International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Regulation of UCP1 in the Browning of Epididymal Adipose Tissue by β3-Adrenergic Agonist: A Role for MicroRNAs Wed, 17 Dec 2014 12:29:55 +0000 Background. White adipose tissue browning may be a promising strategy to combat obesity. UCP1 is strongly induced in White adipose tissue with β3-adrenergic agonist treatment, but the causes of this increase have not been fully elucidated. This study aims to explore more miRNAs involved in the process of browning of visceral adipose tissue. Methods. Total of fourteen mice were randomly divided into control and study group. Study group mice were injected intraperitoneally with CL316243 once daily for seven days; meanwhile the control group were treated with 0.9% NaCl. After a 7-day period, the expression of genes involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues was analyzed by qPCR. Results. qPCR analysis revealed that UCP1, DIO2, CIDEA, and CPT1B in epididymal adipose tissue were overexpressed in CL316243 group. Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose tissue were significantly decreased in CL316243 group. Conclusion. This suggests that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the browning of epididymal adipose tissue by regulating UCP1 gene expression. In this study, we demonstrated that this increase of UCP1 is due, at least in part, to the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose tissue compared to control. Zongji Zheng, Xiaomeng Liu, Qianwei Zhao, Lei Zhang, Chenzhong Li, and Yaoming Xue Copyright © 2014 Zongji Zheng et al. All rights reserved. Interpreting the Consequences of Metformin Accumulation in an Emergency Context: Impact of the Time Frame on the Blood Metformin Levels Wed, 17 Dec 2014 12:24:07 +0000 Objective. To clarify the link between metformin accumulation and its metabolic consequences by taking the time frame for metformin measurement into account. Research Design and Methods. Our database was studied for cases of metformin accumulation and lactic acidosis status available on admission, and then we selected patients in whom arterial pH, blood lactate, and plasma and erythrocyte metformin levels had been determined at the same time point. Results. Seventeen reports were studied on 16 patients, of whom 10 presented lactic acidosis. The time interval between admission and comprehensive testing ranged from 0 to 52 hours. The study parameters were determined simultaneously on admission in only 4 patients. In the 9 patients with lactic acidosis on admission and a delayed metformin assay, lactic acidosis persisted in 6 cases and had resolved in 3 cases by the time the blood sampling for metformin assay was performed. Conversely, lactic acidosis developed after admission in one case. Conclusions. Caution must be taken when interpreting the consequences of metformin accumulation in an emergency context: the patient’s lactic acidosis status will have changed by the time the metformin assay is performed, even though metformin accumulation may still be present. Jean-Daniel Lalau and Farshad Kajbaf Copyright © 2014 Jean-Daniel Lalau and Farshad Kajbaf. All rights reserved. Systematic Review of Surgical Approaches for Adrenal Tumors: Lateral Transperitoneal versus Posterior Retroperitoneal and Laparoscopic versus Robotic Adrenalectomy Wed, 17 Dec 2014 07:49:22 +0000 Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the standard method for resecting benign adrenal gland tumors. Recently, however, laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular as an alternative method. This systematic review evaluates current evidence on adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic adrenalectomy with robotic adrenalectomy. Methods. PubMed, Embase, and ISI Web of Knowledge databases were searched systematically for studies comparing surgical outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic adrenalectomy. The studies were evaluated according to the PRISMA statement. Results. Eight studies comparing laparoscopic PRA and LTA showed that laparoscopic PRA was superior or at least comparable to laparoscopic LTA in operation time, blood loss, pain score, hospital stay, and return to normal activity. Conversion rates and complication rates were similar. Six studies comparing robotic and laparoscopic adrenalectomy found that outcomes and complications were similar. Conclusion. Laparoscopic PRA was more effective than LTA, especially in reducing operation time and hospital stay, but there was no evidence showing that robotic adrenalectomy was superior to laparoscopic adrenalectomy. Cost reductions and further technical advances are needed for wider application of robotic adrenalectomy. Young Jun Chai, Hyungju Kwon, Hyeong Won Yu, Su-jin Kim, June Young Choi, Kyu Eun Lee, and Yeo-Kyu Youn Copyright © 2014 Young Jun Chai et al. All rights reserved. Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in High Blood Pressure: Preliminary Evidence Mon, 15 Dec 2014 11:21:52 +0000 Introduction. Adrenal glands play a major role in the control of blood pressure and mild defects of steroidogenesis and/or inappropriate control of mineralocorticoid production have been reported in high blood pressure (HBP). Patients and Methods. We used a specific protocol for the evaluation of 100 consecutive patients with inappropriate or recent onset HBP. Specific methods were used to confirm HBP and to diagnose secondary forms of HBP. In addition we tested adrenal steroidogenesis with the common cosyntropin test, modified to include the simultaneous measurement of renin and aldosterone besides 17-hydroxyprogesterone (17OHP) and 11-deoxycortisol (S). Results. Secondary forms of HBP were diagnosed in 32 patients, including 14 patients with primary hyperaldosteronism (PA) (14%) and 10 patients with pheochromocytoma (10%). Mild defects of the 21-hydroxylase (21OHD) and 11-hydroxylase (11OHD) enzymes were common (42%). ACTH-dependent aldosterone secretion was found in most patients (54%) and characteristically in those with mild defects of adrenal steroidogenesis (>60%), PA (>75%), and otherwise in patients with apparent essential HBP (EHBP) (32%). Discussion. Mild defects of adrenal steroidogenesis are common in patients with HBP, occurring in almost half of the patients. In those patients as well as in patients with apparent EHBP, aldosterone secretion is commonly dependent on ACTH. João Martin Martins, Sónia do Vale, and Ana Filipa Martins Copyright © 2014 João Martin Martins et al. All rights reserved. Growth Hormone and Reproduction: A Review of Endocrine and Autocrine/Paracrine Interactions Mon, 15 Dec 2014 00:10:44 +0000 The somatotropic axis, consisting of growth hormone (GH), hepatic insulin-like growth factor I (IGF-I), and assorted releasing factors, regulates growth and body composition. Axiomatically, since optimal body composition enhances reproductive function, general somatic actions of GH modulate reproductive function. A growing body of evidence supports the hypothesis that GH also modulates reproduction directly, exerting both gonadotropin-dependent and gonadotropin-independent actions in both males and females. Moreover, recent studies indicate GH produced within reproductive tissues differs from pituitary GH in terms of secretion and action. Accordingly, GH is increasingly used as a fertility adjunct in males and females, both humans and nonhumans. This review reconsiders reproductive actions of GH in vertebrates in respect to these new conceptual developments. Kerry L. Hull and Steve Harvey Copyright © 2014 Kerry L. Hull and Steve Harvey. All rights reserved. Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Reared as Males Sun, 14 Dec 2014 07:52:20 +0000 Background/Aims. Studies on 46,XY partial gonadal dysgenesis (PGD) have focused on molecular, gonadal, genital, and hormone features; little is known about follow-up. Our aim was to analyze long-term outcomes of PGD. Methods. Retrospective longitudinal study conducted at a reference service in Brazil. Ten patients were first evaluated in the 1990s and followed up until the 2010s; follow-up ranged from 13.5 to 19.7 years. All were reared as males and had at least one scrotal testis; two bore NR5A1 mutations. Main outcomes were: associated conditions, pubertal development, and growth. Results. All patients had normal motor development but three presented cognitive impairment; five had various associated conditions. At the end of the prepubertal period, FSH was high or high-normal in 3/6 patients; LH was normal in all. At the last evaluation, FSH was high or high-normal in 8/10; LH was high or high-normal in 5/10; testosterone was decreased in one. Final height in nine cases ranged from −1.57 to 0.80 SDS. All had spontaneous puberty; only one needed androgen therapy. Conclusions. There is good prognosis for growth and spontaneous pubertal development but not for fertility. Though additional studies are required, screening for learning disabilities is advisable. Juliana Gabriel Ribeiro de Andrade, Antonia Paula Marques-de-Faria, Helena Campos Fabbri, Maricilda Palandi de Mello, Gil Guerra-Júnior, and Andréa Trevas Maciel-Guerra Copyright © 2014 Juliana Gabriel Ribeiro de Andrade et al. All rights reserved. Selenium Supplementation for Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis Thu, 11 Dec 2014 07:10:41 +0000 Many studies have reported that selenium (Se) has a close relationship with autoimmune thyroiditis (AIT). The therapeutic effect of Se supplementation in AIT treatment remains unclear. The objective of the present study was to determine the efficacy of Se supplementation for the treatment of AIT. A structured literature search was undertaken to identify all randomized controlled trials conducted in patients with AIT receiving Se supplementation or placebo. Nine studies enrolling a total of 787 patients were included. The results showed that Se supplementation with duration 6 months significantly dropped the TPOAb titers but did not decrease the TgAb titers. Patients assigned to Se supplementation for 12-month duration showed significantly lower TPOAb titers and TgAb titers. Patients after Se supplementation had a higher chance to improve the mood or well-being compared with controls. Se supplementation is associated with a significant decrease in TPOAb titers at 6 and 12 months; meanwhile, the TgAb titers can be dropped at 12 months. After Se supplementation treatment, patients had a higher chance to improve the mood without significant adverse events. Yaofu Fan, Shuhang Xu, Huifeng Zhang, Wen Cao, Kun Wang, Guofang Chen, Hongjie Di, Meng Cao, and Chao Liu Copyright © 2014 Yaofu Fan et al. All rights reserved. Waist-to-Height Ratio Is a Better Anthropometric Index than Waist Circumference and BMI in Predicting Metabolic Syndrome among Obese Mexican Adolescents Tue, 09 Dec 2014 08:31:01 +0000 Objective. To identify the degree of association between anthropometric indices and components of metabolic syndrome (MS) and to determine optimal cut-off points of these indices for predicting MS in obese adolescents. Methods. A cross-sectional study with a sample of () Mexican obese adolescents grouped by sex and the presence/absence of MS. BMI percentile, waist circumference (WC), and waist-to-height ratio (WHtR) were tested. ROC curves of the anthropometric indices were created to identify whether an index was a significant predictor of MS. Results. BMI percentile, WC, and WHtR were significantly correlated with systolic and diastolic blood pressure. As predictors of MS overall patients, the BMI percentile generated an area under curve (AUC) of 0.651 (), cut-off point above the 99th percentile. WC generated an AUC of 0.704 (), cut-off point of ≥90 cm. WHtR demonstrated an AUC of 0.652 (), cut-off point of 0.60. WHtR ≥0.62 and WHtR ≥0.61 generate AUC of 0.737 () and AUC of 0.717 () for predicting hypertension and insulin resistance, respectively, in females. Conclusion. WHtR is a better tool than WC and BMI for identifying cardiometabolic risk. The overall criterion (WHtR ≥ 0.6) could be appropriate for predicting MS in obese Mexican adolescents. Edel Rafael Rodea-Montero, María Lola Evia-Viscarra, and Evelia Apolinar-Jiménez Copyright © 2014 Edel Rafael Rodea-Montero et al. All rights reserved. Computed Tomography Features of Incidentally Detected Diffuse Thyroid Disease Mon, 08 Dec 2014 10:00:15 +0000 Objective. This study aimed to evaluate the CT features of incidentally detected DTD in the patients who underwent thyroidectomy and to assess the diagnostic accuracy of CT diagnosis. Methods. We enrolled 209 consecutive patients who received preoperative neck CT and subsequent thyroid surgery. Neck CT in each case was retrospectively investigated by a single radiologist. We evaluated the diagnostic accuracy of individual CT features and the cut-off CT criteria for detecting DTD by comparing the CT features with histopathological results. Results. Histopathological examination of the 209 cases revealed normal thyroid (), Hashimoto thyroiditis (), non-Hashimoto lymphocytic thyroiditis (), and diffuse hyperplasia (). The CT features suggestive of DTD included low attenuation, inhomogeneous attenuation, increased glandular size, lobulated margin, and inhomogeneous enhancement. ROC curve analysis revealed that CT diagnosis of DTD based on the CT classification of “3 or more” abnormal CT features was superior. When the “3 or more” CT classification was selected, the sensitivity, specificity, positive and negative predictive values, and accuracy of CT diagnosis for DTD were 55.8%, 95.5%, 80.6%, 86.7%, and 85.6%, respectively. Conclusion. Neck CT may be helpful for the detection of incidental DTD. Myung Ho Rho and Dong Wook Kim Copyright © 2014 Myung Ho Rho and Dong Wook Kim. All rights reserved. MicroRNAs in Human Pituitary Adenomas Mon, 08 Dec 2014 09:57:31 +0000 MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers. Xu-Hui Li, Elaine Lu Wang, Hai-Meng Zhou, Katsuhiko Yoshimoto, and Zhi Rong Qian Copyright © 2014 Xu-Hui Li et al. All rights reserved. Clinical Evaluation of Various Thyroid Hormones on Thyroid Function Mon, 08 Dec 2014 07:14:33 +0000 To clarify the clinical value of serums total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) and provide a more eligible and economic strategy to assess thyroid function. A total of 2,673 participants (500 patients with hyperthyroidism, 500 patients with hypothyroidism, and 1,673 healthy people) were involved in our study. Serums TT3, TT4, FT3, and FT4 and thyrotropin (TSH) were measured with VIDAS fluorescent enzyme immunoassay. The Pearson correlation between TT3, TT4, FT3, and FT4 and TSH was determined to identify the most important indicator for thyroid function besides TSH. The correlation of TT4, and FT4 with TSH was statistically significant in healthy individuals (P < 0.01), and the R-values were −0.065 and −0.152, respectively. The correlation of TT4, FT4, TT3, and FT3 with TSH was statistically significant in patients with hyperthyroidism, and the R-values were −0.241, −0.225, −0.195, and −0.176, respectively. The correlation of TT4, FT4, TT3, and FT3 with TSH was statistically significant in patients with hypothyroidism, and the R-values were −0.322, −0.262, −0.179, and −0.136, respectively. In our opinion, TSH and FT4 are the most valuable indicators in assessing thyroid function in a healthy population, and TSH and TT4 are the most meaningful in hyperthyroidism and hypothyroidism. Hong Li, Xiaolan Yuan, Lu Liu, Jiaojiao Zhou, Chunyan Li, Peng Yang, Le Bu, Manna Zhang, and Shen Qu Copyright © 2014 Hong Li et al. All rights reserved. Diabetic Women Suffer More Years of Life Lost Than Diabetic Men Wed, 03 Dec 2014 09:21:16 +0000 Zhi-Jiang Zhang, Genming Zhao, Chuanhua Yu, Yongyi Bi, Qingjun Zhang, and Yiqing Song Copyright © 2014 Zhi-Jiang Zhang et al. All rights reserved. Oxidative Stress: A Link between Diabetes Mellitus and Periodontal Disease Sun, 30 Nov 2014 00:10:28 +0000 Objective. To investigate oxidative stress (OS) and histological changes that occur in the periodontium of subjects with type 2 diabetes mellitus without signs of periodontal disease and to establish if oxidative stress is a possible link between diabetes mellitus and periodontal changes. Materials and Methods. Tissue samples from ten adult patients with type 2 diabetes mellitus (T2D) and eight healthy adults were harvested. The specimens were examined by microscope using standard hematoxylin-eosin stain, at various magnifications, and investigated for tissue levels of malondialdehyde (MDA) and glutathione (GSH). Results. Our results showed that periodontal tissues in patients with T2D present significant inflammation, affecting both epithelial and connective tissues. Mean MDA tissue levels were 3.578 ± 0.60 SD in diabetics versus 0.406 ± 0.27 SD in controls (P < 0.0001), while mean GSH tissue levels were 2.48 ± 1.02 SD in diabetics versus 9.7875 ± 2.42 SD in controls (P < 0.0001). Conclusion. Diabetic subjects had higher MDA levels in their periodontal tissues, suggesting an increased lipid peroxidation in T2D, and decreased GSH tissue levels, suggesting an alteration of the local antioxidant defense mechanism. These results are in concordance with the histological changes that we found in periodontal tissues of diabetic subjects, confirming the hypothesis of OS implication, as a correlation between periodontal disease incidence and T2D. Adriana Monea, Tibor Mezei, Sorin Popsor, and Monica Monea Copyright © 2014 Adriana Monea et al. All rights reserved. Prediction of Extrathyroidal Extension Using Ultrasonography and Computed Tomography Thu, 27 Nov 2014 13:15:28 +0000 Objectives. The aim of the present study was to evaluate the value of high-resolution ultrasound (US) and computed tomography (CT) scan for preoperative prediction of the extrathyroidal extension (ETE). Methods. We analyzed the medical records of 377 patients with papillary thyroid carcinoma (PTC) with preoperative US and CT scan to calculate the sensitivity, specificity, and positive and negative predictive values of characteristics imaging features (such as contact and disruption of thyroid capsule) for the presence of ETE in postoperative pathologic examination. We also evaluated the diagnostic power for several combinations of US and CT findings. Results. ETE was present in 174 (46.2%) based on pathologic reports. The frequency of ETE was greater in the patients with greater degrees of tumor contact and disruption of capsule, as revealed by both US and CT scans (positive predictive value of 72.2% and 81.8%, resp.). Considering positive predictive values and AUC of US and CT categories, separately or combined, a combination of US and CT findings was most accurate for predicting ETE (83.0%, 0.744). Conclusions. This study suggests that ETE can be predicted most accurately by a combination of categories based on the findings of US and CT scans. Doh Young Lee, Tack-Kyun Kwon, Myung-Whun Sung, Kwang Hyun Kim, and J. Hun Hah Copyright © 2014 Doh Young Lee et al. All rights reserved. Retrospective Analysis of Cushing’s Disease with or without Hyperprolactinemia Sun, 23 Nov 2014 08:15:53 +0000 Objective. We compared the characteristics of patients with Cushing’s disease alone with those of patients with Cushing’s disease and hyperprolactinemia. Methods. Eighty-four patients were enrolled between 2002 and 2011, in a hospital in China. Clinical, endocrinological, and histopathological data, MRI scans, and surgical outcomes were reviewed throughout the follow-up period. Results. Patients with Cushing’s disease and hyperprolactinemia had a younger age at diagnosis (30.28 ± 14.23 versus 36.08 ± 10.91 years; ) and a larger adenoma maximal diameter (2.44 ± 1.32 versus 1.44 ± 1.05 cm; ) than patients with Cushing’s disease alone. Menstrual disorders () and visual field defects () were more common and progressive obesity () and hypertension () were less common in patients with Cushing’s disease and hyperprolactinemia. The rate of normalization of hormonal levels was lower (41.7% versus 91.7%; ) and the recurrence rate was higher (36.1% versus 8.3%; ) in patients with Cushing’s disease and hyperprolactinemia. Conclusions. Careful long-term follow-up is needed of patients with Cushing’s disease and hyperprolactinemia. Cheng Huan, Chao Lu, Guang-ming Xu, Xin Qu, and Yuan-ming Qu Copyright © 2014 Cheng Huan et al. All rights reserved. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study Sun, 23 Nov 2014 00:00:00 +0000 Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL) ( and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (; , ;  , and ;  ), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels () and free T and DHEA-S declined significantly ( and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction. René Rodríguez-Gutiérrez, Jesús Zacarías Villarreal-Pérez, Felipe Arturo Morales-Martinez, René Rodríguez-Guajardo, Gloria González-Saldivar, Leonardo G. Mancillas-Adame, Neri Alejandro Alvarez-Villalobos, Fernando Javier Lavalle-Gonzalez, and José Gerardo González-González Copyright © 2014 René Rodríguez-Gutiérrez et al. All rights reserved. Coexistence of Histologically Confirmed Hashimoto’s Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort Tue, 18 Nov 2014 12:42:03 +0000 Purpose. To determine the relationship between Hashimoto’s thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods. We conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) (). However, no correlation was found between HT and LNM of PTC. Conclusion. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression. Xiaoyun Liu, Lijun Zhu, Dai Cui, Zhixiao Wang, Huanhuan Chen, Yu Duan, Meiping Shen, Yunsong Wu, Rong Rong, Zhihong Zhang, Xiaodong Wang, Jiawei Chen, Erik K. Alexander, and Tao Yang Copyright © 2014 Xiaoyun Liu et al. All rights reserved. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models Tue, 18 Nov 2014 09:04:53 +0000 The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives. Carolina Cristina, Guillermina María Luque, Gianina Demarchi, Felicitas Lopez Vicchi, Lautaro Zubeldia-Brenner, Maria Ines Perez Millan, Sofia Perrone, Ana Maria Ornstein, Isabel M. Lacau-Mengido, Silvia Inés Berner, and Damasia Becu-Villalobos Copyright © 2014 Carolina Cristina et al. All rights reserved. Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System Mon, 17 Nov 2014 00:00:00 +0000 Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas. Federica Barbieri, Stefano Thellung, Roberto Würth, Federico Gatto, Alessandro Corsaro, Valentina Villa, Mario Nizzari, Manuela Albertelli, Diego Ferone, and Tullio Florio Copyright © 2014 Federica Barbieri et al. All rights reserved. Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function Mon, 17 Nov 2014 00:00:00 +0000 Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 μmol/l) with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine). Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM), MG induced a significant () increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM), MG significantly inhibited insulin secretion (). In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (), while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (). Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells. Ghada Elmhiri, Luiz Felipe Barella, Didier Vieau, Sylvaine Camous, Paulo C. F. Mathias, and Latifa Abdennebi-Najar Copyright © 2014 Ghada Elmhiri et al. All rights reserved. Free Triiodothyronine Concentrations Are Inversely Associated with Microalbuminuria Sun, 16 Nov 2014 13:23:06 +0000 Thyroid function and microalbuminuria are both associated with vascular disease and endothelial damage. However, whether thyroid function is associated with microalbuminuria is not well established. The objective was to explore the relationship between thyroid hormones and microalbuminuria in Chinese population. A community-based cross-sectional study was performed among 3,346 Chinese adults (aged ≥ 40 years). Serum free triiodothyronine (FT3), free thyroxine (FT4), and TSH (thyroid stimulating hormone) were determined by chemiluminescent microparticle immunoassay. A single-void first morning urine sample was obtained for urinary albumin-creatinine ratio measurement. The prevalence of microalbuminuria decreased according to FT3 quartiles (13.2, 9.5, 8.6, and 8.2%, P for trend = 0.0005). A fully adjusted logistic regression analysis showed that high FT3 levels were associated with low prevalent microalbuminuria. The adjusted odds ratios for microalbuminuria were 0.61 (95% CI, 0.43–0.87, P = 0.007) when comparing the highest with the lowest quartile of FT3. The exclusion of participants with abnormal FT3 did not appreciably change the results (OR = 0.69, 95% CI, 0.49–0.98, P = 0.02). We concluded that serum FT3 levels, even within the normal range, were inversely associated with microalbuminuria in middle-aged and elderly Chinese adults. FT3 concentrations might play a role in the pathogenesis of microalbuminuria. Yulin Zhou, Lei Ye, Tiange Wang, Jie Hong, Yufang Bi, Jie Zhang, Baihui Xu, Jichao Sun, Xiaolin Huang, and Min Xu Copyright © 2014 Yulin Zhou et al. All rights reserved. Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology Sun, 16 Nov 2014 00:00:00 +0000 Estroprogestins (EPs) are combinations of estrogen and progestin with several actions on women’s health. The different pharmacological composition of EPs is responsible for different clinical effects. One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100). This review summarizes clinical pharmacology, cycle control, and effects on lipid and glucose metabolism, coagulation, body weight/body composition, acne, and sexuality of EE20/LNG100. Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group. Cycle control was effective and body weight/body composition did not vary among treated and untreated groups in most studies. The EE20/LNG100 combination shows mild or no effect on lipid and glucose metabolism. Lastly, EE20/LNG100 is associated with a low risk of venous thromboembolism (VTE). In conclusion, in the process of decision making for the individualization of EPs choice, EE20/LNG100 should be considered for its favorable clinical profile. Stefano Lello and Andrea Cavani Copyright © 2014 Stefano Lello and Andrea Cavani. All rights reserved. Evaluating the Effect of Ramadan Fasting on Muslim Patients with Diabetes in relation to Use of Medication and Lifestyle Patterns: A Prospective Study Tue, 11 Nov 2014 11:47:07 +0000 Objectives. This study aimed to examine the effect of Ramadan fasting on HbA1c in Muslim patients with type 2 diabetes. The incidence of hypoglycemia and glycemic changes in relation to the adjustment of doses of antidiabetic agents, diet, and physical activity during Ramadan was also evaluated. Methods. This was a prospective study conducted in an outpatient endocrine clinic. A set of questionnaires was administered to Muslim patients with diabetes who fasted for 10 days. Those who were hospitalized for diabetic ketoacidosis or severe hypoglycemia a month prior to Ramadan or were given short-term corticosteroid therapy were excluded. The patients’ responses and clinical outcomes from the clinic database were collected before, during, and after Ramadan. Results. A total of 153 participants completed the study. The mean HbA1c improved from 8.9% before Ramadan to 8.6% during Ramadan (). Although diet and physical activity did not contribute to changes in glycemia, a significant improvement in HbA1c was observed in patients who had adjustments made to their doses of antidiabetic agents during Ramadan (). In addition, their rate of hypoglycemia was minimal. Conclusions. Ramadan fasting appeared to improve glycemic control, especially in those whose doses of antidiabetic agents were adjusted during Ramadan. Melanie Yee Lee Siaw, Daniel Ek Kwang Chew, Rinkoo Dalan, Shaikh Abdul Kader Kamaldeen Abdul Shakoor, Noorani Othman, Chor Hui Choo, Nur Hidayah Shamsuri, Siti Nurhana Abdul Karim, Sui Yung Chan, and Joyce Yu-Chia Lee Copyright © 2014 Melanie Yee Lee Siaw et al. All rights reserved. Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status Tue, 11 Nov 2014 07:52:27 +0000 Objective. This paper aims to assess 25(OH)D levels in Italian children and adolescents identifying risk factors for 25(OH)D deficiency and to evaluate whether a normal 25(OH)D value can be restored in 25(OH)D-deficient patients. Methods. We evaluated 25(OH)D levels in 679 Italian children and adolescents (≤10, 11–20, 21–30, and >30 ng/mL were defined as severe deficiency, deficiency, insufficiency, and sufficiency, resp.). Of these, 365 25(OH)D-deficient were followed up for 1 year; 205 were treated with cholecalciferol (Arm A: 400 I.U.) and 160 by improving the environmental variables influencing 25(OH)D levels (Arm B). Results. At cross-sectional evaluation, 11.3% showed sufficiency, 30.0% insufficiency, and 58.7% 25(OH)D deficiency. Mean 25(OH)D was  ng/mL. At the enrollment time (), no difference was found between Arms A and B with respect to distribution and 25(OH)D levels. At end time () 26.0% (29.7% in Arm A versus 20.6% in Arm B) showed sufficiency, 38.4% (42.0% versus 34.4%) insufficiency, and 35.6% (28.3% versus 45.0%) 25(OH)D deficiency. Mean 25(OH)D level was  ng/mL. Conclusions. Neither changes of lifestyle nor 400 I.U. cholecalciferol supplementation alone appears to be sufficient to restore adequate 25(OH)D levels. Stefano Stagi, Paola Pelosi, Massimo Strano, Giovanni Poggi, Cristina Manoni, Maurizio de Martino, and Salvatore Seminara Copyright © 2014 Stefano Stagi et al. All rights reserved. The Protective Effect of Beraprost Sodium on Diabetic Cardiomyopathy through the Inhibition of the p38 MAPK Signaling Pathway in High-Fat-Induced SD Rats Tue, 11 Nov 2014 00:00:00 +0000 Objective. To investigate the effect of beraprost sodium (BPS) on diabetic cardiomyopathy and the underlying mechanism. Methods. A total of 40 Sprague Dawley rats were randomly divided into the normal control group () and the model group (). The model group was fed a high-fat diet followed by a one-time dose of streptozotocin (STZ) to establish the diabetes mellitus model. After that, rats were randomly divided into two groups with or without BPS intervention. After 8 weeks, we explored the role of the p38 MAPK signaling pathway in inflammation, oxidative stress, cardiac morphology, and myocardial apoptosis. Results. Compared with control, the ratio of heart-weight to body-weight and the serum levels of SOD and GSH in the BPS group significantly increased, the expression of p38 MAPK, the serum levels of MDA, TGF-β1, TNF-α, HIF-1α, MMP-9, caspase-3, BNP, ANP, and heart Bax expression significantly decreased, and heart Bcl-2 expression significantly increased. H&E staining in diabetic rats showed the cardiac muscle fibers derangement, the widening gap, the pyknotic and fragmented nuclei, and more apoptosis. Conclusions. BPS effectively showed protective effects on diabetic myocardial cells, possibly through the inhibition of p38 MAPK signaling pathway. Jie Li, Li Peng, Hong Du, Yangtian Wang, Bin Lu, Yixin Xu, Xiaozhen Ye, and Jiaqing Shao Copyright © 2014 Jie Li et al. All rights reserved. Erratum to “Growth Retardation in Children with Kidney Disease” Mon, 10 Nov 2014 11:29:55 +0000 Paulina Salas, Viola Pinto, Josefina Rodriguez, Maria Jose Zambrano, and Veronica Mericq Copyright © 2014 Paulina Salas et al. All rights reserved. Correlations of Vascular Architecture and Angiogenesis with Pituitary Adenoma Histotype Sun, 09 Nov 2014 12:22:37 +0000 Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesis Shingo Takano, Hiroyoshi Akutsu, Takuma Hara, Tetsuya Yamamoto, and Akira Matsumura Copyright © 2014 Shingo Takano et al. All rights reserved. Enucleation-Induced Rat Adrenal Gland Regeneration: Expression Profile of Selected Genes Involved in Control of Adrenocortical Cell Proliferation Thu, 06 Nov 2014 12:45:08 +0000 Enucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes. Factors encoded by these genes obscure possible priming effects of various cytokines on initiation of regeneration. In regenerating adrenals we identified over 100 up- or downregulated genes involved in adrenocortical cell proliferation. The changes were most significant at days 2-3 after enucleation and their number decreased during regeneration. For example, expression analysis revealed a notable upregulation of the growth arrest gene, Gadd45, only 24 hours after surgery while expression of cyclin B1 and Cdk1 genes was notably elevated between days 1–8 of regeneration. These changes were accompanied by changes in expression levels of numerous growth factors and immediate-early transcription factors genes. Despite notable differences in mechanisms of adrenal and liver regeneration, in regenerating adrenals we identified genes, the expression of which is well recognized in regenerating liver. Thus, it seems legitimate to suggest that, in the rat, the general model of liver and adrenal regeneration demonstrate some degree of similarity. Marianna Tyczewska, Marcin Rucinski, Agnieszka Ziolkowska, Marta Szyszka, Marcin Trejter, Anna Hochol-Molenda, Krzysztof W. Nowak, and Ludwik K. Malendowicz Copyright © 2014 Marianna Tyczewska et al. All rights reserved. The Association between the Epicardial Adipose Tissue Thickness and Oxidative Stress Parameters in Isolated Metabolic Syndrome Patients: A Multimarker Approach Sun, 02 Nov 2014 14:28:34 +0000 The risk for cardiovascular diseases and type 2 diabetes mellitus significantly increases in the patient population with metabolic syndrome (MeS). The present study aimed to investigate the association between the epicardial adipose tissue thickness (EATT) and the oxidative stress parameters in MeS patients. The study included 181 patients as a patient group of 92 consecutive patients with MeS and a control group of 89 consecutive patients with similar age and gender. EATT was evaluated by transthoracic echocardiography. Serum levels of total oxidant status (TOS), total antioxidative capacity (TAS), paraoxonase-1 (PON-1), and arylesterase activities were measured. EATT was higher in the MeS group compared to the control group ( mm and  mm, resp.; ). The level of TOS was higher in the MeS group compared to the control group (). Additionally, the TAS level was higher in the MeS group compared to the control group (). Furthermore, the serum levels of PON-1 and arylesterase were lower in the MeS group compared to the control group (). EAT may cause an increased risk of cardiovascular diseases by leading to increased oxidative stress in patients with MeS. Bulent Demir, Esra Demir, Gonul Acıksarı, Turgut Uygun, Irem Kırac Utku, Asuman Gedikbasi, Ilker Murat Caglar, Osman Pirhan, Hande Oktay Tureli, Ersan Oflar, İsmail Ungan, Serkan Ciftci, and Osman Karakaya Copyright © 2014 Bulent Demir et al. All rights reserved. Erratum to “Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay” Thu, 30 Oct 2014 06:56:13 +0000 James Freeman, Kimberly Wilson, Ryan Spears, Victoria Shalhoub, and Paul Sibley Copyright © 2014 James Freeman et al. All rights reserved.