International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. The Estimation of First-Phase Insulin Secretion by Using Components of the Metabolic Syndrome in a Chinese Population Sun, 01 Mar 2015 09:16:05 +0000 Aims. There are two phases of insulin secretion, the first (FPIS) and second phase (SPIS). In this study, we built equations to predict FPIS with metabolic syndrome (MetS) components and fasting plasma insulin (FPI). Methods. Totally, 186 participants were enrolled. 75% of participants were randomly selected as the study group to build equations. The remaining 25% of participants were selected as the external validation group. All participants received a frequently sampled intravenous glucose tolerance test, and acute insulin response after the glucose load (AIRg) was obtained. The AIRg was considered as FPIS. Results. When MetS components were only used, the following equation was built: log (FPIS) = 1.477 − 0.119 × fasting plasma glucose (FPG) + 0.079 × body mass index (BMI) − 0.523 × high-density lipoprotein cholesterol (HDL-C). After FPI was added, the second equation was formulated: log (FPIS) = 1.532 − 0.127 × FPG + 0.059 × BMI - 0.511 × HDL-C + 0.375 × log (FPI), which provided a better accuracy than the first one. Conclusions. Using MetS components, the FPIS could be estimated accurately. After adding FPI into the equation, the predictive power increased further. We hope that these equations could be widely used in daily practice. Jiunn-diann Lin, Chun-Hsien Hsu, Yao-Jen Liang, Wei-Cheng Lian, Chang-Hsun Hsieh, Chung-Ze Wu, Dee Pei, and Yen-Lin Chen Copyright © 2015 Jiunn-diann Lin et al. All rights reserved. Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer Wed, 25 Feb 2015 11:42:30 +0000 Purpose. To understand the role of polymorphisms in the LEP (rs7799039 and rs2167270) and LEPR (rs1137101 and rs1137100) genes in DTC susceptibility and their effect on leptin levels. Methods. We studied 153 patients with DTC and 234 controls through TaqMan SNP Genotyping and ELISA, comparing these data to the clinicopathological data of patients with DTC. Results. Patients with AA genotype of rs7799039 had higher levels of serum leptin ( ng/mL) than those with AG genotype ( ng/mL; ). Individuals with AG genotype of rs2167270 also produced higher serum leptin levels ( ng/mL) than the subjects with GG genotype ( ng/mL; ). A multivariate logistic regression adjusted for gender, age, and BMI showed that the AG genotype of rs7799039 was an independent risk for DTC (OR, 11.689; ; 95% CI, 1.516–90.119). Similarly, AG and GG genotypes of rs1137101 increased the susceptibility to DTC (OR, 3.747; ; 95% CI, 1.161–12.092 and OR, 5.437; ; 95% CI, 1.426–20.729). Conclusions. We demonstrated that rs7799039 and rs2167270 polymorphisms modify the serum leptin concentrations in patients with DTC. Furthermore, polymorphisms rs7799039 and rs1137101 increase the risk of DTC development, although they do not correlate with tumor aggressiveness. Marjory Alana Marcello, Antonio Ramos Calixto, Jacqueline Fatima Martins de Almeida, Mariana Bonjiorno Martins, Lucas Leite Cunha, Camila Ayume Amano Cavalari, Elba C. S. Etchebehere, Ligia Vera Montalli da Assumpção, Bruno Geloneze, Andre Lopes Carvalho, and Laura Sterian Ward Copyright © 2015 Marjory Alana Marcello et al. All rights reserved. Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature Tue, 24 Feb 2015 06:47:53 +0000 Malnutrition and starvation’s possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. Janina Kueper, Shaul Beyth, Meir Liebergall, Leon Kaplan, and Josh E. Schroeder Copyright © 2015 Janina Kueper et al. All rights reserved. Expression of P450arom and Estrogen Receptor Alpha in the Oviduct of Chinese Brown Frog (Rana dybowskii) during Prehibernation Mon, 23 Feb 2015 14:22:34 +0000 One specific physiological phenomenon of Chinese brown frog (Rana dybowskii) is that its oviduct expands prior to hibernation instead of expanding during the breeding period. In this study, we investigated the expression of P450arom and estrogen receptors α and β (ERα and ERβ) in the oviduct of Rana dybowskii during the breeding period and prehibernation. The results of the present study showed that there were significant differences in both oviductal weight and size with values markedly higher in prehibernation than in the breeding period. P450arom was observed in stromal tissue in both the breeding period and prehibernation. ERα was expressed in stromal tissue and epithelial cells in both periods, whereas ERβ could not be detected. The mean protein and mRNA levels of P450arom and ERα were significantly higher in prehibernation as compared to the breeding period. Besides, oviductal content of 17β-estradiol was also higher in prehibernation than in the breeding period. These results suggested that estrogen may play autocrine/paracrine roles mediated by ERα in regulating the oviductal hypertrophy during prehibernation. Ji Weng, Yuning Liu, Ying Xu, Ruiqi Hu, Haolin Zhang, Xia Sheng, Gen Watanabe, Kazuyoshi Taya, Qiang Weng, and Meiyu Xu Copyright © 2015 Ji Weng et al. All rights reserved. Ejaculate Oxidative Stress Is Related with Sperm DNA Fragmentation and Round Cells Mon, 23 Feb 2015 07:06:09 +0000 Oxidative stress (OS) plays an essential role in male infertility aetiology by affecting sperm quality, function, and also the integrity of sperm DNA. The assessment of oxidative stress in semen may be an important tool to improve the evaluation of sperm reproductive capacity. The purpose of this study was the evaluation of any possible relation between the unbalance of oxidative stress caused by superoxide anion in the ejaculate with the presence of sperm DNA fragmentation and high concentration of round cells. 56 semen samples from males from couples suffering from infertility were evaluated according to World Health Organisation (WHO) 2010 guidelines. Oxidative stress levels from N1 (low) to N4 (high) were assessed in ejaculates using oxiSperm; DFI (sperm DNA fragmentation index) as assessed by the SCSA (Sperm Chromatin Structure Assay) was used for evaluation of sperm chromatin integrity. Our data show that high oxidative stress (N3-N4 levels) correlated positively with a % and round cells 1.500.000/mL . In conclusion, OS increases sperm DNA damage. Thus evaluation of semen OS extent of sperm DNA damage in infertile man could be useful to develop new therapeutic strategies and improve success of assisted reproduction techniques (ART). Valeria Maria Iommiello, Elena Albani, Alessandra Di Rosa, Alessandra Marras, Francesca Menduni, Giovanna Morreale, Shanti Lia Levi, Benedetta Pisano, and Paolo Emanuele Levi-Setti Copyright © 2015 Valeria Maria Iommiello et al. All rights reserved. Insulin Increases Sestrin 2 Content by Reducing Its Degradation through the PI3K/mTOR Signaling Pathway Sun, 22 Feb 2015 12:04:10 +0000 Sestrin (SESN) is known as a cysteine sulfinic acid reductase. Recently, nonredox functions of SESN in metabolic regulation and antitumor property have been recognized. While mechanisms underlying the expression of SESN are not fully understood. Here we report that insulin markedly increased SESN2 level in HepG2 cells through mTOR activation. To determine whether insulin affects SESN2 degradation, we assessed SESN2 turnover by applying the protein synthesis inhibitor, cycloheximide (CHX), and found that following insulin treatment SESN2 protein levels were reduced significantly slower than non-insulin-treated cells. Furthermore, the proteasomal inhibitor, MG132, dramatically increased SESN2 protein and its ubiquitination level while in the presence of MG132 insulin did not further increase SESN2 content, suggesting that insulin increases SESN2 content mainly via inhibiting its proteasomal degradation. We then explored the potential feedback role of SESN2 in insulin signaling by SESN2 siRNA knockdown in HepG2 cells. Following SESN2 knockdown insulin-stimulated PKB phosphorylation was enhanced and accompanied by reduced PTEN content. Taken together, our study suggests that insulin upregulates SESN2 content via the PI3K/mTOR signaling pathway and this effect is attributed to decreased SESN2 degradation. Furthermore, SESN2 via modulating PTEN plays a negative feedback role in insulin signaling. Dandan Chai, Guoyu Wang, Ziyu Zhou, Hanyan Yang, and Zhiwen Yu Copyright © 2015 Dandan Chai et al. All rights reserved. The “Lipid Accumulation Product” Is Associated with 2-Hour Postload Glucose Outcomes in Overweight/Obese Subjects with Nondiabetic Fasting Glucose Sun, 22 Feb 2015 11:46:35 +0000 “Lipid accumulation product” (LAP) is a continuous variable based on waist circumference and triglyceride concentration previously associated with insulin resistance. We investigated the accuracy of LAP in identifying oral glucose tolerance test (OGTT) abnormalities and compared it to the homeostasis model assessment of insulin resistance (HOMA-IR) in a population of overweight/obese outpatients presenting with nondiabetic fasting glucose. We studied 381 (male: 23%) adult (age: 18–70 years) overweight/obese Caucasians (body mass index: 36.9 ± 5.4 Kg/m2) having fasting plasma glucose < 7.0 mmol/L. OGTT was used to diagnose unknown glucose tolerance abnormalities: impaired glucose tolerance (IGT) and type-2 diabetes mellitus (T2-DM). According to OGTT 92, subjects had an IGT and 33 were diagnosed T2-DM. Logistic regression analysis detected a significant association for both LAP and HOMA-IR with single (IGT and T2-DM) and composite (IGT + T2-DM) abnormal glucose tolerance conditions. However, while the association with diabetes was similar between LAP and HOMA-IR, the relationship with IGT and composite outcomes by models including LAP was significantly superior to those including HOMA-IR ( and , resp.). LAP seems to be an accurate index, performing better than HOMA-IR, for identifying 2-hour postload OGTT outcomes in overweight/obese patients with nondiabetic fasting glucose. Alexis Elias Malavazos, Emanuele Cereda, Federica Ermetici, Riccardo Caccialanza, Silvia Briganti, Mariangela Rondanelli, and Lelio Morricone Copyright © 2015 Alexis Elias Malavazos et al. All rights reserved. Effects of β-Hydroxy-β-methylbutyrate Free Acid Ingestion and Resistance Exercise on the Acute Endocrine Response Sun, 22 Feb 2015 10:15:41 +0000 Objective. To examine the endocrine response to a bout of heavy resistance exercise following acute β-hydroxy-β-methylbutyrate free acid (HMB-FA) ingestion. Design. Twenty resistance trained men were randomized and consumed either 1 g of HMB-FA (BetaTor) or placebo (PL) 30 min prior to performing an acute heavy resistance exercise protocol. Blood was obtained before (PRE), immediately after (IP), and 30 min after exercise (30P). Circulating concentrations of testosterone, growth hormone (GH), insulin-like growth factor (IGF-1), and insulin were assayed. Data were analyzed with a repeated measures ANOVA and area under the curve (AUC) was analyzed by the trapezoidal rule. Results. The resistance exercise protocol resulted in significant elevations from PRE in testosterone , GH , and insulin at IP, with GH and insulin remaining elevated at 30P. A significant interaction was noted between groups in the plasma GH response at IP, which was significantly higher following HMB-FA compared to PL . AUC analysis revealed an elevated GH and IGF-1 response in the HMB-FA group compared to PL. Conclusion. HMB-FA prior to resistance exercise augments the GH response to high volume resistance exercise compared to PL. These findings provide further support for the potential anabolic benefits associated with HMB supplementation. Jeremy R. Townsend, Jay R. Hoffman, Adam M. Gonzalez, Adam R. Jajtner, Carleigh H. Boone, Edward H. Robinson, Gerald T. Mangine, Adam J. Wells, Maren S. Fragala, David H. Fukuda, and Jeffrey R. Stout Copyright © 2015 Jeremy R. Townsend et al. All rights reserved. Antithyroid Antibodies and Thyroid Function in Pediatric Patients with Celiac Disease Thu, 19 Feb 2015 12:46:34 +0000 Objective. Aim of the study was to determine the prevalence of autoimmune thyroid disease, persistence of antithyroid antibodies, effect of gluten-free diet, and long-term outcome of thyroid function in pediatric patients with celiac disease (CD). Methods. 67 patients with CD aged from 1 year to 16 years were screened for thyroid antithyroperoxidase, antithyroglobulin and anti-TSH receptor antibodies, serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone (TSH) at diagnosis and during follow-up. Results. None of the patients had antithyroid antibodies at diagnosis. Antithyroid antibodies became positive in 16.4% of the patients (11/67) 2 to 3 years after the diagnosis of CD. Clinical hypothyroidism was observed only in 3 of 11 CD patients with positive antithyroid antibodies (27.2%). The antithyroid antibodies positive and negative patients did not differ significantly according to compliance to GFD (). A statistically significant difference was observed only in age, in which the patients with positive antithyroid antibodies were younger than the patients with negative antithyroid antibodies (). None of the patients had any change in their thyroid function and antibody profile during their follow-up. Conclusion. Antithyroid antibodies were detected in younger pediatric patients with CD and the prevalence of antithyroid antibodies did not correlate with the duration of gluten intake. Derya Kalyoncu and Nafiye Urganci Copyright © 2015 Derya Kalyoncu and Nafiye Urganci. All rights reserved. High Serum IgG4 Concentrations in Patients with Hashimoto’s Thyroiditis Mon, 16 Feb 2015 13:15:09 +0000 Purpose. Since recent reports suggest that Hashimoto thyroiditis (HT) may be associated with IgG4-related disease, we aimed to find out whether the measurement of serum IgG4 allows for the identification of distinct types of HT, with different clinical, sonographic, and serologic characteristics. Methods. The group studied consisted of 53 patients with HT and 28 healthy individuals who underwent thyroid ultrasonography and body composition analysis. Serum concentrations of IgG4, TSH, anti-peroxidase antibodies (TPOAb), anti-TSH receptor antibodies, TNF-α, TGF-β1, Fas Ligand, TRAIL, and chemokines (CXCL9, CXCL11, and CXCL10) were measured by ELISA or radioimmunoassay. Results. The group with IgG4 level >135 IU/ml accounted for 32.5% of the patients. The signs of fibrosis were present in 27.0% of the high-IgG4 patients and in 9.1% of the normal-IgG4 group. The patients with elevated IgG4 required higher doses of L-thyroxine and had significantly lower level of TPOAb () than the non-IgG4-HT individuals and higher TNF-α level in comparison with the controls (). Conclusions. Our results suggest that the measurement of serum IgG4 allows for an identification of patients with more rapid progression of HT, requiring higher doses of L-thyroxine. Low TPOAb level and the absence of coexisting autoimmune diseases may suggest distinct pathomechanism of this type of thyroiditis. Anna Popławska-Kita, Maria Kościuszko-Zdrodowska, Katarzyna Siewko, Beata Telejko, Justyna Hryniewicka, Robert Milewski, Saeid Soleman Abdelrazek, Małgorzata Szelachowska, and Maria Górska Copyright © 2015 Anna Popławska-Kita et al. All rights reserved. Effect of Weight Loss on Serum Osteocalcin and Its Association with Serum Adipokines Sun, 15 Feb 2015 09:05:22 +0000 Studies have suggested that osteocalcin, a bone formation marker, is related to body metabolism and insulin sensitivity. Whether this relation is mediated through an interaction with adipokines remains unclear. The aim of this study was to assess the effect of weight loss on serum osteocalcin and its relation with three adipokines, adiponectin, chemerin, and resistin. Forty-nine obese nondiabetic males completed a four-month dietary program. Body mass index (BMI) decreased significantly from to (). This was associated with significant reduction in waist circumference, fasting blood glucose, HOMA-IR, total and LDL-cholesterol, bone-specific alkaline phosphatase (BAP), and resistin (). There was significant increase in serum adiponectin and undercarboxylated osteocalcin (uOC) (). The changes in uOC levels were negatively correlated with changes in serum triglycerides (, ) and positively correlated with changes in BAP (, ). In contrast, the changes in uOC were not correlated with changes in BMI, waist circumference, fasting blood glucose, HOMA-IR, total and LDL-cholesterol, hsCRP, vitamin D, and circulating adipokines. We concluded that the increase in serum uOC following weight loss is not related to the changes in circulating adipokines levels. Mohammed S. Albadah, Hafedh Dekhil, Shaffi Ahamed Shaik, Mohammed A. Alsaif, Mustafa Shogair, Shahid Nawaz, and Assim A. Alfadda Copyright © 2015 Mohammed S. Albadah et al. All rights reserved. The Impact of a Pure Protein Load on the Glucose Levels in Type 1 Diabetes Patients Treated with Insulin Pumps Thu, 12 Feb 2015 09:32:01 +0000 We aimed to estimate the impact of ingestion of a pure protein load on the glucose levels in T1DM patients treated with insulin pumps. We examined 10 T1DM patients (6 females, mean age—32.3 years, mean HbA1c—6.8%) treated with insulin pumps equipped with a continuous glucose monitoring system (CGMS). In Phase I, baseline insulin infusion was optimized to minimize the differences in fasting glucose levels to less than 30 mg/dL between any two time points between 9 a.m. and 3 p.m. In Phase II, the patients were exposed to single pure protein load. CGMS record was performed and the glucose pattern was defined for 6 hours of each phase. The maximal glucose level increment was similar for the entire duration of the fasting and the protein load test (26.6 versus 27.6 mg/dL, resp., ). There was only a borderline difference in change between baseline versus 6th hour glucose (12.5 and 19.0 mg/dL, ). Glucose variability, assessed by standard deviation of mean glucose levels, was 36.4 and 37.9 mg/dL, respectively (). The administration of a pure protein load does not seem to have a clinically significant impact on glucose levels in T1DM patients treated with insulin pumps. Tomasz Klupa, Teresa Benbenek-Klupa, Bartlomiej Matejko, Sandra Mrozinska, and Maciej T. Malecki Copyright © 2015 Tomasz Klupa et al. All rights reserved. Corrigendum to “Quality of Life and Sexual Health in the Aging of PCa Survivors” Wed, 11 Feb 2015 12:06:55 +0000 Mauro Gacci, Elisabetta Baldi, Lara Tamburrino, Beatrice Detti, Lorenzo Livi, Cosimo De Nunzio, Andrea Tubaro, Stavros Gravas, Marco Carini, and Sergio Serni Copyright © 2015 Mauro Gacci et al. All rights reserved. Treatment of Prolactinomas in Low-Income Countries Mon, 09 Feb 2015 10:08:03 +0000 Purpose. In low-income countries, prolactinomas are difficult to manage with dopamine agonists (DA). We compared the effectiveness of DA in microprolactinomas as a first line treatment and as adjuvant therapy for residual macroprolactinomas treated surgically. Methods. Our retrospective study analyzed 78 patients, 38 with microprolactinomas and 40 with macroprolactinomas. Microprolactinomas were treated with DA. Macroprolactinomas were treated with microsurgical or endoscopic adenomectomies and adjuvant DA. Surgical remission was defined as normoprolactinemia three months postoperatively, and long-term remission as normoprolactinemia at the last control. Results. Surgical remission was achieved in 9 patients (23%). Postsurgical tumor mass was reduced by 50% (34–68). Residual macroprolactinoma size was greater than microprolactinoma size prior to treatment (10 mm versus 4 mm, ). Both groups received similar doses of DA. Long-term remission occurred in 68% of microprolactinomas and 43% of macroprolactinomas (). Prolactin (PRL) levels at the last control were similar in both groups (23.1 versus 32.9 mcg/L, ). Conclusion. Comparable remission rates and PRL levels were reached in microprolactinomas and macroprolactinomas using similar doses of DA. Although complete tumor resection is the goal of surgery, our study suggests that even partial surgical removal has a role in treatment of prolactinomas since it may enhance the response to DA. Ivan Kruljac, Lora Stanka Kirigin, Mateja Strinović, Jelena Marinković, Hrvoje Ivan Pećina, Vatroslav Čerina, Darko Stipić, and Milan Vrkljan Copyright © 2015 Ivan Kruljac et al. All rights reserved. Clinical Characteristics and Treatment Outcome of 485 Patients with Nonfunctioning Pituitary Macroadenomas Sun, 08 Feb 2015 08:15:50 +0000 Background. Nonfunctioning pituitary adenomas (NFPAs) are the most common benign lesions of the pituitary gland. Objective. To describe our experience with the management of NFPA. Study Design and Methods. Retrospective evaluation of NFPA patients managed between 2008 and 2013. We analyzed data regarding clinical presentation, imaging diagnosis, hormonal status, surgical, radiotherapeutic, and pharmacological treatment, and outcome. Results. 485 patients (54% men, mean age years) were followed for a median of 6.5 years. Visual field abnormalities and headaches were the presenting complaints in 87% and 66%, respectively. The diagnosis of NFPA was made incidentally in 6.2%, and 8% presented with clinical evidence of apoplexy. All patients harbored macroadenomas, with a median volume of 10306 mm3; 57.9% had supra- or parasellar invasion and 19.6% had tumors larger than 4 cm. Central hypothyroidism, hypogonadism, and hypocortisolism were present in 47.2%, 35.9%, and 27.4%, respectively. Surgical resection was performed at least once in 85.7%. Tumor persistence was documented in 27% and was related to the size and invasiveness of the lesion. In selected cases, radiotherapy proved to be effective in controlling or preventing tumor growth. Conclusions. The diagnosis and treatment of NFPA are complex and require a multidisciplinary approach. Guadalupe Vargas, Baldomero Gonzalez, Claudia Ramirez, Aldo Ferreira, Etual Espinosa, Victoria Mendoza, Gerardo Guinto, Blas Lopez-Felix, Erick Zepeda, and Moisés Mercado Copyright © 2015 Guadalupe Vargas et al. All rights reserved. Subclassification of Follicular Neoplasms Recommended by the Japan Thyroid Association Reporting System of Thyroid Cytology Wed, 04 Feb 2015 10:15:31 +0000 Background. The Japan Thyroid Association recently published guidelines for clinical practice for the management of thyroid nodules, which include a diagnostic system for reporting thyroid fine needle aspiration cytology. It is characterized by the subclassification of follicular neoplasms, which is different from other internationally accepted reporting systems. Materials and Methods. This study examined observer variability in the subclassification of follicular neoplasms among 4 reviewers using Papanicolaou-stained smear samples from 20 surgically treated patients with indeterminate cytology. Results. The favor malignant subcategory had high predictive value of malignancy (risk of malignancy: 60–75%) and good agreement among the 4 reviewers . Conclusion. These results clearly confirmed that the risk stratification of follicular neoplasms, which was adapted from cytology practice of high-volume thyroid centers in Japan, can provide clinically helpful information to estimate the risk of malignancy and to triage patients for surgery. Kennichi Kakudo, Kaori Kameyama, Mitsuyoshi Hirokawa, Ryohei Katoh, and Hirotoshi Nakamura Copyright © 2015 Kennichi Kakudo et al. All rights reserved. Sexual Absorption of Vaginal Progesterone: A Randomized Control Trial Tue, 03 Feb 2015 08:13:38 +0000 Objective. To determine if sexual intercourse reduces absorption of vaginal progesterone gel in women and to determine if progesterone is absorbed by the male during intercourse. Study Design. Prospective, randomized, cross over, controlled study of 20 reproductive-aged women and their male sexual partners randomized to receive vaginal progesterone gel (Crinone 8% gel, Actavis Inc., USA) or placebo cream. Serum progesterone for both male and female partners were measured 10 hours after intercourse. One week later, subjects were crossed over to receive the opposite formulation. In the third week, women used progesterone gel at night and abstained from intercourse. Results. Serum progesterone was significantly reduced with vaginal progesterone gel + intercourse compared with vaginal progesterone gel + abstinence . Men absorbed significant progesterone during intercourse with a female partner using vaginal progesterone gel compared to placebo . Conclusion(s). Vaginal progesterone gel is reduced in women after intercourse which may decrease drug efficacy during luteal phase support. Because men absorb low levels of progesterone during intercourse, exposure could cause adverse effects such as decreased libido. This study is registered under Clinical Trial number NCT01959464. Kathryn S. Merriam, Kristina A. Leake, Mollie Elliot, Michelle L. Matthews, Rebecca S. Usadi, and Bradley S. Hurst Copyright © 2015 Kathryn S. Merriam et al. All rights reserved. Value of 18-F-FDG PET/CT and CT in the Diagnosis of Indeterminate Adrenal Masses Mon, 02 Feb 2015 13:49:20 +0000 The purpose of this paper was to study the value of 18-FDG PET/CT and reassess the value of CT for the characterization of indeterminate adrenal masses. 66 patients with 67 indeterminate adrenal masses were included in our study. CT/MRI images and 18F-FDG PET/CT data were evaluated blindly for tumor morphology, enhancement features, apparent diffusion coefficient values, maximum standardized uptake values, and adrenal-to-liver maxSUV ratio. The study population comprised pathologically confirmed 16 adenomas, 19 metastases, and 32 adrenocortical carcinomas. Macroscopic fat was observed in 62.5% of the atypical adenomas at CT but not in malignant masses. On 18F-FDG PET/CT, SUVmax and adrenal-to-liver maxSUV ratio were significantly lower in adenomas than in malignant tumors. An SUVmax value of less than 3.7 or an adrenal-to-liver maxSUV ratio of less than 1.29 is highly predictive of benignity. Nathalie Launay, Stéphane Silvera, Florence Tenenbaum, Lionel Groussin, Frédérique Tissier, Etienne Audureau, Olivier Vignaux, Bertrand Dousset, Xavier Bertagna, and Paul Legmann Copyright © 2015 Nathalie Launay et al. All rights reserved. Anaplastic Thyroid Carcinoma: Molecular Tools for Diagnosis and Therapy Sat, 31 Jan 2015 10:30:46 +0000 Ginesa Garcia-Rostan, Giovanni Tallini, and Giuliana Salvatore Copyright © 2015 Ginesa Garcia-Rostan et al. All rights reserved. Targeting Bone Metabolism in Patients with Advanced Prostate Cancer: Current Options and Controversies Sat, 31 Jan 2015 08:27:50 +0000 Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC) who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL), antiresorptive agents have been shown to improve bone mineral density (BMD) and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs) in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy. Tilman Todenhöfer, Arnulf Stenzl, Lorenz C. Hofbauer, and Tilman D. Rachner Copyright © 2015 Tilman Todenhöfer et al. All rights reserved. Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line Thu, 29 Jan 2015 07:10:01 +0000 Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated. The ATC-derived cell line SW1736 has been treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the PARP inhibitor PJ34, alone or in combination. In terms of cell viability, the combination index value was always lower than 1 at various tested dosages, indicating, therefore, synergy in a wide range of doses for both compounds. Synergy was also observed in induction of apoptosis. In terms of thyroid-specific gene expression, synergy was observed for TSHR mRNA levels but not for NIS, TTF1, TTF2, and PAX8 mRNA levels. Altogether, these data suggest that the combined use of HDAC and PARP inhibitors may be a useful strategy for treatment of ATC. Federica Baldan, Catia Mio, Lorenzo Allegri, Cinzia Puppin, Diego Russo, Sebastiano Filetti, and Giuseppe Damante Copyright © 2015 Federica Baldan et al. All rights reserved. Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis Thu, 29 Jan 2015 06:46:44 +0000 It has been suggested that cancer stem cells (CSC) may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC) has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA) analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2), in the control cell cycle (TP53, CCND1), and in mitochondrial activity (COX8A). The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated. Walter Arancio, Valeria Carina, Giuseppe Pizzolanti, Laura Tomasello, Maria Pitrone, Concetta Baiamonte, Marco Calogero Amato, and Carla Giordano Copyright © 2015 Walter Arancio et al. All rights reserved. Regulation of the Human Ghrelin Promoter Activity by Transcription Factors, NF-κB and Nkx2.2 Wed, 28 Jan 2015 11:25:50 +0000 To examine the gene expression of ghrelin, a growth hormone releasing and appetite stimulating hormone from stomach, we constructed human ghrelin promoter-reporter vectors and analyzed the promoter activity. The ghrelin promoter activity was high when cultured cells that express ghrelin mRNA endogenously like TT or ECC10 cells were used, indicating that these cells contain factors necessary for full expression of the human ghrelin gene. The human ghrelin promoter contains both positive and negative regulatory regions. A transient decrease of the promoter activity was found when the reporter vector with the −1600 fragment of the human ghrelin promoter was transfected into cultured cells. We then examined the effect of several transcription factors on the ghrelin promoter activity and found that NF-κB suppressed and that Nkx2.2, a homeodomain-containing transcription factor that is important for ghrelin cell development in pancreas, activates the promoter activity. These transcription factors may be possible targets for the control of ghrelin gene expression. Yuki Shiimura, Hideko Ohgusu, Takahiro Sato, and Masayasu Kojima Copyright © 2015 Yuki Shiimura et al. All rights reserved. Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated? Wed, 28 Jan 2015 09:40:51 +0000 Objective. This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients. Design and Methods. 86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study. Results. FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (, ), FT4 (, ), or TSH (, ) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 ( and ) but not between Ki67 and FT4 ( and ) or TSH ( and ). In HER2(−) patients, there was no significant correlation between Ki67 and FT3 (, ), FT4 (, ), or TSH (, ). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(−) tumors. No difference was detected in phospho-p42/total p42 ERK levels. Conclusions. TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling. Iordanis Mourouzis, Alexandros Tzovaras, Basil Armonis, Alexandros Ardavanis, Maria Skondra, John Misitzis, Demetrios Pectasides, and Constantinos Pantos Copyright © 2015 Iordanis Mourouzis et al. All rights reserved. Clinicopathological Risk Factors and Biochemical Predictors of Safe Discharge after Total Thyroidectomy and Central Compartment Node Dissection for Thyroid Cancer: A Prospective Study Mon, 26 Jan 2015 11:47:52 +0000 To determine the clinicopathological risk factors and reliable biochemical predictors of the development of hypocalcemic symptoms after total thyroidectomy on the basis of serum calcium and intact parathyroid hormone (PTH) levels measured 1 hour after surgery, a prospective study was performed on 817 patients who underwent a total thyroidectomy with central compartment node dissection (CCND) due to well-differentiated thyroid cancer. We evaluated the correlations between hypocalcemic symptom development and clinicopathological factors. And the predictability for hypocalcemic symptom development of intact PTH cut-offs (<10 pg/mL and <20 pg/mL, resp.) according to serum calcium level subgroup was analyzed. Female gender () was the only independent risk factor for hypocalcemic symptom development in multivariate regression analysis. The negative predictive value (NPV) of intact PTH, signifying nondevelopment of hypocalcemic symptoms, was higher than the positive predictive value (PPV) which signified development of hypocalcemic symptoms. In addition, when we applied the different adoption of the intact PTH cut-off according to serum calcium level, we could obtain more increased NPVs. A female gender and the application of more specific cut-offs for intact PTH according to the serum calcium levels measured 1 hour after surgery may help the patients to be more safely discharged. Yu-mi Lee, Ja Young Cho, Tae-Yon Sung, Tae Yong Kim, Ki-Wook Chung, Suck Joon Hong, and Jong Ho Yoon Copyright © 2015 Yu-mi Lee et al. All rights reserved. Determinants of Vitamin D Levels in Children and Adolescents with Down Syndrome Tue, 20 Jan 2015 06:19:20 +0000 Background. Poor studies have evaluated 25-hydroxycholecalciferol (25(OH)D) levels in Down syndrome (DS). Objective. To assess in DS subjects serum 25(OH)D value, to identify risk factors for vitamin D deficiency, and to evaluate whether a normal 25(OH)D value can be restored with a 400 I.U. daily supplement of cholecalciferol in respect to controls. Methods. We have longitudinally evaluated 31 DS patients (aged 4.5–18.9 years old) and 99 age- and sex-matched healthy controls. In these subjects, we analysed calcium, phosphate, parathyroid hormone (PTH), 25(OH)D concentrations, and calcium and 25(OH)D dietary intakes, and we quantified outdoor exposure. After 12.3 months (range 8.1–14.7 months) of 25(OH)D supplementation, we reevaluated these subjects. Results. DS subjects showed reduced 25(OH)D levels compared to controls (), in particular DS subjects with obesity () and autoimmune diseases history (). PTH levels were significantly higher in DS subjects than controls (). After cholecalciferol supplementation, 25(OH)D levels were significantly ameliorated (), even if reduced compared to controls (), in particular in DS subjects with obesity () and autoimmune diseases (). Conclusions. Hypovitaminosis D is very frequent in DS subjects, in particular in presence of obesity and autoimmune diseases. In these subjects, there could be a need for higher cholecalciferol supplementation. Stefano Stagi, Elisabetta Lapi, Silvia Romano, Sara Bargiacchi, Alice Brambilla, Sabrina Giglio, Salvatore Seminara, and Maurizio de Martino Copyright © 2015 Stefano Stagi et al. All rights reserved. Atherogenic Dyslipidemia and Cardiovascular Risk Factors in Obese Children Mon, 12 Jan 2015 14:12:31 +0000 Childhood obesity when associated with serum lipoprotein changes triggers atherosclerosis. Evidences suggest that the atherosclerotic process begins in childhood and that the extent of early atherosclerosis of the aorta and coronary arteries can be associated with lipoprotein levels and obesity. Furthermore, many studies in childhood demonstrate an important relationship between parameters of insulin sensitivity, body fat distribution, and the development of lipid abnormalities. This review focuses on the most recent findings on the relationship between obesity, dyslipidemia, and cardiovascular risk in children. Ebe D’Adamo, Ornella Guardamagna, Francesco Chiarelli, Andrea Bartuli, Daniela Liccardo, Federica Ferrari, and Valerio Nobili Copyright © 2015 Ebe D’Adamo et al. All rights reserved. Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy Mon, 12 Jan 2015 12:59:48 +0000 Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures. Kyung-Hee Kim, Min-Hee Kim, Ye-Jee Lim, Ihn Suk Lee, Ja-Seong Bae, Dong-Jun Lim, Ki Hyun Baek, Jong Min Lee, Moo-Il Kang, and Bong-Yun Cha Copyright © 2015 Kyung-Hee Kim et al. All rights reserved. Identification of Differentially Expressed Genes in Pituitary Adenomas by Integrating Analysis of Microarray Data Tue, 06 Jan 2015 13:48:05 +0000 Pituitary adenomas, monoclonal in origin, are the most common intracranial neoplasms. Altered gene expression as well as somatic mutations is detected frequently in pituitary adenomas. The purpose of this study was to detect differentially expressed genes (DEGs) and biological processes during tumor formation of pituitary adenomas. We performed an integrated analysis of publicly available GEO datasets of pituitary adenomas to identify DEGs between pituitary adenomas and normal control (NC) tissues. Gene function analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) networks analysis was conducted to interpret the biological role of those DEGs. In this study we detected 3994 DEGs (2043 upregulated and 1951 downregulated) in pituitary adenoma through an integrated analysis of 5 different microarray datasets. Gene function analysis revealed that the functions of those DEGs were highly correlated with the development of pituitary adenoma. This integrated analysis of microarray data identified some genes and pathways associated with pituitary adenoma, which may help to understand the pathology underlying pituitary adenoma and contribute to the successful identification of therapeutic targets for pituitary adenoma. Peng Zhao, Wei Hu, Hongyun Wang, Shengyuan Yu, Chuzhong Li, Jiwei Bai, Songbai Gui, and Yazhuo Zhang Copyright © 2015 Peng Zhao et al. All rights reserved. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males Mon, 05 Jan 2015 06:38:30 +0000 Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3 and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3 metabolism, the vitamin D3 25-hydroxylase (CYP27A1) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3 CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (, age: 55.7 ± 4.7 years). Two tagging SNPs, CYP27A1 rs4674344 and CYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with the CYP27A1 rs4674344 SNP and the ratio of adiponectin/leptin (A/L ratio) was most correlated to the CYP27A1 rs4674344 SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0, ) and significantly negatively associated after adjustment. For each MetS component associated with the CYP27A1 rs4674344 SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion, CYP27A1 rs4674344 SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage. Kai-Hung Cheng, Edward Hsi, Chia-Chu Liu, Chun-Nung Huang, Yung-Chin Lee, Chih-Sheng Chu, Bo-Ying Bao, Chu-Fen Chang, Shu-Pin Huang, Po-Lin Kuo, and Wen-Ter Lai Copyright © 2015 Kai-Hung Cheng et al. All rights reserved.