International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Differential Regulation of Morphology and Estrogen Receptor-Alpha Expression in the Vagina of Ovariectomized Adult Virgin Rats by Estrogen Replacement: A Histological Study Wed, 24 Aug 2016 17:52:31 +0000 Background. To determine the exact role of estrogen in vaginal tissue morphology and estrogen receptor-alpha (ERα) distribution in the vagina, which remains controversial. Methods. Sixty rats were randomly categorized: sham-operated (sham), ovariectomy (OVX), and four estradiol treatments (estradiol valerate at 0.4, 0.8, 1.6, and 3.2 mg/kg/day) for 2 weeks. Thereafter, vaginal samples were biopsied from the distal- and proximal-half portions. The percentage of ERα-immunoreactive cells and the ERα score were quantified using immunohistochemistry to assess changes in ERα expression and distribution. Results. OVX induced significant vaginal atrophy and organic index. Estrogen-replacement therapy (ERT) reversed vaginal atrophy. The vaginal distal-half areas showed lower ERα% than the proximal-half areas. The ERα% increased sharply 4 weeks after OVX, especially in the epithelial layer (). ERT elicited different degrees of reductions in tissues after the 2-week treatment, but the ERα% in only the epithelium recovered in parallel with that in the sham group (). The OVX group showed higher ERα histological scores than the sham group, and the distal-half area changed more evidently than the proximal-half area. ERα expression was nearly unchanged after ERT (). Conclusions. ERT is effective for treating obesity and vulvovaginal atrophy caused by hypoestrogenism and advancing age in menopausal women but cannot recover the distribution and expression of ERα. Ting Li, Yuanyuan Ma, Hong Zhang, Ping Yan, Lili Huo, Yongyan Hu, Xi Chen, Ting Li, Miao Zhang, and Zhaohui Liu Copyright © 2016 Ting Li et al. All rights reserved. Polymorphisms of Vitamin D Signaling Pathway Genes and Calcium-Sensing Receptor Gene in respect to Survival of Hemodialysis Patients: A Prospective Observational Study Tue, 23 Aug 2016 13:39:52 +0000 We evaluated in the 7-year prospective study whether variants in vitamin D pathway genes and calcium-sensing receptor gene (CASR) are determinants of mortality in hemodialysis (HD) patients (). HRM analysis was used for GC rs2298849, GC rs1155563, RXRA rs10776909, RXRA rs10881578, and CASR rs7652589 genotyping. GC rs7041, RXRA rs749759, VDR rs2228570, and VDR rs1544410 were genotyped using PCR-RFLP analysis. The minor allele in GC rs2298849 was associated with all-cause mortality in univariate analysis (HR 1.330, 95% CI 1.046–1.692, ). Bearers of the minor allele in GC rs2298849 demonstrated higher infection/neoplasm mortality than major allele homozygotes also in multivariate analysis (HR 2.116, 95% CI 1.096–4.087, ). Cardiovascular mortality was associated with major homozygosity (CC) in VDR rs2228570 (HR 1.896, 95% CI 1.163–3.091, ). CC genotype patients were more often dyslipidemic than TT genotype subjects (46.1% versus 31.9%, ). Dyslipidemics showed higher frequency of rs1544410_rs2228570 haplotype AC than nondyslipidemics (26 versus 18%, ), whereas TT genotype patients were at lower risk of dyslipidemia compared with CC/CT genotype patients (HR 0.59, 95% CI 0.37–0.96, ). In conclusion, GC rs2298849 and VDR rs2228570 SNPs are associated with survival on HD. VDR-related cardiovascular mortality may occur due to connections of rs2228570 with dyslipidemia. Alicja E. Grzegorzewska, Monika K. Świderska, Adrianna Mostowska, Wojciech Warchoł, and Paweł P. Jagodziński Copyright © 2016 Alicja E. Grzegorzewska et al. All rights reserved. Myoinositol as a Safe and Alternative Approach in the Treatment of Infertile PCOS Women: A German Observational Study Tue, 23 Aug 2016 06:31:37 +0000 The use of  mg myoinositol +  μg folic acid per day is a safe and promising tool in the effective improvement of symptoms and infertility for patients with a polycystic ovary syndrome (PCOS). Using a questionnaire an observational study was performed under German gynecologists to collect data on ovulation and pregnancy rates in PCOS patients with infertility. In this observational study, 3602 infertile women used myoinositol and folic acid between 2 and 3 months in a dosage of  mg myoinositol +  μg folic acid per day. In a subgroup of 32 patients, hormonal values for testosterone, free testosterone, and progesterone were analyzed before and after 12 weeks of treatment. The mean time of use was 10.2 weeks. During this time 70% of these women had a restored ovulation, and 545 pregnancies were obtained. This means a pregnancy rate of 15.1% of all the myoinositol and folic acid users. In 19 cases a concomitant medication with clomiphene or dexamethasone was used. One twin pregnancy was documented. Testosterone levels changed from 96.6 ng/ml to 43.3 ng/ml and progesterone from 2.1 ng/ml to 12.3 ng/ml () after 12 weeks of treatment. No relevant side effects were present among the patients. This study could show that a new treatment option for patients with a PCOS and infertility is available. The achieved pregnancy rates are at least in an equivalent or even superior range than those reported by the use of metformin. Pedro-Antonio Regidor and Adolf Eduard Schindler Copyright © 2016 Pedro-Antonio Regidor and Adolf Eduard Schindler. All rights reserved. Prospective Randomized Study on the Influence of Myoinositol in PCOS Women Undergoing IVF in the Improvement of Oocyte Quality, Fertilization Rate, and Embryo Quality Mon, 22 Aug 2016 15:23:22 +0000 Polycystic ovarian syndrome (PCOS) is one of the pathological factors involved in the failure of in vitro fertilization (IvF). The aim of the present study was to investigate if the combination of myoinositol + folic acid was able to improve the oocyte quality, the ratio between follicles and retrieved oocytes, the fertilization rate, and the embryo quality in PCOS patients undergoing IvF treatments. 29 patients with PCOS underwent IvF protocols for infertility treatment and were randomized prospectively into two groups. Group A (placebo) with 15 patients and group B (4000 mg myoinositol + 400 μg folic acid per day) with 14 patients. The patients of group B used for two months myoinositol + folic acid before starting the IvF protocol and data were obtained concerning number of follicles, number of oocytes, quality of oocytes, fertilization rates, and embryo quality in both groups. The ratio follicle/retrieved oocyte was better in the myoinositol group (= group B). Out of the 233 oocytes collected in the myoinositol group 136 were fertilized, whereas only 128 out of 300 oocytes in the placebo group were fertilized. More metaphase II and I oocytes were retrieved in relation to the total amount of oocytes in the myoinositol. More embryos of grade I quality were obtained in the myoinositol. The duration of stimulation was 9,7 days (±3,3) in the myoinositol group and 11,2 (±1,8) days in the placebo group and the number of used FSH units was lower in the myoinositol group: 1750 FSH units (mean) versus 1850 units (mean). Our evidence suggests that myoinositol therapy in women with PCOS results in better fertilization rates and a clear trend to a better embryo quality. As the number of retrieved oocytes was smaller in the myoinositol group, the risk of hyper stimulation syndrome can be reduced in these patients. Bernd Lesoine and Pedro-Antonio Regidor Copyright © 2016 Bernd Lesoine and Pedro-Antonio Regidor. All rights reserved. Myo-Inositol in the Treatment of Teenagers Affected by PCOS Thu, 18 Aug 2016 16:29:28 +0000 Objective. To compare the effectiveness of myo-inositol (MI) and oral contraceptive pills (OCPs) in monotherapy and MI in combination with OCPs in the treatment of teenagers affected by polycystic ovary syndrome (PCOS). Methods. 61 adolescent girls aged 13–19 years, with PCOS, were involved in the prospective, open-label study. Patients were randomized into three groups: I group, 20 patients receiving drospirenone 3 mg/ethinyl estradiol 30 μg; II group, 20 patients receiving 4 g myo-inositol plus 400 mg folic acid; III group, 21 patients receiving both medications. Results. After receiving MI significant reduction in weight, BMI, glucose, C-peptide, insulin, HOMA-IR, FT, and LH was detected. The levels of SHBG, TT, FAI, DHEA-S, and AMH did not change statistically significantly. After receiving OCPs weight and BMI slightly increased, but metabolic parameters did not change. Combination of MI and OCPs did not change weight and BMI, but reduction in C-peptide, insulin, and HOMA-IR was detected. TT, FT, FAI, DHEA-S, LH, and AMH levels decreased and SHBG increased. Conclusions. Administration of MI is a safe and effective method to prevent and correct metabolic disorders in teenagers affected by PCOS. With combination of MI and OCPs antiandrogenic effects are enhanced, negative impact of OCPs on weight gain is balanced, and metabolic profile is improved. Lali Pkhaladze, Ludmila Barbakadze, and Nana Kvashilava Copyright © 2016 Lali Pkhaladze et al. All rights reserved. Incidental Parathyroidectomy during Total Thyroidectomy: Risk Factors and Consequences Thu, 18 Aug 2016 12:46:50 +0000 Objective. To evaluate the incidence of accidental parathyroidectomy in our series of total thyroidectomies, to investigate its clinical and biochemical consequences, and to identify potential risk factors. Methods. Patients who underwent total thyroidectomy between January 2006 and December 2015 were retrospectively analyzed. Pathology reports were reviewed to identify those cases who had an incidental parathyroidectomy and these were compared to patients with no parathyroidectomy, in terms of clinical (age, sex, and symptoms of hypocalcemia), pathological (thyroid specimen weight, Hashimoto thyroiditis, and malignancy), and biochemical (serum calcium and phosphate levels) factors. Results. 281 patients underwent total thyroidectomy during the study period. Incidental parathyroidectomy was noticed in 24.9% of cases, with 44.3% of parathyroid glands found in an intrathyroidal location. Evidence of postoperative biochemical hypocalcemia was noticed in 28.6% of patients with parathyroidectomy, compared with 13.3% in the no-parathyroidectomy group (). Symptomatic hypocalcemia was observed in 5.7% and 3.8%, respectively (). Age, sex, thyroid specimen weight, Hashimoto thyroiditis, and malignancy did not differ significantly between the two groups. Conclusions. Our study found an association of incidental parathyroidectomy with transient postoperative biochemical hypocalcemia, but not with clinically symptomatic disease. Age, sex, thyroid gland weight, Hashimoto thyroiditis, and malignancy were not identified as risk factors. Dimitrios K. Manatakis, Dimitrios Balalis, Vasiliki N. Soulou, Dimitrios P. Korkolis, Georgios Plataniotis, and Emmanouil Gontikakis Copyright © 2016 Dimitrios K. Manatakis et al. All rights reserved. Prognostic Value of Invasion, Markers of Proliferation, and Classification of Giant Pituitary Tumors, in a Georeferred Cohort in Brazil of 50 Patients, with a Long-Term Postoperative Follow-Up Thu, 18 Aug 2016 08:50:09 +0000 Although some pituitary adenomas may have an aggressive behavior, the vast majority are benign. There are still controversies about predictive factors regarding the biological behavior of these particular tumors. This study evaluated potential markers of invasion and proliferation compared to current classification patterns and epidemiogeographical parameters. The study included 50 patients, operated on for tumors greater than 30 mm, with a mean postoperative follow-up of 15.2 ± 4.8 years. Pituitary magnetic resonance was used to evaluate regrowth, invasion, and extension to adjacent tissue. Three tissue biomarkers were analyzed: p53, Ki-67, and c-erbB2. Tumors were classified according to a combination of histological and radiological features, ranging from noninvasive and nonproliferative (grade 1A) to invasive-proliferative (grade 2B). Tumors grades 2A and 2B represented 42% and 52%, respectively. Ki-67 () and c-erbB2 () had no significant relation to tumor progression status. P53 (), parasellar invasion (), and classification, grade 2B (), were associated with worse clinical outcome. Parasellar invasion prevails as strong predictive factor of tumor recurrence. Severe suprasellar extension should be considered as invasion parameter and could impact prognosis. No environmental factors or geographical cluster were associated with tumor behavior. Juliano Coelho de Oliveira Zakir, Luiz Augusto Casulari, José Wilson Corrêa Rosa, João Willy Corrêa Rosa, Paulo Andrade de Mello, Albino Verçosa de Magalhães, and Luciana Ansaneli Naves Copyright © 2016 Juliano Coelho de Oliveira Zakir et al. All rights reserved. Estimation of the Relative Contribution of Postprandial Glucose Exposure to Average Total Glucose Exposure in Subjects with Type 2 Diabetes Thu, 18 Aug 2016 07:22:11 +0000 We hypothesized that the relative contribution of fasting plasma glucose (FPG) versus postprandial plasma glucose (PPG) to glycated haemoglobin (HbA1c) could be calculated using an algorithm developed by the A1c-Derived Average Glucose (ADAG) study group to make HbA1c values more clinically relevant to patients. The algorithm estimates average glucose (eAG) exposure, which can be used to calculate apparent PPG (aPPG) by subtracting FPG. The hypothesis was tested in a large dataset (comprising 17 studies) from the vildagliptin clinical trial programme. We found that 24 weeks of treatment with vildagliptin monotherapy () reduced the relative contribution of aPPG to eAG from 8.12% to 2.95% (by 64%, ). In contrast, when vildagliptin was added to metformin (), the relative contribution of aPPG to eAG insignificantly increased from 1.59% to 2.56%. In conclusion, glucose peaks, which are often prominent in patients with type 2 diabetes, provide a small contribution to the total glucose exposure assessed by HbA1c, and the ADAG algorithm is not robust enough to assess this small relative contribution in patients receiving combination therapy. Bo Ahrén and James E. Foley Copyright © 2016 Bo Ahrén and James E. Foley. All rights reserved. Chronic Glucocorticoid-Rich Milieu and Liver Dysfunction Thu, 11 Aug 2016 10:32:29 +0000 We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing’s syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation. Hernán Gonzalo Villagarcía, Vanesa Sabugo, María Cecilia Castro, Guillermo Schinella, Daniel Castrogiovanni, Eduardo Spinedi, María Laura Massa, and Flavio Francini Copyright © 2016 Hernán Gonzalo Villagarcía et al. All rights reserved. Metabolism and Ovarian Function in PCOS Women: A Therapeutic Approach with Inositols Thu, 04 Aug 2016 09:52:16 +0000 Polycystic ovary syndrome (PCOS) is characterized by chronical anovulation and hyperandrogenism which may be present in a different degree of severity. Insulin-resistance and hyperinsulinemia are the main physiopathological basis of this syndrome and the failure of inositol-mediated signaling may concur to them. Myo (MI) and D-chiro-inositol (DCI), the most studied inositol isoforms, are classified as insulin sensitizers. In form of glycans, DCI-phosphoglycan and MI-phosphoglycan control key enzymes were involved in glucose and lipid metabolism. In form of phosphoinositides, they play an important role as second messengers in several cellular biological functions. Considering the key role played by insulin-resistance and androgen excess in PCOS patients, the insulin-sensitizing effects of both MI and DCI were tested in order to ameliorate symptoms and signs of this syndrome, including the possibility to restore patients’ fertility. Accumulating evidence suggests that both isoforms of inositol are effective in improving ovarian function and metabolism in patients with PCOS, although MI showed the most marked effect on the metabolic profile, whereas DCI reduced hyperandrogenism better. The purpose of this review is to provide an update on inositol signaling and correlate data on biological functions of these multifaceted molecules, in view of a rational use for the therapy in women with PCOS. Antonio Simone Laganà, Paola Rossetti, Massimo Buscema, Sandro La Vignera, Rosita Angela Condorelli, Giuseppe Gullo, Roberta Granese, and Onofrio Triolo Copyright © 2016 Antonio Simone Laganà et al. All rights reserved. The Adrenal Gland Volume Measurements in Manifestation of the Metabolic Status in Type-2 Diabetes Mellitus Patients Tue, 02 Aug 2016 13:34:03 +0000 Objectives. The aim of our study was to investigate the differences in adrenal gland volume between nondiabetic controls and Type-2 diabetic patients and to examine the influence of glycemic control in diabetes mellitus on adrenal gland volume. Methods. From March 2 to November 25, 2015, 62 consecutive patients with Type-2 DM along with 62 nondiabetics matched by age, gender, and BMI were enrolled in this prospective study. Our diabetes patients were categorized into two groups, well-controlled and poorly controlled diabetes groups. Adrenal volumetric measurements were performed by two radiologists, prospectively and independently, with semiautomatic software. Interobserver reliability was studied using the interobserver correlation coefficient (ICC). Results. The total adrenal volume (TAV) was significantly higher in Type-2 diabetic patients when compared with nondiabetic patients (). When we investigated diabetic patients according to glycemic controls, the TAVs in controlled diabetic patients were significantly higher than in those of the poorly controlled or uncontrolled diabetic patients (). Nondiabetic control patients have significantly smaller TAVs when compared to controlled and poorly or noncontrolled diabetic patients (). Conclusion. Our study suggests that adrenal gland volume measurement may be used as an indirect marker of glycemic control in patients with diabetes. Ismail Serifoglu, Ibrahim Ilker Oz, and Muammer Bilici Copyright © 2016 Ismail Serifoglu et al. All rights reserved. Genome-Wide DNA Methylation in Mixed Ancestry Individuals with Diabetes and Prediabetes from South Africa Sun, 31 Jul 2016 06:27:05 +0000 Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings. Tandi E. Matsha, Carmen Pheiffer, Stephen E. Humphries, Junaid Gamieldien, Rajiv T. Erasmus, and Andre P. Kengne Copyright © 2016 Tandi E. Matsha et al. All rights reserved. Expression of miRNA and Occurrence of Distant Metastases in Patients with Hürthle Cell Carcinoma Thu, 28 Jul 2016 09:40:58 +0000 Background. Hürthle cell thyroid carcinoma (HCTC) is a rare type of thyroid carcinoma. In the present study, we investigated whether the expression of miRNAs of interest is associated with the occurrence of metastases in patients with HCTC. Materials and Methods. In 39 patients with HCTC (22 with nonmetastatic and 17 with regional or distant metastatic disease), the expression levels of six miRNAs (miR-138, miR-183, miR-221, miR-222, miR-768-3p, and miR-885-5p) and U6 snRNA as endogenous control were determined in FFPE samples of primary tumor and normal thyroid tissue using TaqMan miRNA assays. Results. In patients with HCTC, miR-138 and miR-768-3p were downregulated in tumor samples compared to normal tissue ( and , resp.). These two miRNAs were also significantly downregulated in tumor samples of patients with metastatic disease ( and , resp.) but not in patients with nonmetastatic disease ( and , resp.). In patients with nonmetastatic disease, miR-221 and miR-885-5p were slightly, albeit significantly, upregulated in tumorous compared to normal tissue ( and , resp.). Conclusion. Expression of miRNA (miR-183, miR-221, and miR-885-5p) in tumor tissue is associated with the occurrence of distant metastases in patients with HCTC. Rok Petric, Barbara Gazic, Katja Goricar, Vita Dolzan, Radan Dzodic, and Nikola Besic Copyright © 2016 Rok Petric et al. All rights reserved. Evaluation of Subclinical Hypothyroidism in Children and Adolescents: A Single-Center Study Wed, 27 Jul 2016 10:12:14 +0000 The main purpose of our retrospective study was to evaluate the medical care of the patients with subclinical hypothyroidism (sHT) and to investigate the rationale for administering L-thyroxine (LT-4) to young sHT patients. Patients and Methods. Based on a retrospective review of the charts of 261 patients referred to the Endocrinology Outpatient Clinic between 2009 and 2014 with suspicion of sHT, 55 patients were enrolled for further analysis. Data collected was baseline age, anthropometric measurements, serum TSH, fT4, fT3, anti-thyroid autoantibodies, positive family history, absence/presence of clinical symptoms, length of follow-up, and data concerning LT-4 therapy (therapy: T1; no therapy: T0). Results. T1 encompassed 33 (60.0%) patients. There were no differences between T1 and T0 () with regard to age, TSH concentrations, BMI -score, and hSDS values, though follow-up was longer in T1 (). Four (11.8%) children in T1 and none in T0 had a positive family history of thyroid disorders. Fifteen (68.2%) patients in group T0 became euthyroid. One (1.8%) girl (T1) developed overt hypothyroidism. Conclusions. A small percentage of patients can proceed to overt hypothyroidism. Only positive family history seemed to influence the decision to initiate LT-4 therapy. Further prospective studies are warranted in order to establish treatment indications, if any, and the mean recommended dosage of LT-4. Kamila Such, Aneta Gawlik, Aleksandra Dejner, Malgorzata Wasniewska, Agnieszka Zachurzok, Aleksandra Antosz, Tomasz Gawlik, and Ewa Malecka-Tendera Copyright © 2016 Kamila Such et al. All rights reserved. Biology of Beige Adipocyte and Possible Therapy for Type 2 Diabetes and Obesity Tue, 26 Jul 2016 14:34:11 +0000 All mammals own two main forms of fat. The classical white adipose tissue builds up energy in the form of triglycerides and is useful for preventing fatigue during periods of low caloric intake and the brown adipose tissue instead of inducing fat accumulation can produce energy as heat. Since adult humans possess significant amounts of active brown fat depots and their mass inversely correlates with adiposity, brown fat might play an important role in human obesity and energy homeostasis. New evidence suggests two types of thermogenic adipocytes with distinct developmental and anatomical features: classical brown adipocytes and beige adipocytes. Beige adipocyte has recently attracted special interest because of its ability to dissipate energy and the possible ability to differentiate itself from white adipocytes. Importantly, adult human brown adipocyte appears to be mainly composed of beige-like adipocytes, making this cell type an attractive therapeutic target for obesity and obesity-related diseases. Because many epigenetic changes can affect beige adipocyte differentiation, the knowledge of the circumstances that affect the development of beige adipocyte cells may be important for therapeutic strategies. In this review we discuss some recent observations arising from the great physiological capacity of these cells and their possible role as ways to treat obesity and diabetes mellitus type 2. Fernando Lizcano and Diana Vargas Copyright © 2016 Fernando Lizcano and Diana Vargas. All rights reserved. Relationship between Branched-Chain Amino Acids, Metabolic Syndrome, and Cardiovascular Risk Profile in a Chinese Population: A Cross-Sectional Study Tue, 26 Jul 2016 14:23:12 +0000 Objective. This study aimed to evaluate the relationship between branched-chain amino acids (BCAAs), metabolic syndrome (MS), and other cardiovascular (CV) risk factors in middle-aged and elderly Chinese population at high risk for the development of cardiovascular disease (CVD). Methods. 1302 subjects were enrolled from the Huai’an Diabetes Prevention Program. Results. BCAAs levels were positively correlated with MS, its components, and CV risk profile. The odds ratio (OR) for MS among subjects in the fourth quartile of BCAAs levels showed a 2.17-fold increase compared with those in the first quartile. BCAAs were independently associated with high Framingham risk score even after adjusting for MS and its components (). Additionally, the OR for high CV risk was 3.20-fold () in participants in the fourth BCAAs quartile with MS compared with participants in the first BCAAs quartile without MS. Conclusions. Increased BCAAs levels are independent risk factors of MS and CVD in addition to the traditional factors in middle-aged and elderly Chinese population. The development of CVD in MS patients with high level BCAAs is accelerated. Intervention studies are needed to investigate whether the strategy of BCAAs reduction has impacts on endpoints in patients with higher CV risk. This study is registered with ChiCTR-TRC-14005029. Wen Hu, Luning Sun, Yingyun Gong, Ying Zhou, Panpan Yang, Zhengqin Ye, Jinxiang Fu, Aijie Huang, Zhenzhen Fu, Weinan Yu, Yang Zhao, Tao Yang, and Hongwen Zhou Copyright © 2016 Wen Hu et al. All rights reserved. The Association of Adiposity Indices and Plasma Vitamin D in Young Females in Saudi Arabia Mon, 25 Jul 2016 16:02:03 +0000 Background. Vitamin D deficiency is a global health problem. Some evidences indicate its association with metabolic syndrome, type II diabetes, and cardiovascular diseases. In the current study we aim to study the association of vitamin D level and indicators of adiposity in young Saudi females. Subjects and Methods. 87 young healthy Saudi females were recruited from University of Dammam, Dammam, Saudi Arabia. Each subject filled vitamin D questionnaire and had exercise stress test to determine VO2 peak. Body weight, BMI, waist and hip circumference, and ratios were determined. Blood was analyzed for 25-OH vitamin D, glucose, triglycerides, total cholesterol, and differential cholesterol. Results. 25-OH vitamin D/body weight was negatively associated with waist circumference and waist/stature ratio. No significant difference was found between the groups of BMI with regard to the data of questionnaire or 25-OH vitamin D/body weight. Obese and overweight subjects had lower VO2 peak. Conclusion. In young Saudi females we found that the relative value of vitamin D to body weight is a better indicator of vitamin D status particularly in obese subjects and it is negatively associated with adiposity measures of waist circumference and waist/stature ratio. Lubna Ibrahim Al Asoom Copyright © 2016 Lubna Ibrahim Al Asoom. All rights reserved. Upregulation of TSHR, TTF-1, and PAX8 in Nodular Goiter Is Associated with Iodine Deficiency in the Follicular Lumen Mon, 25 Jul 2016 08:44:41 +0000 Objective. It has been testified that iodine regulates thyroid function by controlling thyroid-restricted genes expression and is closely related to diffuse goiter and thyroid dysfunction. However, the effects of follicular lumen iodine, the main form of iodine reserve in the body, on thyroid-restricted genes in nodular goiter are poorly understood. In this study, correlations between follicular lumen iodine and the expressions of thyroid stimulating hormone receptor (TSHR), its transcription factors TTF-1, and PAX8 in nodular goiter were investigated. Patients. In this study, 30 resection specimens clinically histopathologically confirmed to have nodular goiter and 30 normal thyroid specimens from adjacent tissues of nodular goiter are used. Measurement. Western blot immunohistochemistry was performed to assay TSHR, TTF-1, and PAX8 in thyrocytes of nodular goiter as well as in extranodular normal thyroid tissues. Meanwhile, follicular lumen iodine of both nodular goiter and extranodular normal thyroid tissues was detected as well. Results. The TSHR, TTF-1, and PAX8 in nodular goiter were significantly higher than those in the controls. The iodine content in nodular goiter was significantly lower than those in control tissues. Conclusion. Upregulation of TSHR, TTF-1, and PAX8 is associated with low follicular lumen iodine content in nodular goiter. Huibin Huang, Lijun Chen, Bo Liang, Huiyao Cai, Qingyan Cai, and Yaxiong Shi Copyright © 2016 Huibin Huang et al. All rights reserved. A Combined Therapy with Myo-Inositol and D-Chiro-Inositol Improves Endocrine Parameters and Insulin Resistance in PCOS Young Overweight Women Thu, 14 Jul 2016 09:20:55 +0000 Introduction. We evaluated the effects of a therapy that combines myo-inositol (MI) and D-chiro-inositol (DCI) in young overweight women affected by polycystic ovary syndrome (PCOS), characterized by oligo- or anovulation and hyperandrogenism, correlated to insulin resistance. Methods. We enrolled 46 patients affected by PCOS and, randomly, we assigned them to two groups, A and B, treated, respectively, with the association of MI plus DCI, in a 40 : 1 ratio, or with placebo (folic acid) for six months. Thus, we analyzed pretreatment and posttreatment FSH, LH, 17-beta-Estradiol, Sex Hormone Binding Globulin, androstenedione, free testosterone, dehydroepiandrosterone sulphate, HOMA index, and fasting glucose and insulin. Results. We recorded a statistically significant reduction of LH, free testosterone, fasting insulin, and HOMA index only in the group treated with the combined therapy of MI plus DCI; in the same patients, we observed a statistically significant increase of 17-beta-Estradiol levels. Conclusions. The combined therapy of MI plus DCI is effective in improving endocrine and metabolic parameters in young obese PCOS affected women. Elena Benelli, Scilla Del Ghianda, Caterina Di Cosmo, and Massimo Tonacchera Copyright © 2016 Elena Benelli et al. All rights reserved. Melatonin in Epilepsy: A New Mathematical Model of Diurnal Secretion Wed, 13 Jul 2016 14:11:35 +0000 Purpose. The main objective of the study was to create a mathematical model that describes the melatonin circadian secretion and, then the functionality of the model was tested by a comparison of the melatonin secretions in children with and without epilepsy. Material and Methods. The patients were divided into the epilepsy group (EG, ) and the comparison group (CG, ). The melatonin level was assessed by a radioimmunoassay method. The diurnal melatonin secretion was described using a nonlinear least squares method. Spearman’s rank correlation coefficient was chosen to estimate the dependence of the acquired data. The model reproduces blood concentration profiles and its parameters were statistically analyzed using the Mann-Whitney-Wilcoxon test and logistic regression. Results. The correlation analysis performed for the EG and CG groups showed moderate correlations between age and the melatonin secretion model parameters. Patients with epilepsy are characterized by an increased phase shift of melatonin release. Justyna Paprocka, Marek Kijonka, Marcin Pęcka, and Maria Sokół Copyright © 2016 Justyna Paprocka et al. All rights reserved. The Effect of Metformin on Adolescents with Type 1 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Tue, 12 Jul 2016 09:03:10 +0000 Background. The effect of metformin in combination with insulin in adolescents with type 1 diabetes (T1DM) is controversial. Methods and Results. The PubMed and EMBASE online databases were searched. Five double-blind randomized controlled trials (RCTs) that included 301 adolescents with T1DM were identified. Metformin plus insulin was associated with reduced hemoglobin A1C levels, total daily insulin dosage, body mass index (BMI), and body weight. However, the subgroup analysis demonstrated that HbA1c levels were not significantly changed in overweight/obese adolescents and were significantly reduced in the general patients. On the contrary, BMI and body weight were significantly reduced in overweight/obese adolescents but not in the general patients. Metformin was associated with higher incidence of adverse events. Conclusions. Among adolescents with T1DM, administering adjunctive metformin therapy in addition to insulin was associated with improved HbA1c levels, total daily insulin dosage, BMI, and body weight. However, there may be differences in the effects of this regimen between overweight/obese and nonobese adolescents. The risk of an adverse event may be increased with metformin treatment. These results provide strong evidence supporting future high-quality, large-sample trials. Wei Liu and Xiao-Jie Yang Copyright © 2016 Wei Liu and Xiao-Jie Yang. All rights reserved. Factors in Gestational Diabetes Mellitus Predicting the Needs for Insulin Therapy Mon, 11 Jul 2016 09:20:53 +0000 Objective. To identify factors predicting the need for insulin therapy in pregnancies complicated by gestational diabetes mellitus (GDM). Methods. A total of 1352 patients with GDM diagnosed by the 75-g/2-h oral glucose tolerance test (OGTT) were enrolled in this study. Univariate and multivariate analysis were performed; receiver operating characteristics (ROC) were also drawn. Results. There was a significant difference in factors such as maternal age, pregestational BMI, first visit SBP, first visit DBP, FBG of first visit, FBG at time of OGTT, 75-g OGTT glucose value (fasting, after 1 h and 2 h), and serum HbA1c level at diagnosis between patients with insulin therapy and patients with medical nutrition therapy (MNT) alone. Multivariate analysis showed that higher FBG at time of OGTT, first 75 g OGTT 2 h plasma glucose, and HbA1c concentration at diagnosis lead to more likely need of insulin therapy. Conclusion. The probability of insulin therapy can be estimated in pregnant women with GDM based on fasting and 2 h glucose values during OGTT and HbA1c value at diagnosis of GDM. Ya Zhang, Jiashen Shao, Feifei Li, and Xianming Xu Copyright © 2016 Ya Zhang et al. All rights reserved. Midkine: A Novel Biomarker to Predict Malignancy in Patients with Nodular Thyroid Disease Thu, 30 Jun 2016 13:28:02 +0000 Background. Midkine (MK), a new heparin-binding growth factor, plays important roles in a variety of biological phenomena such as carcinogenesis, inflammation, and angiogenesis. In this study, we aimed to evaluate serum midkine (SMK) and nodular midkine (NMK) levels in patients with thyroid nodules to predict malignancy and whether there was any association between. Methods. A total of 105 patients (74 women, 31 men) with thyroid nodules were enrolled. The levels of SMK and NMK were measured. Any possible correlation between SMK, NMK, and biochemical, cytopathological, or radiological variables was investigated. Results. Both SMK and NMK were found to be higher in hypoechoic nodules with an irregular border and without a halo (). Serum MK levels were significantly higher in nodules with microcalcifications than nodules with macrocalcification or without calcification (). SMK levels were found to be correlated with NMK levels (SMK 0.63 ng/ml versus 1.04 ng/mL and NMK 0.55 ng/mL versus 0.55 ng/mL, , ). Conclusion. Both SMK and NMK can predict tumorigenesis of highly malignant/suspicious thyroid cytopathology and also well correlated with sonographic features of thyroid nodules. We suggest that MK levels may serve as an alternative biomarker, in conjunction with the cytopathological results in preoperative assessment of thyroid nodules. Fatih Kuzu, Dilek Arpaci, Mustafa Unal, Ayfer Altas, Gürkan Haytaoglu, Murat Can, Figen Barut, Furuzan Kokturk, Sevil Uygun Ilikhan, and Taner Bayraktaroglu Copyright © 2016 Fatih Kuzu et al. All rights reserved. Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population Wed, 29 Jun 2016 11:41:45 +0000 Despite 70 years of experience treating thyrotoxic patients with radioiodine not all patients are successfully treated by a single dose. Multiple factors predicting radioiodine efficacy have been reported. The aim of this study was to assess whether ethnicity was associated with radioiodine response. A retrospective review was performed of patients who received radioiodine therapy for thyrotoxicosis from 1 January 2008 to 31 December 2010 and had follow-up available of a minimum of 12 months. 224 patients were included, 82.4% female, and 63.7% had Graves’s disease. Radioiodine failed in 21.5% of patients overall, with a higher failure rate in the indigenous population (35.2%). When controlling for other influencing factors by logistic regression, there continued to be an increased risk for the indigenous group (OR 2.82) and those treated with antithyroid drugs following radioiodine (OR 2.04). Younger age was also associated with an increased risk of failing radioiodine therapy (OR 0.97 for each year of age). Cure rates following radioiodine were lower for indigenes independent of factors known to affect radioiodine outcome. This is the first report demonstrating ethnicity as a possible independent variable for radioiodine efficacy. Further work is needed to investigate the cause of this difference. Jade A. U. Tamatea, John V. Conaglen, and Marianne S. Elston Copyright © 2016 Jade A. U. Tamatea et al. All rights reserved. Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer Wed, 29 Jun 2016 07:42:53 +0000 Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (; ). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer. Zhigang Hu, Pengxin Zhao, Kaili Zhang, Leilei Zang, Haiying Liao, and Weiyuan Ma Copyright © 2016 Zhigang Hu et al. All rights reserved. The Frequency of Langerhans Islets β-Cells Autoantibodies (Anti-GAD) in Georgian Children and Adolescents with Chronic Autoimmune Thyroiditis Mon, 27 Jun 2016 15:55:50 +0000 Aim. Chronic autoimmune thyroiditis and type 1 diabetes mellitus are organ-specific autoimmune diseases. There is large evidence that autoimmunity against the thyroid gland in patients with type 1 diabetes mellitus is increased, but little is known about anti-islet cell autoimmune status in patients with chronic autoimmune thyroiditis. We evaluated the concentration of antibodies against glutamic acid decarboxylase (GAD) which are widely used as a diagnostic and predictive tool for type 1 diabetes mellitus, in school-aged Georgian children with chronic autoimmune thyroiditis. Methods. The frequency of anti-GAD antibodies was measured in Georgian school-aged children with chronic autoimmune thyroiditis and compared to healthy age and sex matched controls. Results. Of the 41 patients with chronic autoimmune thyroiditis 4 (9.8%) were positive for GAD antibodies. The frequency of GAD positivity in the chronic autoimmune thyroiditis group was significantly higher than in the control subjects (). Conclusion. In the study we found that the frequency of GAD antibody positivity in autoimmune thyroiditis patients was significantly higher (9.8%, ) than in the control group. Our findings support the concept that patients with autoimmune thyroid disease may develop type 1 diabetes mellitus in future life. Mariam Balakhadze, Elene Giorgadze, and Marina Lomidze Copyright © 2016 Mariam Balakhadze et al. All rights reserved. Cardiac Effects of Thyrotropin Oversuppression with Levothyroxine in Young Women with Differentiated Thyroid Cancer Thu, 23 Jun 2016 09:10:40 +0000 Background. We investigated the cardiac effects of TSH (thyroid-stimulating hormone) oversuppression in women with thyroidectomized differentiated thyroid cancer (DTC) during levothyroxine suppression therapy. Methods. Fourteen young female patients with DTC were enrolled. The duration of TSH-suppressive therapy was 5 to 9 years. They satisfied the following criteria: (1) a serum level of TSH < 0.1 mU/L in the intermediate-risk or TSH < 0.3 mU/L in the low-recurrence-risk group and (2) having been receiving a fixed dose of LT4 before the study. Controls matched for age, sex, and body mass index (BMI) were compared in terms of the levels of serum free T4, free T3, TSH, plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and cardiac functions and structures. Results. DTC patients and control subjects were well matched in heart rate and blood pressure. There were marked differences in serum TSH () and free T4 (). However, there were no differences between the groups in serum free T3 and plasma NT-pro-BNP. Furthermore, there were nonsignificant differences in cardiac functions and structures between the groups. Conclusions. This study shows that TSH suppression therapy in women with DTC may be safe with respect to cardiac functions and structures despite intermittent oversuppression of TSH during long-term suppressive therapy. Trial Registration. This trial is registered with identifier NCT02645786. Kyung-Soon Hong, Jung-Woo Son, Ohk Hyun Ryu, Moon-Gi Choi, Ji Yeon Hong, and Seong Jin Lee Copyright © 2016 Kyung-Soon Hong et al. All rights reserved. Vitamin D Status Is Negatively Correlated with Insulin Resistance in Chinese Type 2 Diabetes Mon, 20 Jun 2016 10:43:18 +0000 Objectives. Vitamin D deficiency plays a role in insulin resistance and the pathogenesis of type 2 diabetes mellitus. Little information is available about the association between vitamin D status and insulin resistance in the Chinese population. Currently, vitamin D status is evaluated by the concentrations of serum 25-hydroxyvitamin D [25(OH)D]. This study explores the relationship between insulin resistance and serum 25-hydroxyvitamin D concentrations in Chinese patients with type 2 diabetes mellitus. Subjects and Methods. This study included 117 patients with type 2 diabetes. The following variables were measured: 25-hydroxyvitamin D [25(OH)D], glycosylated hemoglobin A1c (HbA1c), fasting blood glucose (FBS), fasting blood insulin (FINS), fasting blood C-peptide, serum creatinine (SCr), glomerular filtration rate (eGFR), body mass index (BMI), and homeostatic model estimates of insulin resistance (HOMA-IR). Results. The cases were divided into three groups: Group 1 (G1) with 25(OH)D ≤ 20 ng/mL [≤50 nmol/L], Group 2 (G2) with 25(OH)D values from 20 ng/mL [50 nmol/L] to 30 ng/mL [75 nmol/L], and Group 3 (G3) with 25(OH)D ≥ 30 ng/mL [≥75 nmol/L], with 52.6%, 26.3%, and 21.1% of subjects in Groups 1–3, respectively. There was a negative correlation between 25(OH)D and HOMA-IR (β = −0.314, ) adjusted by age, BMI, and eGFR. Conclusion. Better vitamin D status may be protective of glucose homeostasis since 25(OH)D was negatively associated with insulin resistance in Chinese patients with type 2 diabetes. Jie Zhang, Jianhong Ye, Gang Guo, Zhenhao Lan, Xing Li, Zhiming Pan, Xianming Rao, Zongji Zheng, Fangtao Luo, Luping Lin, Zhihua Lin, and Yaoming Xue Copyright © 2016 Jie Zhang et al. All rights reserved. Total Endoscopic Thyroidectomy with Intraoperative Laryngeal Nerve Monitoring Mon, 20 Jun 2016 08:57:02 +0000 Objective. To evaluate the clinical efficacy of laryngeal nerve (LN) monitoring (LNM) during total endoscopic thyroidectomy via breast approach, with emphasis on the identification rates for RLN and EBSLN and the incidence of RLN paralysis. Materials and Methods. This retrospective study included 280 patients who underwent endoscopic thyroidectomy with or without LNM. RLN and EBSLN were identified using endoscopic magnification in the control group, while they were localized additionally by LNM in the LNM group. Demographic parameters and surgical outcomes were analyzed by statistical methods. Patients in the control group were also stratified by the side of thyroidectomy to determine difference in left and right RLN injury rates. Results. All procedures were successfully conducted without permanent LN damage. The identification rates for RLN and EBSLN were high in the LNM group compared to those of the control group, and the risk difference (RD) of temporary RLN injury between two groups was 6.3%. The risk of damage was slightly higher for the left RLN than for the right RLN in the control group, which was performed by a right-hand surgeon. Conclusion. The joint application of LNM and endoscopic magnified view endows total endoscopic thyroidectomy with ease, safety, and efficiency. Bin Lv, Bin Zhang, and Qing-Dong Zeng Copyright © 2016 Bin Lv et al. All rights reserved. Predictive Factors of Development of Graves’ Ophthalmopathy for Patients with Juvenile Graves’ Disease Thu, 16 Jun 2016 14:25:15 +0000 Background. Due to low incidence of Graves’ ophthalmopathy (GO) among children, the manifestation is poorly analyzed, posing a risk to late identification of insidious disease. Purposes. To identify predictive factors that may influence the development of GO in pediatric and young patients with Graves’ disease (GD). Methods. A cross-sectional study of patients newly diagnosed with pediatric or juvenile GD during 2002–2012 was conducted at the Hospital of Lithuanian University of Health Sciences. Ocular evaluation was based on European Group on Graves’ Orbitopathy survey. The ocular manifestations were analyzed in relation to demographic, environmental, and clinical factors. Results. In total, 130 patients with juvenile GD were included; 29.2% had GO. Median age at GD onset was 17 yrs (IQR 4–29). Main symptoms of GO were eyelids retraction (73.7%), proptosis (65.8%), injection of conjunctiva (42.1%), and eyeball motility disturbance (21.1%). Major significant and independent risk factors for GO development were high initial concentration of FT4 (OR = 5.963), TTHAb (OR = 6.358), stress (OR = 6.030), and smoking (OR = 7.098). Conclusion. The major factors that could influence GO development were smoking, stress, and increased levels of initial TRAb, FT4. Slight proptosis, retraction of eyelids, and conjunctive injection were found as predominant ophthalmological symptoms in juvenile GO. Dalia Jarusaitiene, Rasa Verkauskiene, Vytautas Jasinskas, and Jurate Jankauskiene Copyright © 2016 Dalia Jarusaitiene et al. All rights reserved.