International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . 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. Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome Thu, 16 Jun 2016 08:02:04 +0000 Objective. Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: years) KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT). Results. KS children and adolescents showed significantly reduced AD-SoS () and BTT () z-scores compared to the controls. However, KS patients presented significantly higher PTH () and significantly lower 25(OH)D (), osteocalcin (), and bone alkaline phosphatase levels (). Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages. Stefano Stagi, Mariarosaria Di Tommaso, Cristina Manoni, Perla Scalini, Francesco Chiarelli, Alberto Verrotti, Elisabetta Lapi, Sabrina Giglio, Laura Dosa, and Maurizio de Martino Copyright © 2016 Stefano Stagi et al. All rights reserved. Stroke Risk among Patients with Type 2 Diabetes Mellitus in Zhejiang: A Population-Based Prospective Study in China Tue, 14 Jun 2016 07:49:05 +0000 Objective. This study aimed to explore the incidence of stroke and stroke subtypes among patients with type 2 diabetes mellitus (T2DM) based on the long-term surveillance data in Zhejiang, China, during 2007 to 2013. Materials and Methods. During January 1, 2007, and December 31, 2013, a total of 327,268 T2DM and 307,984 stroke patients were registered on Diabetes and Stroke Surveillance System, respectively. Stroke subtypes were classified according to standard definitions of subarachnoid hemorrhage, intracerebral hemorrhage, and ischemic stroke. The incidence of stroke and stroke subtypes was calculated by standardized incidence ratio (SIRs) with 95% confidence intervals (CIs) compared with general population. Results. The incidence of stroke and stroke subtypes among patients with T2DM was significantly higher than in general population. Stroke risk was found significantly increased with an SIR of 3.87 (95% CI 3.76–3.99) and 3.38 (95% CI 3.27–3.48) in females and males, respectively. The excess risk of stroke was mainly attributable to the significantly higher risk of cerebral infarctions with the risk for T2DM being four times that for general population. Conclusions. The relationship between stroke and T2DM was strong, especially in female. The incidence of stroke and stroke subtypes among patients with T2DM was up to 3-fold higher than in general population in Zhejiang province, especially the subtype of cerebral infarctions. Lihua Guo, Min Yu, Jieming Zhong, Haibin Wu, Jin Pan, Weiwei Gong, Meng Wang, Fangrong Fei, and Ruying Hu Copyright © 2016 Lihua Guo et al. All rights reserved. Treating Woman with Myo-Inositol Vaginal Suppositories Improves Partner’s Sperm Motility and Fertility Tue, 14 Jun 2016 06:27:41 +0000 Motility is the feature that allows spermatozoa to actively reach and penetrate the female gamete during fertilization. When this function is altered, and especially decreased, troubles in conceiving may occur. In this study, we demonstrated that treating fertile women with myo-inositol (MI) vaginal suppositories ameliorated their partners’ sperm motility and also positively affected their conceiving capacity, without changes in cervical mucus structural and biochemical characteristics. Indeed, by means of the postcoital test on female cervical mucus, a significant improvement especially in progressive sperm motility was recorded after MI suppository use. Concomitantly, after MI treatment, a reduction of immotile spermatozoa percentage was observed. Importantly, MI vaginal supplementation positively correlated with a pregnancy for 5 of the 50 couples enrolled in the study, leading us to speculate that this substance may substantially contribute to create in the cervical mucus an ideal milieu that makes spermatozoa more motile and functionally able to fertilize. Even though the detailed mechanism is still unclear, these results should encourage MI vaginal use for the clinical improvement of male infertility, through their partners. Mario Montanino Oliva, Roberta Poverini, Rosella Lisi, Maria Cristina Carra, and Franco Lisi Copyright © 2016 Mario Montanino Oliva et al. All rights reserved. Alteration of Thyroid-Related Hormones within Normal Ranges and Early Functional Outcomes in Patients with Acute Ischemic Stroke Wed, 08 Jun 2016 05:50:47 +0000 This study evaluated the prognostic value of thyroid-related hormones within normal ranges after acute ischemic stroke. This was a retrospective study and we reviewed 1072 ischemic stroke patients consecutively admitted within 72 h after symptom onset. Total triiodothyronine (T3), total thyroxine (T4), free T3, free T4, and thyroid-stimulating hormone (TSH) were assessed to determine their values for predicting functional outcome at the first follow-up clinic visits, which usually occurred 2 to 4 weeks after discharge from the hospital. 722 patients were finally included. On univariate analysis, poor functional outcome was associated with presence of atrial fibrillation as the index event. Furthermore, score of National Institutes of Health Stroke Scale (NIHSS), total T4, free T4, and C-reactive protein at admission were significantly higher in patients with poor functional outcome, whereas free T3 and total T3 were significantly lower. On multiple logistic regression analysis, lower total T3 concentrations remained independently associated with poor functional outcome [odds ratio (OR), 0.10; 95% confidence interval (CI), 0.01–0.84; ]. The only other variables independently associated with poor functional outcome were NIHSS scores. In sum, lower total T3 concentrations that were within the normal ranges were independently associated with poor short-term outcomes. Xiao-yan Xu, Wen-yu Li, and Xing-yue Hu Copyright © 2016 Xiao-yan Xu et al. All rights reserved. Association of Renal Resistive Index, Renal Pulsatility Index, Systemic Hypertension, and Albuminuria with Survival in Dogs with Pituitary-Dependent Hyperadrenocorticism Tue, 31 May 2016 13:40:39 +0000 An increased renal resistive index (RI) and albuminuria are markers of target organ damage secondary to systemic hypertension. This study evaluated associations between systemic blood pressure (SBP), renal RI, pulsatility index (PI), and albuminuria in dogs with pituitary-dependent hyperadrenocorticism (PDH). Predictors of overall mortality were investigated. Twenty client-owned dogs with PDH and 20 clinically healthy client-owned dogs as matched controls were included. Incidence rates of systemic hypertension (SBP ≥ 160 mmHg), albuminuria, and increased renal RI (≥ 0.70) and PI (≥ 1.45) in the control group were 5%, 0%, 5%, and 0%, respectively, compared to 35%, 40%, 50%, and 35%, respectively, in the PDH group (, , , and , resp.). No association between systemic hypertension, renal RI, renal PI, and albuminuria was observed. PDH was the only predictor of albuminuria and increased renal RI. Survival was not affected by increased renal PI, systemic hypertension, or albuminuria. Increased renal RI (≥ 0.70) was the only predictor of overall mortality in dogs with PDH. Hung-Yin Chen, Yu-Hsin Lien, and Hui-Pi Huang Copyright © 2016 Hung-Yin Chen et al. All rights reserved. Thyroid Hormone Profile in Patients Ingesting Soft Gel Capsule or Liquid Levothyroxine Formulations with Breakfast Mon, 30 May 2016 14:07:38 +0000 Background. Recently, it has been shown that liquid L-T4 formulation can be ingested with breakfast. This study looked to extend these findings by investigating whether a soft gel capsule formulation of L-T4 could also be ingested at breakfast time. Methods. 60 patients (18–65 yrs), previously submitted to thyroidectomy for proven benign goitre in stable euthyroidism receiving liquid L-T4 therapy ingested with breakfast, were enrolled. TSH, fT4, and fT3 levels were assessed in all the patients who were switched from liquid L-T4 to a soft gel capsule formulation at the same dosage of L-T4. After 6 months, TSH, fT4, and fT3 levels were determined again. Results. There were no differences in TSH levels, but fT3 and fT4 levels during treatment with the soft gel capsule were significantly lower than those at enrolment with the liquid L-T4 formulation (TSH median (min–max): 1.9 (0.5–4.0) versus 2.2 (0.5–4.5) mIU/L, fT3: 2.5 (2.4–3.1) versus 2.7 (2.4–3.3) pg/mL, , and fT4: 9.9 (8.0–13) versus 10.6 (8.6–13.8) pg/mL, ). Conclusion. Both liquid and soft gel formulations of L-T4 can be taken with breakfast. However, liquid L-T4 would be the preferred formulation for patients in whom even small changes in fT4 and fT3 levels are to be avoided. Carlo Cappelli, Ilenia Pirola, Elena Gandossi, Alessandra Cristiano, Linda Daffini, Barbara Agosti, Claudio Casella, and Maurizio Castellano Copyright © 2016 Carlo Cappelli et al. All rights reserved. Circulating CTRP1 Levels in Type 2 Diabetes and Their Association with FGF21 Mon, 23 May 2016 09:28:52 +0000 The goal of this study was to investigate whether circulating C1q/TNF-α-related protein 1 (CTRP1) levels are associated with diabetes. In addition, relationships between CTRP1 and other diabetes-related cytokines were elucidated, including adiponectin and fibroblast growth factor 21 (FGF21). A total of 178 subjects (78 men and 100 women) aged 29–70 years (mean age, 46.1 years) were randomly selected. The sera from a normal glucose tolerance group () and a prediabetes/type 2 diabetes group () were collected; then, circulating levels of CTRP1, adiponectin, and FGF21 were determined via enzyme-linked immunosorbent assay in all sera. Subjects with either prediabetes or diabetes exhibited higher circulating CTRP1 levels than healthy subjects. Sera analysis revealed that CTRP1 was positively correlated with age, body mass index, fasting blood glucose, and circulating FGF21 levels. However, CTRP1 was negatively correlated with total cholesterol and total circulating adiponectin levels in univariate analysis. In addition, multivariate analysis found that CTRP1 was independently associated with age, fasting blood glucose, and circulating FGF21 levels. CTRP1 was correlated with homeostasis model assessment-β (HOMA-β), but no correlation was observed with HOMA-insulin resistance. In conclusion, circulating CTRP1 levels are increased in subjects with type 2 diabetes and are positively associated with circulating FGF21 levels. Sora Han, Jong Dai Kim, Sunyi Lee, Ae Lee Jeong, Jeong Su Park, Hyo Jeong Yong, Ariundavaa Boldbaatar, Hye In Ka, Eun-Jung Rhee, Won-Young Lee, and Young Yang Copyright © 2016 Sora Han et al. All rights reserved. Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature Sun, 22 May 2016 11:07:53 +0000 The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1–3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined. F. J. Valenzuela, J. Vera, C. Venegas, S. Muñoz, S. Oyarce, K. Muñoz, and C. Lagunas Copyright © 2016 F. J. Valenzuela et al. All rights reserved. Thyroid Hormones, Autoantibodies, Ultrasonography, and Clinical Parameters for Predicting Thyroid Cancer Sun, 22 May 2016 10:02:58 +0000 Our objective was to evaluate thyroid nodule malignancy prediction using thyroid function tests, autoantibodies, ultrasonographic imaging, and clinical data. We conducted a retrospective cohort study in 1400 patients with nodular thyroid disease (NTD). The thyroid stimulating hormone (TSH) concentration was significantly higher in patients with differentiated thyroid cancer (DTC) versus benign thyroid nodular disease (BTND) (). The receiver operating characteristic curve of TSH showed an AUC of 0.58 (95% CI 0.53–0.62, ), sensitivity of 74%, and specificity of 57% at a cut-off of 1.59 mIU/L. There was an incremental increase in TSH concentration along with the increasing tumor size (). Thyroglobulin antibody (TgAb) concentration was associated with an increased risk of malignancy (), but this association was lost when the effect of TSH was taken into account (). Thyroid ultrasonographic characteristics, including fewer than three nodules, hypoechoic appearance, solid component, poorly defined margin, intranodular or peripheral-intranodular flow, and punctate calcification, can be used to predict the risk of thyroid cancer. In conclusion, our study suggests that preoperative serum TSH concentration, age, and ultrasonographic features can be used to predict the risk of malignancy in patients with NTD. Lin-zheng He, Tian-shu Zeng, Lin Pu, Shi-xiu Pan, Wen-fang Xia, and Lu-lu Chen Copyright © 2016 Lin-zheng He et al. All rights reserved. Regulation of Lipid Metabolism and Beyond Thu, 12 May 2016 17:24:57 +0000 Youngah Jo, Hiroaki Okazaki, Young-Ah Moon, and TongJin Zhao Copyright © 2016 Youngah Jo et al. All rights reserved. Interaction between Angiotensin II and Insulin/IGF-1 Exerted a Synergistic Stimulatory Effect on ERK1/2 Activation in Adrenocortical Carcinoma H295R Cells Thu, 12 May 2016 10:48:15 +0000 The cross talk between angiotensin II (Ang II) and insulin has been described mainly in cardiovascular cells, hepatocytes, adipocytes, and so forth, and to date no such cross talk was reported in adrenal. In this study, we examined the interaction between Ang II and insulin/IGF-1 in ERK and AKT signaling pathways and expression of steroidogenic enzymes in H295R cells. Compared to the control, 100 nM Ang II increased phospho-ERK1/2 approximately 3-fold. Insulin (100 nM) or IGF-1 (10 nM) alone raised phospho-ERK1/2 1.8- and 1.5-fold, respectively, while, after pretreatment with 100 nM Ang II for 30 min, insulin (100 nM) or IGF-1 (10 nM) elevated phospho-ERK1/2 level 8- and 7-fold, respectively. The synergistic effect of Ang II and insulin/IGF-1 on ERK1/2 activation was inhibited by selective AT1 receptor blocker, PKC inhibitor, and MEK1/2 inhibitor. Ang II marginally suppressed AKT activation under the basal condition, while it had no effect on phospho-AKT induced by insulin/IGF-1. Ang II significantly stimulated mRNA expression of CYP11B1 and CYP11B2, and such stimulatory effects were enhanced when cells were cotreated with insulin/IGF-1. We are led to conclude that Ang II in combination with insulin/IGF-1 had an evident synergistic stimulatory effect on ERK1/2 activation in H295R cells and the effect may be responsible for the enhanced steroid hormone production induced by Ang II plus insulin/IGF-1. An-li Tong, Fen Wang, Yun-ying Cui, Chun-yan Li, and Yu-xiu Li Copyright © 2016 An-li Tong et al. All rights reserved. The Effect of Levothyroxine Discontinuation Timing on Postoperative Hypothyroidism after Hemithyroidectomy for Papillary Thyroid Microcarcinoma Wed, 11 May 2016 11:31:08 +0000 Objective. No previous studies regarding the appropriate timing of thyroid hormone discontinuation after hemithyroidectomy have been published. This study aimed to identify the appropriate timing for levothyroxine discontinuation after hemithyroidectomy among patients with papillary thyroid microcarcinoma (PTMC). Methods. This study retrospectively evaluated 304 patients who underwent ≥1 attempt to discontinue levothyroxine after hemithyroidectomy for treating PTMC between January 2008 and December 2013. Fifty-three patients were excluded because of preoperative hypothyroidism or hyperthyroidism, a history of thyroid hormone or antithyroid therapy, no available serological data, or a postoperative follow-up of <24 months. We evaluated the associations of successful levothyroxine discontinuation with patient age, sex, preoperative serological data, underlying thyroid gland histopathology, anteroposterior diameter of the residual thyroid gland, number of discontinuation attempts, and initial discontinuation timing. Results. Among the 251 included patients, 125 patients (49.8%) achieved successful levothyroxine discontinuation during the follow-up period after hemithyroidectomy. There was a significant difference in the outcomes for patients who underwent an initial discontinuation attempt at ≤3 months and ≥4 months after hemithyroidectomy (p < 0.001). There were significant differences in the discontinuation outcomes according to underlying thyroid histopathology (p = 0.001), preoperative thyroid-stimulating hormone levels (p < 0.001), and number of discontinuation attempts (p < 0.001). Conclusions. Among patients with PTMC, the initial levothyroxine discontinuation attempt is recommended at ≥4 months after hemithyroidectomy. Tae Kwun Ha, Dong Wook Kim, Ha Kyoung Park, Jin Wook Baek, Yoo Jin Lee, Young Mi Park, Do Hun Kim, Soo Jin Jung, and Ki Jung Ahn Copyright © 2016 Tae Kwun Ha et al. All rights reserved. Human Papilloma Virus Infection in Patients with Male Accessory Gland Infection: Usefulness of the Ultrasound Evaluation Tue, 03 May 2016 15:21:15 +0000 This study evaluated the ultrasound (US) features of 20 patients with MAGI and concomitant papilloma virus (HPV) infection compared to 20 patients with microbial (presence of Chlamydia trachomatis alone) MAGI and 20 patients with amicrobial (inflammatory) MAGI. Patients with HPV infection showed significantly () higher total prostate, seminal vesicles, and epididymal US signs (18.0 ± 2.0) compared to the other 2 groups (12.0 ± 4.0 versus 10.0 ± 3.0, resp.). In addition, patients with MAGI and HPV had a higher prevalence of complicated forms of MAGI [prostatovesiculitis (PV) and prostate-vesiculo-epididymitis (PVE)] and a higher frequency of the fibrosclerotic variant compared to the other groups (70.0 ± 10.0% versus 48.0 ± 5.0% versus 15.0 ± 10.0%). Moreover, HPV infected patients had a higher number of US criteria suggestive for MAGI in the periurethral region of the prostate compared to the other groups. In particular, the patients showed a higher ratio between periurethral and lobar US criteria distribution (5.0 versus 0.5). Finally, the seminal fluid concentration of leukocytes (2.0 ± 0.2 versus 1.3 ± 0.3 versus 1.0 ± 0.3 mil/mL) was significantly higher and sperm progressive motility was significantly lower in these patients compared to other groups. Rosita A. Condorelli, Enzo Vicari, Laura M. Mongioi, Giorgio I. Russo, Giuseppe Morgia, Sandro La Vignera, and Aldo E. Calogero Copyright © 2016 Rosita A. Condorelli et al. All rights reserved. Lipid Profile in Adolescent Girls with Type 1 Diabetes Mellitus and Hyperandrogenemia Wed, 27 Apr 2016 13:08:48 +0000 Study Objectives. The study aim was to evaluate whether hyperandrogenemia in adolescent girls with type 1 diabetes mellitus (T1DM) may adversely influence lipid profile. Design and Participants. Lipid levels in 16 diabetic girls with biochemical hyperandrogenemia (T1DM-H) aged 16.3 ± 1.2 years were compared to 38 diabetic girls with normal androgen levels (T1DM-N) aged 15.8 ± 1.2 years. 15 healthy girls served as controls (CG). In all patients, anthropometric measurements were done, and androgens and SHBG were assessed. Results. In T1DM-H, total cholesterol (TC) and low density cholesterol (LDL-ch) were significantly higher than in CG (196.1 ± 41.2 versus 162.7 ± 31.7 mg/dL, ; 117.3 ± 33.1 versus 91.3 ± 27.8 mg/dL, , resp.). Their LDL-ch, non-high density cholesterol (non-HDL-ch) concentrations, and LDL/HDL ratio were also significantly higher than in T1DM-N (117.3 ± 33.1 versus 97.7 ± 26.7 mg/dL, ; 137.3 ± 42.9 versus 113.3 ± 40.4 mg/dL, ; 2.8 ± 3.7 versus 1.6 ± 0.5, , resp.). In stepwise multiple linear regression, free androgen index (FAI) and waist-to-hip ratio (WHR) were associated with TC (, ), non-HDL-ch (, ), and LDL-ch (, ). Triglycerides and LDL/HDL ratio were (, , , resp.) related to testosterone, FAI, WHR, and mean HbA1c. Conclusion. Lipid profile in diabetic adolescent girls is adversely influenced by the androgens level, particularly in the group with higher WHR and poorer glycemic control. Agnieszka Zachurzok, Grazyna Deja, Aneta Gawlik, Agnieszka Drosdzol-Cop, Katarzyna Klimek, and Ewa Malecka-Tendera Copyright © 2016 Agnieszka Zachurzok et al. All rights reserved. Adipokines and Insulin Resistance in Young Adult Survivors of Childhood Cancer Sun, 24 Apr 2016 15:35:50 +0000 We examined the association between adipokines (leptin, adiponectin, and resistin), radiotherapy, measurement of body fat, and insulin resistance among young adult survivors of childhood cancer (CCS). Materials and Methods. Seventy-six survivors were included (mean age years). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA-IR). The serum levels of adipokines were assayed by immunoassays. Fat mass was evaluated by DXA. Results. Mean adiponectin level and mean body FAT were higher in the examined females than in males ( ng/mL versus  ng/mL, ; % versus %, ). Among CCS, one of 75 patients met the criteria of insulin resistance, and in 14 patients there was impaired fasting glucose. The multiple regression model for females showed that leptin/adiponectin ratio (LA ratio) significantly affected HOMA-IR (increase of 0.024 per each unit of LA ratio; ). Radiotherapy had no effect on serum adipokines and IR. Conclusion. The observed results support the hypothesis that adiponectin might be associated with insulin resistance and it can not be ruled out that changes in the mean level of adiponectin per FAT mass or leptin/adiponectin ratio may precede the occurrence of insulin resistance in the future. Eryk Latoch, Katarzyna Muszynska-Roslan, Agata Panas, Anna Panasiuk, Malgorzata Sawicka-Zukowska, Beata Zelazowska-Rutkowska, Ewa Zabrocka, and Maryna Krawczuk-Rybak Copyright © 2016 Eryk Latoch et al. All rights reserved. The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats Sun, 24 Apr 2016 13:53:21 +0000 Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats. Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation. Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated. Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney. Li Peng, Jie Li, Yixing Xu, Yangtian Wang, Hong Du, Jiaqing Shao, and Zhimin Liu Copyright © 2016 Li Peng et al. All rights reserved. 11β-Hydroxysteroid Dehydrogenase 2 in Preeclampsia Thu, 21 Apr 2016 12:38:05 +0000 Preeclampsia is a serious medical problem affecting the mother and her child and influences their health not only during the pregnancy, but also many years after. Although preeclampsia is a subject of many research projects, the etiology of the condition remains unclear. One of the hypotheses related to the etiology of preeclampsia is the deficiency in placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), the enzyme which in normal pregnancy protects the fetus from the excess of maternal cortisol. The reduced activity of the enzyme was observed in placentas from pregnancies complicated with preeclampsia. That suggests the overexposure of the developing child to maternal cortisol, which in high levels exerts proapoptotic effects and reduces fetal growth. The fetal growth restriction due to the diminished placental 11β-HSD2 function may be supported by the fact that preeclampsia is often accompanied with fetal hypotrophy. The causes of the reduced function of 11β-HSD2 in placental tissue are still discussed. This paper summarizes the phenomena that may affect the activity of the enzyme at various steps on the way from the gene to the protein. Katarzyna Kosicka, Anna Siemiątkowska, and Franciszek K. Główka Copyright © 2016 Katarzyna Kosicka et al. All rights reserved. FGF21 Is Associated with Acanthosis Nigricans in Obese Patients Wed, 13 Apr 2016 13:54:46 +0000 Objective. We aimed to investigate the relationship between FGF21 and obesity-related acanthosis nigricans (AN). Methods. 40 obese patients without AN (OB group), 40 obese patients with AN (AN group), and 40 healthy volunteers (control group, CON) were included in this study. Weight, BMI, lipid profile, FFA, UA, and CRP were measured in all participants. Oral glucose tolerance tests (OGTT) were performed and serum glucose and plasma insulin were measured. Serum FGF21 was measured by ELISA. Results. Compared with OB group, AN group had higher levels of fasting insulin and homeostasis model of assessment for insulin resistance (HOMA-IR) (), but lower serum levels of blood glucose. The difference of FGF21 among three groups was significant and AN group showed the highest serum level of FGF21 (). Serum FGF21 was most positively correlated with fasting insulin and HOMA-IR. Multiple logistic analysis showed that FGF21 was the independent risk factor for AN (OR 4.550; 95% CI 1.054–19.635; ). Conclusion. AN patients had more serious hyperinsulinemia but better serum levels of blood glucose than OB. Increased FGF21 is associated with AN in obese patients and may be considered as compensatory response to the decreased insulin sensitivity. Yueye Huang, Jie Yang, Yan Li, Jiaqi Chen, Kexiu Song, Xingchun Wang, Le Bu, Xiaoyun Cheng, Jiying Wang, and Shen Qu Copyright © 2016 Yueye Huang et al. All rights reserved. Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese Wed, 13 Apr 2016 12:04:05 +0000 Objective. We aim to investigate the long-term benefits of growth hormone (GH) therapy in short stature adolescents and adults with pituitary stalk interruption syndrome (PSIS), which would be beneficial for future clinical applications. Design and Methods. In this study, initial height, final height, total height gain, and GH treatment history were retrospectively investigated in 75 Chinese PSIS patients. We compared height gain between the GH treated cohort and untreated cohort and explored the impact of different GH therapy duration on height gain. Results. For GH treated patients, their final height (SDS) increased from (−6.93~2.80) at bone age (BA) of 11.2 (5.0~17.0) years to (−7.82~1.05) at BA of 16.6 (8.0~18.0) years (). And GH treated patients had more height gain than the untreated patients (). There was a significant difference between the different GH therapy duration groups (): GH 0 versus GH 3, ; GH 1 versus GH 3, ; GH 2 versus GH 3, . Conclusion. Adult Chinese PSIS patients with short stature benefited the most from at least 12 months of GH therapy. Although patient diagnosis age was lagged behind in the developing countries, GH treatment was still effective for them and resulted in a higher final height and more height gain. Cheng-Zhi Wang, Ling-Ling Guo, Bai-Yu Han, An-Ping Wang, Hong-Yan Liu, Xing Su, Qing-Hua Guo, and Yi-Ming Mu Copyright © 2016 Cheng-Zhi Wang et al. All rights reserved. Ghrelin Protects against Dexamethasone-Induced INS-1 Cell Apoptosis via ERK and p38MAPK Signaling Tue, 12 Apr 2016 11:52:05 +0000 Glucocorticoid excess induces apoptosis of islet cells, which may result in diabetes. In this study, we investigated the protective effect of ghrelin on dexamethasone-induced INS-1 cell apoptosis. Our data showed that ghrelin (0.1 μM) inhibited dexamethasone-induced (0.1 μM) apoptosis of INS-1 cells and facilitated cell proliferation. Moreover, ghrelin upregulated Bcl-2 expression, downregulated Bax expression, and decreased caspase-3 activity. The protective effect of ghrelin against dexamethasone-induced INS-1 cell apoptosis was mediated via growth hormone secretagogue receptor 1a. Further studies revealed that ghrelin increased ERK activation and decreased p38MAPK expression after dexamethasone treatment. Ghrelin-mediated protection of dexamethasone-induced apoptosis of INS-1 cells was attenuated using the ERK inhibitor U0126 (10 μM), and cell viability increased using the p38MAPK inhibitor SB203580 (10 μM). In conclusion, ghrelin could protect against dexamethasone-induced INS-1 cell apoptosis, at least partially via GHS-R1a and the signaling pathway of ERK and p38MAPK. Chengshuo Zhang, Le Li, Bochao Zhao, Ao Jiao, Xin Li, Ning Sun, and Jialin Zhang Copyright © 2016 Chengshuo Zhang et al. All rights reserved. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells Tue, 12 Apr 2016 11:25:47 +0000 Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif. Maëlle Lempereur, Claire Majewska, Amandine Brunquers, Sumalee Wongpramud, Bénédicte Valet, Philippe Janssens, Monique Dillemans, Laurence Van Nedervelde, and Dominique Gallo Copyright © 2016 Maëlle Lempereur et al. All rights reserved. Maternal and Fetal Lipid and Adipokine Profiles and Their Association with Obesity Tue, 12 Apr 2016 11:16:44 +0000 Background. Maternal metabolic changes impact fetal metabolism resulting in a higher risk for developing chronic diseases later in life. The aim of this study was to assess the association between maternal and fetal adipokine and lipid profiles, as well as the influence of maternal weight on this association. Methods. Healthy pregnant women at term who delivered by C-section were enrolled. Maternal and fetal glucose, lipid profile, adiponectin, leptin, and resistin levels were analyzed by obesity and maternal weight gain. Statistics included descriptives, correlations, and mean differences (SPSS v20.0). Results. Adiponectin and resistin concentrations were higher in fetal blood, while leptin was lower (). A significant inverse association between maternal resistin and fetal LDL-cholesterol (LDL-C) (; ) was observed. A positive correlation was found between maternal and fetal resistin (; ). Women with excessive weight gain had higher leptin levels and their fetuses showed higher LDL-C levels (). Conclusions. Maternal resistin showed an inverse association with fetal LDL-C, suggesting that maternal adiposity status may play an active role in the regulation of fetal lipid profile and consequently, in fetal programming. Excessive maternal weight gain during pregnancy may exert an effect over metabolic mediators in both mother and newborn. Mario Solis-Paredes, Salvador Espino y Sosa, Guadalupe Estrada-Gutierrez, Sonia Nava-Salazar, Veronica Ortega-Castillo, Mario Rodriguez-Bosch, Eyerahi Bravo-Flores, Aurora Espejel-Nuñez, Maricruz Tolentino-Dolores, Rubí Gaona-Estudillo, Nancy Martinez-Bautista, and Otilia Perichart-Perera Copyright © 2016 Mario Solis-Paredes et al. All rights reserved. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats Thu, 07 Apr 2016 14:05:29 +0000 It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (). The mean fasting blood glucose was 126.25 ± 23.4 mg/dL in hypothyroidism-induced group and 102.63 ± 15.51 mg/dL in the control group, with a statistically significant difference between the groups (). The two groups did not differ statistically significantly with respect to visfatin levels (). In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD. Şule Demir, Mustafa Ünübol, Serap Ünübol Aypak, Emrah İpek, Serdar Aktaş, Gamze Sevri Ekren, Murat Yılmaz, Recai Tunca, and Engin Güney Copyright © 2016 Şule Demir et al. All rights reserved.