International Journal of Endocrinology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Spectrum of Endocrine Disorders in Central Ghana Thu, 23 Feb 2017 08:24:00 +0000 Background. Although an increasing burden of endocrine disorders is recorded worldwide, the greatest increase is occurring in developing countries. However, the spectrum of these disorders is not well described in most developing countries. Objective. The objective of this study was to profile the frequency of endocrine disorders and their basic demographic characteristics in an endocrine outpatient clinic in Kumasi, central Ghana. Methods. A retrospective review was conducted on endocrine disorders seen over a five-year period between January 2011 and December 2015 at the outpatient endocrine clinic of Komfo Anokye Teaching Hospital. All medical records of patients seen at the endocrine clinic were reviewed by endocrinologists and all endocrinological diagnoses were classified according to ICD-10. Results. 3070 adults enrolled for care in the endocrine outpatient service between 2011 and 2015. This comprised 2056 females and 1014 males (female : male ratio of 2.0 : 1.0) with an overall median age of 54 (IQR, 41–64) years. The commonest primary endocrine disorders seen were diabetes, thyroid, and adrenal disorders at frequencies of 79.1%, 13.1%, and 2.2%, respectively. Conclusions. Type 2 diabetes and thyroid disorders represent by far the two commonest disorders seen at the endocrine clinic. The increased frequency and wide spectrum of endocrine disorders suggest the need for well-trained endocrinologists to improve the health of the population. Osei Sarfo-Kantanka, Fred Stephen Sarfo, Eunice Oparebea Ansah, and Ishmael Kyei Copyright © 2017 Osei Sarfo-Kantanka et al. All rights reserved. An Approach to Macroscopic Central Lymph Nodes Detected during Surgery in Patients with Thyroid Micropapillary Carcinoma: Should We Resort to Dissection? Thu, 23 Feb 2017 08:13:23 +0000 Background. High-resolution ultrasonography and the ability to perform fine-needle aspiration biopsy even for nodules smaller than three millimeters have considerably increased the detection rate of thyroid micropapillary carcinoma (TMPC). Despite favorable prognosis, the prevalence of cervical lymph node metastases in patients with TMPC is approximately 30%. Aim. In this study, we aimed to determine the central lymph node metastasis rate and its relation to the characteristics of the tumor. Methods. One hundred nine patients who underwent surgery due to TMPC between December 2009 and January 2014 were analyzed retrospectively. Patients were divided into two groups according to whether they underwent lymph node dissection and the two groups were then compared with respect to tumor size and multicentricity, age, and presence of lymphocytic thyroiditis. Results. There were no statistically significant differences between the two groups of patients in terms of tumor size, tumor multicentricity, age, and presence of lymphocytic thyroiditis. When the patient group that received lymph node dissection was further analyzed, it was found that patients with lymphocytic thyroiditis had a significantly lower number of metastatic lymph nodes. Conclusion. Central lymph node dissection in TMPC patients with macroscopic lymph node detected intraoperatively would ensure accurate staging without an increase in morbidity. Osman Kurukahvecioglu, Kursat Dikmen, Hasan Bostanci, Murat Akin, and Ferit Taneri Copyright © 2017 Osman Kurukahvecioglu et al. All rights reserved. Does Good Aerobic Capacity Attenuate the Effects of Aging on Cardiovascular Risk Factors? Results from a Cross-Sectional Study in a Latino Population Tue, 21 Feb 2017 14:14:52 +0000 Background. High aerobic capacity is associated with low cardiovascular (CV) risk. The aim of this study was to determine the CV RF burden in subjects with aerobic capacity ≥10 METs and compare it with those having <10 METs. Methods. Cross-sectional study in 2646 subjects (mean age 48 ± 12 years). Demographics, medical history, physical activity, cardiovascular RFs, fasting lipids and blood glucose levels, blood pressure, and anthropometric measurements were collected. Aerobic capacity was determined by exercise stress test. The ACC/AHA 2013 pooled cohort equation was used to calculate CV risk. Logistic models were built to determine the probability of having ≥2 RFs versus 0‐1 RF, by age and sex, according to aerobic capacity. Results. 15% of subjects had aerobic METs. The ACC/AHA scores were 15% in men and 6% in women with <10 METs and 5% and 2%, respectively, in those with ≥10 METs. The probability of having ≥2 RFs increased with age in both groups; however, it was significantly higher in subjects with <10 METs (odds ratio [OR]: 2.54; 95% CI: 1.92–3.35). Conclusions. METs is associated with a better CV RF profile and lower CV risk score in all age groups, regardless of gender. Giovanna Valentino, Mónica Acevedo, Lorena Orellana, María José Bustamante, Verónica Kramer, Marcela Adasme, Fernando Baraona, Gastón Chamorro, Jorge Jalil, and Carlos Navarrete Copyright © 2017 Giovanna Valentino et al. All rights reserved. Sex Differences in the Effect of Type 2 Diabetes on Major Cardiovascular Diseases: Results from a Population-Based Study in Italy Mon, 20 Feb 2017 07:51:15 +0000 The aim of the study is to assess sex difference in association between type 2 diabetes and incidence of major cardiovascular events, that is, myocardial infarction, stroke, and heart failure, using information retrieved by diabetes register. The inhabitants of Reggio Emilia (Italy) aged 30–84 were followed during 2012–2014. Incidence rate ratios and 95% confidence intervals were calculated using multivariate Poisson model. The age- and sex-specific event rates were graphed. Subjects with type 2 diabetes had an excess risk compared to their counterparts without diabetes for all the three major cardiovascular events. The excess risk is similar in women and men for stroke (1.8 times) and heart failure (2.7 times), while for myocardial infarction, the excess risk in women is greater than the one observed in men (IRR 2.58, 95% CI 2.22–3.00 and IRR 1.78, 95% CI 1.60–2.00, resp.; of interaction ). Women had always a lesser risk than men, but in case of myocardial infarction, the women with type 2 diabetes lost part of advantage gained by women free of diabetes (IRR 0.61, 95% CI 0.53–0.72 and IRR 0.36, 95% CI 0.33–0.39, resp.). In women with type 2 diabetes, the risk of major cardiovascular events is anticipated by 20–30 years, while in men it is by 15–20. Paola Ballotari, Francesco Venturelli, Marina Greci, Paolo Giorgi Rossi, and Valeria Manicardi Copyright © 2017 Paola Ballotari et al. All rights reserved. Influence of Normo- and Hypogonadal Condition, Hyperuricemia, and High-Fructose Diet on Renal Changes in Male Rats Wed, 15 Feb 2017 11:13:59 +0000 Background. There is a gender disparity in the incidence, prevalence, and progression of renal disease. The object of this paper is to evaluate the presence and type of renal lesion in normogonadic and hypogonadic male rats in a mild hyperuricemia induced condition and exposed to a high-fructose diet. Methods. 56 adult male Wistar rats were used. Animals were divided into two groups, one normogonadic (NGN) and one hypogonadic (HGN), and each group was divided into four subgroups in accordance with the treatment: control with only water (C), fructose (F), oxonic acid (OA), and fructose + oxonic acid (FOA). Renal changes were evaluated by measuring glomerulosclerosis, fibrosis, and arteriolar media/lumen (M/L) ratio. Results. The OA and FOA groups presented significantly hypertension (). The OA group significantly increased () the percentage of glomerulosclerosis as well as the FOA group (). When comparing NGN versus HGN, we observed a trend to a lower glomerulosclerosis in the latter. A higher arteriolar M/L ratio was observed in the OA () and FOA (). Conclusion. Hyperuricemia conditions and a high-fructose diet favor blood pressure increase together with changes in the arteriolar media/lumen ratio and renal glomerular damage. These changes were more apparent in normogonadic animals. Jimena Soutelo, Yanina Alejandra Samaniego, Elsa Zotta, María Cecilia Fornari, Carlos Reyes Toso, and Osvaldo Juan Ponzo Copyright © 2017 Jimena Soutelo et al. All rights reserved. Treatment with Myo-Inositol and Selenium Ensures Euthyroidism in Patients with Autoimmune Thyroiditis Wed, 15 Feb 2017 10:18:48 +0000 Clinical evidences have highlighted the efficacy of myo-inositol and selenium in the treatment of autoimmune thyroiditis. Aim of this study was to further analyze the role of myo-inositol plus selenium (Myo-Ins-Se) in restoring a normal thyroid function of Hashimoto’s patients with subclinical hypothyroidism. Eighty-six patients with Hashimoto’s thyroiditis having thyroid-stimulating hormone (TSH) levels between 3 and 6 mIU/L, elevated serum antithyroid peroxidase (TPOAb) and/or antithyroglobulin (TgAb), and normal free thyroxine (fT4) and free triiodothyronine (fT3) levels were enrolled in the study: one hyperthyroid subject with TSH about 0.14 μU/ml was included in this trial as a single case. Patients were assigned to receive Myo-Ins-Se. TSH, TPOAb, and TgAb levels were significantly decreased in patients treated with combined Myo-Ins-Se after 6 months of treatment. In addition, a significant fT3 and fT4 increase, along with an amelioration of their quality of life, was observed. Remarkably, TSH values of the hyperthyroid patient increased from 0.14 μU/ml up to 1.02 μU/ml, showing a complete restoration of TSH values at a normal range. In conclusion, the administration of Myo-Ins-Se is significantly effective in decreasing TSH, TPOAb, and TgAb levels, as well as enhancing thyroid hormones and personal wellbeing, therefore restoring euthyroidism in patients diagnosed with autoimmune thyroiditis. Maurizio Nordio and Sabrina Basciani Copyright © 2017 Maurizio Nordio and Sabrina Basciani. All rights reserved. Fine Needle Aspiration of Thyroid Nodules Using the Bethesda System for Reporting Thyroid Cytopathology: An Institutional Experience in a Rural Setting Thu, 09 Feb 2017 07:54:11 +0000 Background. Fine needle aspiration (FNA) remains the first-line diagnostic in management of thyroid nodules and reduces unnecessary surgeries. However, it is still challenging since cytological results are not always straightforward. This study aimed to examine the results of thyroid FNA using the Bethesda system for reporting thyroid cytopathology (TBSRTC) to establish the level of accuracy of FNA procedures in a rural practice setting. Method. A retrospective chart review was conducted on existing thyroid FNA performed in a referral endocrine center between December 2011 and November 2015. Results. A total of 159 patients (18–88 years old) and 236 nodule aspirations were performed and submitted for evaluation. 79% were benign, 3% atypia/follicular lesion of unknown significance (AUS/FLUS), 5% follicular neoplasm/suspicious for follicular neoplasm (FN/SFN), 4% suspicious for malignancy (one case was indeed an atypical parathyroid neoplasm by surgical pathology), 2% malignant, and 7% nondiagnostic. Two cases also had advanced molecular analysis on FNA specimens before thyroidectomy. Conclusion. The diagnostic yield of FNA cytology from our practice in a rural setting suggests that accuracy and specificity are comparable to results from larger centers. Aili Guo, Yuuki Kaminoh, Terra Forward, Frank L. Schwartz, and Scott Jenkinson Copyright © 2017 Aili Guo et al. All rights reserved. Serum Osteoprotegerin Is a Potential Biomarker of Insulin Resistance in Chinese Postmenopausal Women with Prediabetes and Type 2 Diabetes Tue, 31 Jan 2017 08:18:24 +0000 The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (), impaired glucose regulation (IGR) (), and normal glucose regulation group (NGR) (), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) () and T2DM group (183.20 ± 56.53 pg/mL) (), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009, ) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes. Peng Duan, Min Yang, Meilin Wei, Jia Liu, and Ping Tu Copyright © 2017 Peng Duan et al. All rights reserved. Selenium and Thyroid Disease: From Pathophysiology to Treatment Tue, 31 Jan 2017 07:51:44 +0000 Introduction. Selenium is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet, geographic area, and soil composition. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones. Methods. We performed a review of the literature on selenium’s role in thyroid function using PubMed/MEDLINE. Results. Regarding thyroid pathology, selenium intake has been particularly associated with autoimmune disorders. The literature suggests that selenium supplementation of patients with autoimmune thyroiditis is associated with a reduction in antithyroperoxidase antibody levels, improved thyroid ultrasound features, and improved quality of life. Selenium supplementation in Graves’ orbitopathy is associated with an improvement of quality of life and eye involvement, as well as delayed progression of ocular disorders. The organic form of selenium seems to be the preferable formulation for supplementation or treatment. Conclusion. Maintaining a physiological concentration of selenium is a prerequisite to prevent thyroid disease and preserve overall health. Supplementation with the organic form is more effective, and patients with autoimmune thyroiditis seem to have benefits in immunological mechanisms. Selenium supplementation proved to be clinically beneficial in patients with mild to moderate Graves’ orbitopathy. Mara Ventura, Miguel Melo, and Francisco Carrilho Copyright © 2017 Mara Ventura et al. All rights reserved. Pediatric TSH Reference Intervals and Prevalence of High Thyroid Antibodies in the Lebanese Population Wed, 18 Jan 2017 09:04:59 +0000 The aims of this study are to establish reference values for TSH in Lebanese schoolchildren; to look at the relationship between TSH and age, gender, BMI, socioeconomic status (SES), and thyroid antibodies (TAb); and to investigate the prevalence of abnormal TAb in this population. 974 Lebanese schoolchildren aged 8–18 years were recruited from 10 schools of different SES. Third-generation TSH, TPO-Ab, and Tg-Ab measurements were performed using the IMMULITE chemiluminescent immunoassay. The mean TSH is  μUI/ml. TSH values are inversely correlated with age , are higher in boys than in girls (resp., and  μUI/ml, ), and are positively correlated with BMI . They are also significantly higher in subjects from low-SES schools and in girls with positive TAb . In boys, TSH is independently associated with age, BMI, and schools’ SES (, , and , resp.) while in girls, the association is only significant for age and TAb ( and , resp.). The prevalence of TAb is 4.3% (3% for TPO-Ab and 2.1% for Tg-Ab). Our results showed higher TSH values in the pediatric Lebanese population compared to western populations. TSH varies according to age, gender, BMI, and SES and is associated in girls with TAb. Marie-Hélène Gannagé-Yared, Nicole Balech, Vanessa Farah, Marianne Antar, Rindala Saliba, and Elise Chahine Copyright © 2017 Marie-Hélène Gannagé-Yared et al. All rights reserved. The Effect of Sitagliptin on the Regression of Carotid Intima-Media Thickening in Patients with Type 2 Diabetes Mellitus: A Post Hoc Analysis of the Sitagliptin Preventive Study of Intima-Media Thickness Evaluation Tue, 17 Jan 2017 11:22:33 +0000 Background. The effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on the regression of carotid IMT remains largely unknown. The present study aimed to clarify whether sitagliptin, DPP-4 inhibitor, could regress carotid intima-media thickness (IMT) in insulin-treated patients with type 2 diabetes mellitus (T2DM). Methods. This is an exploratory analysis of a randomized trial in which we investigated the effect of sitagliptin on the progression of carotid IMT in insulin-treated patients with T2DM. Here, we compared the efficacy of sitagliptin treatment on the number of patients who showed regression of carotid IMT of ≥0.10 mm in a post hoc analysis. Results. The percentages of the number of the patients who showed regression of mean-IMT-CCA (28.9% in the sitagliptin group versus 16.4% in the conventional group, P = 0.022) and left max-IMT-CCA (43.0% in the sitagliptin group versus 26.2% in the conventional group, P = 0.007), but not right max-IMT-CCA, were higher in the sitagliptin treatment group compared with those in the non-DPP-4 inhibitor treatment group. In multiple logistic regression analysis, sitagliptin treatment significantly achieved higher target attainment of mean-IMT-CCA ≥0.10 mm and right and left max-IMT-CCA ≥0.10 mm compared to conventional treatment. Conclusions. Our data suggested that DPP-4 inhibitors were associated with the regression of carotid atherosclerosis in insulin-treated T2DM patients. This study has been registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000007396). Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Masahiko Gosho, Iichiro Shimomura, and Hirotaka Watada Copyright © 2017 Tomoya Mita et al. All rights reserved. Myoinositol: The Bridge (PONTI) to Reach a Healthy Pregnancy Sun, 15 Jan 2017 13:10:29 +0000 The use of folic acid in the periconceptional period can prevent about 70% of neural tube defects (NTDs). In the remaining cases, no medical prevention is available, and those conditions should be defined as folate-resistant NTDs. Rodent models suggest that some folate-resistant NTDs can be prevented by inositol (myoinositol and chiroinositol) supplementation prior to pregnancy. Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of NTDs even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs. We further report on the largest case series of pregnancies treated with myoinositol and folic acid. At our institution, a sequential study during 12 years involved mothers at risk of fetal NTDs, and 29 babies from 27 pregnancies were born after periconceptional combined myoinositol and folic acid supplementation. No case of NTDs was observed, despite the high recurrence risk in the mothers. Taken together, those data suggest that periconceptional folic acid plus myoinositol can reduce both the occurrence and recurrence risks of NTDs in a greater number of cases than folic acid alone. Pietro Cavalli and Elena Ronda Copyright © 2017 Pietro Cavalli and Elena Ronda. All rights reserved. Corrigendum to “Pancreatic Function, Type 2 Diabetes, and Metabolism in Aging” Thu, 12 Jan 2017 07:56:31 +0000 Zhenwei Gong and Radhika H. Muzumdar Copyright © 2017 Zhenwei Gong and Radhika H. Muzumdar. All rights reserved. To Identify Predictors of Central Lymph Node Metastasis in Patients with Clinically Node-Negative Conventional Papillary Thyroid Carcinoma Thu, 15 Dec 2016 14:50:24 +0000 Objective. The aim of this study was to identify the risk factors associated with central lymph node metastasis (CLNM) in patients with clinically node-negative conventional papillary thyroid carcinoma (cN0 CPTC). Methods. A total of 190 cN0 CPTC patients who underwent thyroidectomy with prophylactic central neck dissection (pCND) in the Department of General Surgery at Guangdong General Hospital between March 2014 and December 2015 were assessed retrospectively. The relations of CLNM with clinicopathologic characteristics of cN0 CPTC were analyzed by univariate and multivariate logistic regression. Results. The incidence of CLNM in patients with cN0 CPTC was 63.2% (120 of 190 cases). Univariate analysis showed that age <45 years (), tumor size >2 cm (), multifocality (), and bilaterality () were significantly associated with the increased incidence of CLNM in cN0 CPTC. No significant correlations were found between CLNM and other variables such as gender (), capsular invasion (), extrathyroidal invasion (), and lymphadenectomy (). Multivariate logistic regression analysis revealed that age <45 years (), tumor size >2 cm (), and bilaterality () were independent risk factors of CLNM in patients with cN0 CPTC. Conclusions. Metastatic disease to central compartment lymph nodes is prevalent in patients with cN0 CPTC. Age <45 years, tumor size >2 cm, and bilaterality are independent risk factors of CLNM, which allow for selective CND in patients with cN0 CPTC. Jiru Yuan, Gang Zhao, Jialin Du, Xiaoyi Chen, Xiaodong Lin, Zhengbo Chen, and Zeyu Wu Copyright © 2016 Jiru Yuan et al. All rights reserved. Multidisciplinary Management of Pituitary Apoplexy Thu, 15 Dec 2016 12:11:30 +0000 Pituitary apoplexy is a rare clinical syndrome due to ischemic or haemorrhagic necrosis of the pituitary gland which complicates 2–12% of pituitary tumours, especially nonfunctioning adenomas. In many cases, it results in severe neurological, ophthalmological, and endocrinological consequences and may require prompt surgical decompression. Pituitary apoplexy represents a rare medical emergency that necessitates a multidisciplinary approach. Modalities of treatment and times of intervention are still largely debated. Therefore, the management of patients with pituitary apoplexy is often empirically individualized and clinical outcome is inevitably related to the multidisciplinary team’s skills and experience. This review aims to highlight the importance of a multidisciplinary approach in the management of pituitary apoplexy and to discuss modalities of presentation, treatment, and times of intervention. Adriana Albani, Francesco Ferraù, Filippo Flavio Angileri, Felice Esposito, Francesca Granata, Felicia Ferreri, and Salvatore Cannavò Copyright © 2016 Adriana Albani et al. All rights reserved. Influence of Androgen Receptor Gene CAG and GGC Polymorphisms on Male Sexual Function: A Cross-Sectional Study Thu, 15 Dec 2016 09:14:39 +0000 Background. No study has assessed the possible involvement of GGC androgen receptor (AR) polymorphism in sexual function. Our aim is to evaluate the association between CAG and GGC AR polymorphisms in this function. Methods. We retrospectively examined eighty-five outpatients. Clinical, biochemical, and genetic parameters were considered. Sexual assessment was performed using the International Index of Erectile Function (IIEF) which evaluates erectile function (EF), orgasmic function (OF), sexual desire (SD), intercourse satisfaction (IS), and overall satisfaction (OS). Results. In the whole sample, CAG repeats were inversely correlated with EF, OF, and total IIEF-15 score, whereas GGC tracts did not show any significant correlation with sexual function. CAG relationship with IIEF items retained significance only in the eugonadal but not in the hypogonadal cohort. On the other hand, GGC tracts were not found to be significantly correlated with IIEF variables in either eugonadal or hypogonadal subjects. In eugonadal subjects, logistic regression pointed out that a higher number of CAG triplets were associated with lower values of EF, OF, SD, OS, and total IIEF independently from other confounders. Conclusions. GGC polymorphism seems not to exert any influence on sexual function, whereas CAG polymorphism appears to affect sexual parameters only in eugonadal subjects. Giacomo Tirabassi, Giovanni Corona, Sara Falzetti, Nicola delli Muti, Mario Maggi, and Giancarlo Balercia Copyright © 2016 Giacomo Tirabassi et al. All rights reserved. Maternal Diet Supplementation with n-6/n-3 Essential Fatty Acids in a 1.2 : 1.0 Ratio Attenuates Metabolic Dysfunction in MSG-Induced Obese Mice Mon, 05 Dec 2016 05:55:04 +0000 Essential polyunsaturated fatty acids (PUFAs) prevent cardiometabolic diseases. We aimed to study whether a diet supplemented with a mixture of n-6/n-3 PUFAs, during perinatal life, attenuates outcomes of long-term metabolic dysfunction in prediabetic and obese mice. Seventy-day-old virgin female mice were mated. From the conception day, dams were fed a diet supplemented with sunflower oil and flaxseed powder (containing an n-6/n-3 PUFAs ratio of 1.2 : 1.0) throughout pregnancy and lactation, while control dams received a commercial diet. Newborn mice were treated with monosodium L-glutamate (MSG, 4 mg g−1 body weight per day) for the first 5 days of age. A batch of weaned pups was sacrificed to quantify the brain and pancreas total lipids; another batch were fed a commercial diet until 90 days of age, where glucose homeostasis and glucose-induced insulin secretion (GIIS) as well as retroperitoneal fat and Lee index were assessed. MSG-treated mice developed obesity, glucose intolerance, insulin resistance, pancreatic islet dysfunction, and higher fat stores. Maternal flaxseed diet-supplementation decreased n-6/n-3 PUFAs ratio in the brain and pancreas and blocked glucose intolerance, insulin resistance, GIIS impairment, and obesity development. The n-6/n-3 essential PUFAs in a ratio of 1.2 : 1.0 supplemented in maternal diet during pregnancy and lactation prevent metabolic dysfunction in MSG-obesity model. Josiane Morais Martin, Rosiane Aparecida Miranda, Luiz Felipe Barella, Kesia Palma-Rigo, Vander Silva Alves, Gabriel Sergio Fabricio, Audrei Pavanello, Claudinéia Conationi da Silva Franco, Tatiane Aparecida Ribeiro, Jesuí Vergílio Visentainer, Elton Guntendeorfer Banafé, Clayton Antunes Martin, Paulo Cezar de Freitas Mathias, and Júlio Cezar de Oliveira Copyright © 2016 Josiane Morais Martin et al. All rights reserved. Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences Sun, 04 Dec 2016 14:21:15 +0000 Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fractures, resulting in disabilities and increased mortality. The pathophysiological mechanisms linking diabetes to osteoporosis have not been fully explained, but alterations in bone structure and quality are well described in diabetic subjects, likely due to a combination of different factors. Insulin deficiency and dysfunction, obesity and hyperinsulinemia, altered level of oestrogen, leptin, and adiponectin as well as diabetes-related complications, especially peripheral neuropathy, orthostatic hypotension, or reduced vision due to retinopathy may all be associated with an impairment in bone metabolism and with the increased risk of fractures. Finally, medications commonly used in the treatment of T2DM may have an impact on bone metabolism and on fracture risk, particularly in postmenopausal women. When considering the impact of hypoglycaemic drugs on bone, it is important to balance their potential direct effects on bone quality with the risk of falling-related fractures due to the associated hypoglycaemic risk. In this review, experimental and clinical evidence connecting bone metabolism and fracture risk to T2DM is discussed, with particular emphasis on hypoglycaemic treatments and gender-specific implications. Giuseppina T. Russo, Annalisa Giandalia, Elisabetta L. Romeo, Morabito Nunziata, Marco Muscianisi, Maria Concetta Ruffo, Antonino Catalano, and Domenico Cucinotta Copyright © 2016 Giuseppina T. Russo et al. All rights reserved. Erratum to “Inositols in the Treatment of Insulin-Mediated Diseases” Sun, 04 Dec 2016 13:46:55 +0000 Giovanna Muscogiuri, Stefano Palomba, Antonio Simone Laganà, and Francesco Orio Copyright © 2016 Giovanna Muscogiuri et al. All rights reserved. Gender Differences in Risks of Coronary Heart Disease and Stroke in Patients with Type 2 Diabetes Mellitus and Their Association with Metabolic Syndrome in China Wed, 30 Nov 2016 13:28:10 +0000 Coronary heart disease (CHD) and stroke are common complications of type 2 diabetes mellitus (T2DM). We aimed to explore the differences in the risks of CHD and stroke between Chinese women and men with T2DM and their association with metabolic syndrome (MS). This study included 1514 patients with T2DM. The Asian Guidelines of ATPIII (2005) were used for MS diagnosis, and the UKPDS risk engine was used to evaluate the 10-year CHD and stroke risks. Women had lower CHD risk (15.3% versus 26.3%), fatal CHD risk (11.8% versus 19.0%), stroke risk (8.4% versus 10.3%), and fatal stroke risk (1.4% versus 1.6%) compared with men with T2DM (–0.001). The CHD risk (28.4% versus 22.6%, ) was significantly higher in men with MS than in those without MS. The CHD (16.2% versus 11.0%, ) and stroke risks (8.9% versus 5.8%, ) were higher in women with MS than in those without MS. In conclusion, our findings indicated that Chinese women with T2DM are less susceptible to CHD and stroke than men. Further, MS increases the risk of both these events, highlighting the need for comprehensive metabolic control in T2DM. Mei-Fang Yao, Jie He, Xue Sun, Xiao-Li Ji, Yue Ding, Yi-Ming Zhao, Han-Yu Lou, Xiao-Xiao Song, Li-Zhen Shan, Ying-Xiu Kang, Song-Zhao Zhang, and Peng-Fei Shan Copyright © 2016 Mei-Fang Yao et al. All rights reserved. 408 Cases of Genital Ambiguity Followed by Single Multidisciplinary Team during 23 Years: Etiologic Diagnosis and Sex of Rearing Mon, 28 Nov 2016 14:10:41 +0000 Objective. To evaluate diagnosis, age of referral, karyotype, and sex of rearing of cases with disorders of sex development (DSD) with ambiguous genitalia. Methods. Retrospective study during 23 years at outpatient clinic of a referral center. Results. There were 408 cases; 250 (61.3%) were 46,XY and 124 (30.4%) 46,XX and 34 (8.3%) had sex chromosomes abnormalities. 189 (46.3%) had 46,XY testicular DSD, 105 (25.7%) 46,XX ovarian DSD, 95 (23.3%) disorders of gonadal development (DGD), and 19 (4.7%) complex malformations. The main etiology of 46,XX ovarian DSD was salt-wasting 21-hydroxylase deficiency. In 46,XX and 46,XY groups, other malformations were observed. In the DGD group, 46,XY partial gonadal dysgenesis, mixed gonadal dysgenesis, and ovotesticular DSD were more frequent. Low birth weight was observed in 42 cases of idiopathic 46,XY testicular DSD. The average age at diagnosis was 31.7 months. The final sex of rearing was male in 238 cases and female in 170. Only 6.6% (27 cases) needed sex reassignment. Conclusions. In this large DSD sample with ambiguous genitalia, the 46,XY karyotype was the most frequent; in turn, congenital adrenal hyperplasia was the most frequent etiology. Malformations associated with DSD were common in all groups and low birth weight was associated with idiopathic 46,XY testicular DSD. Georgette Beatriz De Paula, Beatriz Amstalden Barros, Stela Carpini, Bruna Jordan Tincani, Tais Nitsch Mazzola, Mara Sanches Guaragna, Cristiane Santos da Cruz Piveta, Laurione Candido de Oliveira, Juliana Gabriel Ribeiro Andrade, Guilherme Guaragna-Filho, Pedro Perez Barbieri, Nathalia Montibeler Ferreira, Marcio Lopes Miranda, Ezequiel Moreira Gonçalves, Andre Moreno Morcillo, Nilma Lucia Viguetti-Campos, Sofia Helena Valente Lemos-Marini, Roberto Benedito de Paiva Silva, Antonia Paula Marques-de-Faria, Maricilda Palandi De Mello, Andrea Trevas Maciel-Guerra, and Gil Guerra-Junior Copyright © 2016 Georgette Beatriz De Paula et al. All rights reserved. GC Gene Polymorphisms and Vitamin D-Binding Protein Levels Are Related to the Risk of Generalized Aggressive Periodontitis Mon, 28 Nov 2016 11:23:02 +0000 Objective. To explore whether GC (group-specific component) rs17467825, rs4588, and rs7041 polymorphisms are associated with generalized aggressive periodontitis. Methods. This case-control study recruited 372 patients with generalized aggressive periodontitis (group AgP) and 133 periodontal healthy subjects (group HP). GC rs17467825, rs4588, and rs7041 genotypes and plasmatic vitamin D-binding protein (DBP) were measured. Analysis of single SNP and multiple SNPs was performed and relevance between plasmatic DBP and haplotypes was analyzed. Results. GC rs17467825 GG genotype was statistically associated with lower risk for generalized aggressive periodontitis under the recessive model (OR = 0.52, 95% CI: 0.30–0.92, ). GC rs17467825 and rs4588 had strong linkage disequilibrium with and . Haplotype (GC rs17467825, rs4588) GC was associated with the less risk for generalized aggressive periodontitis (OR = 0.29, 95% CI: 0.09–0.96, ). In group AgP, individuals with combined genotype (GC rs17467825, rs4588) AG+CA had significantly lower plasmatic DBP level than those with the other two combined genotypes (AG+CA versus AA+CC ; AG+CA versus GG+AA ). Conclusions. GC rs17467825 genotype GG and haplotype (GC rs17467825, rs4588) GC are associated with generalized aggressive periodontitis. The association may be acquired through regulating DBP levels. The functions of GC gene and DBP in inflammatory disease need to be further studied. Wenli Song, Xian’e Wang, Yu Tian, Xin Zhang, Ruifang Lu, and Huanxin Meng Copyright © 2016 Wenli Song et al. All rights reserved. Larger Thyroid Volume and Adequate Iodine Nutrition in Chinese Schoolchildren: Local Normative Reference Values Compared with WHO/IGN Thu, 24 Nov 2016 13:59:26 +0000 Objective. Thyroid volume measured by ultrasound to define goiter needs reliable local thyroid volume reference from iodine-sufficient populations. The aim of this study is to explore the reference interval for normal thyroid volume in schoolchildren aged 8–10 years from Zhejiang Province, China. Methods. A probability-proportionate-to-size sampling method was applied to select a representative sample of 1213 children aged 8–10 years in Zhejiang Province to detect the thyroid volume, salt iodine, and urine iodine. Results. Median urinary iodine concentration in involved schoolchildren was 178.30 (125.00) μg l−1, with the percentage of samples less than 100 μg l−1 as 12.69% and more than 300 μg l−1 as 15.25%. Thyroid volume was significantly correlated with age and anthropometric measurements independently of each other. The 97th percentile of thyroid volume in our study was larger generally than the new international reference. Conclusions. The iodine nutritional status in Zhejiang Province was at an adequate level. Despite some limitations in this study, we initially established the reference values for thyroid volume in 8–10-year-old schoolchildren in Zhejiang Province, China, as a local reference to be used for monitoring iodine deficiency disorders. Zhe Mo, Xiaoming Lou, Guangming Mao, Zhifang Wang, Wenming Zhu, Zhijian Chen, and Xiaofeng Wang Copyright © 2016 Zhe Mo et al. All rights reserved. Long-Term Clinical Outcomes of Invasive Giant Prolactinomas after a Mean Ten-Year Followup Wed, 23 Nov 2016 14:26:55 +0000 Objective. The aim of this study is to observe clinical outcomes after more than ten years of followup in a group of patients with invasive giant prolactinomas (IGPs) treated with dopamine agonists (DAs). Methods. Twenty-five patients met the criteria of IGPs, among which 16 patients primarily received bromocriptine (BRC) and the other nine had undergone unsuccessful microsurgery prior to BRC treatment. Results. After a mean follow-up period of months, the clinical symptoms in all patients improved by different degrees. Tumor volume was decreased by a mean of 98.6%, and the tumors of 19 patients had almost completely disappeared. The mean duration of treatment at maximal doses of BRC was 48.5 months. At the last follow-up visit, nineteen patients had normal PRL levels, and 14 of these patients had received the low-dose BRC treatment (at an average of ). Younger patients < 25 years had a significantly higher rate of persistent hyperprolactinemia after long-term BRC treatment (). Conclusion. DAs are a first-line therapy for IGPs because they can effectively achieve long-term control in both shrinking tumor volume and normalizing the PRL level, and majority of patients need low-dose DA maintenance. Younger patients are prone to persistent hyperprolactinemia despite long-term DA treatment. Ze Rui Wu, Yong Zhang, Lin Cai, Shao Jian Lin, Zhi Peng Su, Yong Xu Wei, Han Bing Shang, Wen Lei Yang, Wei Guo Zhao, and Zhe Bao Wu Copyright © 2016 Ze Rui Wu et al. All rights reserved. The Changes of Serum Leptin and Kisspeptin Levels in Chinese Children and Adolescents in Different Pubertal Stages Sun, 20 Nov 2016 10:14:32 +0000 The aim of the study is to investigate the changes of serum leptin and kisspeptin levels in children and adolescents with different pubertal stages and nutritional states. A total of 647 Chinese children and adolescents were recruited, and serum estradiol, testosterone, pituitary gonadotropins, leptin, and kisspeptin levels were measured. The results showed that serum leptin levels of boys in T2 stage were the highest among the five stages, while they showed a gradual increase from T1 to T5 stage in girls and reached the highest in T5 stage (). Conversely, serum kisspeptin levels of boys were higher in T4 and T5 stages than those in T1 stage, while its levels of girls were the highest in T2 stage, 21.4% higher than those in T1 stage (). Both leptin and kisspeptin levels were positively correlated with BMI, WC, and weight in all boys and girls (all ). In conclusion, kisspeptin levels were firstly found to be notably changed in pubertal stages and nutritional status in Chinese children and adolescents with a significant sexual dimorphism. Obese/overweight girls had higher kisspeptin levels, and there was a positive correlation between kisspeptin and FSH and LH and obesity-related parameters in all boys and girls. Hui juan Zhu, Su juan Li, Hui Pan, Naishi Li, Dian xi Zhang, Lin jie Wang, Hong bo Yang, Qinyong Wu, and Feng ying Gong Copyright © 2016 Hui juan Zhu et al. All rights reserved. The Roles of PI3K/AKT/mTOR and MAPK/ERK Signaling Pathways in Human Pheochromocytomas Sun, 20 Nov 2016 09:53:11 +0000 Objectives. The roles of PI3K/AKT/mTOR and MAPK/ERK pathways involved in the pathogenesis of pheochromocytoma and paraganglioma (PPGL) were demonstrated mostly by in vitro studies with rat or mouse cells and were mainly studied at transcriptional level. This study aimed to investigate the effect of these pathways on the proliferation of human PPGL cells and the activation of these pathways in PPGLs. Methods. Human PPGL cells were treated with sunitinib and inhibitors of PI3K (LY294002), MEK1/2 (U0126), and mTORC1/2 (AZD8055). Cell proliferation was detected by MTT assay. Protein phosphorylation was detected by Western blotting. Results. In most PPGLs, AKT, ERK1/2, and mTOR were activated. LY294002 (10 μM), U0126 (10 μM), AZD8055 (1 μM), and sunitinib (1 μM) inhibited PPGL cell proliferation in ten primary cultures of tissues, including four from patients with gene mutations. MEK1/2 inhibitor decreased mTOR phosphorylation. Inhibition of mTOR reduced phosphorylation of AKT and ERK1/2. Sunitinib inhibited phospho-ERK1/2 and phospho-mTOR. Conclusion. Our study suggested that PI3K/AKT/mTOR and MAPK/ERK signaling pathways play vital roles in human PPGL and are activated in most PPGLs. Inhibiting multiple pathways might be a novel therapeutic approach for PPGLs. Juan Du, Anli Tong, Fen Wang, Yunying Cui, Chunyan Li, Yushi Zhang, and Zhaoli Yan Copyright © 2016 Juan Du et al. All rights reserved. Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells Sun, 20 Nov 2016 07:45:50 +0000 Sex Hormone Binding Globulin (SHBG) is the major serum carrier of sex hormones. However, growing evidence suggests that SHBG is internalised and plays a role in regulating intracellular hormone action. This study was to determine whether SHBG plays a role in testosterone uptake, metabolism, and action in the androgen sensitive LNCaP prostate cancer cell line. Internalisation of SHBG and testosterone, the effects of SHBG on testosterone uptake, metabolism, regulation of androgen responsive genes, and cell growth were assessed. LNCaP cells internalised SHBG by a testosterone independent process. Testosterone was rapidly taken up and effluxed as testosterone-glucuronide; however this effect was reduced by the presence of SHBG. Addition of SHBG, rather than reducing testosterone bioavailability, further increased testosterone-induced expression of prostate specific antigen and enhanced testosterone-induced reduction of androgen receptor mRNA expression. Following 38 hours of testosterone treatment cell morphology changed and growth declined; however, cotreatment with SHBG abrogated these inhibitory effects. These findings clearly demonstrate that internalised SHBG plays an important regulatory and intracellular role in modifying testosterone action and this has important implications for the role of SHBG in health and disease. Huika Li, Thy Pham, Brett C. McWhinney, Jacobus P. Ungerer, Carel J. Pretorius, Derek J. Richard, Robin H. Mortimer, Michael C. d’Emden, and Kerry Richard Copyright © 2016 Huika Li et al. All rights reserved. Association between Sleep Duration and Measurable Cardiometabolic Risk Factors in Healthy Korean Women: The Fourth and Fifth Korean National Health and Nutrition Examination Surveys (KNHANES IV and V) Sun, 13 Nov 2016 14:18:57 +0000 Study Objectives. To examine the association between sleep duration and prevalence of metabolic syndrome (MetS) and its components in healthy Korean women. Design. Cross-sectional study, using the Fourth and Fifth Korean National Health and Nutrition Examination Surveys. Methods. Among 8505 women (25–70 years) from KNHANES IV and V, participants were classified into five sleep groups based on self-reported sleep duration. MetS and its components were defined using the criteria set forth in National Cholesterol Education Program-Adult Treatment Panel III. We used multivariate logistic regression analysis. Results. After adjusting for various confounders, shorter sleep duration (≤6 h) was found to have an association with low risk of reduced high-density lipoprotein cholesterol and increased triglycerides, whereas very long sleep duration was found to have high risk of increased triglycerides. However, abdominal obesity showed an opposite trend: short sleep duration was associated with higher risk of abdominal obesity than long sleep duration. Fasting glucose levels increased as sleep duration increased, but without significance. Moreover, blood pressure was not significantly associated with sleep duration. Consequently, MetS was less prevalent in those with short sleep duration. Conclusions. Sleep duration was positively associated with MetS, especially dyslipidemia and fasting hyperglycemia, but inversely associated with abdominal obesity. Hyeyeon Min, Yoo Jin Um, Bum Sup Jang, Doosup Shin, EunJoo Choi, Sang Min Park, and Kiheon Lee Copyright © 2016 Hyeyeon Min et al. All rights reserved. Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update Sun, 13 Nov 2016 14:10:57 +0000 The prevalence of gestational diabetes mellitus is increasing in parallel with the rising prevalence of type 2 diabetes and obesity around the world. Current evidence strongly suggests that women who have had gestational diabetes mellitus are at greater risk of cardiovascular disease later in life. Given the growing prevalence of gestational diabetes mellitus, it is important to identify appropriate reliable markers of cardiovascular disease and specific treatment strategies capable of containing obesity, diabetes, and metabolic syndrome in order to reduce the burden of cardiovascular disease in the women affected. S. Burlina, M. G. Dalfrà, N. C. Chilelli, and A. Lapolla Copyright © 2016 S. Burlina et al. All rights reserved. Body Composition in Adult Patients with Thalassemia Major Thu, 10 Nov 2016 08:48:05 +0000 Objective. To assess body composition in adult male and female patients with thalassemia major by dual-energy X-ray absorptiometry (DXA) and to compare the findings with a group of healthy age-matched controls. Methods. Our study group included sixty-two patients (27 males, mean age 36 years, and 35 females, mean age 36.4 years) and fifteen age-matched healthy controls. All patients had an established diagnosis of thalassemia major and followed a regular blood transfusion scheme since childhood and chelation treatment. Fat, lean, and bone mineral density (BMD) were assessed with dual-energy X-ray absorptiometry. Ferritin levels and body mass index of all patients and controls were also recorded. Student t-test and Wilcoxon test were performed and statistical significance was set at . Results. BMD and whole body lean mass are lower in both male and female adult patients compared with controls ( in both groups), whereas whole body fat mass was found to have no statistically significant difference compared to controls. Regional trunk fat around the abdomen was found to be lower in male patients compared to controls (). Conclusion. Severe bone loss and diminished lean mass are expected in adult male and female patients with thalassemia major. Fat changes seem to affect mainly male patients. Marianna Vlychou, Evangelos Alexiou, Paschalis Thriskos, Ioannis Fezoulidis, and Katerina Vassiou Copyright © 2016 Marianna Vlychou et al. All rights reserved.