal tissue due to its external texture.

Pituitary apoplexy (PA) is a life-threatening clinical syndrome. Dopamine receptor agonists are the drugs of choice in the treatment of prolactinomas. The use of cabergoline is reported to cause an increased risk of PA, particularly in macroprolactinomas of cystic nature. In this report, we present a patient with a cystic macroprolactinoma who developed PA on the 16th week of cabergoline treatment.

Objective. This study aims to determine the frequency and prognostic significance of lactic acidosis in children with diabetic ketoacidosis (DKA) admitted to the pediatric intensive care unit. Methods. The study was carried out retrospectively by examining the patients admitted to the pediatric intensive care unit for the treatment of DKA. The ages of the patients ranged from 2 to 18 years. The patients with the following parameters were enrolled in the study: serum blood glucose>200 mg/dL, ketonuria presence, venous blood gas pH ≤7.1, bicarbonate <15. Results. A total of 56 patients were included in the study with a mean age of 111.07 ± 51.13 months. The recovery time from DKA was 16.05 ± 6.25 h in the group with low lactate level and it was 13.57 ± 8.34 h in the group with high lactate level with no statistically significant difference. There was a negative correlation between lactate levels and the recovery time from DKA. Conclusion. Lactic acidosis is common in DKA, and unlike other conditions, such as sepsis, it is not always a finding of poor prognosis that predicts the severity of the disease or mortality. We think that high lactate may even protect against possible brain edema-cerebral damage in DKA.