International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. The Clinicopathological Features of BRAF Mutated Papillary Thyroid Cancers in Chinese Patients Mon, 27 Jul 2015 13:36:24 +0000 The mutation is commonly found in papillary thyroid cancers (PTCs) at different frequencies in different regions. However, the association between the mutation and clinicopathological features in Chinese PTC patients is unknown. A total of 543 Chinese patients with histologically confirmed PTC were enrolled in this study. For the BRAF mutation assay, the target fragments were amplified and sequenced with an ABI 3500 gene analyzer. In 170 of 543 samples (31.3%), the mutation was detected. In the bivariate analysis, the mutation showed an association with bilaterality, tumor size, extrathyroidal invasion, and lymph node metastases (LNM). However, in the multivariate analysis, the mutation was positively related to only tumor size (>1 cm) and extrathyroidal invasion. In addition, the multivariate analysis also showed that the age at diagnosis (<45 y) and tumor size (>1 cm) were independent predictors for LNM. In this study, the mutation is positively associated with worse prognostic factors, including larger tumor size and the tumor extending to the thyroid capsule or extrathyroidal region; however, it is not an independent predictor for LNM. Li-Bo Yang, Lin-Yong Sun, Yong Jiang, Ying Tang, Zhi-Hui Li, Hong-Ying Zhang, Hong Bu, and Feng Ye Copyright © 2015 Li-Bo Yang et al. All rights reserved. Comparison of the Spine and Hip BMD Assessments Derived from Quantitative Computed Tomography Mon, 27 Jul 2015 13:23:00 +0000 Quantification of bone mineral density (BMD) is being used as the main method to diagnose osteoporosis. Dual-energy X-ray absorptiometry (DXA) is the most common tools for measuring BMD. Compared to DXA, quantitative computed tomography (QCT) can determine in three dimensions the true volumetric BMD (vBMD) at any skeletal site. In addition to the spine, the hip is an important site for axial BMD measurement. This study examines lumbar spine and hip BMD of Chinese adults by QCT. Age related changes in bone mass derived by QCT measurements were determined. The osteoporosis QCT detection rates at the spine and hip are assessed in both female and male, and agreement of skeletal status category between the spine and hip in older adults is also assessed. Xiao-Hui Ma, Wei Zhang, Yan Wang, Peng Xue, and Yu-Kun Li Copyright © 2015 Xiao-Hui Ma et al. All rights reserved. Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats Mon, 27 Jul 2015 13:17:41 +0000 Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (−27%) and at tissue level (−12%), Tb bone volume fraction (−29%), Tb thickness (−14%), and Tb number (−17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties—nanoindentation hardness, elastic modulus, and plastic deformation—nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se. Shidi Hu, Jin Li, Lu Liu, Ruchun Dai, Zhifeng Sheng, Xianping Wu, Xiqiao Feng, Xuefeng Yao, Eryuan Liao, Evan Keller, and Yebin Jiang Copyright © 2015 Shidi Hu et al. All rights reserved. Mechanism and Treatment Strategy of Osteoporosis after Transplantation Mon, 27 Jul 2015 13:11:33 +0000 Osteoporosis (OP) has emerged as a frequent and devastating complication of organ solid transplantation process. Bone loss after organ transplant is related to adverse effects of immunosuppressants on bone remodeling and bone quality. Many factors contribute to the pathogenesis of OP in transplanted patients. Many mechanisms of OP have been deeply approached. Drugs for OP can be generally divided into “bone resorption inhibitors” and “bone formation accelerators,” the former hindering bone resorption by osteoclasts and the latter increasing bone formation by osteoblasts. Currently, bisphosphonates, which are bone resorption inhibitors drugs, are more commonly used clinically than others. Using the signaling pathway or implantation bone marrow stem cell provides a novel direction for the treatment of OP, especially OP after transplantation. This review addresses the mechanism of OP and its correlation with organ transplantation, lists prevention and management of bone loss in the transplant recipient, and discusses the recipients of different age and gender. Lei Song, Xu-Biao Xie, Long-Kai Peng, Shao-Jie Yu, and Ya-Ting Peng Copyright © 2015 Lei Song et al. All rights reserved. Validity of 12-Month Falls Recall in Community-Dwelling Older Women Participating in a Clinical Trial Mon, 27 Jul 2015 12:54:50 +0000 Objectives. To compare 12-month falls recall with falls reported prospectively on daily falls calendars in a clinical trial of women aged ≥70 years. Methods. 2,096 community-dwelling women at high risk of falls and/or fracture completed a daily falls calendar and standardised interviews when falls were recorded, for 12 months. Data were compared to a 12-month falls recall question that categorised falls status as “no falls,” “a few times,” “several,” and “regular” falls. Results. 898 (43%) participants reported a fall on daily falls calendars of whom 692 (77%) recalled fall(s) at 12 months. Participants who did not recall a fall were older (median 79.3 years versus 77.8 years, ). Smaller proportions of fallers who sustained an injury or accessed health care failed to recall a fall (all ). Among participants who recalled “no fall,” 85% reported zero falls on daily calendars. Few women selected falls categories of “several times” or “regular” (4.1% and 0.4%, resp.) and the sensitivity of these categories was low (30% to 33%). Simply categorising participants into fallers or nonfallers had 77% sensitivity and 94% specificity. Conclusion. For studies where intensive ascertainment of falls is not feasible, 12-month falls recall questions with fewer responses may be an acceptable alternative. Kerrie M. Sanders, Amanda L. Stuart, David Scott, Mark A. Kotowicz, and Geoff C. Nicholson Copyright © 2015 Kerrie M. Sanders et al. All rights reserved. Effects of Alendronate Sodium Content on the Interface Strengths of Composite Acrylic Bone Cement Mon, 27 Jul 2015 12:25:42 +0000 Objective. Aim to study how the content of alendronate affected shear strengths at bone-bone cement-metal interfaces. Methods. All samples were divided into 6 groups, G0–G5. On the 1st and 60th day after surgery, bone-bone cement interface shear strengths and bone densities were examined. Interface strengths of metal-bone cement specimens were studied before immersion and 4 weeks after immersion. Results. On the 60th day, bone-bone cement interface shear strengths and bone densities showed significant differences (), and compared with G0, G2–G5 values increased significantly (), and the peak value was met in G3. Compared with the 1st day, on the 60th postoperative day both factors decreased significantly in G0 and G1 (). Four weeks after immersion, with the increasing dose of alendronate, the shear strengths decreased gradually and in G5 decreased significantly (). Compared with before immersion, the metal-bone cement interface strengths decreased significantly 4 weeks after immersion (). Conclusions. 50–500 mg alendronate in 50 g cement powders could prevent the decrease of shear strengths at bone-bone cement interfaces and had no effect on metal-bone cement interface strengths. While the addition dose was 100 mg, bone cement showed the best strengths. De-Ye Song, Xin-Zhan Mao, Mu-liang Ding, and Jiang-Dong Ni Copyright © 2015 De-Ye Song et al. All rights reserved. Low Magnesium Exacerbates Osteoporosis in Chronic Kidney Disease Patients with Diabetes Mon, 27 Jul 2015 11:06:13 +0000 The aim of this study is to investigate the impact of serum Mg on bone mineral metabolism in chronic kidney disease (CKD) patients with or without diabetes. A total of 56 CKD patients not receiving dialysis were recruited and divided into two groups, one group of 27 CKD patients with diabetes and another group of 29 CKD patients without diabetes. Biochemical determinations were made, and the estimated glomerular filtration rate (eGFR) was measured. Bone mineral density was measured by dual-energy X-ray absorptiometry. Serum Mg was inversely correlated with serum Ca and positively correlated with serum parathyroid hormone (PTH) , alkaline phosphatase , and phosphate in the CKD patients with diabetes. The CKD patients with diabetes had lower serum albumin and a higher proportion of hypomagnesemia and osteoporosis than the nondiabetic patients did . Serum Mg was inversely correlated with eGFR in the CKD patients with or without diabetes . Serum Mg showed an inverse correlation with 25-hydroxyvitamin D in CKD patients without diabetes . Furthermore, the diabetic CKD patients with low serum Mg had a lower iPTH and a higher serum Ca/Mg ratio than the other CKD patients. The lower serum Mg subgroup showed a higher incidence of osteoporosis than the moderate and higher serum Mg subgroups did (66.7%, 39.4%, and 29.4%, resp.). In conclusion, low serum Mg may impact iPTH and exacerbates osteoporosis in CKD patients, particularly with diabetes. Jui-Hua Huang, Fu-Chou Cheng, and Hsu-Chen Wu Copyright © 2015 Jui-Hua Huang et al. All rights reserved. The Inhibitory Effect of Alisol A 24-Acetate from Alisma canaliculatum on Osteoclastogenesis Mon, 27 Jul 2015 10:36:24 +0000 Osteoporosis is a disease that decreases bone mass. The number of patients with osteoporosis has been increasing, including an increase in patients with bone fractures, which lead to higher medical costs. Osteoporosis treatment is all-important in preventing bone loss. One strategy for osteoporosis treatment is to inhibit osteoclastogenesis. Osteoclasts are bone-resorbing multinucleated cells, and overactive osteoclasts and/or their increased number are observed in bone disorders including osteoporosis and rheumatoid arthritis. Bioactivity-guided fractionations led to the isolation of alisol A 24-acetate from the dried tuber of Alisma canaliculatum. Alisol A 24-acetate inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1, which plays an essential role in osteoclast differentiation. Furthermore, it inhibited the expression of DC-STAMP and cathepsin K, which are related to cell-cell fusion of osteoclasts and bone resorption, respectively. Therefore, alisol A 24-acetate could be developed as a new structural scaffold for inhibitors of osteoclast differentiation in order to develop new drugs against osteoporosis. Kwang-Jin Kim, Alain Simplice Leutou, Jeong-Tae Yeon, Sik-Won Choi, Seong Hwan Kim, Sung-Tae Yee, Kyung Hee Choi, Sang-Jip Nam, and Young-Jin Son Copyright © 2015 Kwang-Jin Kim et al. All rights reserved. Vitamin D and Osteoporosis in HIV/HCV Coinfected Patients: A Literature Review Mon, 27 Jul 2015 10:34:52 +0000 Vitamin D deficiency further increases the risk of osteoporosis in HIV-positive patients coinfected with hepatitis C virus (HCV); however, it is still unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. The aim of this review was to identify studies on associative vitamin D deficiency patterns in high-risk populations such as HIV/HCV coinfected patients. We did this by searching MEDLINE and EMBASE databases, from inception to August 2014, and included bibliographies. The final 12 articles selected are homogeneous in terms of age but heterogeneous in terms of sample size, participant recruitment, and data source. Most of the HIV/HCV coinfected patients have less than adequate levels of vitamin D. After reviewing the selected articles, we concluded that vitamin D deficiency should be regarded as a continuum and that the lower limit of the ideal range is debatable. We found that vitamin D deficiency might influence liver disease progression in HIV/HCV coinfected patients. Methodological issues in evaluating vitamin D supplementation as a relatively inexpensive therapeutic option are discussed, as well as the need for future research, above all on its role in reducing the risk of HCV-related fracture by modifying liver fibrosis progression. Paola Di Carlo, Lucia Siracusa, Giovanni Mazzola, Piero Colletti, Maurizio Soresi, Lydia Giannitrapani, Valentina Li Vecchi, and Giuseppe Montalto Copyright © 2015 Paola Di Carlo et al. All rights reserved. Sarco-Osteoporosis: Prevalence and Association with Frailty in Chinese Community-Dwelling Older Adults Mon, 27 Jul 2015 10:05:57 +0000 The aim was to apply AWGS criteria to estimate the prevalence of sarco-osteoporosis and investigate its relationship with frailty, in a sample of 316 community-dwelling Chinese older people. Regression analysis was performed using frailty as the dependent variable. The results showed that the prevalence rate of sarco-osteoporosis was 10.4% in older men and 15.1% in older women. ≧80 years old (OR 4.8; 95% CI, 3.05–10.76; ), women (OR 2.6; 95% CI, 1.18–2.76; ), and higher level of comorbidity (OR 3.71; 95% CI, 1.61–10.43; ) were independently associated with the likelihood of being sarco-osteoporosis. In the frail group, sarco-osteoporosis occurred in 26.3% of men, in 38.5% of women, and in lower proportion in the prefrail (13.6% of men; 16.2% of women) and nonfrail group (1.6% of men; 1.9% of women) (, resp.). Furthermore, the likelihood of being frail/prefrail was substantially higher in the presence of sarco-osteoporosis (OR 4.16; 95% CI, 2.17–17.65; in men; and OR 4.67; 95% CI, 2.42–18.86; in women). The results indicate that patients with sarco-osteoporosis are more likely to be ≧80 yrs with higher burden of comorbidities and to have frailty/prefrailty, especially for women. Yan-Jiao Wang, Yi Wang, Jun-Kun Zhan, Zhi-Yong Tang, Jie-Yu He, Pan Tan, Hui-Qian Deng, Wu Huang, and You-Shuo Liu Copyright © 2015 Yan-Jiao Wang et al. All rights reserved. Elastography Evaluation of Benign Thyroid Nodules in Patients Affected by Hashimoto’s Thyroiditis Mon, 27 Jul 2015 07:29:03 +0000 The aim of the present prospective study was to evaluate the predictive value of elastography in benign thyroid nodules of patients affected by Hashimoto’s thyroiditis (HT). From January 2011 to January 2012, 242 nodules in patients affected by HT were submitted to fine needle aspiration cytology (FNAC). All of the patients underwent sonography and elastography performed before FNAC. 230 (95%) nodules were benign, 8 papillary cancers, and 4 follicular lesions. Score 1 was found in 79.1% of benign lesions (sensitivity 79.1%; specificity 66.7%; PPV 97.8%; NPV 14.3%; accuracy 78.5%; ). In order to evaluate the outcome of thyroid ultrasound echogenicity in relation to elastography features of nodule(s), all the patients with benign nodules were stratified according to their hypoechoic pattern of thyroid (mild-moderate and severe). Following stratification score 1 was found in 84.2% of benign nodules (sensitivity 75.0%; specificity 88.9%; PPV 27.3%; NPV 98.4%; accuracy 88.2%; ) of patients with a mild-moderate ultrasound thyroid hypoechogenicity, whereas it was found in 60% of benign nodules of patients with a marked thyroid hypoechogenicity. Elastography appears to have limited value in detecting thyroid cancer in patients affected by Hashimoto’s thyroiditis with severe hypoechoic thyroid tissue. Carlo Cappelli, Ilenia Pirola, Elena Gandossi, Annamaria Formenti, Barbara Agosti, and Maurizio Castellano Copyright © 2015 Carlo Cappelli et al. All rights reserved. Association between rs12045440 Polymorphism in the CAPZB Intron and Serum TSH Concentrations in Chinese Thyroid Tumor Patients Sun, 26 Jul 2015 14:03:01 +0000 The aim of this study was to investigate the possible influence of different genotypes of the lead single nucleotide polymorphisms (SNPs) rs10917468 and rs12045440 in the CAPZB gene on the thyroid function in papillary thyroid carcinoma (PTC) and benign thyroid neoplasm (BN) patients. In the study, a significant association was detected between rs12045440 and serum TSH concentrations in thyroid tumor patients (). After the adjustment of relevant covariates, the difference between the mean serum TSH levels in different genotypes of rs12045440 was still significant in the BN group () but was not significant in the PTC cases (). No significant association of rs10917468 with TSH levels was found. The SNP rs12045440 was associated with the serum TSH concentrations in Chinese thyroid tumor patients, especially in benign thyroid tumor cases. Shouhao Feng, Shengli Lin, Jidong Zou, Yulong Wang, Qinghai Ji, and Zhenghua Lv Copyright © 2015 Shouhao Feng et al. All rights reserved. A Novel Mutation in the CYP11B1 Gene Causes Steroid 11β-Hydroxylase Deficient Congenital Adrenal Hyperplasia with Reversible Cardiomyopathy Wed, 22 Jul 2015 11:15:11 +0000 Congenital adrenal hyperplasia (CAH) due to steroid 11β-hydroxylase deficiency is the second most common form of CAH, resulting from a mutation in the CYP11B1 gene. Steroid 11β-hydroxylase deficiency results in excessive mineralcorticoids and androgen production leading to hypertension, precocious puberty with acne, enlarged penis, and hyperpigmentation of scrotum of genetically male infants. In the present study, we reported 3 male cases from a Saudi family who presented with penile enlargement, progressive darkness of skin, hypertension, and cardiomyopathy. The elder patient died due to heart failure and his younger brothers were treated with hydrocortisone and antihypertensive medications. Six months following treatment, cardiomyopathy disappeared with normal blood pressure and improvement in the skin pigmentation. The underlying molecular defect was investigated by PCR-sequencing analysis of all coding exons and intron-exon boundary of the CYP11B1 gene. A novel biallelic mutation c.780 G>A in exon 4 of the CYP11B1 gene was found in the patients. The mutation created a premature stop codon at amino acid 260 (), resulting in a truncated protein devoid of 11β-hydroxylase activity. Interestingly, a somatic mutation at the same codon (c.779 G>A, ) was reported in a patient with papillary thyroid cancer (COSMIC database). In conclusion, we have identified a novel nonsense mutation in the CYP11B1 gene that causes classic steroid 11β-hydroxylase deficient CAH. Cardiomyopathy and cardiac failure can be reversed by early diagnosis and treatment. Mohammad A. Alqahtani, Ayed A. Shati, Minjing Zou, Ali M. Alsuheel, Abdullah A. Alhayani, Saleh M. Al-Qahtani, Hessa M. Gilban, Brain F. Meyer, and Yufei Shi Copyright © 2015 Mohammad A. Alqahtani et al. All rights reserved. Surgical and Pathological Changes after Radiofrequency Ablation of Thyroid Nodules Tue, 21 Jul 2015 13:24:58 +0000 Background. Radiofrequency ablation (RFA) has been recently advocated as an effective technique for the treatment of symptomatic benign thyroid nodules. It is not known to what extent it may affect any subsequent thyroid surgery and/or histological diagnosis. Materials and Methods. RFA was performed on 64 symptomatic Thy2 nodules (benign nodules) and 6 symptomatic Thy3 nodules (follicular lesions/follicular neoplasms). Two Thy3 nodules regrew after the procedure, and these patients accepted to undergo a total thyroidectomy. Here we present how RFA has affected the operation and the final pathological features of the surgically removed nodules. Results and Conclusions. RFA is effective for the treatment of Thy2 nodules, but it should not be recommended as first-line therapy for the treatment of Thy3 nodules (irrespective of their mutational status), as it delays surgery in case of malignancy. Moreover, it is unknown whether RFA might promote residual tumor progression or neoplastic progression of Thy3 lesions. Nevertheless, here we show for the first time that one session of RFA does not affect subsequent thyroid surgery and/or histological diagnosis. Chiara Dobrinja, Stella Bernardi, Bruno Fabris, Rita Eramo, Petra Makovac, Gabriele Bazzocchi, Lanfranco Piscopello, Enrica Barro, Nicolò de Manzini, Deborah Bonazza, Maurizio Pinamonti, Fabrizio Zanconati, and Fulvio Stacul Copyright © 2015 Chiara Dobrinja et al. All rights reserved. Ghrelin’s Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality Thu, 16 Jul 2015 12:36:23 +0000 Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells. Antonia Diaz-Ganete, Gloria Baena-Nieto, Isabel M. Lomas-Romero, Jose Francisco Lopez-Acosta, Irene Cozar-Castellano, Francisco Medina, Carmen Segundo, and Alfonso M. Lechuga-Sancho Copyright © 2015 Antonia Diaz-Ganete et al. All rights reserved. Insulin Resistance of Normal Weight Central Obese Adolescents in Korea Stratified by Waist to Height Ratio: Results from the Korea National Health and Nutrition Examination Surveys 2008–2010 Thu, 16 Jul 2015 08:45:47 +0000 Background. To evaluate insulin resistance of normal weight central obese 13–18-year-old male and female adolescents stratified by waist to height ratio (WHR). Methods. Data were obtained from the Korea National Health and Nutrition Examination Survey (K-NHANES) conducted during 2008–2010. Central obesity was defined as that in the upper quartile of age and sex specific WHR. Subjects were classified into no central obesity normal weight (NW), central obesity normal weight (CONW), no central obesity overweight (OW), and central obesity overweight (COOW). Results. The prevalence of CONW was 9.6% (83/832) in female and 7.0% (61/909) in male. CONW showed higher levels of insulin (), HOMA-IR (), and ALT () than NW in female. CONW had higher levels of insulin (), HOMA-IR (), and WBC count () and lower level of HDL () than NW in male. WHR and BMI had similar significant correlations with MS components. CONW showed 2.5 times (95% confidence interval, 1.21–5.00) more likelihood to have high insulin resistance than NW in male. Conclusions. Screening for central obesity using WHR in clinical setting is recommended. Won Kyoung Cho, Hyojin Kim, Hyun Young Lee, Kyung Do Han, Yeon Jin Jeon, In Ah Jung, Shin Hee Kim, Kyoung Soon Cho, So Hyun Park, Min Ho Jung, and Byung-Kyu Suh Copyright © 2015 Won Kyoung Cho et al. All rights reserved. An Intensive Lifestyle Intervention Is an Effective Treatment of Morbid Obesity: The TRAMOMTANA Study—A Two-Year Randomized Controlled Clinical Trial Wed, 15 Jul 2015 09:49:29 +0000 Bariatric surgery is currently the most effective therapy to induce weight loss in morbidly obese patients. Objective. This controlled, clinical trial with a two-year intervention was aimed at comparing the efficacy of two nonsurgical approaches versus bariatric surgery, on body weight changes and metabolic parameters in morbidly obese patients. Methods. Patients were randomized to an Intensive Lifestyle Intervention (ILI) () or Conventional Obesity Therapy (COT) (). The ILI group received behavioral therapy and nutritional counseling. The COT group received standard medical treatment. They were compared with a third group, Surgical Obesity Group (SOG) (). Results. Patients who received ILI had a greater percentage of weight loss than patients receiving COT (−11.3% versus −1.6%; ). Interestingly 31.4% of patients included in the ILI group were no longer morbidly obese after just six months of intervention, increasing to 44.4% after 24 months of intervention. The percentage weight loss in SOG was −29.6% after that same period of time. Conclusions. ILI was associated with significant weight loss when compared to COT, in a group of patients with obesity. An ILI approach could be an alternative therapy to patients with obesity, who are not candidates to undergo bariatric surgery. This trial is registered with EudraCT 2009-013737-24. Bartolomé Burguera, Juan Jesús Tur, Antonio Jorge Escudero, María Alos, Alberto Pagán, Baltasar Cortés, Xavier Francesc González, and Joan B. Soriano Copyright © 2015 Bartolomé Burguera et al. All rights reserved. The Benefits and Risks of Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma: Prospective Cohort Study Mon, 13 Jul 2015 12:16:29 +0000 Objectives. This study evaluated the benefits of performing prophylactic central neck dissection (CND) with total thyroidectomy (TT) in management of papillary thyroid carcinoma (PTC) patients who were clinically node-negative at presentation. Methods. A total of 257 patients with stage T1 or T2 PTC and without preoperative evidence of lymph node involvement (N0) were enrolled in this prospective study. The patients were randomly assigned to two groups: (1) a total thyroidectomy (TT) group () or (2) a TT plus CND group (). The two groups were compared for their perioperative data, complication rates, disease recurrence rates, and clinical outcomes. Results. The two groups of patients were similar in age, sex ratio, follow-up duration, and tumor size (, 0.359, 0.214, and 0.878, resp.). The two groups showed similar rates of disease recurrence (3.9% in the TT group versus 3.3% in the TT plus CND group); however, complications occurred more frequently in the TT plus CND group; especially transient hypocalcemia (). Conclusions. Patients treated with TT plus CND had a higher rate of complications with similar recurrence rate. We believe that CND may not be routinely recommended when treating patients with PTC. Doh Young Lee, Kyoung Ho Oh, Jae-Gu Cho, Soon-Young Kwon, Jeong-Soo Woo, Seung-Kuk Baek, and Kwang-Yoon Jung Copyright © 2015 Doh Young Lee et al. All rights reserved. Graves’ Orbitopathy Sun, 12 Jul 2015 07:02:32 +0000 Yuji Hiromatsu, Jack R. Wall, George J. Kahaly, and Hirohiko Kakizaki Copyright © 2015 Yuji Hiromatsu et al. All rights reserved. Consequence of Menin Deficiency in Mouse Adipocytes Derived by In Vitro Differentiation Thu, 02 Jul 2015 12:03:22 +0000 Lipoma in patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome is a type of benign fat-cell tumor that has biallelic inactivation of MEN1 that encodes menin and could serve as a model to investigate normal and pathologic fat-cell (adipocyte) proliferation and function. The role of menin and its target genes in adipocytes is not known. We used in vitro differentiation to derive matched normal and menin-deficient adipocytes from wild type (WT) and menin-null (Men1-KO) mouse embryonic stem cells (mESCs), respectively, or 3T3-L1 cells without or with menin knockdown to investigate cell size, lipid content, and gene expression changes. Adipocytes derived from Men1-KO mESCs or after menin knockdown in 3T3-L1 cells showed a 1.5–1.7-fold increase in fat-cell size. Global gene expression analysis of mESC-derived adipocytes showed that lack of menin downregulated the expression of many differentially methylated genes including the tumor suppressor long noncoding RNA Meg3 but upregulated gene expression from the prolactin gene family locus. Our results show that menin deficiency leads to fat-cell hypertrophy and provide model systems that could be used to study the regulation of fat-cell size. Vaishali I. Parekh, Sita D. Modali, Shruti S. Desai, and Sunita K. Agarwal Copyright © 2015 Vaishali I. Parekh et al. All rights reserved. Effect of Advanced Glycation End Products on Human Thyroglobulin’s Antigenicity as Identified by the Use of Sera from Patients with Hashimoto’s Thyroiditis and Gestational Diabetes Mellitus Thu, 02 Jul 2015 12:03:16 +0000 Advanced glycation end products (AGEs) are formed on proteins after exposure to high concentrations of glucose and modify protein’s immunogenicity. Herein, we investigated whether the modification of thyroglobulin (Tg) by AGEs influences its antigenicity and immunogenicity. Human Tg was incubated in vitro with increasing concentrations of D-glucose-6-phosphate in order to produce Tgs with different AGE content (AGE-Tg). Native Tg and AGE-Tgs were used in ELISA to assess the serum antibody reactivity of two patient groups, pregnant women with gestational diabetes (GDM), and patients with Hashimoto’s thyroiditis (HT). We produced in vitro AGE-Tg with low and high AGE content, 13 and 49 AGE units/mg Tg, respectively. All HT patients’ sera presented the same antibody reactivity profile against native Tg and AGE-Tgs, indicating that the modification of Tg by AGEs did not alter its antigenicity. Similarly, the GDM patients’ sera did not discriminate among the two forms of Tg, native or artificially glycated, suggesting that the modification of Tg by AGEs might not alter its immunogenicity. The modification of Tg by AGEs has no obvious effect on neither its antigenicity nor, most likely, its immunogenicity. It seems that other Tg modifications might account for the production of aTgAbs in patients with GDM. A. Hatzioannou, I. Kanistras, E. Mantzou, E. Anastasiou, M. Peppa, V. Sarantopoulou, P. Lymberi, and M. Alevizaki Copyright © 2015 A. Hatzioannou et al. All rights reserved. Isolated Subclinical Hyperthyrotropinemia in Obese Children: Does Levothyroxine (LT4) Improve Weight Reduction during Combined Behavioral Therapy? Thu, 02 Jul 2015 06:50:00 +0000 Objective. The study aim was to analyze whether anthropometrical parameters and TSH values in obese children with isolated subclinical hypothyroidism (IsHT) treated with levothyroxine (LT4) and weight reduction program differ from those managed by dietary and behavior counselling only. Material and Methods. 51 obese children with IsHT, who were treated according to the same weight reduction program, were retrospectively analyzed. They were divided into two groups: Group 1, , and Group 2, , without or with LT4 therapy, respectively. Changes in anthropometrical (delta BMI z-score) and hormonal (delta TSH) status were analyzed at the first follow-up visit. Results. In both groups significant decrease of TSH and BMI z-score values were noted. TSH normalized in 80.9% of children from Group 1 versus 90.5% from Group 2, p = NS. Delta BMI z-score was insignificantly higher in Group 1 compared to Group 2. Delta TSH was significantly related to initial TSH level in children treated by lifestyle intervention program only. Conclusions. In obese children with sHT dietary-behavioral management intervention contributed to reduction of body mass index, irrespective of levothyroxine use. This finding suggests that moderately elevated levels of TSH are a consequence rather than cause of overweight and pharmacological treatment should be avoided. Pawel Matusik, Aneta Gawlik, Aleksandra Januszek-Trzciakowska, and Ewa Malecka-Tendera Copyright © 2015 Pawel Matusik et al. All rights reserved. Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives Thu, 02 Jul 2015 06:22:51 +0000 Osteoarthritis is a debilitating and degenerative disease which affects millions of people worldwide. The causes and mechanisms of osteoarthritis remain to be fully understood. Vitamin D has been hypothesised to play essential roles in a number of diseases including osteoarthritis. Many cell types within osteoarthritic joints appear to experience negative effects often at increased sensitivity to vitamin D. These findings contrast clinical research which has identified vitamin D deficiency to have a worryingly high prevalence among osteoarthritis patients. Randomised-controlled trial is considered to be the most rigorous way of determining the effects of vitamin D supplementation on the development of osteoarthritis. Studies into the effects of low vitamin D levels on pain and joint function have to date yielded controversial results. Due to the apparent conflicting effects of vitamin D in knee osteoarthritis, further research is required to fully elucidate its role in the development and progression of the disease as well as assess the efficacy and safety of vitamin D supplementation as a therapeutic strategy. Thomas Mabey and Sittisak Honsawek Copyright © 2015 Thomas Mabey and Sittisak Honsawek. All rights reserved. Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves’ Orbitopathy Mon, 29 Jun 2015 11:43:38 +0000 Aim. To study the efficacy and safety of subantimicrobial dose (SD) doxycycline(50 mg/d) in patients with active and moderate-to-severe Graves’ orbitopathy (GO). Methods. Thirteen patients with active and moderate-to-severe GO received once daily oral doxycycline (50 mg/d) for 12 wk. Treatment response at 24 wk was used as the primary outcome, measured by a composite of improvement in Clinical Activity Score (CAS), diplopia, motility, soft tissue swelling, proptosis, and eyelid aperture. Secondary outcome was the change of quality of life score (QoL, including visual functioning subscale and appearance subscale). Adverse events were also recorded. Results. Overall improvement was noted in eight out of 13 patients (61.5%, 95% CI 31.6%–86.1%). Both CAS and soft tissue swelling significantly ameliorated in eight patients at 24 wk. Five patients (38.5%) had improvement in ocular motility of ≥8 degrees. Eyelid aperture (46.2%) also decreased remarkably. For QoL, a significant improvement in appearance subscale () was noted during the study, whereas no difference was observed in visual functioning subscale (). Two patients reported mild stomachache at 12 wk. Conclusions. SD doxycycline appears to be effective and safe for the treatment of active and moderate-to-severe GO. It might serve as a new promising therapeutic strategy for GO. This trial is registered with NCT01727973. Miaoli Lin, Yuxiang Mao, Siming Ai, Guangming Liu, Jian Zhang, Jianhua Yan, Huasheng Yang, Aimin Li, Yusha Zou, and Dan Liang Copyright © 2015 Miaoli Lin et al. All rights reserved. Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study Sun, 28 Jun 2015 12:28:17 +0000 The clinical utility of the functional TSH receptor autoantibodies was prospectively evaluated in patients with thyroid-associated orbitopathy (TAO). Ophthalmic, endocrine, and serological investigations were performed in 101 consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb) and blocking (TBAb) antibody levels were measured with two bioassays using cells that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results are expressed as percentage of specimen-to-reference ratio (SRR %). Blocking activity is defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone. All 101 consecutively followed-up patients with severe and active TAO were TBAb negative. In contrast, 91 (90%) were TSAb positive of whom 90 had Graves’ disease. Serum TSAb levels correlated with the diplopia score (), total severity eye score (), proptosis (), lid aperture (), upper lid retraction (), keratopathy (), and thyroid binding inhibiting immunoglobulins (TBII, ) and negatively with the duration of TAO (). Median serum values of TSAb were SRR% 418 (range 28% to 795%). TSAb, not TBAb, are highly prevalent in severe/active TAO and serum TSAb levels correlate with clinical disease severity. E. Kampmann, T. Diana, M. Kanitz, D. Hoppe, and G. J. Kahaly Copyright © 2015 E. Kampmann et al. All rights reserved. Results after En Bloc Lateral Wall Decompression Surgery with Orbital Fat Resection in 111 Patients with Graves’ Orbitopathy Sun, 28 Jun 2015 12:17:15 +0000 Purpose. To evaluate the effect of en bloc lateral wall decompression with additional orbital fat resection in terms of exophthalmos reduction and complications. Methods. A retrospective, noncomparative case series study from 1999 to 2011 (chart review) in Graves’ orbitopathy (GO) patients. The standardized surgical technique involved removal of the lateral orbital wall including the orbital rim via a lid crease approach combined with additional orbital fat resection. Exophthalmos, diplopia, retrobulbar pressure sensation, and complications were analyzed pre- and postoperatively. Results. A total of 111 patients (164 orbits) with follow-up >3 months were analysed. Mean exophthalmos reduction was 3.05mm and preoperative orbital pressure sensation resolved or improved in all patients. Visual acuity improved significantly in patients undergoing surgery for rehabilitative or vision threatening purposes. Preoperative diplopia improved in 10 patients (9.0%) but worsened in 5 patients (4.5%), necessitating surgical correction in 3 patients. There were no significant complications; however, one patient had slight hollowing of the temporalis muscle around the scar that did not necessitate revision, and another patient with a circumscribed retraction of the scar itself underwent surgical correction. Conclusions. The study confirms the efficiency of en bloc lateral wall decompression in GO in a large series of patients, highlighting the low risk of disturbance of binocular functions and of cosmetic blemish in the temporal midface region. Nicole Fichter and Rudolf F. Guthoff Copyright © 2015 Nicole Fichter and Rudolf F. Guthoff. All rights reserved. Predictors of the Dose-Effect Relationship regarding Unilateral Inferior Rectus Muscle Recession in Patients with Thyroid Eye Disease Sun, 28 Jun 2015 11:42:19 +0000 Purpose. To evaluate whether inferior rectus muscle (IRM) thickness, the degree of adipose change in the IRM, smoking status, and the previous history of orbital radiotherapy can predict the dose-effect relationship regarding unilateral IRM recession in thyroid eye disease (TED). Methods. Twenty-five patients were retrospectively reviewed. We calculated the largest IRM cross-sectional area and evaluated the degree of adipose change in the IRM using magnetic resonance imaging. The degree of adipose change and smoking status were classified using grading scales (0–3); previous orbital radiotherapy was graded as 0 when a history was not available and 1 when it was available. The correlation between the dose-effect relationship and the hypothesized predictive factors was evaluated using stepwise multiple regression analysis. Results. The multiple regression model, with the exception of the history of the previous orbital radiotherapy, estimated a significant dose-effect relationship for the parameters evaluated ( = 0.013XIRM AREA  − 0.222XADIPOSE  − 0.102XSMOKING + 1.694; r = 0.668; adjusted r2 = 0.367; P = 0.005). Conclusions. The dose-effect relationship regarding unilateral IRM recession in TED could be predicted using IRM thickness, degree of intramuscular adipose change, and smoking status but could not be predicted using the previous orbital radiotherapy history. Yasuhiro Takahashi and Hirohiko Kakizaki Copyright © 2015 Yasuhiro Takahashi and Hirohiko Kakizaki. All rights reserved. Liver Dysfunction Associated with Intravenous Methylprednisolone Pulse Therapy in Patients with Graves’ Orbitopathy Sun, 28 Jun 2015 11:29:36 +0000 Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment for the active phase of moderate to severe Graves’ orbitopathy (GO). However, acute and severe liver damage has been reported during and after IVMP therapy. In this retrospective study, we investigated risk factors for liver dysfunction during and after IVMP therapy based on 175 Japanese patients with moderate to severe GO and treated at our center between 2003 and 2011. The results showed that seven patients developed severe liver dysfunction with elevated serum alanine aminotransferase (ALT > 300 U/L). Mild (40–100 U/L) and moderate (100–300 U/L) increases of ALT occurred in 62 patients (35%) and 10 patients (6%), respectively. Liver dysfunction was more frequently observed in males, in patients receiving high-dose methylprednisolone, and patients aged over 50 years. Preexistent viral hepatitis was significantly associated with liver dysfunction (65% in patients positive for hepatitis B core antibody and patients positive for hepatitis C virus antibodies). Our study confirmed the association of liver dysfunction with IVMP during and after treatment. It suggests that, in patients with GO, evaluation of preexisting risk factors—including viral hepatitis—and careful weekly monitoring of liver function during IVMP therapy and monthly thereafter for 12 months are warranted. Hiroyuki Eguchi, Junichi Tani, Saori Hirao, Munehisa Tsuruta, Ichiro Tokubuchi, Kentaro Yamada, Masataka Kasaoka, Yasuo Teshima, Tatsuyuki Kakuma, and Yuji Hiromatsu Copyright © 2015 Hiroyuki Eguchi et al. All rights reserved. Cushing’s Disease: The Relevance of a Combined Dexamethasone Desmopressin Test as a Component of Postoperative Hormonal Evaluation Mon, 22 Jun 2015 11:37:17 +0000 Background. The risk of Cushing’s disease (CD) recurring may persist for years, even after initially successful surgery. Objective. To prospectively assess the relevance of a combined dexamethasone desmopressin test (CDDT) as a component of postoperative hormonal evaluation, including the dynamics of ACTH and cortisol concentrations. Material and Methods. We included 28 patients after TSS for CD. Eighteen months after surgery the standard hormonal evaluation was performed, followed by a CDDT. Results. Fifteen patients (53.6%) were in remission whereas in 13 subjects (46.4%) hypercortisolemia was confirmed. Positive results of CDDT were observed in 12 noncured patients (92.3%) and in one subject in remission (6.7%). Negative results were obtained in 12 patients with remission (80%) and in one noncured patient (7.7%). With 2 patients in CD remission (13.3%) the test results were inconclusive. We confirmed a high compatibility between CDDT and standard hormonal assessment results (; ). Significant differences in ACTH and cortisol levels at each CDDT time point between the two studied subgroups were shown. Conclusions. A negative CDDT result can be regarded as one of the factors indicative of CD remission during follow-up. Additionally, CDDT can help distinguish persistent hypercortisolemia from naturally recurring adrenal function after TSS. Przemysław Witek, Grzegorz Zieliński, and Katarzyna Szamotulska Copyright © 2015 Przemysław Witek et al. All rights reserved. Gender-Specific Effect of -102G>A Polymorphism in Insulin Induced Gene 2 on Obesity in Chinese Children Tue, 16 Jun 2015 13:11:48 +0000 Background. Insulin induced gene 2 (INSIG2) encodes a protein that has a biological effect on regulation of adipocyte metabolism and body weight. This study aimed to investigate the association of INSIG2 gene -102G>A polymorphism with obesity related phenotypes in Chinese children and test gender-specific effects. Methods. The 2,030 independent individuals aged from 7 to 18 years, including 705 obese cases and 1,325 nonobese controls, were recruited from local schools. We measured the obesity-related phenotypes and detected the serum lipids. We genotype -102G>A polymorphism by using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results. In all individuals, we found that the GG/GA genotype of INSIG2 -102G>A polymorphism was associated with risk of severe obesity (OR = 1.62, 95% CI: 1.11–2.36, and ) under the dominant model. The association with severe obesity existed only in boys (OR = 1.91, 95% CI: 1.15–3.17, ). The GG/GA genotype of -102G>A polymorphism was also associated with higher waist circumference ( cm, ) in boys. No similar association was found in girls. The polymorphism was not associated with other obesity-related phenotypes, neither in all individuals nor in gender-specific population. Conclusions. This study identified a gender-specific effect of INSIG2 -102G>A polymorphism on risk of severe obesity and waist circumference in Chinese boys. Fang-Hong Liu, Jie-Yun Song, Yi-Ning Zhang, Jun Ma, and Hai-Jun Wang Copyright © 2015 Fang-Hong Liu et al. 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