International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . 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. All rights reserved. Analysis of Circulating MicroRNAs In Vivo following Administration of Dexamethasone and Adrenocorticotropin Tue, 16 Jun 2015 12:44:46 +0000 Purpose. The interaction of hormones of the pituitary-adrenal axis and adrenal cortex-associated circulating microRNAs is mostly unknown. We have studied the effects of dexamethasone and adrenocorticotropin on the expression of five circulating microRNAs (hsa-miR-27a, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, and hsa-miR-503) reported to be related to the adrenal cortex in plasma samples. Methods. Expression of microRNAs was studied in plasma samples of 10 individuals examined by 1 mg dexamethasone suppression test and another 10 individuals stimulated by 250 μg tetracosactide (adrenocorticotropin). Total RNA was isolated and microRNA expression was analyzed by real-time reverse transcription quantitative polymerase chain reaction normalized to cel-miR-39 as reference. Results. Only circulating hsa-miR-27a proved to be significantly modulated in vivo by hormonal treatments: its expression was upregulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Secreted hsa-miR-27a was significantly induced by dexamethasone in vitro in NCI-H295R cells, as well. The expression of hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration. Conclusions. hsa-miR-27a expression is modulated by hormones of the hypothalamic-pituitary-adrenal axis both in vitro and in vivo. The biological relevance of hsa-miR-27a modulation by hormones is unclear, but the responsiveness of circulating microRNAs to hormones of the pituitary-adrenal axis is noteworthy. Ivan Igaz, Gábor Nyírő, Zoltán Nagy, Henriett Butz, Zsolt Nagy, Pál Perge, Peter Sahin, Miklós Tóth, Károly Rácz, Peter Igaz, and Attila Patócs Copyright © 2015 Ivan Igaz et al. All rights reserved. Vitamin D Status and VDR Genotype in NF1 Patients: A Case-Control Study from Southern Brazil Tue, 16 Jun 2015 12:40:59 +0000 Neurofibromatosis type 1 (NF1) patients are more likely to have vitamin D deficiency when compared to the general population. This study aimed to determine the levels of 25-OH-vitamin D [25(OH)D] in individuals with NF1 and disease-unaffected controls and analyze FokI and BsmI VDR gene polymorphisms in a case and in a control group. Vitamin D levels were compared between a group of 45 NF1 patients from Southern Brazil and 45 healthy controls matched by sex, skin type, and age. Genotypic and allelic frequencies of VDR gene polymorphisms were obtained from the same NF1 patients and 150 healthy controls. 25(OH)D deficiency or insufficiency was not more frequent in NF1 patients than in controls (). We also did not observe an association between FokI and BsmI VDR gene polymorphisms and vitamin D levels in NF1 patients, suggesting that their deficient or insufficient biochemical phenotypes are not associated with these genetic variants. The differences between the groups in genotypic and allelic frequencies for FokI and BsmI VDR gene polymorphisms were small and did not reach statistical significance. These polymorphisms are in partial linkage disequilibrium and the haplotype frequencies also did not differ in a significant way between the two groups (). Larissa Souza Mario Bueno, Clévia Rosset, Ernestina Aguiar, Fernando de Souza Pereira, Patrícia Izetti Ribeiro, Rosana Scalco, Camila Matzenbacher Bittar, Cristina Brinckmann Oliveira Netto, Guilherme Gischkow Rucatti, José Artur Chies, Suzi Alves Camey, and Patricia Ashton-Prolla Copyright © 2015 Larissa Souza Mario Bueno et al. All rights reserved. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits Sun, 14 Jun 2015 13:05:38 +0000 Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control and hypothyroid groups (, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson’s Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. Julia Rodríguez-Castelán, Margarita Martínez-Gómez, Francisco Castelán, and Estela Cuevas Copyright © 2015 Julia Rodríguez-Castelán et al. All rights reserved. Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women Tue, 09 Jun 2015 13:49:37 +0000 Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin. Nasser M. Rizk and Elham Sharif Copyright © 2015 Nasser M. Rizk and Elham Sharif. All rights reserved. Changes in Serum TSH and T4 Levels after Switching the Levothyroxine Administration Time from before Breakfast to before Dinner Sun, 07 Jun 2015 09:47:02 +0000 Background. Levothyroxine is commonly used in the treatment of patients with hypothyroidism. Levothyroxine is most often administered in the morning, on an empty stomach, in order to increase its oral absorption. However, many patients have difficulties taking levothyroxine in the morning. Aim. The aim of this study was evaluating the effect of changing levothyroxine administration time from before breakfast to before dinner on the serum levels of TSH and T4. Subjects and Methods. Fifty patients between 18 and 75 years old with hypothyroidism were included in the study and were randomly divided into two groups. Each group received two tablets per day (one levothyroxine tablet and one placebo tablet) 30 minutes before breakfast and 1 hour before dinner. After two months, the administration time for the tablets was changed for each group, and the new schedule was continued for a further two-month period. The serum TSH and T4 levels were measured before and after treatment in each group. Results. Changing the levothyroxine administration time resulted in 1.47 ± 0.51 µIU/mL increase in TSH level () and 0.35 ± 1.05 µg/dL decrease in T4 level (). Conclusions. Changing the levothyroxine administration time from before breakfast to before dinner reduced the therapeutic efficacy of levothyroxine. S. Ala, O. Akha, Z. Kashi, A. Bahar, H. Askari Rad, N. Sasanpour, and A. Shiva Copyright © 2015 S. Ala et al. All rights reserved. Shear Wave Velocity: A New Quantitative Index to Estimate the Status of Thyroid in Diffuse Thyroid Disease Wed, 03 Jun 2015 11:20:02 +0000 Objective. The purpose of the study was to assess the application value of VTQ in DTD. Research Design and Methods. Thirty healthy subjects and 74 DTD patients were involved. The thyroid stiffness, which was expressed by SWV, was measured by VTQ and compared between the patients and healthy people. The relationship between SWV and thyroid serological indexes was also analyzed. Results. The thyroid SWVs of DTD patients were higher than those of the healthy ( m/s versus  m/s, ). There was no significant difference between the thyroid SWVs in GD and HT patients (). The SWVs in patients with GD and HT were both higher than those of the healthy (). The area under the ROC curve was 0.938 for SWV to distinguish between DTD and healthy thyroid. With a cutoff value of 2.02 m/s, the sensitivity and specificity were 81.12% and 100.00%, respectively. Additionally, we found a positive liner correlation between thyroid SWV and TSH in DTD patients (). Conclusion. SWV is a good indicator of the thyroid tissue stiffness, which might be considered helpful in screening DTD. What is more, SWV might have a potential in assessing the thyroid function. Lin-Yao Du, Qiao Ji, Xiu-Juan Hou, Xiao-Lei Wang, and Xian-Li Zhou Copyright © 2015 Lin-Yao Du et al. All rights reserved. The Prevalence and Associated Risk Factors of Impaired Glucose Regulation in Chinese Adults: A Population-Based Cross-Sectional Study Tue, 02 Jun 2015 11:38:32 +0000 The goal of this study was to determine the prevalence and associated risk factors of impaired glucose regulation (IGR) in the population of Tongzhou, China, and to provide scientific basis for preventive interventions. In the study, the overall age-standardized prevalence of IGR (16.0%) in Tongzhou residents was higher than that in the national population (15.0%). There was no significant geographic difference in prevalence of IGR between urban and rural males. Older age, elevated blood pressure, high serum lipids, overweight, and central obesity were significantly associated with increased risk of IGR. Dong Zhao, Nannan Wu, Jing Yang, Simo Liu, Ning Zhang, Xuhong Wang, and Haibin Zhang Copyright © 2015 Dong Zhao et al. All rights reserved. Regulation of Cardiovascular Metabolism by Hormones and Growth Factors Tue, 02 Jun 2015 07:02:44 +0000 Cristian Ibarra, Sergio Lavandero, and Manuel Estrada Copyright © 2015 Cristian Ibarra et al. All rights reserved. Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull© Energy Drink Consumption Mon, 01 Jun 2015 12:58:16 +0000 Objectives. To assess the effect of Red Bull© on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals (). Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull© intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500 mL of Red Bull©. Results. Mean ABP and HR were significantly increased at rest after Red Bull© intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull© consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull© consumption compared to control condition. Intake of Red Bull© significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject’s attention as well as performance in mental stress test. Conclusion. This study demonstrated that Red Bull© has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system. Ana Cavka, Marko Stupin, Ana Panduric, Ana Plazibat, Anita Cosic, Lidija Rasic, Zeljko Debeljak, Goran Martinovic, and Ines Drenjancevic Copyright © 2015 Ana Cavka et al. All rights reserved. The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes Mon, 01 Jun 2015 11:46:25 +0000 In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 g/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation by β-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications. Kira V. Derkach, Vera M. Bondareva, Oxana V. Chistyakova, Lev M. Berstein, and Alexander O. Shpakov Copyright © 2015 Kira V. Derkach et al. All rights reserved. Myocardial Infarction and Stroke Risk in Young Healthy Men Treated with Injectable Testosterone Mon, 01 Jun 2015 09:28:38 +0000 This study was conducted to examine the association between testosterone therapy and new myocardial infarction (MI) and stroke events in a series of patients treated at Low T Centers across the United States, consisting of mainly young (mean age = 46), otherwise, healthy men. Electronic medical records were queried between the years 2009 and 2014 to identify patients diagnosed with hypogonadism, MI, and stroke, as indicated by ICD-9 codes. The incidence of MI and stroke events was compared to community-based registries. 39,936 patients recruited from 40 Low T Centers across the United States were treated and 19,968 met eligibility criteria for receiving testosterone treatment. The incidence rate ratio (IRR) for MI in testosterone- (T-) treated versus nontreated patients was 0.14 (C.I. = 0.08 to 0.18, ) whereas the IRR for stroke for T-treated versus nontreated patients was 0.11 (C.I. = 0.02 to 0.13, ). There was no evidence of worsening preexisting MI or stroke in patients treated with testosterone. The experience in Low T Centers shows that, in an injectable testosterone patient registry, testosterone is generally safe for younger men who do not have significant risk factors. Of patients that developed MI with testosterone, there was no association with testosterone or hematocrit levels. Robert S. Tan, Kelly R. Cook, and William G. Reilly Copyright © 2015 Robert S. Tan et al. All rights reserved. Optimizing Bone Health in Duchenne Muscular Dystrophy Mon, 01 Jun 2015 08:10:05 +0000 Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA. Jason L. Buckner, Sasigarn A. Bowden, and John D. Mahan Copyright © 2015 Jason L. Buckner et al. All rights reserved. Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters Mon, 01 Jun 2015 07:29:06 +0000 Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function. Carlo Dal Lin, Francesco Tona, and Elena Osto Copyright © 2015 Carlo Dal Lin et al. All rights reserved. Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women Mon, 01 Jun 2015 07:25:55 +0000 Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events. Dinka Pavicic Baldani, Lana Skrgatic, and Roya Ougouag Copyright © 2015 Dinka Pavicic Baldani et al. All rights reserved. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue Mon, 01 Jun 2015 07:21:48 +0000 Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. Miroslav Šram, Zvonimir Vrselja, Igor Lekšan, Goran Ćurić, Kristina Selthofer-Relatić, and Radivoje Radić Copyright © 2015 Miroslav Šram et al. All rights reserved. Mechanisms Linking Inflammation to Insulin Resistance Thu, 28 May 2015 13:46:14 +0000 Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies. Li Chen, Rui Chen, Hua Wang, and Fengxia Liang Copyright © 2015 Li Chen et al. All rights reserved. Temozolomide Therapy for Aggressive Pituitary Tumors: Results in a Small Series of Patients from Argentina Wed, 27 May 2015 05:54:47 +0000 We evaluated results of temozolomide (TMZ) therapy in six patients, aged 34–78 years, presenting aggressive pituitary tumors. In all the patients tested O6-methylguanine-DNA methyltransferase (MGMT) immunoexpression in surgical specimens was absent. Patients received temozolomide 140–320 mg/day for 5 days monthly for at least 3 months. In two patients minimum time for evaluation could not be reached because of death in a 76-year-old man with a malignant prolactinoma and of severe neutro-thrombopenia in a 47-year-old woman with nonfunctioning pituitary adenoma. In two patients (a 34-year-old acromegalic woman and a 39-year-old woman with Nelson’s syndrome) no response was observed after 4 and 6 months, respectively, and the treatment was stopped. Conversely, two 52- and 42-year-old women with Cushing’s disease had long-term total clinical and radiological remissions which persisted after stopping temozolomide. We conclude that TMZ therapy may be of variable efficacy depending on—until now—incompletely understood factors. Cooperative work on a greater number of cases of aggressive pituitary tumors should be crucial to establish the indications, doses, and duration of temozolomide administration. Oscar D. Bruno, Lea Juárez-Allen, Silvia B. Christiansen, Marcos Manavela, Karina Danilowicz, Carlos Vigovich, and Reynaldo M. Gómez Copyright © 2015 Oscar D. Bruno et al. All rights reserved. Diabetes Mellitus 2014 Mon, 25 May 2015 07:07:54 +0000 Ilias Migdalis, David Leslie, Anastasia Mavrogiannaki, Nikolaos Papanas, Paul Valensi, and Helen Vlassara Copyright © 2015 Ilias Migdalis et al. All rights reserved. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D Sun, 24 May 2015 12:05:47 +0000 Background. The role of phospholipase D (PLD) as a positive modulator of glucose uptake activation by insulin in muscle and adipose cells has been demonstrated. The role of PLD in the regulation of glucose metabolism by insulin in the primary hepatocytes has been determined in this study. Methods. For this purpose, we studied effects of inhibitors of PLD on glucose uptake and glycogen synthesis stimulation by insulin. To determine the PLD activity, the method based on determination of products of transphosphatidylation reaction, phosphatidylethanol or phosphatidylbutanol, was used. Results. Inhibition of PLD by a general antagonist (1-butanol) or specific inhibitor, halopemide, or N-hexanoylsphingosine, or by cellular ceramides accumulated in doxorubicin-treated hepatocytes decreased insulin-stimulated glucose metabolism. Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production. Halopemide could nullify this effect. Addition of propranolol, as well as inhibitors of phosphatidylinositol 3-kinase (PI3-kinase) (wortmannin, LY294002) or suppressors of Akt phosphorylation/activity, luteolin-7-O-glucoside or apigenin-7-O-glucoside, to the culture media could block cell response to insulin action. Conclusion. PLD plays an important role in the insulin signaling in the hepatocytes. PLD is activated downstream of PI3-kinase and Akt and is highly sensitive to ceramide content in the liver cells. Nataliya A. Babenko and Vitalina S. Kharchenko Copyright © 2015 Nataliya A. Babenko and Vitalina S. Kharchenko. All rights reserved.