International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of the Most Aggressive Thyroid Cancer Thu, 21 Aug 2014 06:54:26 +0000 Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer. It shows a wide spectrum of morphological presentations and the diagnosis could be challenging due to its high degree of dedifferentiation. Molecular and genetic features of ATC are widely heterogeneous as well and many efforts have been made to find a common profile in order to clarify its cancerogenetic process. A comprehensive review of the current literature is here performed, focusing on histopathological and genetic features. Moira Ragazzi, Alessia Ciarrocchi, Valentina Sancisi, Greta Gandolfi, Alessandra Bisagni, and Simonetta Piana Copyright © 2014 Moira Ragazzi et al. All rights reserved. Serum Thyrotropin Is Positively Correlated with the Metabolic Syndrome Components of Obesity and Dyslipidemia in Chinese Adolescents Thu, 21 Aug 2014 06:54:12 +0000 Metabolic syndrome is a medical disorder characterized by obesity, hyperglycemia, dyslipidemia, and hypertension. Thyroid hormone has been shown to affect many metabolic processes. This study was undertaken to explore the relationship between serum thyrotropin and components of metabolic syndrome in Chinese adolescents. Waist circumference (76.4 ± 10.7 versus 70.0 ± 10.6 cm, = 0.006) and body mass index (23.90 ± 4.20 versus 21.51 ± 4.16 kg/m2, = 0.011) were significantly greater among adolescents with subclinical hypothyroidism compared with euthyroid subjects. The risk of obesity in the subclinical hypothyroid group was 3.444 times that in the euthyroid group (odds ratio = 3.444, 95% confidence interval (CI): 1.570–7.553). Serum TSH was significantly positively correlated with waist circumference (β = 1.512, = 0.019), TC (β = 0.160, = 0.003), LDL-C (β = 0.032, = 0.008), and TG (β = 0.095, = 0.001). The TSH level in the metabolic syndrome group was significantly higher than that in nonmetabolic syndrome group (2.65 [2.28–3.80] versus 2.53 [1.92–3.45] mIU/L, = 0.032). Serum TSH within the reference range was positively associated with TC (β = 0.173, = 0.013), LDL-C (β = 0.031, = 0.043), and TG (β = 0.132, = 0.021). Increased serum TSH in adolescents may be a potential risk factor for metabolic syndrome. Jingfan Zhang, Ranhua Jiang, Ling Li, Ping Li, Xue Li, Zinan Wang, Liang Li, and Weiping Teng Copyright © 2014 Jingfan Zhang et al. All rights reserved. Clinical Characteristics Related to Central Lymph Node Metastasis in cN0 Papillary Thyroid Carcinoma: A Retrospective Study of 916 Patients Thu, 21 Aug 2014 00:00:00 +0000 Background. Papillary thyroid carcinoma (PTC) is a form of thyroid cancer with high risk of cervical lymph node metastasis. Aim. The aim of this study was to investigate the incidence and the predictive factors for occult ipsilateral central lymph node (CLN) metastasis in the patients with papillary thyroid carcinoma. Methods. A total of 916 PTC patients (1017 lesions) undergoing central lymph node dissection in our hospital from 2005 to 2011 were enrolled. The relationship between CLN metastasis and clinical factors such as gender, age, tumor size, tumor number, capsule invasion, and tumor location was analyzed. Results. Occult CLN metastasis was observed in 52.41% (533/1017) of PTC lesions, respectively. Multivariate analysis showed that age ≤ 35 years, tumor size > 1.5 cm, present capsule invasion/extracapsular invasion, and tumor located in upper/middle pole/whole lobe were risk factors of CLN metastasis. Conclusions. Tumor located in upper/middle pole/whole lobe, less than 35 years old, tumor size > 1.5 cm, and present capsule invasion/extracapsular invasion were risk factors of CLN metastasis. We recommend performing ipsilateral prophylactic CLN dissection in cN0 PTC patients. Lie-Hao Jiang, Chao Chen, Zhuo Tan, Xiao-Xiao Lu, Si-Si Hu, Qing-Liang Wang, Xiu-Xiu Hou, Jun Cao, and Ming-Hua Ge Copyright © 2014 Lie-Hao Jiang et al. All rights reserved. The Optimal Approach for Laparoscopic Adrenalectomy through Mono Port regarding Left or Right Sides: A Comparative Study Wed, 20 Aug 2014 12:47:52 +0000 Introduction. Several studies have shown the feasibility and safety of both transperitoneal and posterior retroperitoneal approaches for single incision laparoscopic adrenalectomy, but none have compared the outcomes according to the left- or right-sided location of the adrenal glands. Materials and Methods. From 2009 to 2013, 89 patients who received LAMP (laparoscopic adrenalectomy through mono port) were analyzed. The surgical outcomes attained using the transperitoneal approach (TPA) and posterior retroperitoneal approach (PRA) were analyzed and compared. Results and Discussion. On the right side, no significant differences were found between the LAMP-TPA and LAMP-PRA groups in terms of patient characteristics and clinicopathological data. However, outcomes differed in which LAMP-PRA group had a statistically significant shorter mean operative time (84.13 ± 41.47 min versus 116.84 ± 33.17 min; ), time of first oral intake (1.00 ± 0.00 days versus 1.21 ± 0.42 days; ), and length of hospitalization (2.17 ± 0.389 days versus 3.68 ± 1.38 days; ), whereas in left-sided adrenalectomies LAMP-TPA had a statistically significant shorter mean operative time (83.85 ± 27.72 min versus 110.95 ± 29.31 min; ). Conclusions. We report that LAMP-PRA is more appropriate for right-sided laparoscopic adrenalectomies due to anatomical characteristics and better surgical outcomes. For left-sided laparoscopic adrenalectomies, however, we propose LAMP-TPA as a more suitable method. Wooseok Byon, Keehoon Hyun, Ji-Sup Yun, Yong Lai Park, and Chan Heun Park Copyright © 2014 Wooseok Byon et al. All rights reserved. Albuminuria Is Associated with Left Ventricular Hypertrophy in Patients with Early Diabetic Kidney Disease Wed, 20 Aug 2014 11:44:52 +0000 Aims. Left ventricular hypertrophy (LVH) and albuminuria are both markers for cardiovascular diseases (CVDs) in patients with type 2 diabetes mellitus (T2DM). We speculate that albuminuria in T2DM patients with early diabetic kidney disease (DKD) could predict LVH. Methods. 333 diabetic patients (219 non-DKD and 114 early DKD) were enrolled. The association between albuminuria and LVMI was examined using multivariate linear regression and logistic regression. Results. The rate of LVH was significantly higher in patients with early DKD versus those without DKD (57.0% versus 32.9%; ). Multivariate linear regression analysis demonstrated that albuminuria status (no, micro-, and macroalbuminuria; ), age (), systolic blood pressure (), and the use of ACEI/ARB drug () were independently associated with LVMI. The risks were substantially higher for LVH in the microalbuminuria group (odds ratio 2.473 (95% confidence interval 1.370–4.464)) and macroalbuminuria group (odds ratio 3.940 (95% confidence interval 1.553–9.993)) compared with that in non-DKD group. Concentric hypertrophy was the most common geometric pattern in patients with early DKD (36.0%), followed by eccentric hypertrophy (21.0%). Conclusions. Albuminuria is associated with higher LVMI and higher rate of LVH in patients with early phase DKD. Nan Wu, Weiwei Zhao, Kuanping Ye, Yintao Li, Min He, Bin Lu, and Renming Hu Copyright © 2014 Nan Wu et al. All rights reserved. Polymorphism of the FTO Gene Influences Body Weight in Children with Type 1 Diabetes without Severe Obesity Tue, 19 Aug 2014 12:06:41 +0000 The objective was to compare the impact of clinical and genetic factors on body mass index (BMI) in children with type 1 diabetes (T1DM) without severe obesity. A total of 1,119 children with T1DM (aged 4–18 years) were qualified to take part in the study. All children were genotyped for variants of FTO, MC4R, INSIG2, FASN, NPC1, PTER, SIRT1, MAF, IRT1, and CD36. Results. Variants of FTO showed significant association with BMI-SDS in the T1DM group. The main factors influencing BMI-SDS in children with T1DM included female gender (), poor metabolic control (), and carriage of the A allele of the FTO rs9939609 gene (). Conclusion. Our research indicates, when assessing, the risk of overweight and obesity carriage of the A allele in the rs9939609 site of the FTO gene adds to that of female gender and poor metabolic control. This trial is registered with (NCT01279161). Włodzimierz Łuczyński, Wojciech Fendler, Anna Ramatowska, Agnieszka Szypowska, Agnieszka Szadkowska, Wojciech Młynarski, Miron Chumiecki, Przemysława Jarosz-Chobot, Joanna Chrzanowska, Anna Noczyńska, Agnieszka Brandt, Małgorzata Myśliwiec, Barbara Głowińska-Olszewska, Paweł Bernatowicz, Oksana Kowalczuk, and Artur Bossowski Copyright © 2014 Włodzimierz Łuczyński et al. All rights reserved. Obesity as a Risk Factor for Tendinopathy: A Systematic Review Tue, 19 Aug 2014 07:31:19 +0000 Purpose. In the last few years, evidence has emerged to support the possible association between increased BMI and susceptibility to some musculoskeletal diseases. We systematically review the literature to clarify whether obesity is a risk factor for the onset of tendinopathy. Methods. We searched PubMed, Cochrane Central, and Embase Biomedical databases using the keywords “obesity,” “overweight,” and “body mass index” linked in different combinations with the terms “tendinopathy,” “tendinitis,” “tendinosis,” “rotator cuff,” “epicondylitis,” “wrist,” “patellar,” “quadriceps,” “Achilles,” “Plantar Fascia,” and “tendon.” Results. Fifteen studies were included. No level I study on this subject was available, and the results provided are ambiguous. However, all the 5 level II studies report the association between obesity measured in terms of BMI and tendon conditions, with OR ranging between 1.9 (95% CI: 1.1–2.2) and 5.6 (1.9–16.6). Conclusions. The best evidence available to date indicates that obesity is a risk factor for tendinopathy. Nevertheless, further studies should be performed to establish the real strength of the association for each type of tendinopathy, especially because the design of the published studies does not allow identifying a precise cause-effect relationship and the specific role of obesity independently of other metabolic conditions. Francesco Franceschi, Rocco Papalia, Michele Paciotti, Edoardo Franceschetti, Alberto Di Martino, Nicola Maffulli, and Vincenzo Denaro Copyright © 2014 Francesco Franceschi et al. All rights reserved. MicroRNA Deregulation in Anaplastic Thyroid Cancer Biology Tue, 19 Aug 2014 00:00:00 +0000 Anaplastic thyroid cancer (ATC) is among the most lethal types of cancers, characterized as a fast-growing and highly invasive thyroid tumor that is unresponsive to surgery and radioiodine, blunting therapeutic efficacy. Classically, genetic alterations in tumor suppressor TP53 are frequent, and cumulative alterations in different signaling pathways, such as MAPK and PI3K, are detected in ATC. Recently, deregulation in microRNAs (miRNAs), a class of small endogenous RNAs that regulate protein expression, has been implicated in tumorigenesis and cancer progression. Deregulation of miRNA expression is detected in thyroid cancer. Upregulation of miRNAs, such as miR-146b, miR-221, and miR-222, is observed in ATC and also in differentiated thyroid cancer (papillary and follicular), indicating that these miRNAs’ overexpression is essential in maintaining tumorigenesis. However, specific miRNAs are downregulated in ATC, such as those of the miR-200 and miR-30 families, which are important negative regulators of cell migration, invasion, and epithelial-to-mesenchymal transition (EMT), processes that are overactivated in ATC. Therefore, molecular interference to restore the expression of tumor suppressor miRNAs, or to blunt overexpressed oncogenic miRNAs, is a promising therapeutic approach to ameliorate the treatment of ATC. In this review, we will explore the importance of miRNA deregulation for ATC cell biology. Cesar Seigi Fuziwara and Edna Teruko Kimura Copyright © 2014 Cesar Seigi Fuziwara and Edna Teruko Kimura. All rights reserved. Glycemic Control Outcomes by Gender in the Pay-for-Performance System: A Retrospective Database Analysis in Patients with Type 2 Diabetes Mellitus Mon, 18 Aug 2014 08:32:49 +0000 Background. The purpose of this study was to investigate how the degree of glycemic control in patients with type 2 diabetes associated with lifestyle interventions as well as sociodemographic factors and further examine the differences by gender. Methods. This was a retrospective study using data collected from a diabetes quality improvement plan that began in 2002 in a medical center in Taiwan. Statistic analysis was used to determine the associations of sociodemographic data, lifestyle intervention, and treatment regimens with changes in HbA1c levels (between the initial visit and the latest follow-up measured level), and the differences were then sorted by the sex of the patients. Results. Our results showed that HbA1c averaged 7.50% for males and 7.80% for females at the initial visit, compared to levels averaging 7.50% for males and 7.70% for females at the most recent follow-up visit. There was no significant change () in HbA1c in males, but there was a 0.10% () reduction in females. The duration of the diabetes and medication regimen was associated with the decrease seen in the females. Conclusions. The results of these analyses provide important insights for policy makers to formulate healthcare policies related to chronic diseases or illnesses. Shao-Ping Yuan, Chien-Ning Huang, Hung-Chang Liao, Yu-Tzu Lin, and Ya-huei Wang Copyright © 2014 Shao-Ping Yuan et al. All rights reserved. Effects of Recombinant Human Thyrotropin Administration on 24-Hour Arterial Pressure in Female Undergoing Evaluation for Differentiated Thyroid Cancer Mon, 18 Aug 2014 06:57:52 +0000 Objective. Thyroid-stimulating-hormone (TSH) receptors are expressed in endothelial cells. We investigated whether elevated TSH levels after acute recombinant TSH (rhTSH) administration may result in alterations in blood pressure (BP) in premenopausal women with well-differentiated thyroid carcinoma (DTC). Designs. Thirty euthyroid DTC female patients were evaluated by rhTSH stimulation test (mean age years). A 24 h ambulatory systolic and diastolic blood pressure (SBP, DBP) monitoring (24 hr ABPM) was performed on days 2-3(D2-3). TSH was measured on day 1(D1), day 3(D3), and day 5(D5). Central blood pressure was evaluated on D3. Twenty-three patients were studied 1–4 weeks earlier (basal measurements). Results. TSH levels were D1: median 0.2 mU/L, D3: median 115.0 mU/L, and D5: median 14.6 mU/L. There were no significant associations between TSH on D1 and D3 and any BP measurements. Median D5 office-SBP and 24 h SBP, DBP, and central SBP were correlated with D5-TSH (). In those where a basal 24 h ABPM had been performed median pulse pressure was higher after rhTSH-test (). Conclusions. TSH, when acutely elevated, may slightly increase SBP, DBP, and central SBP. This agrees with previous reports showing positive associations of BP with TSH. Gianna Rentziou, Katerina Saltiki, Efstathios Manios, Kimon Stamatelopoulos, Eleni Koroboki, Anastasia Vemmou, Emily Mantzou, Nikolaos Zakopoulos, and Maria Alevizaki Copyright © 2014 Gianna Rentziou et al. All rights reserved. Relationship between the Prevalence of Thyroid Nodules and Metabolic Syndrome in the Iodine-Adequate Area of Hangzhou, China: A Cross-Sectional and Cohort Study Sun, 17 Aug 2014 11:06:50 +0000 Objective. The association between thyroid nodule (TN) prevalence and metabolic syndrome (MetS) has only rarely been examined in iodine-adequate areas and needs further clarification. We investigated correlations between MetS and TN prevalence in the iodine-adequate area of Hangzhou, China. Material and Method. A cross-sectional study that screened and recruited individuals for cohort research 3 years later. The 13522 subjects (8926 men, 4596 women) were screened in 2009 for all MetS components, thyroid ultrasound (US), and thyroid function. Cohort research recruited 1610 subjects who were screened in both 2009 and 2012, of whom 1061 underwent follow-up research. Results. The prevalence of TN was higher in the MetS (+) group than in the MetS (−) group (χ2 = 69.63, P < 0.001) and higher in women than in men (χ2 = 11.65, P = 0.001). Waist circumference (WC) was positively related to the prevalence of TN (OR = 1.022, P < 0.001). Individuals with greater WC in 2009 were more likely to suffer from TN in 2012 (RR = 1.434, P = 0.024). Elevated triglyceride level was a risk factor for developing new TN (RR = 1.001, P = 0.035). Conclusion. Both greater WC and elevated triglycerides are risk factors for new TN in this iodine-adequate area in China. Junhua Yin, Changchun Wang, Qin Shao, Dihong Qu, Zhenya Song, Pengfei Shan, Tao Zhang, Jun Xu, Qin Liang, Songzhao Zhang, and Jian Huang Copyright © 2014 Junhua Yin et al. All rights reserved. Effectiveness of Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion for Children with Type 1 Diabetes Mellitus in Clinical Practice Thu, 14 Aug 2014 09:48:36 +0000 Aims. To determine whether multiple daily injections (MDIs) or continuous subcutaneous insulin infusion (CSII) contributes to better glucose control in children with different type 1 diabetes duration. Methods. Subjects were grouped according to early (1 year after disease onset; 1A) or late (1–3 years after onset; 2A) MDIs/CSII treatment initiation. Corresponding control groups (1B, 2B) received insulin injections twice daily. Results. HbA1c levels were consistently lower in group 1A than in group 1B (6 months (T2): 7.37% versus 8.21%; 12 months (T3): 7.61% versus 8.41%; 24/36 months (T4/T5): 7.61% versus 8.72%; all ), but were lower in group 2A than in group 2B only at T2 (8.36% versus 9.19%; ). Levels were lower in group 1A than in group 2A when disease duration was matched (7.61% versus 8.49%; ). Logistic regression revealed no correlation between HbA1c level and MDIs/CSII therapy. HbA1c levels were only negatively related to insulin dosage. Conclusions. Blood glucose control was better in patients receiving MDIs/CSII than in those receiving conventional treatment. Early MDIs/CSII initiation resulted in prolonged maintenance of low HbA1c levels compared with late initiation. MDIs/CSII therapy should be combined with comprehensive management. Chun-xiu Gong, Li-ya Wei, Di Wu, Bing-yan Cao, Xi Meng, and Lin-lin Wang Copyright © 2014 Chun-xiu Gong et al. All rights reserved. Rare Mutations of Peroxisome Proliferator-Activated Receptor Gamma: Frequencies and Relationship with Insulin Resistance and Diabetes Risk in the Mixed Ancestry Population from South Africa Thu, 14 Aug 2014 08:21:12 +0000 Background. Genetic variants in the nuclear transcription receptor, PPARG, are associated with cardiometabolic traits, but reports remain conflicting. We determined the frequency and the clinical relevance of PPARG SNPs in an African mixed ancestry population. Methods. In a cross-sectional study, 820 participants were genotyped for rs1800571, rs72551362, rs72551363, rs72551364, and rs3856806, using allele-specific TaqMan technology. The homeostatic model assessment of insulin (HOMA-IR), β-cells function (HOMA-B%), fasting insulin resistance index (FIRI), and the quantitative insulin-sensitivity check index (QUICKI) were calculated. Results. No sequence variants were found except for the rs3856806. The frequency of the PPARG-His447His variant was 23.8% in the overall population group, with no difference by diabetes status (). The His447His allele T was associated with none of the markers of insulin resistance overall and by diabetes status. In models adjusted for 2-hour insulin, the T allele was associated with lower prevalent diabetes risk (odds ratio 0.56 (95% CI 0.31–0.95)). Conclusion. Our study confirms the almost zero occurrences of known rare PPARG SNPs and has shown for the first time in an African population that one of the common SNPs, His447His, may be protective against type 2 diabetes. Z. Vergotine, A. P. Kengne, R. T. Erasmus, Y. Y. Yako, and T. E. Matsha Copyright © 2014 Z. Vergotine et al. All rights reserved. Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice Mon, 11 Aug 2014 08:26:57 +0000 Background. Liraglutide (a glucagon-like peptide 1 analog) was used for the treatment of type 2 diabetes (T2DM) which could produce glucose-dependent insulin secretion. Aim. The aim was to investigate whether liraglutide could improve myofibril and mitochondria injury in skeletal muscle and the mechanisms in diabetic KKAy mice. Method. We divided the male KKAy mice into 2 groups: liraglutide group (250 μg/kg/day liraglutide subcutaneous injection) and model group; meanwhile, the male C57BL/6J mice were considered as the control. After 6 weeks, the ultrastructure of skeletal muscle was observed by electron microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), phosphatidylinositol 3-kinase (PI3K), and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and phospho-Akt2 (p-Akt2) were measured by Western blot. Results. Liraglutide significantly ameliorated the injury of mitochondria by increasing the number (+441%) and the area (+113%) of mitochondria and mitochondrial area/100 µm2 (+396%) in skeletal muscle of KKAy mice. The results of real-time PCR and Western blot showed that liraglutide downregulated PTP1B while it upregulated PI3K and GLUT4 (). The protein level of p-Akt2/Akt2 was also increased (). Conclusion. These results revealed that liraglutide could improve myofibril and mitochondria injury in skeletal muscle against T2DM via PTP1B and PI3K/Akt2 signaling pathway. Wenjun Ji, Xinlin Chen, Juan Lv, Meng Wang, Shuting Ren, Bingxiang Yuan, Bing Wang, and Lina Chen Copyright © 2014 Wenjun Ji et al. All rights reserved. Dipeptidyl Peptidase-4 Inhibitors as a Third-Line Oral Antihyperglycaemic Agent in Patients with Type 2 Diabetes Mellitus: The Impact of Ethnicity Sun, 10 Aug 2014 12:40:29 +0000 Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined. Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment. Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7–8.9) to 7.2% (6.8–7.6) and 26 patients (32.5%) achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [−1.00% (0.6–1.3) vs −0.90% (0.4–1.6)]. Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients. X. Zhang, B. Brooks, L. Molyneaux, E. Landy, R. Banatwalla, T. Wu, J. Wong, B. Su, and D. K. Yue Copyright © 2014 X. Zhang et al. All rights reserved. No Obesity Paradox—BMI Incapable of Adequately Capturing the Relation of Obesity with All-Cause Mortality: An Inception Diabetes Cohort Study Thu, 07 Aug 2014 10:37:16 +0000 Background. To reconcile “the obesity paradox,” we tested if (1) the contribution of anthropometric measures to mortality was nonlinear and (2) the confounding of hip circumference contributed to the obesity paradox recently observed among diabetic patients. Methods. We analyzed data of diabetic patients attending a community-based prospective, “Tehran lipid and glucose study.” In the mortality analysis, anthropometric measures—body mass index (BMI), waist, and hip circumference—were assessed using Cox models incorporating cubic spline functions. Results. During 12 990 person-years follow-up, BMI levels below 27 and those above 40 kg·m−2 were associated with increased mortality. When we added waist circumference to the BMI in the multivariate-adjusted model, the steepness of BMI-mortality association curve slope for values below 27 kg·m−2 increased, whereas the steepness of BMI-mortality association curve slope for values above this threshold decreased. Further adjusting the model for hip circumference, the steepness of the slopes of the association curve moved towards null on both extremes and no associations between BMI and all-cause mortality remained. Conclusion. BMI harbors intermixed positive and negative confounding effects on mortality of waist and hip circumference. Failing to control for the confounding effect of hip circumference may stymie unbiased hazard estimation and render conclusions paradoxical. Mohammadreza Bozorgmanesh, Banafsheh Arshi, Farhad Sheikholeslami, Fereidoun Azizi, and Farzad Hadaegh Copyright © 2014 Mohammadreza Bozorgmanesh et al. All rights reserved. Glucocorticoid Functional Reserve in Full-Spectrum Intensity of Primary Hypothyroidism Thu, 07 Aug 2014 06:07:26 +0000 Adrenal function might be impaired in patients with primary hypothyroidism. The objective was to evaluate adrenocortical function using the low-dose cosyntropin test in patients with primary hypothyroidism. Consequently a prospective, longitudinal, controlled study of sixty adult patients with primary hypothyroidism was carried out. Patients naïve to L-T4 treatment were compared with control participants. A low-dose cosyntropin test was done before and after L-T4 therapy. Thirty and sixty minutes after the low-dose cosyntropin, the mean cortisol values were lower in the cases group (612.6 ± 133.1 and 603.4 ± 153.7 nmol/L) when compared to the control group (677.0 ± 82.4 and 669.9 ± 83.7 nmol/L) ( and 0.003), respectively. After L-T4 therapy, this difference was lost. Four out of 60 cases (6.7%) taking a cortisol cutoff value of 500 mmol/L and 11 out of 60 (18.3%) having 550 mmol/L as the cutoff had adrenal insufficiency before L-T4 therapy. After L-T4 therapy, 50% and 81% of the cases had normal cortisol response. In conclusion, patients with different degrees of intensity of primary hypothyroidism had improved cortisol response after reaching euthyroidism. The incidence of adrenal insufficiency was 6.7–18.3% and more than 50% of the cases had a normal cortisol response after L-T4 therapy. René Rodríguez-Gutiérrez, Camilo González-Velázquez, Gerardo González-Saldívar, Jesús Zacarías Villarreal-Pérez, and José Gerardo González-González Copyright © 2014 René Rodríguez-Gutiérrez et al. All rights reserved. Glucose Intolerance after a Recent History of Gestational Diabetes Thu, 07 Aug 2014 05:30:45 +0000 Aim. Our aim was to evaluate the uptake of our current screening strategy postpartum and the risk factors for glucose intolerance in women with a recent history of gestational diabetes (GDM). Methods. Retrospective analysis of files of women with a recent history of GDM diagnosed with the Carpenter and Coustan criteria from 01-01-2010 till 31-12-2013. Multivariable logistic regression was used to adjust for confounders. Results. Of all 231 women with a recent history of GDM, 21.4% (46) did not attend the scheduled postpartum OGTT. Of the women tested, 39.1% (66) had glucose intolerance and 5.3% (9) had diabetes. These women were more often overweight (39.7% versus 25.3%, = 0.009), were more often treated with basal-bolus insulin injections (52.0% versus 17.4%, = 0.032), and had a lower beta-cell function and lower insulin sensitivity, remaining significant after adjustment for age, BMI, and ethnicity (insulin secretion sensitivity index-2 (ISSI-2) in pregnancy 1.5 ± 0.5 versus 1.7 ± 0.4, = 0.029; ISSI-2 postpartum 1.5 (1.2–1.9) versus 2.2 (1.8–2.6), = 0.020; Matsuda index postpartum 3.8 (2.6–6.2) versus 6.0 (4.3–8.8), = 0.021). Conclusion. Glucose intolerance is frequent in early postpartum and these women have a lower beta-cell function and lower insulin sensitivity. One fifth of women did not attend the scheduled OGTT postpartum. Katrien Benhalima, Liesbeth Leuridan, Peggy Calewaert, Roland Devlieger, Johan Verhaeghe, and Chantal Mathieu Copyright © 2014 Katrien Benhalima et al. All rights reserved. Tuberculosis of the Adrenal Gland: A Case Report and Review of the Literature of Infections of the Adrenal Gland Wed, 06 Aug 2014 00:00:00 +0000 Infections of the adrenal glands remain an important cause of adrenal insufficiency, especially in the developing world. Indeed, when Thomas Addison first described the condition that now bears his name over 150 years ago, the vast majority of cases were attributable to tuberculosis. Here we describe a classic, but relatively uncommon, presentation in the United States of adrenal insufficiency followed by a review of the current literature pertaining to adrenal infections. Jagriti Upadhyay, Praveen Sudhindra, George Abraham, and Nitin Trivedi Copyright © 2014 Jagriti Upadhyay et al. All rights reserved. Vitamin D and Its Relationship with Obesity and Muscle Tue, 05 Aug 2014 00:00:00 +0000 The skin synthesis of vitamin D represents the first step of a metabolic pathway whose features have been extensively studied and clarified in the last decades. In particular, the production of active and inactive forms of the hormone and the actions of the corresponding enzymes have offered new insights into the knowledge of vitamin D metabolism. Additionally, the description of the different organs and tissues expressing the vitamin D receptor and its possible functions, as well as its genetic determinants, have allowed focusing on the interrelationship between vitamin D and many physiological and pathological functions. In this context, many studies reported the association between vitamin D and adipose tissue metabolism, as well as the possible role of the hormone in obesity, weight, and fat mass distribution. Finally, many reports focused on the vitamin D-related effects on skeletal muscle, particularly on the mechanisms by which vitamin D could directly affect muscle mass and strength. This paper is mainly aimed to review vitamin D metabolism and its relationship with obesity and skeletal muscle function. Cristiana Cipriani, Jessica Pepe, Sara Piemonte, Luciano Colangelo, Mirella Cilli, and Salvatore Minisola Copyright © 2014 Cristiana Cipriani et al. All rights reserved. Effects of Dipeptidyl Peptidase-4 Inhibition with MK-0431 on Syngeneic Mouse Islet Transplantation Mon, 04 Aug 2014 09:58:46 +0000 Dipeptidyl peptidase (DPP)-4 inhibitors increase circulating levels of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide which may promote β-cell proliferation and survival. This study tested if DPP-4 inhibition with MK-0431 is beneficial for diabetic mice syngeneically transplanted with a marginal number of islets. We syngeneically transplanted 150 C57BL/6 mouse islets under the kidney capsule of each streptozotocin-diabetic mouse and then treated recipients with or without MK-0431 (30 mg/kg/day, po) for 6 weeks. After islet transplantation, blood glucose levels decreased in both MK-0431-treated and control groups. However, the blood glucose and area under the curve of the intraperitoneal glucose tolerance test at 2, 4, and 6 weeks were not significantly different between MK-0431-treated mice and controls. During 6 weeks, both groups exhibited increased body weights over time. However, the weight between two groups did not differ throughout the study period. At 6 weeks after transplantation, the graft beta-cell mass (0.024 ± 0.005 versus 0.023 ± 0.007 mg, ) and insulin content (140 ± 48 versus 231 ± 63 ng, ) were comparable in the MK-0431-treated group and controls. Our results indicate posttransplant DPP-4 inhibition with MK-0431 in the diabetic recipient with a marginal number of islets is not beneficial to transplantation outcome or islet grafts. Jyuhn-Huarng Juang, Chien-Hung Kuo, Ying-Hsiu Liu, Han-Ying Chang, and Chiung-Tong Chen Copyright © 2014 Jyuhn-Huarng Juang et al. All rights reserved. Evaluating the Efficacy of Primary Treatment for Graves’ Disease Complicated by Thyrotoxic Periodic Paralysis Sun, 03 Aug 2014 00:00:00 +0000 Objective. Thyrotoxic periodic paralysis (TPP) is a potentially life-threatening complication of Graves’ disease (GD). The present study compared the long-term efficacy of antithyroid drugs (ATD), radioactive iodine (RAI), and surgery in GD/TPP. Methods. Sixteen patients with GD/TPP were followed over a 14-year period. ATD was generally prescribed upfront for 12–18 months before RAI or surgery was considered. Outcomes such as thyrotoxic or TPP relapses were compared between the three modalities. Results. Eight (50.0%) patients had ATD alone, 4 (25.0%) had RAI, and 4 (25.0%) had surgery as primary treatment. Despite being able to withdraw ATD in all 8 patients for 37.5 (22–247) months, all subsequently developed thyrotoxic relapses and 4 (50.0%) had ≥1 TPP relapses. Of the four patients who had RAI, two (50%) developed thyrotoxic relapse after 12 and 29 months, respectively, and two (50.0%) became hypothyroid. The median required RAI dose to render hypothyroidism was 550 (350–700) MBq. Of the 4 patients who underwent surgery, none developed relapses but all became hypothyroid. Conclusion. To minimize future relapses, more definitive primary treatment such as RAI or surgery is preferred over ATD alone. If RAI is chosen over surgery, a higher dose (>550 MBq) is recommended. Rita Yuk-Kwan Chang, Brian Hung-Hin Lang, Ai Chen Chan, and Kai Pun Wong Copyright © 2014 Rita Yuk-Kwan Chang et al. All rights reserved. The Importance of the Prenyl Group in the Activities of Osthole in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro Thu, 24 Jul 2014 08:35:34 +0000 Osteoporosis treatment always aimed at keeping the balance of bone formation and bone resorption. Recently, prenyl group in natural products has been proposed as an active group to enhance the osteogenesis process. Osthole has both the prenyl group and bone-protective activities, but the relationship is still unknown. In this study we found that osthole exerted a potent ability to promote proliferation and osteogenic function of rat bone marrow stromal cells and osteoblasts, including improved cell viability, alkaline phosphatase activity, enhanced secretion of collagen-I, bone morphogenetic protein-2, osteocalcin and osteopontin, stimulated mRNA expression of insulin-like growth factor-1, runt-related transcription factor-2, osterix, OPG (osteoprotegerin), RANKL (receptor activator for nuclear factor-B ligand), and the ratio of OPG/RANKL, as well as increasing the formation of mineralized nodules. However, 7-methoxycoumarin had no obvious effects. Osthole also inhibited osteoclastic bone resorption to a greater extent than 7-methoxycoumarin, as shown by a lower tartrate-resistant acid phosphatase activity and lower number and smaller area of resorption pits. Our findings demonstrate that osthole could be a potential agent to stimulate bone formation and inhibit bone resorption, and the prenyl group plays an important role in these bone-protective effects. Yuan-Kun Zhai, Ya-Lei Pan, Yin-Bo Niu, Chen-Rui Li, Xiang-Long Wu, Wu-Tu Fan, Ting-Li Lu, Qi-Bing Mei, and Cory J. Xian Copyright © 2014 Yuan-Kun Zhai et al. All rights reserved. Baicalein Protects against Type 2 Diabetes via Promoting Islet β-Cell Function in Obese Diabetic Mice Wed, 23 Jul 2014 09:48:22 +0000 In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of β-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herb Scutellaria baicalensis, improved glucose tolerance and enhanced glucose-stimulated insulin secretion (GSIS) in high-fat diet (HFD-) induced middle-aged obese mice. Baicalein had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in obese mice. Using another mouse model of type 2 diabetes generated by high-fat diet (HFD) feeding and low doses of streptozotocin injection, we found that baicalein treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in these middle-aged obese diabetic mice, which are associated with the improved islet β-cell survival and mass. In the in vitro studies, baicalein significantly augmented GSIS and promoted viability of insulin-secreting cells and human islets cultured either in the basal medium or under chronic hyperlipidemic condition. These results demonstrate that baicalein may be a naturally occurring antidiabetic agent by directly modulating pancreatic β-cell function. Yu Fu, Jing Luo, Zhenquan Jia, Wei Zhen, Kequan Zhou, Elizabeth Gilbert, and Dongmin Liu Copyright © 2014 Yu Fu et al. All rights reserved. Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis Wed, 23 Jul 2014 08:15:01 +0000 Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. Vittorio Locatelli and Vittorio E. Bianchi Copyright © 2014 Vittorio Locatelli and Vittorio E. Bianchi. All rights reserved. Association between Serum Uric Acid Level and Metabolic Syndrome and Its Sex Difference in a Chinese Community Elderly Population Wed, 23 Jul 2014 00:00:00 +0000 Objective. This study aimed to evaluate the association between serum uric acid (SUA) levels within a normal to high range and the risk of metabolic syndrome (MetS) among community elderly and explore the sex difference. Design and Methods. A cross-sectional study was conducted in a representative urban area of Beijing between 2009 and 2010. A two-stage stratified clustering sampling method was used and 2102 elderly participants were included. Results. The prevalence of hyperuricemia and MetS was 16.7% and 59.1%, respectively. There was a strong association between hyperuricemia and four components of MetS in women and three components in men. Multiple logistic regression analysis showed ORs of hyperuricemia for MetS were 1.67 (95% CI: 1.11–2.50) in men and 2.73 (95% CI: 1.81–4.11) in women. Even in the normal range, the ORs for MetS increased gradually according to SUA levels. MetS component number also showed an increasing trend across SUA quartile in both sexes (P for trend < 0.01). Conclusion. This study suggests that higher SUA levels, even in the normal range, are positively associated with MetS among Chinese community elderly, and the association is stronger in women than men. Physicians should recognize MetS as a frequent comorbidity of hyperuricemia and take early action to prevent subsequent disease burden. Miao Liu, Yao He, Bin Jiang, Lei Wu, Shanshan Yang, Yiyan Wang, and Xiaoying Li Copyright © 2014 Miao Liu et al. All rights reserved. Leptin Effects on the Regenerative Capacity of Human Periodontal Cells Tue, 22 Jul 2014 12:01:52 +0000 Obesity is increasing throughout the globe and characterized by excess adipose tissue, which represents a complex endocrine organ. Adipose tissue secrets bioactive molecules called adipokines, which act at endocrine, paracrine, and autocrine levels. Obesity has recently been shown to be associated with periodontitis, a disease characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium, and also with compromised periodontal healing. Although the underlying mechanisms for these associations are not clear yet, increased levels of proinflammatory adipokines, such as leptin, as found in obese individuals, might be a critical pathomechanistic link. The objective of this study was to examine the impact of leptin on the regenerative capacity of human periodontal ligament (PDL) cells and also to study the local leptin production by these cells. Leptin caused a significant downregulation of growth (TGFβ1, and VEGFA) and transcription (RUNX2) factors as well as matrix molecules (collagen, and periostin) and inhibited SMAD signaling under regenerative conditions. Moreover, the local expression of leptin and its full-length receptor was significantly downregulated by inflammatory, microbial, and biomechanical signals. This study demonstrates that the hormone leptin negatively interferes with the regenerative capacity of PDL cells, suggesting leptin as a pathomechanistic link between obesity and compromised periodontal healing. Marjan Nokhbehsaim, Sema Keser, Andressa Vilas Boas Nogueira, Andreas Jäger, Søren Jepsen, Joni Augusto Cirelli, Christoph Bourauel, Sigrun Eick, and James Deschner Copyright © 2014 Marjan Nokhbehsaim et al. All rights reserved. The TG/HDL-C Ratio Might Be a Surrogate for Insulin Resistance in Chinese Nonobese Women Mon, 21 Jul 2014 06:56:33 +0000 Obejective. To examine the discriminatory power of triglyceride (TG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) for insulin resistance (IR) in a normoglycaemic Chinese population. Methods. The data were collected from 711 individuals. The normoglycaemic individuals were eventually included in the study (n = 533, age: 62.8 ± 6.6 years, male: 56.8%), who were with a fasting plasma glucose < 6.1 mmol/L and without a history of diabetes. IR was defined as the upper quintile (≥1.6) of homeostasis model assessment of IR. Area under the receiver operating characteristic curve (AROC) was used to examine the discriminatory power. Results. The discriminatory power of TG/HDL-C for IR was acceptable in women with a BMI < 24 kg/m2 or waist circumference < 80 cm (AROCs: 0.718 and 0.713, resp.); however, the discriminatory power was not acceptable in the obese women. TG/HDL-C was not an acceptable marker of IR in men. The discriminatory power of TG for IR was not acceptable in both men and women. Conclusions. The discriminatory power of TG/HDL-C for IR differs by gender and obesity index in the normoglycaemic Chinese population, and TG/HDL-C could discriminate IR in the nonobese and normoglycaemic women. Jiyun He, Sen He, Kai Liu, Yong Wang, Di Shi, and Xiaoping Chen Copyright © 2014 Jiyun He et al. All rights reserved. Increased Incidence of Thyroid Dysfunction and Autoimmunity in Patients with Vernal Keratoconjunctivitis Sun, 20 Jul 2014 12:15:05 +0000 Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; ). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; ) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; ). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, ). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity. Stefano Stagi, Neri Pucci, Laura Di Grande, Cinzia de Libero, Roberto Caputo, Stefano Pantano, Ivan Mattei, Francesca Mori, Maurizio de Martino, and Elio Novembre Copyright © 2014 Stefano Stagi et al. All rights reserved. Cannabinoid Receptor 1 Gene Polymorphisms and Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome and in Healthy Controls Thu, 17 Jul 2014 10:08:48 +0000 Context. Polycystic ovary syndrome (PCOS) is frequently associated with nonalcoholic fatty liver disease (NAFLD). The endocannabinoid system may play a crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid receptor 1 gene (CNR1) may be responsible for individual susceptibility to obesity and related conditions. Objective. To determine the role of genetic variants of CNR1 in the etiopathology of NAFLD in women with PCOS. Design and Setting. Our department (a tertiary referral center) conducted a cross-sectional, case-controlled study. Subjects. 173 women with PCOS (aged 20–35) and 125 healthy, age- and weight-matched controls were studied. Methods. Hepatic steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms of CNR1 (rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674) were genotyped. Results. Frequency of the G allele of rs806381 () and the GG genotype of rs10485170 () was significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674 was higher in PCOS women with NAFLD (not significantly, ). In multivariate stepwise regression, allele G of rs806381 was associated with PCOS + NAFLD phenotype. Conclusion. Our preliminary results suggest the potential role of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women. Justyna Kuliczkowska Plaksej, Lukasz Laczmanski, Andrzej Milewicz, A. Lenarcik-Kabza, Anna Trzmiel-Bira, Urszula Zaleska-Dorobisz, Felicja Lwow, and Lidia Hirnle Copyright © 2014 Justyna Kuliczkowska Plaksej et al. All rights reserved.