International Journal of Endocrinology The latest articles from Hindawi © 2017 , Hindawi Limited . All rights reserved. Salt, Aldosterone, and Parathyroid Hormone: What Is the Relevance for Organ Damage? Tue, 19 Sep 2017 07:06:42 +0000 Structured interventions on lifestyle have been suggested as a cost-effective strategy for prevention of cardiovascular disease. Epidemiologic studies demonstrate that dietary salt restriction effectively decreases blood pressure, but its influence on cardiovascular morbidity and mortality is still under debate. Evidence gathered from studies conducted in patients with primary aldosteronism, essential hypertension, or heart failure demonstrates that long-term exposure to elevated aldosterone results in cardiac structural and functional changes that are independent of blood pressure. Animal experiments and initial clinical studies indicate that aldosterone damages the heart only in the context of an inappropriately elevated salt status. Recent evidence suggests that aldosterone might functionally interact with the parathyroid hormone and thereby affect calcium homeostasis with important sequelae for bone mineral density and strength. The interaction between aldosterone and parathyroid hormone might have implications also for the heart. Elevated dietary salt is associated on the one hand with increased urinary calcium excretion and, on the other hand, could facilitate the interaction between aldosterone and parathyroid hormone at the cellular level. This review summarizes the evidence supporting the contribution of salt and aldosterone to cardiovascular disease and the possible cardiac and skeletal consequences of the mutual interplay between aldosterone, parathyroid hormone, and salt. Cristiana Catena, Gian Luca Colussi, Gabriele Brosolo, Nicole Bertin, Marileda Novello, Andrea Palomba, and Leonardo A. Sechi Copyright © 2017 Cristiana Catena et al. All rights reserved. Does HbA1c Level Have Clinical Implications in Diabetic Patients Undergoing Coronary Artery Bypass Grafting? A Systematic Review and Meta-Analysis Sun, 17 Sep 2017 00:00:00 +0000 Aims/Introduction. The aim of the present study was to investigate whether HbA1c was related to clinical outcomes in diabetic patients undergoing CABG surgery. Materials and Methods. A literature search was carried out satisfying the predefined inclusion criteria from Pubmed, Embase, and Cochrane Library. Differences were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) to assess the relationships of preoperative HbA1c levels and clinical prognosis in diabetic patients. Results. 7895 diabetic patients undergoing CABG surgery from eight published studies were finally involved in this meta-analysis. Combined analyses revealed that the higher HbA1c level was significantly associated with increased risks of all-cause mortality (OR 1.56, 95%CI 1.29–1.88), myocardial infarction (OR 2.37, 95%CI 1.21–4.64), and stroke (OR 2.07, 95%CI 1.29–3.32) after CABG surgery. However, there was no significant relationship between HbA1c levels and renal failure (OR 2.08, 95%CI 0.96–4.54) in diabetic patients undergoing CABG surgery. Conclusions. Our meta-analysis demonstrated that the HbA1c level is potentially associated with increased risks of all-cause mortality, myocardial infarction, and stroke in diabetic subjects undergoing CABG surgery. However, further clinical studies with larger sample sizes and longer follow-up period are urgently warranted. Jia Zheng, Jing Cheng, Tong Wang, Qian Zhang, and Xinhua Xiao Copyright © 2017 Jia Zheng et al. All rights reserved. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review Tue, 12 Sep 2017 08:31:26 +0000 Vitamins D and K are both fat-soluble vitamins and play a central role in calcium metabolism. Vitamin D promotes the production of vitamin K-dependent proteins, which require vitamin K for carboxylation in order to function properly. The purpose of this review is to summarize available evidence of the synergistic interplay between vitamins D and K on bone and cardiovascular health. Animal and human studies suggest that optimal concentrations of both vitamin D and vitamin K are beneficial for bone and cardiovascular health as supported by genetic, molecular, cellular, and human studies. Most clinical trials studied vitamin D and K supplementation with bone health in postmenopausal women. Few intervention trials studied vitamin D and K supplementation with cardiovascular-related outcomes. These limited studies indicate that joint supplementation might be beneficial for cardiovascular health. Current evidence supports the notion that joint supplementation of vitamins D and K might be more effective than the consumption of either alone for bone and cardiovascular health. As more is discovered about the powerful combination of vitamins D and K, it gives a renewed reason to eat a healthy diet including a variety of foods such as vegetables and fermented dairy for bone and cardiovascular health. Adriana J. van Ballegooijen, Stefan Pilz, Andreas Tomaschitz, Martin R. Grübler, and Nicolas Verheyen Copyright © 2017 Adriana J. van Ballegooijen et al. All rights reserved. Swim Training Attenuates Inflammation and Improves Insulin Sensitivity in Mice Fed with a High-Fat Diet Sun, 10 Sep 2017 00:00:00 +0000 Exercise could afford multiple beneficial effects on obesity-related metabolic disorders. To address this issue, C57BL/6J mice were used to investigate the effects of 13 weeks of swim training on HFD-induced obesity and related insulin resistance and inflammation. Our results show that swim training can significantly prevent HFD-induced weight gain and increase resting energy expenditure without affecting food intake. The insulin sensitivity was enhanced in the HFD + swim group than in the HFD + sedentary group. Moreover, swim training considerably decreased serum LPS content and downregulates epididymis white adipose tissue (eWAT) expression of the inflammatory mediator Tnf-α, Il-6, and Mcp-1. In summary, 13 weeks of swim training could reverse HFD-induced metabolic disorders including insulin resistance and inflammation. Guangzeng Zhang, Pengfei Yu, and Xiaomeng Liu Copyright © 2017 Guangzeng Zhang et al. All rights reserved. The Clinical Values of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 Levels in Blood and Thyroid Nodules Thu, 07 Sep 2017 02:42:03 +0000 Aim. Insulin-like growth factor-1 (IGF-1) is a potent mitogen for many cells. IGF-1 plays a role in the pathogenesis of various tumors with its mutagenic and antiapoptotic properties. The aim of this study was to determine both the serum and intranodular levels of IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) in patients with nodular thyroid diseases. Materials and Methods. In this study, 80 subjects who performed fine-needle aspiration biopsy (FNAB) were required in order to investigate the effects of serum and intranodular IGF-1 and IGFBP-3 in the pathogenesis of nodules. After performing FNAB, IGF-1 and IGFBP-3 levels were determined in blood and aspiration samples. Results. The serum levels of IGF-1 (232.8 ± 12.9 ng/ml) and IGFBP-3 (4.8 μg/ml) were found significantly higher than that of the intranodular IGF-1 (39.1 ng/ml) and intranodular IGFBP-3 levels (0.173 μg/ml) (). Intranodular levels of IGF-1 and IGFBP-3 were higher in subjects with multinodular thyroid gland than those of subjects with solitary nodules (). A positive correlation between the nodule size and the serum IGFBP-3 levels was detected (, ). Conclusion. This study demonstrated the possible role of both IGF-1 and IGFBP-3 in the growth and the formation of multinodularity of thyroid nodules. Ayfer Altas, Fatih Kuzu, Dilek Arpaci, Mustafa Unal, Murat Can, Figen Barut, Furuzan Kokturk, Sevil Uygun Ilikhan, and Taner Bayraktaroglu Copyright © 2017 Ayfer Altas et al. All rights reserved. Chronic Hyperglycemia Modulates Rat Osteoporotic Cortical Bone Microarchitecture into Less Fragile Structures Thu, 07 Sep 2017 00:00:00 +0000 There is controversy concerning the diabetes impact on bone quality, notorious in type 2 diabetic postmenopausal women. One pointed cause might be uncontrolled glycemia. In this study, the effect of chronic hyperglycemia in bone turnover, morphology, and biomechanics was evaluated in female Wistar rats in the presence/absence of estrogens (ovariectomy). Animals () were divided into sham, ovariectomized (OVX), hyperglycemic (streptozotocin 40 mg/kg, single-dose i.p.-STZ), and hyperglycemic-ovariectomized (STZ + OVX) animals. Blood biomarkers were estimated 60 days postovariectomy. Body weight, vertebral microarchitecture (L4-histomorphometry), femur biomechanical properties (bending tests), tibia ultrastructure (scanning electron microscopy), and femur and urinary calcium (atomic absorption) were also evaluated. The increased PINP/CTX ratio of hyperglycemic animals and the similar ratio between STZ + OVX and healthy animals contrasting with the lower ratio of OVX (in line with its histomorphometric data) suggest a tendency for improved bone formation in hyperglycemic-ovariectomized animals. The increased tibia medullar canal, which contrasts with the unaffected cortical thickness of both hyperglycemic groups while that of OVX decreased, was associated to the increased stiffness and strength of STZ + OVX bones compared to those of OVX, in line with the observed ultrastructure. Concluding, chronic hyperglycemia in ovariectomized female rats causes bone morphological changes that translate positively in the ultrastructure and mechanical properties of cortical bones. Cristina de Mello-Sampayo, Alaíde Alves Agripino, Duarte Stilwell, Bruno Vidal, Ana Luisa Fernando, Beatriz Silva-Lima, Maria Fátima Vaz, Helena Canhão, and M. Cristina Marques Copyright © 2017 Cristina de Mello-Sampayo et al. All rights reserved. Relationship between Subclinical Thyroid Dysfunction and the Risk of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Cohort Studies Thu, 31 Aug 2017 00:00:00 +0000 Background. Evidence on the association between subclinical thyroid dysfunction and the risk of cardiovascular outcomes are conflicting. Methods and Results. PubMed, EMbase, Web of Science, Cochrane Library, and China Biology Medicine (CBM) databases were searched from inception to July 10, 2016. A total of 16 studies were included for meta-analysis. We found that subclinical hypothyroidism was not correlated with coronary heart disease (CHD) (RR = 1.17; 95% CI, 0.91–1.52), total mortality (RR = 1.02; 95% CI, 0.93–1.13), cardiovascular mortality (RR = 1.06; 95% CI, 0.77–1.45), heart failure (RR = 1.17; 95% CI, 0.87–1.57), and atrial fibrillation (RR = 1.05; 95% CI, 0.91–1.21), except CHD mortality (RR = 1.37; 95% CI, 1.03–1.84). Subgroup analysis indicated a higher estimation risk in CHD (RR = 1.54; 95% CI, 1.00–2.39), cardiovascular mortality (RR = 2.14; 95% CI, 1.43–3.22), and CHD mortality (RR = 1.54; 95% CI, 1.11–2.15) among participants < 65 years. Furthermore, subclinical hyperthyroidism was found to be associated with CHD (RR = 1.20; 95% CI, 1.02–1.42), total mortality (RR = 1.27; 95% CI, 1.07–1.51), and CHD mortality (RR = 1.45; 95% CI, 1.12–1.86). Conclusions. Subclinical hypothyroidism is likely associated with an increased risk of CHD mortality, and subclinical hyperthyroidism is likely associated with increased risk of CHD, CHD mortality, and total mortality. Jing Sun, Liang Yao, Yuan Fang, Ruifei Yang, Yaolong Chen, Kehu Yang, and Limin Tian Copyright © 2017 Jing Sun et al. All rights reserved. The Association of Thyrotropin and Autoimmune Thyroid Disease in Developing Papillary Thyroid Cancer Tue, 29 Aug 2017 06:22:59 +0000 Background. Papillary thyroid carcinoma (PTC) is the most common type of malignant thyroid neoplasm. However, the incidence of PTC with autoimmune thyroid disease (AITD) varies between studies. This study aims to investigate whether patients with AITD have increased incidence of PTC. We also analyzed the relationship of serum thyroid-stimulating hormone (TSH) levels and PTC in relation to AITD based on histopathological data. Methods. A total of 533 participants who underwent thyroidectomy were enrolled in this retrospective study based on clinicohistopathological data and known thyroid autoantibodies. Patients were divided into PTC and benign groups according to histopathologic diagnosis. Age, gender, body mass index, and serum TSH level before thyroidectomy were recorded. Results. Of the 533 enrolled patients, 159 (29.8%) were diagnosed with PTC, of which 38 (35.5%) had Hashimoto’s thyroiditis (HT). More patients with HT were female, and patients with HT, Graves’ disease, and thyroid nodules with higher TSH level had a higher incidence of PTC. Conclusions. A high proportion of the patients with PTC had HT. There was a trend that a higher serum TSH level was associated with a greater risk of thyroid cancer. I-Shuan Lee, An-Tsz Hsieh, Ting-Wei Lee, Ting-I Lee, and Yu-Mei Chien Copyright © 2017 I-Shuan Lee et al. All rights reserved. Perspectives on Peripheral Neuropathy as a Consequence of Metformin-Induced Vitamin B12 Deficiency in T2DM Sun, 27 Aug 2017 00:00:00 +0000 Peripheral neuropathy (PN) is a primary complication of type 2 diabetes mellitus (T2DM) and a direct manifestation of vitamin B12 deficiency. Examining the effects of metformin use on PN status became imperative following clinical studies that showed the vitamin B12-lowering effect of the medication. The complexity of the topic and the inconsistency of the results warrant consideration of topic-specific perspectives for better understanding of the available evidence and more appropriate design of future studies. Marwan A. Ahmed, George L. Muntingh, and Paul Rheeder Copyright © 2017 Marwan A. Ahmed et al. All rights reserved. Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia Thu, 24 Aug 2017 00:00:00 +0000 Objective. This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas–kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia. Methods. A total of 19 patients with simultaneous pancreas–kidney transplantation (SPK) with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF)), 22 diabetic patients with uremia who underwent renal transplantation (RT), and 20 normal individuals (CON) were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479 μg/g, which was significantly higher than 229 μg/g in CRF patients and 197 μg/g in RT patients. Using 200 μg/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin. Conclusions. The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects. Guanghui Pei, Wu Lv, Xiaohang Li, Guoqing Zhang, and Jialin Zhang Copyright © 2017 Guanghui Pei et al. All rights reserved. The Biphasic Effect of Vitamin D on the Musculoskeletal and Cardiovascular System Wed, 23 Aug 2017 06:47:10 +0000 This narrative review summarizes beneficial and harmful vitamin D effects on the musculoskeletal and cardiovascular system. Special attention is paid to the dose-response relationship of vitamin D with clinical outcomes. In infants and adults, the risk of musculoskeletal diseases is highest at circulating 25-hydroxyvitamin D (25OHD) concentrations below 25 nmol/L and is low if 40–60 nmol/L are achieved. However, evidence is also accumulating that in elderly people the risk of falls and fractures increases again at circulating 25OHD levels > 100 nmol/L. Cohort studies report a progressive increase in cardiovascular disease (CVD) events at 25OHD levels < 50 nmol/L. Nevertheless, meta-analyses of randomized controlled trials suggest only small beneficial effects of vitamin D supplements on surrogate parameters of CVD risk and no reduction in CVD events. Evidence is accumulating for adverse vitamin D effects on CVD outcomes at 25OHD levels > 100 nmol/L, but the threshold may be influenced by the level of physical activity. In conclusion, dose-response relationships indicate deleterious effects on the musculoskeletal system and probably on the cardiovascular system at circulating 25OHD levels < 40–60 nmol/L and >100 nmol/L. Future studies should focus on populations with 25OHD levels < 40 nmol/L and should avoid vitamin D doses achieving 25OHD levels > 100 nmol/L. Armin Zittermann Copyright © 2017 Armin Zittermann. All rights reserved. Novel and Simple Ultrasonographic Methods for Estimating the Abdominal Visceral Fat Area Tue, 22 Aug 2017 07:27:07 +0000 Objectives. To evaluate the abdominal visceral fat area (VFA), we developed novel ultrasonographic (US) methods for estimating. Methods. 100 male volunteers were recruited, and their VFA was calculated by two novel US methods, the triangle method and the ellipse method. The VFA calculated by these methods was compared with the VFA calculated by CT. Results. Both the VFA calculated by the triangle method (, ) and the ellipse method (, ) showed a high correlation coefficient with the VFA calculated by CT. Also, the VFA calculated by our novel methods were significantly increased in subjects with one or more metabolic risk factors than in those without any risk factors. Furthermore, the correlation coefficients obtained using the two methods were enhanced by the addition of multiple regression analysis (with the triangle method, , ; with the ellipse method, , ). Conclusions. The VFA calculated by the triangle or ellipse method showed a high correlation coefficient with the VFA calculated by CT. These US methods are easy to use, they involve no radiation exposure, and the measurements can be conducted frequently. We hope that our simple methods would be widely adopted for the evaluation of VFA. Takeharu Asano, Naoto Kubota, Norihiro Koizumi, Kazunori Itani, Tsuyoshi Mitake, Kazuhito Yuhashi, Hongen Liao, Mamoru Mitsuishi, Shigemi Takeishi, Toshiaki Takahashi, Shin Ohnishi, Shiro Sasaki, Ichiro Sakuma, and Takashi Kadowaki Copyright © 2017 Takeharu Asano et al. All rights reserved. Corrigendum to “In Vitro Antioxidant Treatment of Semen Samples in Assisted Reproductive Technology: Effects of Myo-Inositol on Nemaspermic Parameters” Sun, 20 Aug 2017 00:00:00 +0000 Mariangela Palmieri, Palma Papale, Antonietta Della Ragione, Giuseppa Quaranta, Giovanni Russo, and Sabatino Russo Copyright © 2017 Mariangela Palmieri et al. All rights reserved. Association of Polymorphisms in Toll-Like Receptors 4 and 9 with Autoimmune Thyroid Disease in Korean Pediatric Patients Sun, 20 Aug 2017 00:00:00 +0000 Background. Toll-like receptors (TLRs) have been suggested to be associated with the development of AITD. Methods. Fifteen single-nucleotide polymorphisms in 7 TLR genes were analyzed in 104 Korean children (girls = 86, boys = 18) with AITD (Hashimoto disease (HD) = 44, Graves’ disease (GD) = 60, thyroid-associated ophthalmopathy (TAO) = 29, and non-TAO = 31) with 183 controls. Results. GD showed higher frequencies of the TLR4 rs1927911 C allele than control. TAO showed a lower frequency of the TLR4 rs1927911 CT genotype and non-TAO showed a higher frequency of the TLR4 rs1927911 CC genotype than control. The frequency of the TLR9 rs187084 CC genotype in TAO was higher than that in non-TAO. GD females showed a higher frequency of the TLR4 rs10759932 T allele, rs1927911 CC genotype, and the rs1927911 C allele than controls. GD males showed a higher frequency of the TLR4 rs10759932 CC genotype and rs1927911 TT genotype and lower frequency of the rs1927911 CT genotype than control. The frequency of the TLR4 rs10759932 CC genotype, C allele and rs1927911 TT genotype, and T allele in a GD female were lower than in a GD male. Conclusions. Our results suggest that TLR4 and 9 polymorphisms might contribute to the pathogenesis of GD and TAO. Won Kyoung Cho, Jung-Pil Jang, Eun-Jeong Choi, Moonbae Ahn, Shin Hee Kim, Kyoung Soon Cho, So Hyun Park, In Cheol Baek, Min Ho Jung, Tai-Gyu Kim, and Byung-Kyu Suh Copyright © 2017 Won Kyoung Cho et al. All rights reserved. Latent Inflammation and Insulin Resistance in Adipose Tissue Thu, 17 Aug 2017 00:00:00 +0000 Obesity is a growing problem in modern society and medicine. It closely associates with metabolic disorders such as type 2 diabetes mellitus (T2DM) and hepatic and cardiovascular diseases such as nonalcoholic fatty liver disease, atherosclerosis, myocarditis, and hypertension. Obesity is often associated with latent inflammation; however, the link between inflammation, obesity, T2DM, and cardiovascular diseases is still poorly understood. Insulin resistance is the earliest feature of metabolic disorders. It mostly develops as a result of dysregulated insulin signaling in insulin-sensitive cells, as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare. Here, we argue that inflammatory signaling provides a link between latent inflammation, obesity, insulin resistance, and metabolic disorders. We further hypothesize that insulin-activated PI3-kinase pathway and inflammatory signaling mediated by several IκB kinases may constitute negative feedback leading to insulin resistance at least in the fat tissue. Finally, we discuss perspectives for anti-inflammatory therapies in treating the metabolic diseases. I. S. Stafeev, A. V. Vorotnikov, E. I. Ratner, M. Y. Menshikov, and Ye. V. Parfyonova Copyright © 2017 I. S. Stafeev et al. All rights reserved. BMI Modulates the Effect of Thyroid Hormone on Lipid Profile in Euthyroid Adults Sun, 13 Aug 2017 00:00:00 +0000 The impacts of thyroid hormones (TH) on lipid profile in euthyroid adults have gained much attention. It is currently unknown whether BMI influences such interaction. In the present study, we investigate the role of BMI in modulating the association between TH and lipid parameters in 1372 euthyroid healthy adults. Our results show that thyroid parameters are differentially associated with lipid profile. FT3 is positively correlated with total cholesterol (, ) and LDL cholesterol levels (, ). FT4 is negatively correlated with TG (, ) while positively correlated with HDL cholesterol levels (, ). TSH is positively associated with TG (, ) and total cholesterol levels (, ). Importantly, BMI modulates the effect of TH on lipid profile: the interaction of FT4 and BMI and the interaction of FT3 and BMI reach statistical significance in predicting TG and HDL cholesterol levels, respectively. Stratified according to BMI levels, most associations between TH and lipid profile are significant only in normal-weight group. In conclusion, in euthyroid adults, high normal FT3, TSH levels, and low normal FT4 levels are associated with unfavorable lipid profile. BMI mediates the effect of thyroid function on lipid profile in euthyroid adults. Yanqiu Wang, Qinglei Yin, Min Xu, Qicheng Ni, Weiqing Wang, and Qidi Wang Copyright © 2017 Yanqiu Wang et al. All rights reserved. The Association between Bone Quality and Atherosclerosis: Results from Two Large Population-Based Studies Wed, 09 Aug 2017 07:23:05 +0000 Objective. It is highly debated whether associations between osteoporosis and atherosclerosis are independent of cardiovascular risk factors. We aimed to explore the associations between quantitative ultrasound (QUS) parameters at the heel with the carotid artery intima-media thickness (IMT), the presence of carotid artery plaques, and the ankle-brachial index (ABI). Methods. The study population comprised 5680 men and women aged 20–93 years from two population-based cohort studies: Study of Health in Pomerania (SHIP) and SHIP-Trend. QUS measurements were performed at the heel. The extracranial carotid arteries were examined with B-mode ultrasonography. ABI was measured in a subgroup of 3853 participants. Analyses of variance and linear and logistic regression models were calculated and adjusted for major cardiovascular risk factors. Results. Men but not women had significantly increased odds for carotid artery plaques with decreasing QUS parameters independent of diabetes mellitus, dyslipidemia, and hypertension. Beyond this, the QUS parameters were not significantly associated with IMT or ABI in fully adjusted models. Conclusions. Our data argue against an independent role of bone metabolism in atherosclerotic changes in women. Yet, in men, associations with advanced atherosclerosis, exist. Thus, men presenting with clinical signs of osteoporosis may be at increased risk for atherosclerotic disease. V. Lange, M. Dörr, U. Schminke, H. Völzke, M. Nauck, H. Wallaschofski, and A. Hannemann Copyright © 2017 V. Lange et al. All rights reserved. Regulation of Corticosteroidogenic Genes by MicroRNAs Wed, 09 Aug 2017 06:01:41 +0000 The loss of normal regulation of corticosteroid secretion is important in the development of cardiovascular disease. We previously showed that microRNAs regulate the terminal stages of corticosteroid biosynthesis. Here, we assess microRNA regulation across the whole corticosteroid pathway. Knockdown of microRNA using Dicer1 siRNA in H295R adrenocortical cells increased levels of CYP11A1, CYP21A1, and CYP17A1 mRNA and the secretion of cortisol, corticosterone, 11-deoxycorticosterone, 18-hydroxycorticosterone, and aldosterone. Bioinformatic analysis of genes involved in corticosteroid biosynthesis or metabolism identified many putative microRNA-binding sites, and some were selected for further study. Manipulation of individual microRNA levels demonstrated a direct effect of miR-125a-5p and miR-125b-5p on CYP11B2 and of miR-320a-3p levels on CYP11A1 and CYP17A1 mRNA. Finally, comparison of microRNA expression profiles from human aldosterone-producing adenoma and normal adrenal tissue showed levels of various microRNAs, including miR-125a-5p to be significantly different. This study demonstrates that corticosteroidogenesis is regulated at multiple points by several microRNAs and that certain of these microRNAs are differentially expressed in tumorous adrenal tissue, which may contribute to dysregulation of corticosteroid secretion. These findings provide new insights into the regulation of corticosteroid production and have implications for understanding the pathology of disease states where abnormal hormone secretion is a feature. Stacy Robertson, Louise A. Diver, Samantha Alvarez-Madrazo, Craig Livie, Ayesha Ejaz, Robert Fraser, John M. Connell, Scott M. MacKenzie, and Eleanor Davies Copyright © 2017 Stacy Robertson et al. All rights reserved. Baseline Demographic and Clinical Characteristics of Patients with Adrenal Incidentaloma from a Single Center in China: A Survey Mon, 07 Aug 2017 07:37:47 +0000 Aim. To investigate the clinical and endocrinological characteristics of patients with adrenal incidentaloma (AI). Materials and Methods. This retrospective study enrolled 1941 AI patients hospitalized at the Department of Endocrinology, Chinese PLA General Hospital, Beijing, China, between January 1997 and December 2016. The patient gender, age at visits, imaging features, functional status, and histological results were analyzed. Results. Of the 1941 patients, 984 (50.70%) were men. The median age was 52 years (interquartile range: 44–69 years). 140 cases had bilateral AI. Endocrine evaluation showed that 1411 (72.69%) patients had nonfunctional tumor, 152 (7.83%) had subclinical Cushing syndrome (SCS), and 82 (4.33%) had primary hyperaldosteronism. A total of 925 patients underwent operation for removal of 496 cortical adenomas (53.62%), 15 adrenal cortical carcinomas (1.62%), and 172 pheochromocytomas (18.59%). The bilateral group had a higher proportion of SCS (18.57% versus 7.10%, , ). A mass size of 46 mm was of great value in distinguishing malignant tumors from the benign tumors, with sensitivity of 88.2% and specificity of 95.5%. Conclusions. We reported the baseline demographic and clinical characteristics of patients with AI in a large series from a single center in China. Lele Li, Guoqing Yang, Ling Zhao, Jingtao Dou, Weijun Gu, Zhaohui Lv, Juming Lu, and Yiming Mu Copyright © 2017 Lele Li et al. All rights reserved. Thickness of Extraocular Muscle and Orbital Fat in MRI Predicts Response to Glucocorticoid Therapy in Graves’ Ophthalmopathy Sun, 06 Aug 2017 00:00:00 +0000 33 patients with active, moderate-severe Graves’ ophthalmopathy (GO) received 4.5 g methylprednisolone for 12 weeks and were divided by efficacy into two groups (responsive and unresponsive). All patients and 10 controls underwent orbital MRI examination at baseline. No significant difference was seen in baseline clinical characteristics between the two GO groups. The values of exophthalmos were higher in both GO groups than in the control and were higher in the responsive group versus the unresponsive group. Compared to the unresponsive group, the responsive group had a thicker inferior rectus as well as thinner orbital fat. The inferior rectus/fat ratio was significantly higher in the responsive group versus the unresponsive group. Multivariate logistic regression analysis showed that the exophthalmos value and inferior rectus/fat ratio were significantly associated with the response to glucocorticoid (GC). ROC analysis revealed that the cut-off points of the inferior rectus/fat ratio combined with the exophthalmos value to indicate efficacy were 1.42 and 20.78. For moderate-severe GO patients with CAS > 3, the combined inferior rectus/fat ratio and exophthalmos value in MRI may be a valuable indicator to predict the response to GC therapy. Lingling Xu, Linna Li, Cuihua Xie, Meiping Guan, and Yaoming Xue Copyright © 2017 Lingling Xu et al. All rights reserved. 2D-Shear Wave Elastography in the Evaluation of Parathyroid Lesions in Patients with Hyperparathyroidism Sun, 06 Aug 2017 00:00:00 +0000 Background and Aims. 2D-shear wave elastography (2D-SWE) is a relatively new elastographic technique. The aim of the present study is to determine the values of the elasticity indexes (EI) measured by 2D-SWE in parathyroid benign lesions (adenomas or hyperplasia) and to establish if this investigation is helpful for the preoperative identification of the parathyroid adenoma. Material and Methods. The study groups were represented by 22 patients with primary or tertiary hyperparathyroidism, diagnosed by specific tests, and 43 healthy controls, in whom the thyroid parenchyma was evaluated, in order to compare the EI of the thyroid tissue with those of the parathyroid lesions. Results. The mean EI measured by 2D-SWE in the parathyroid lesions was 10.2 ± 4.9 kPa, significantly lower than that of the normal thyroid parenchyma (19.5 ± 7.6 kPa; ), indicating soft tissue. For a cutoff value of 12.5 kPa, the EI assessed by 2D-SWE had a sensitivity of 93% and a specificity of 86% (AUC = 0.949; ) for predicting parathyroid lesions. Conclusion. A value lower than 12.5 kPa for the mean EI measured by 2D-SWE can be used to confirm that the lesion/nodule is a parathyroid adenoma. Ioana Golu, Ioan Sporea, Lavinia Moleriu, Anca Tudor, Marioara Cornianu, Adrian Vlad, Romulus Timar, Melania Balas, Daniela Amzar, and Mihaela Vlad Copyright © 2017 Ioana Golu et al. All rights reserved. Variants of Interleukin-22 Gene Confer Predisposition to Autoimmune Thyroid Disease Thu, 03 Aug 2017 00:00:00 +0000 As there are no previous studies on the interleukin-22 (IL-22) variants in autoimmune thyroid disease (AITD), the present study aimed to explore the association between polymorphisms of IL-22 and the predisposition to AITD. The study had 975 AITD patients, including 639 Graves’ disease (GD) and 336 Hashimoto’s thyroiditis (HT) individuals and 851 healthy cohorts. Ligase detection reaction (LDR) and direct sequencing method were used for genotyping the IL-22 gene polymorphisms at rs2046068, rs2227478, rs2227485, rs11611206, and rs1179251. In comparison to female controls, genotype CC of rs1179251 was increased in the female AITD patients. Alleles C at rs2046068, C at rs2227478, and C at rs1179251 linked to the susceptibility of HT males. Genotype CC in rs1179251 was higher in male HT. Variants at rs2046068, rs2227478, and rs1179251 were associated with the AITD teenagers. Besides, genotype GG in rs11611206 was correlated with thyroid-associated ophthalmopathy (TAO). Moreover, allele G at rs11611206 was associated with decreased risk for TAO by 28.9%. Similarly, genotype CC of rs1179251 and genotype GG of rs11611206 were associated with Graves’ ophthalmopathy (GO). Allele G in rs11611206 increased people with HT towards the predisposition of hypothyroidism. In conclusion, genetic variants of IL-22 are associated with the occurrence of AITD. Rong-hua Song, Qian Li, Wen Wang, Qiu-ming Yao, Xiao-qing Shao, and Jin-an Zhang Copyright © 2017 Rong-hua Song et al. All rights reserved. Screening for Cushing Syndrome at the Primary Care Level: What Every General Practitioner Must Know Thu, 27 Jul 2017 09:16:12 +0000 Cushing’s syndrome is a rare entity, and a high index of suspicion is needed for screening in a primary care setting. The clinical awareness of the primary care physician (PCP) to the highly indicative signs and symptoms such as facial plethora, proximal myopathy, reddish purple striae, and easy bruisability should alert him to look for biochemical evidence of Cushing’s syndrome through any of the first-line screening tests, namely, 24-hour urinary free cortisol, overnight dexamethasone suppression test, or late-night salivary cortisol. Commonly used random cortisol measurements are unreliable; hence, general practitioners are encouraged to understand the use of these more reliable tests with increased sensitivity and specificity for screening Cushing’s syndrome. In this write-up, we set out to increase awareness about the presentation of Cushing’s syndrome and current recommended screening methods as well as their strengths and weaknesses. We relied mainly on the recommendations by the Endocrine Society Guidelines. Ernest Yorke, Yacoba Atiase, Josephine Akpalu, and Osei Sarfo-Kantanka Copyright © 2017 Ernest Yorke et al. All rights reserved. Association of SUDOSCAN Values with Vibration Perception Threshold in Chinese Patients with Type 2 Diabetes Mellitus Thu, 20 Jul 2017 04:07:24 +0000 Aims/Introduction. SUDOSCAN has been proved to be an efficient method in detecting diabetic microvascular complications. In this study, we determine to detect the possible relationship between vibration perception threshold (VPT) and cardiac autonomic neuropathy (CAN) values produced by SUDOSCAN. Materials and Methods. A total of 920 Chinese patients with T2DM were enrolled in the study. Spearman correlation analysis and multivariate regression analysis were performed to determine the relation between CAN and VPT values. Mean VPT values across the CAN value tertiles were analyzed stratified by HbA1c status. Results. In the study, we discovered a relatively high correlation between CAN value and both VPT values from dorsal feet and toes. Multivariate regression analyses also showed a significant relation between VPT and CAN values after adjusting all covariates. The mean value of VPT decreased across the SUDOSCAN-CAN value quartiles in both groups, and it was higher in patients with HbA1C > 9% than in patients with HbA1C < 9% across all quartiles of the SUDOSCAN-CAN except for the VPT mean in the low quartile of the SUDOSCAN-CAN value. Conclusions. All these results suggested that SUDOSCAN-CAN result was associated with VPT value which indicated a probable link between VPT value and cardiovascular autonomic dysfunction. Xiaoming Zhu, Fei Mao, Siying Liu, Hangping Zheng, Bin Lu, and Yiming Li Copyright © 2017 Xiaoming Zhu et al. All rights reserved. Angiotensin-Converting Enzyme Inhibition and Parathyroid Hormone Secretion Thu, 20 Jul 2017 00:00:00 +0000 Background. Prior studies suggest that renin-angiotensin-aldosterone system (RAAS) inhibitors decrease parathyroid hormone (PTH) secretion. Objective. To evaluate the effect of angiotensin-converting enzyme inhibitors (ACEi) on serum PTH in participants with and without primary hyperparathyroidism (P-HPT). Methods. An open-label, single-arm, pilot study whereby participants with and without P-HPT had PTH were evaluated before and after 1 week of maximally tolerated lisinopril therapy. Results. A total of 12 participants with, and 15 participants without, P-HPT successfully completed the protocol. Following 1 week of lisinopril, participants with P-HPT had a decrease in systolic blood pressure (SBP) (−6.4 mmHg, ), an increase in plasma renin activity (PRA) (+1.50 ng/mL/h, ), and a decrease in PTH (79.5 (21.6) to 70.9 (19.6) pg/mL,  pg/mL, ); however, serum and urine calcium did not change. In contrast, although 1 week of lisinopril significantly decreased SBP and increased PRA among participants without P-HPT, there were no changes in PTH or calcium. Conclusion. In this short pilot investigation, 1 week of maximally titrated ACEi did not impact PTH in participants without P-HPT, but resulted in a modest and marginally significant reduction of PTH but not calcium, among participants with P-HPT. This trial is registered with NCT01691781. Sarah Zaheer, Jenifer M. Brown, Molly Connors, Jonathan S. Williams, Gail K. Adler, and Anand Vaidya Copyright © 2017 Sarah Zaheer et al. All rights reserved. Corrigendum to “Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences” Sun, 16 Jul 2017 00:00:00 +0000 Giuseppina T. Russo, Annalisa Giandalia, Elisabetta L. Romeo, Nunziata Morabito, Marco Muscianisi, Maria Concetta Ruffo, Antonino Catalano, and Domenico Cucinotta Copyright © 2017 Giuseppina T. Russo et al. All rights reserved. Central Precocious Puberty and Response to GnRHa Therapy in Children with Cerebral Palsy and Moderate to Severe Motor Impairment: Data from a Longitudinal, Case-Control, Multicentre, Italian Study Sun, 16 Jul 2017 00:00:00 +0000 Background. Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available. Methods. This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits. Results. No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (−0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: −0.49 ± 0.91 versus 0.21 ± 0.33, ). Conclusions. Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitary-gonadal-axis in these patients. Patrizia Bruzzi, Maria Francesca Messina, Alessandra Bartoli, Barbara Predieri, Laura Lucaccioni, Simona Filomena Madeo, Alberto Verrotti, Filippo De Luca, and Lorenzo Iughetti Copyright © 2017 Patrizia Bruzzi et al. All rights reserved. Plasma lncRNA GAS8-AS1 as a Potential Biomarker of Papillary Thyroid Carcinoma in Chinese Patients Tue, 11 Jul 2017 00:00:00 +0000 Background. Long noncoding RNAs (lncRNAs) were recently shown to have potential in the diagnosis and prognosis for numerous cancers. lncRNA GAS8-AS1 is decreased in papillary thyroid cancer (PTC) tissue, but its plasma expression and clinical value in patients with PTC remain unknown. Materials and Methods. We investigated the expression profile of plasma GAS8-AS1 in 97 patients with PTC and 39 patients with nodular goiter by quantitative real-time polymerase chain reaction. Results. GAS8-AS1 expression in plasma was downregulated in patients with PTC in comparison with those in nodular goiters (). A low level of plasma GAS8-AS1 expression was correlated with lymph node metastasis (LNM) (). Multivariate analysis showed that a reduced GAS8-AS1 level in plasma was associated with LNM (). The area under the receiver operating characteristic curve for GAS8-AS1 was 0.746 in LNM prediction (). Conclusion. The present study indicates that circulating GAS8-AS1 is a potential biomarker for PTC diagnosis and LNM prediction. Dongxue Zhang, Xin Liu, Bojun Wei, Guoliang Qiao, Tao Jiang, and Zhenwen Chen Copyright © 2017 Dongxue Zhang et al. All rights reserved. Bacterial Profile and Antibiotic Resistance in Patients with Diabetic Foot Ulcer in Guangzhou, Southern China: Focus on the Differences among Different Wagner’s Grades, IDSA/IWGDF Grades, and Ulcer Types Tue, 11 Jul 2017 00:00:00 +0000 Objective. To understand the bacterial profile and antibiotic resistance patterns in diabetic foot infection (DFI) in different Wagner’s grades, IDSA/IWGDF grades, and different ulcer types in Guangzhou, in order to provide more detailed suggestion to the clinician about the empirical antibiotic choice. Methods. 207 bacteria were collected from 117 DFIs in Sun Yat-sen Memorial Hospital from Jan.1, 2010, to Dec.31, 2015. The clinical data and microbial information were analyzed. Results. The proportion of Gram-negative bacteria (GNB) was higher than Gram-positive bacteria (GPB) (54.1% versus 45.9%), in which Enterobacteriaceae (73.2%) and Staphylococcus (65.2%) were predominant, respectively. With an increasing of Wagner’s grades and IDSA/IWGDF grades, the proportion of GNB bacterial infection, especially Pseudomonas, was increased. Neuro-ischemic ulcer (N-IFU) was more susceptible to GNB infection. Furthermore, with the aggravation of the wound and infection, the antibiotic resistance rates were obviously increased. GPB isolated in ischemic foot ulcer (IFU) showed more resistance than the N-IFU, while GNB isolates were on the opposite. Conclusions. Different bacterial profiles and antibiotic sensitivity were found in different DFU grades and types. Clinician should try to stay updated in antibiotic resistance pattern of common pathogens in their area. This paper provided them the detailed information in this region. Xiaoying Xie, Yunwen Bao, Lijia Ni, Dan Liu, Shaona Niu, Haixiong Lin, Hongyu Li, Chaohui Duan, Li Yan, Songyin Huang, and Zhaofan Luo Copyright © 2017 Xiaoying Xie et al. All rights reserved. STK11 rs2075604 Polymorphism Is Associated with Metformin Efficacy in Chinese Type 2 Diabetes Mellitus Sun, 09 Jul 2017 00:00:00 +0000 Metformin is a classical oral antidiabetic drug, often recommended to be the first-choice treatment of type 2 diabetes mellitus (T2DM). Based on the previous research on STK11 and diabetes, we aimed to investigate the distributive characteristic of STK11 rs2075604 polymorphism and the potential influence of STK11 rs2075604 polymorphism on metformin efficacy among Chinese T2DM patients. There was no significant difference between T2DM patients (G = 64.8%, T = 35.2%) and healthy subjects (G = 62.7%, T = 37.2%) in STK11 rs2075604 genotype and allele frequencies. After 12 weeks of treatment, 62 patients were defined as the responders and 32 patients as nonresponders according to the decrease of HbA1c level. And the GT + TT genotype in STK11 rs2075604 can decrease HbA1c level more significantly than the GG genotype. Furthermore, the allele frequency of T in the STK11 rs2075604 was higher in the responders than the nonresponders (43.55% versus 26.56%). The T allele in the STK11 rs2075604 had a 2.133 times great chance of responding to metformin treatment. In conclusion, this study suggested that the STK11 rs2075604 genetic polymorphism was significantly associated with metformin efficacy in Chinese T2DM patients and the carriers of the T allele may gain a better therapeutic metformin efficacy compared with the G allele. This trial is registered with clinical study registration number NCT03155087. Qingchu Li, Cuilin Li, Haoyun Li, Liu Zeng, Zhiqiang Kang, Yu Mao, Xinyue Tang, Panpan Zheng, Li He, Fang Luo, and Zhi Li Copyright © 2017 Qingchu Li et al. All rights reserved.