International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Anaplastic Thyroid Carcinoma: Molecular Tools for Diagnosis and Therapy Sat, 31 Jan 2015 10:30:46 +0000 Ginesa Garcia-Rostan, Giovanni Tallini, and Giuliana Salvatore Copyright © 2015 Ginesa Garcia-Rostan et al. All rights reserved. Targeting Bone Metabolism in Patients with Advanced Prostate Cancer: Current Options and Controversies Sat, 31 Jan 2015 08:27:50 +0000 Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC) who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL), antiresorptive agents have been shown to improve bone mineral density (BMD) and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs) in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy. Tilman Todenhöfer, Arnulf Stenzl, Lorenz C. Hofbauer, and Tilman D. Rachner Copyright © 2015 Tilman Todenhöfer et al. All rights reserved. Synergy between HDAC and PARP Inhibitors on Proliferation of a Human Anaplastic Thyroid Cancer-Derived Cell Line Thu, 29 Jan 2015 07:10:01 +0000 Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated. The ATC-derived cell line SW1736 has been treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the PARP inhibitor PJ34, alone or in combination. In terms of cell viability, the combination index value was always lower than 1 at various tested dosages, indicating, therefore, synergy in a wide range of doses for both compounds. Synergy was also observed in induction of apoptosis. In terms of thyroid-specific gene expression, synergy was observed for TSHR mRNA levels but not for NIS, TTF1, TTF2, and PAX8 mRNA levels. Altogether, these data suggest that the combined use of HDAC and PARP inhibitors may be a useful strategy for treatment of ATC. Federica Baldan, Catia Mio, Lorenzo Allegri, Cinzia Puppin, Diego Russo, Sebastiano Filetti, and Giuseppe Damante Copyright © 2015 Federica Baldan et al. All rights reserved. Anaplastic Thyroid Carcinoma: A ceRNA Analysis Pointed to a Crosstalk between SOX2, TP53, and microRNA Biogenesis Thu, 29 Jan 2015 06:46:44 +0000 It has been suggested that cancer stem cells (CSC) may play a central role in oncogenesis, especially in undifferentiated tumours. Anaplastic thyroid carcinoma (ATC) has characteristics suggestive of a tumour enriched in CSC. Previous studies suggested that the stem cell factor SOX2 has a preeminent hierarchical role in determining the characteristics of stem cells in SW1736 ATC cell line. In detail, silencing SOX2 in SW1736 is able to suppress the expression of the stem markers analysed, strongly sensitizing the line to treatment with chemotherapeutic agents. Therefore, in order to further investigate the role of SOX2 in ATC, a competing endogenous RNA (ceRNA) analysis was conducted in order to isolate new functional partners of SOX2. Among the interactors, of particular interest are genes involved in the biogenesis of miRNAs (DICER1, RNASEN, and EIF2C2), in the control cell cycle (TP53, CCND1), and in mitochondrial activity (COX8A). The data suggest that stemness, microRNA biogenesis and functions, p53 regulatory network, cyclin D1, and cell cycle control, together with mitochondrial activity, might be coregulated. Walter Arancio, Valeria Carina, Giuseppe Pizzolanti, Laura Tomasello, Maria Pitrone, Concetta Baiamonte, Marco Calogero Amato, and Carla Giordano Copyright © 2015 Walter Arancio et al. All rights reserved. Regulation of the Human Ghrelin Promoter Activity by Transcription Factors, NF-κB and Nkx2.2 Wed, 28 Jan 2015 11:25:50 +0000 To examine the gene expression of ghrelin, a growth hormone releasing and appetite stimulating hormone from stomach, we constructed human ghrelin promoter-reporter vectors and analyzed the promoter activity. The ghrelin promoter activity was high when cultured cells that express ghrelin mRNA endogenously like TT or ECC10 cells were used, indicating that these cells contain factors necessary for full expression of the human ghrelin gene. The human ghrelin promoter contains both positive and negative regulatory regions. A transient decrease of the promoter activity was found when the reporter vector with the −1600 fragment of the human ghrelin promoter was transfected into cultured cells. We then examined the effect of several transcription factors on the ghrelin promoter activity and found that NF-κB suppressed and that Nkx2.2, a homeodomain-containing transcription factor that is important for ghrelin cell development in pancreas, activates the promoter activity. These transcription factors may be possible targets for the control of ghrelin gene expression. Yuki Shiimura, Hideko Ohgusu, Takahiro Sato, and Masayasu Kojima Copyright © 2015 Yuki Shiimura et al. All rights reserved. Are Thyroid Hormone and Tumor Cell Proliferation in Human Breast Cancers Positive for HER2 Associated? Wed, 28 Jan 2015 09:40:51 +0000 Objective. This study investigated whether thyroid hormone (TH) levels are correlated to cell proliferation (Ki67), in euthyroid breast cancer patients. Design and Methods. 86 newly diagnosed breast cancer patients with estrogen receptor (ER) positive tumors, who referred for surgery, were included in the study. Results. FT3, FT4, and TSH were within normal range. No correlation was seen between Ki67 and FT3 (, ), FT4 (, ), or TSH (, ) in all patients studied. However, subgroup analysis showed that, in HER2(+) patients, a negative correlation existed between FT3 levels and Ki67 ( and ) but not between Ki67 and FT4 ( and ) or TSH ( and ). In HER2(−) patients, there was no significant correlation between Ki67 and FT3 (, ), FT4 (, ), or TSH (, ). Phospho-p44/total p44 ERK levels were found to be increased by 2-fold in HER2(+) versus HER2(−) tumors. No difference was detected in phospho-p42/total p42 ERK levels. Conclusions. TH profile is not altered in patients with newly diagnosed breast cancer. However, FT3 levels, even within normal range, are negatively correlated with cell proliferation in HER2(+) breast cancer tumors. This response may be due to the interaction between ERK and TH signaling. Iordanis Mourouzis, Alexandros Tzovaras, Basil Armonis, Alexandros Ardavanis, Maria Skondra, John Misitzis, Demetrios Pectasides, and Constantinos Pantos Copyright © 2015 Iordanis Mourouzis et al. All rights reserved. Clinicopathological Risk Factors and Biochemical Predictors of Safe Discharge after Total Thyroidectomy and Central Compartment Node Dissection for Thyroid Cancer: A Prospective Study Mon, 26 Jan 2015 11:47:52 +0000 To determine the clinicopathological risk factors and reliable biochemical predictors of the development of hypocalcemic symptoms after total thyroidectomy on the basis of serum calcium and intact parathyroid hormone (PTH) levels measured 1 hour after surgery, a prospective study was performed on 817 patients who underwent a total thyroidectomy with central compartment node dissection (CCND) due to well-differentiated thyroid cancer. We evaluated the correlations between hypocalcemic symptom development and clinicopathological factors. And the predictability for hypocalcemic symptom development of intact PTH cut-offs (<10 pg/mL and <20 pg/mL, resp.) according to serum calcium level subgroup was analyzed. Female gender () was the only independent risk factor for hypocalcemic symptom development in multivariate regression analysis. The negative predictive value (NPV) of intact PTH, signifying nondevelopment of hypocalcemic symptoms, was higher than the positive predictive value (PPV) which signified development of hypocalcemic symptoms. In addition, when we applied the different adoption of the intact PTH cut-off according to serum calcium level, we could obtain more increased NPVs. A female gender and the application of more specific cut-offs for intact PTH according to the serum calcium levels measured 1 hour after surgery may help the patients to be more safely discharged. Yu-mi Lee, Ja Young Cho, Tae-Yon Sung, Tae Yong Kim, Ki-Wook Chung, Suck Joon Hong, and Jong Ho Yoon Copyright © 2015 Yu-mi Lee et al. All rights reserved. Determinants of Vitamin D Levels in Children and Adolescents with Down Syndrome Tue, 20 Jan 2015 06:19:20 +0000 Background. Poor studies have evaluated 25-hydroxycholecalciferol (25(OH)D) levels in Down syndrome (DS). Objective. To assess in DS subjects serum 25(OH)D value, to identify risk factors for vitamin D deficiency, and to evaluate whether a normal 25(OH)D value can be restored with a 400 I.U. daily supplement of cholecalciferol in respect to controls. Methods. We have longitudinally evaluated 31 DS patients (aged 4.5–18.9 years old) and 99 age- and sex-matched healthy controls. In these subjects, we analysed calcium, phosphate, parathyroid hormone (PTH), 25(OH)D concentrations, and calcium and 25(OH)D dietary intakes, and we quantified outdoor exposure. After 12.3 months (range 8.1–14.7 months) of 25(OH)D supplementation, we reevaluated these subjects. Results. DS subjects showed reduced 25(OH)D levels compared to controls (), in particular DS subjects with obesity () and autoimmune diseases history (). PTH levels were significantly higher in DS subjects than controls (). After cholecalciferol supplementation, 25(OH)D levels were significantly ameliorated (), even if reduced compared to controls (), in particular in DS subjects with obesity () and autoimmune diseases (). Conclusions. Hypovitaminosis D is very frequent in DS subjects, in particular in presence of obesity and autoimmune diseases. In these subjects, there could be a need for higher cholecalciferol supplementation. Stefano Stagi, Elisabetta Lapi, Silvia Romano, Sara Bargiacchi, Alice Brambilla, Sabrina Giglio, Salvatore Seminara, and Maurizio de Martino Copyright © 2015 Stefano Stagi et al. All rights reserved. Atherogenic Dyslipidemia and Cardiovascular Risk Factors in Obese Children Mon, 12 Jan 2015 14:12:31 +0000 Childhood obesity when associated with serum lipoprotein changes triggers atherosclerosis. Evidences suggest that the atherosclerotic process begins in childhood and that the extent of early atherosclerosis of the aorta and coronary arteries can be associated with lipoprotein levels and obesity. Furthermore, many studies in childhood demonstrate an important relationship between parameters of insulin sensitivity, body fat distribution, and the development of lipid abnormalities. This review focuses on the most recent findings on the relationship between obesity, dyslipidemia, and cardiovascular risk in children. Ebe D’Adamo, Ornella Guardamagna, Francesco Chiarelli, Andrea Bartuli, Daniela Liccardo, Federica Ferrari, and Valerio Nobili Copyright © 2015 Ebe D’Adamo et al. All rights reserved. Identification of Intermediate- to High-Risk Papillary Thyroid Carcinoma Patients Who May Be Safely Managed without the Performance of Delayed Stimulated Thyroglobulin Measurements following Total Thyroidectomy and Radioactive Iodine Therapy Mon, 12 Jan 2015 12:59:48 +0000 Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients. Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis. Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%. Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures. Kyung-Hee Kim, Min-Hee Kim, Ye-Jee Lim, Ihn Suk Lee, Ja-Seong Bae, Dong-Jun Lim, Ki Hyun Baek, Jong Min Lee, Moo-Il Kang, and Bong-Yun Cha Copyright © 2015 Kyung-Hee Kim et al. All rights reserved. Identification of Differentially Expressed Genes in Pituitary Adenomas by Integrating Analysis of Microarray Data Tue, 06 Jan 2015 13:48:05 +0000 Pituitary adenomas, monoclonal in origin, are the most common intracranial neoplasms. Altered gene expression as well as somatic mutations is detected frequently in pituitary adenomas. The purpose of this study was to detect differentially expressed genes (DEGs) and biological processes during tumor formation of pituitary adenomas. We performed an integrated analysis of publicly available GEO datasets of pituitary adenomas to identify DEGs between pituitary adenomas and normal control (NC) tissues. Gene function analysis including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) networks analysis was conducted to interpret the biological role of those DEGs. In this study we detected 3994 DEGs (2043 upregulated and 1951 downregulated) in pituitary adenoma through an integrated analysis of 5 different microarray datasets. Gene function analysis revealed that the functions of those DEGs were highly correlated with the development of pituitary adenoma. This integrated analysis of microarray data identified some genes and pathways associated with pituitary adenoma, which may help to understand the pathology underlying pituitary adenoma and contribute to the successful identification of therapeutic targets for pituitary adenoma. Peng Zhao, Wei Hu, Hongyun Wang, Shengyuan Yu, Chuzhong Li, Jiwei Bai, Songbai Gui, and Yazhuo Zhang Copyright © 2015 Peng Zhao et al. All rights reserved. The Associations of Novel Vitamin D3 Metabolic Gene CYP27A1 Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males Mon, 05 Jan 2015 06:38:30 +0000 Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3 and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3 metabolism, the vitamin D3 25-hydroxylase (CYP27A1) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3 CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (, age: 55.7 ± 4.7 years). Two tagging SNPs, CYP27A1 rs4674344 and CYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with the CYP27A1 rs4674344 SNP and the ratio of adiponectin/leptin (A/L ratio) was most correlated to the CYP27A1 rs4674344 SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0, ) and significantly negatively associated after adjustment. For each MetS component associated with the CYP27A1 rs4674344 SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion, CYP27A1 rs4674344 SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage. Kai-Hung Cheng, Edward Hsi, Chia-Chu Liu, Chun-Nung Huang, Yung-Chin Lee, Chih-Sheng Chu, Bo-Ying Bao, Chu-Fen Chang, Shu-Pin Huang, Po-Lin Kuo, and Wen-Ter Lai Copyright © 2015 Kai-Hung Cheng et al. All rights reserved. Serum Leptin Levels in Polycystic Ovary Syndrome and Its Relationship with Metabolic and Hormonal Profile in Pakistani Females Tue, 23 Dec 2014 09:15:52 +0000 The study aimed to investigate the levels of serum leptin in PCOS females and to correlate it with metabolic and hormonal parameters. Sixty-two PCOS and ninety normal cycling (NC) females with matched age and body mass index (BMI) were recruited for this cross-sectional study. Serum leptin, FSH, LH, E2, free testosterone, progesterone, thyroid profile, and FBG levels were measured. The mean leptin levels in PCOS and NC were not significantly different (45.56 ng/mL ± 1.49 vs 41.78 ± 1.31 ng/mL, ); however, leptin levels showed a strong correlation with BMI in PCOS and NC group (, ; , , resp.). High E2 levels in NC had a significant correlation with leptin whereas FBG correlated with leptin in PCOS (, ). TSH had a substantial correlation (, ; , ) in PCOS and NC, respectively. There was no significant difference found in circulating leptin concentration between PCOS and NC subjects. Leptin levels in PCOS were related with metabolic impairments manifested by disturbance in FBG levels and impairment of reproductive functions in terms of reduced E2 secretion. Mukhtiar Baig, Rehana Rehman, Saba Tariq, and Syeda Sadia Fatima Copyright © 2014 Mukhtiar Baig et al. All rights reserved. Reevaluation of Acromegalic Patients in Long-Term Remission according to Newly Proposed Consensus Criteria for Control of Disease Sun, 21 Dec 2014 07:33:25 +0000 Acromegaly guidelines updated in 2010 revisited criteria of disease control: if applied, it is likely that a percentage of patients previously considered as cured might present postglucose GH nadir levels not adequately suppressed, with potential implications on management. This study explored GH secretion, as well as hormonal, clinical, neuroradiological, metabolic, and comorbid profile in a cohort of 40 acromegalic patients considered cured on the basis of the previous guidelines after a mean follow-up period of 17.2 years from remission, in order to assess the impact of the current criteria. At the last follow-up visit, in the presence of normal IGF-I concentrations, postglucose GH nadir was over 0.4 μg/L in 11 patients (Group A) and below 0.4 μg/L in 29 patients (Group B); moreover, Group A showed higher basal GH levels than Group B, whereas a significant decline of both GH and postglucose GH nadir levels during the follow-up was observed in Group B only. No differences in other evaluated parameters were found. These results seem to suggest that acromegalic patients considered cured on the basis of previous guidelines do not need a more intensive monitoring than patients who met the current criteria of disease control, supporting instead that the cut-off of 0.4 mcg/L might be too low for the currently used GH assay. Elisa Verrua, Emanuele Ferrante, Marcello Filopanti, Elena Malchiodi, Elisa Sala, Claudia Giavoli, Maura Arosio, Andrea Gerardo Lania, Cristina Lucia Ronchi, Giovanna Mantovani, Paolo Beck-Peccoz, and Anna Spada Copyright © 2014 Elisa Verrua et al. All rights reserved. Regulation of UCP1 in the Browning of Epididymal Adipose Tissue by β3-Adrenergic Agonist: A Role for MicroRNAs Wed, 17 Dec 2014 12:29:55 +0000 Background. White adipose tissue browning may be a promising strategy to combat obesity. UCP1 is strongly induced in White adipose tissue with β3-adrenergic agonist treatment, but the causes of this increase have not been fully elucidated. This study aims to explore more miRNAs involved in the process of browning of visceral adipose tissue. Methods. Total of fourteen mice were randomly divided into control and study group. Study group mice were injected intraperitoneally with CL316243 once daily for seven days; meanwhile the control group were treated with 0.9% NaCl. After a 7-day period, the expression of genes involved in WAT browning and potential UCP1-targeting miRNAs in adipose tissues was analyzed by qPCR. Results. qPCR analysis revealed that UCP1, DIO2, CIDEA, and CPT1B in epididymal adipose tissue were overexpressed in CL316243 group. Furthermore, potential UCP1-targeting miR-9 and miR-338-3p in epididymal adipose tissue were significantly decreased in CL316243 group. Conclusion. This suggests that potential UCP1-targeting miR-9 and miR-338-3p may be involved in the browning of epididymal adipose tissue by regulating UCP1 gene expression. In this study, we demonstrated that this increase of UCP1 is due, at least in part, to the decreased expression of certain UCP1-targeting miRNAs in epididymal adipose tissue compared to control. Zongji Zheng, Xiaomeng Liu, Qianwei Zhao, Lei Zhang, Chenzhong Li, and Yaoming Xue Copyright © 2014 Zongji Zheng et al. All rights reserved. Interpreting the Consequences of Metformin Accumulation in an Emergency Context: Impact of the Time Frame on the Blood Metformin Levels Wed, 17 Dec 2014 12:24:07 +0000 Objective. To clarify the link between metformin accumulation and its metabolic consequences by taking the time frame for metformin measurement into account. Research Design and Methods. Our database was studied for cases of metformin accumulation and lactic acidosis status available on admission, and then we selected patients in whom arterial pH, blood lactate, and plasma and erythrocyte metformin levels had been determined at the same time point. Results. Seventeen reports were studied on 16 patients, of whom 10 presented lactic acidosis. The time interval between admission and comprehensive testing ranged from 0 to 52 hours. The study parameters were determined simultaneously on admission in only 4 patients. In the 9 patients with lactic acidosis on admission and a delayed metformin assay, lactic acidosis persisted in 6 cases and had resolved in 3 cases by the time the blood sampling for metformin assay was performed. Conversely, lactic acidosis developed after admission in one case. Conclusions. Caution must be taken when interpreting the consequences of metformin accumulation in an emergency context: the patient’s lactic acidosis status will have changed by the time the metformin assay is performed, even though metformin accumulation may still be present. Jean-Daniel Lalau and Farshad Kajbaf Copyright © 2014 Jean-Daniel Lalau and Farshad Kajbaf. All rights reserved. Systematic Review of Surgical Approaches for Adrenal Tumors: Lateral Transperitoneal versus Posterior Retroperitoneal and Laparoscopic versus Robotic Adrenalectomy Wed, 17 Dec 2014 07:49:22 +0000 Background. Laparoscopic lateral transperitoneal adrenalectomy (LTA) has been the standard method for resecting benign adrenal gland tumors. Recently, however, laparoscopic posterior retroperitoneal adrenalectomy (PRA) has been more popular as an alternative method. This systematic review evaluates current evidence on adrenalectomy techniques, comparing laparoscopic LTA with PRA and laparoscopic adrenalectomy with robotic adrenalectomy. Methods. PubMed, Embase, and ISI Web of Knowledge databases were searched systematically for studies comparing surgical outcomes of laparoscopic LTA versus PRA and laparoscopic versus robotic adrenalectomy. The studies were evaluated according to the PRISMA statement. Results. Eight studies comparing laparoscopic PRA and LTA showed that laparoscopic PRA was superior or at least comparable to laparoscopic LTA in operation time, blood loss, pain score, hospital stay, and return to normal activity. Conversion rates and complication rates were similar. Six studies comparing robotic and laparoscopic adrenalectomy found that outcomes and complications were similar. Conclusion. Laparoscopic PRA was more effective than LTA, especially in reducing operation time and hospital stay, but there was no evidence showing that robotic adrenalectomy was superior to laparoscopic adrenalectomy. Cost reductions and further technical advances are needed for wider application of robotic adrenalectomy. Young Jun Chai, Hyungju Kwon, Hyeong Won Yu, Su-jin Kim, June Young Choi, Kyu Eun Lee, and Yeo-Kyu Youn Copyright © 2014 Young Jun Chai et al. All rights reserved. Mild Adrenal Steroidogenic Defects and ACTH-Dependent Aldosterone Secretion in High Blood Pressure: Preliminary Evidence Mon, 15 Dec 2014 11:21:52 +0000 Introduction. Adrenal glands play a major role in the control of blood pressure and mild defects of steroidogenesis and/or inappropriate control of mineralocorticoid production have been reported in high blood pressure (HBP). Patients and Methods. We used a specific protocol for the evaluation of 100 consecutive patients with inappropriate or recent onset HBP. Specific methods were used to confirm HBP and to diagnose secondary forms of HBP. In addition we tested adrenal steroidogenesis with the common cosyntropin test, modified to include the simultaneous measurement of renin and aldosterone besides 17-hydroxyprogesterone (17OHP) and 11-deoxycortisol (S). Results. Secondary forms of HBP were diagnosed in 32 patients, including 14 patients with primary hyperaldosteronism (PA) (14%) and 10 patients with pheochromocytoma (10%). Mild defects of the 21-hydroxylase (21OHD) and 11-hydroxylase (11OHD) enzymes were common (42%). ACTH-dependent aldosterone secretion was found in most patients (54%) and characteristically in those with mild defects of adrenal steroidogenesis (>60%), PA (>75%), and otherwise in patients with apparent essential HBP (EHBP) (32%). Discussion. Mild defects of adrenal steroidogenesis are common in patients with HBP, occurring in almost half of the patients. In those patients as well as in patients with apparent EHBP, aldosterone secretion is commonly dependent on ACTH. João Martin Martins, Sónia do Vale, and Ana Filipa Martins Copyright © 2014 João Martin Martins et al. All rights reserved. Growth Hormone and Reproduction: A Review of Endocrine and Autocrine/Paracrine Interactions Mon, 15 Dec 2014 00:10:44 +0000 The somatotropic axis, consisting of growth hormone (GH), hepatic insulin-like growth factor I (IGF-I), and assorted releasing factors, regulates growth and body composition. Axiomatically, since optimal body composition enhances reproductive function, general somatic actions of GH modulate reproductive function. A growing body of evidence supports the hypothesis that GH also modulates reproduction directly, exerting both gonadotropin-dependent and gonadotropin-independent actions in both males and females. Moreover, recent studies indicate GH produced within reproductive tissues differs from pituitary GH in terms of secretion and action. Accordingly, GH is increasingly used as a fertility adjunct in males and females, both humans and nonhumans. This review reconsiders reproductive actions of GH in vertebrates in respect to these new conceptual developments. Kerry L. Hull and Steve Harvey Copyright © 2014 Kerry L. Hull and Steve Harvey. All rights reserved. Long-Term Follow-Up of Patients with 46,XY Partial Gonadal Dysgenesis Reared as Males Sun, 14 Dec 2014 07:52:20 +0000 Background/Aims. Studies on 46,XY partial gonadal dysgenesis (PGD) have focused on molecular, gonadal, genital, and hormone features; little is known about follow-up. Our aim was to analyze long-term outcomes of PGD. Methods. Retrospective longitudinal study conducted at a reference service in Brazil. Ten patients were first evaluated in the 1990s and followed up until the 2010s; follow-up ranged from 13.5 to 19.7 years. All were reared as males and had at least one scrotal testis; two bore NR5A1 mutations. Main outcomes were: associated conditions, pubertal development, and growth. Results. All patients had normal motor development but three presented cognitive impairment; five had various associated conditions. At the end of the prepubertal period, FSH was high or high-normal in 3/6 patients; LH was normal in all. At the last evaluation, FSH was high or high-normal in 8/10; LH was high or high-normal in 5/10; testosterone was decreased in one. Final height in nine cases ranged from −1.57 to 0.80 SDS. All had spontaneous puberty; only one needed androgen therapy. Conclusions. There is good prognosis for growth and spontaneous pubertal development but not for fertility. Though additional studies are required, screening for learning disabilities is advisable. Juliana Gabriel Ribeiro de Andrade, Antonia Paula Marques-de-Faria, Helena Campos Fabbri, Maricilda Palandi de Mello, Gil Guerra-Júnior, and Andréa Trevas Maciel-Guerra Copyright © 2014 Juliana Gabriel Ribeiro de Andrade et al. All rights reserved. Selenium Supplementation for Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis Thu, 11 Dec 2014 07:10:41 +0000 Many studies have reported that selenium (Se) has a close relationship with autoimmune thyroiditis (AIT). The therapeutic effect of Se supplementation in AIT treatment remains unclear. The objective of the present study was to determine the efficacy of Se supplementation for the treatment of AIT. A structured literature search was undertaken to identify all randomized controlled trials conducted in patients with AIT receiving Se supplementation or placebo. Nine studies enrolling a total of 787 patients were included. The results showed that Se supplementation with duration 6 months significantly dropped the TPOAb titers but did not decrease the TgAb titers. Patients assigned to Se supplementation for 12-month duration showed significantly lower TPOAb titers and TgAb titers. Patients after Se supplementation had a higher chance to improve the mood or well-being compared with controls. Se supplementation is associated with a significant decrease in TPOAb titers at 6 and 12 months; meanwhile, the TgAb titers can be dropped at 12 months. After Se supplementation treatment, patients had a higher chance to improve the mood without significant adverse events. Yaofu Fan, Shuhang Xu, Huifeng Zhang, Wen Cao, Kun Wang, Guofang Chen, Hongjie Di, Meng Cao, and Chao Liu Copyright © 2014 Yaofu Fan et al. All rights reserved. Waist-to-Height Ratio Is a Better Anthropometric Index than Waist Circumference and BMI in Predicting Metabolic Syndrome among Obese Mexican Adolescents Tue, 09 Dec 2014 08:31:01 +0000 Objective. To identify the degree of association between anthropometric indices and components of metabolic syndrome (MS) and to determine optimal cut-off points of these indices for predicting MS in obese adolescents. Methods. A cross-sectional study with a sample of () Mexican obese adolescents grouped by sex and the presence/absence of MS. BMI percentile, waist circumference (WC), and waist-to-height ratio (WHtR) were tested. ROC curves of the anthropometric indices were created to identify whether an index was a significant predictor of MS. Results. BMI percentile, WC, and WHtR were significantly correlated with systolic and diastolic blood pressure. As predictors of MS overall patients, the BMI percentile generated an area under curve (AUC) of 0.651 (), cut-off point above the 99th percentile. WC generated an AUC of 0.704 (), cut-off point of ≥90 cm. WHtR demonstrated an AUC of 0.652 (), cut-off point of 0.60. WHtR ≥0.62 and WHtR ≥0.61 generate AUC of 0.737 () and AUC of 0.717 () for predicting hypertension and insulin resistance, respectively, in females. Conclusion. WHtR is a better tool than WC and BMI for identifying cardiometabolic risk. The overall criterion (WHtR ≥ 0.6) could be appropriate for predicting MS in obese Mexican adolescents. Edel Rafael Rodea-Montero, María Lola Evia-Viscarra, and Evelia Apolinar-Jiménez Copyright © 2014 Edel Rafael Rodea-Montero et al. All rights reserved. Computed Tomography Features of Incidentally Detected Diffuse Thyroid Disease Mon, 08 Dec 2014 10:00:15 +0000 Objective. This study aimed to evaluate the CT features of incidentally detected DTD in the patients who underwent thyroidectomy and to assess the diagnostic accuracy of CT diagnosis. Methods. We enrolled 209 consecutive patients who received preoperative neck CT and subsequent thyroid surgery. Neck CT in each case was retrospectively investigated by a single radiologist. We evaluated the diagnostic accuracy of individual CT features and the cut-off CT criteria for detecting DTD by comparing the CT features with histopathological results. Results. Histopathological examination of the 209 cases revealed normal thyroid (), Hashimoto thyroiditis (), non-Hashimoto lymphocytic thyroiditis (), and diffuse hyperplasia (). The CT features suggestive of DTD included low attenuation, inhomogeneous attenuation, increased glandular size, lobulated margin, and inhomogeneous enhancement. ROC curve analysis revealed that CT diagnosis of DTD based on the CT classification of “3 or more” abnormal CT features was superior. When the “3 or more” CT classification was selected, the sensitivity, specificity, positive and negative predictive values, and accuracy of CT diagnosis for DTD were 55.8%, 95.5%, 80.6%, 86.7%, and 85.6%, respectively. Conclusion. Neck CT may be helpful for the detection of incidental DTD. Myung Ho Rho and Dong Wook Kim Copyright © 2014 Myung Ho Rho and Dong Wook Kim. All rights reserved. MicroRNAs in Human Pituitary Adenomas Mon, 08 Dec 2014 09:57:31 +0000 MicroRNAs (miRNAs) are a class of recently identified noncoding RNAs that regulate gene expression at posttranscriptional level. Due to the large number of genes regulated by miRNAs, miRNAs play important roles in many cellular processes. Emerging evidence indicates that miRNAs are dysregulated in pituitary adenomas, a class of intracranial neoplasms which account for 10–15% of diagnosed brain tumors. Deregulated miRNAs and their targets contribute to pituitary adenomas progression and are associated with cell cycle control, apoptosis, invasion, and pharmacological treatment of pituitary adenomas. To provide an overview of miRNAs dysregulation and functions of these miRNAs in pituitary adenoma progression, we summarize the deregulated miRNAs and their targets to shed more light on their potential as therapeutic targets and novel biomarkers. Xu-Hui Li, Elaine Lu Wang, Hai-Meng Zhou, Katsuhiko Yoshimoto, and Zhi Rong Qian Copyright © 2014 Xu-Hui Li et al. All rights reserved. Clinical Evaluation of Various Thyroid Hormones on Thyroid Function Mon, 08 Dec 2014 07:14:33 +0000 To clarify the clinical value of serums total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), and free thyroxine (FT4) and provide a more eligible and economic strategy to assess thyroid function. A total of 2,673 participants (500 patients with hyperthyroidism, 500 patients with hypothyroidism, and 1,673 healthy people) were involved in our study. Serums TT3, TT4, FT3, and FT4 and thyrotropin (TSH) were measured with VIDAS fluorescent enzyme immunoassay. The Pearson correlation between TT3, TT4, FT3, and FT4 and TSH was determined to identify the most important indicator for thyroid function besides TSH. The correlation of TT4, and FT4 with TSH was statistically significant in healthy individuals (P < 0.01), and the R-values were −0.065 and −0.152, respectively. The correlation of TT4, FT4, TT3, and FT3 with TSH was statistically significant in patients with hyperthyroidism, and the R-values were −0.241, −0.225, −0.195, and −0.176, respectively. The correlation of TT4, FT4, TT3, and FT3 with TSH was statistically significant in patients with hypothyroidism, and the R-values were −0.322, −0.262, −0.179, and −0.136, respectively. In our opinion, TSH and FT4 are the most valuable indicators in assessing thyroid function in a healthy population, and TSH and TT4 are the most meaningful in hyperthyroidism and hypothyroidism. Hong Li, Xiaolan Yuan, Lu Liu, Jiaojiao Zhou, Chunyan Li, Peng Yang, Le Bu, Manna Zhang, and Shen Qu Copyright © 2014 Hong Li et al. All rights reserved. Diabetic Women Suffer More Years of Life Lost Than Diabetic Men Wed, 03 Dec 2014 09:21:16 +0000 Zhi-Jiang Zhang, Genming Zhao, Chuanhua Yu, Yongyi Bi, Qingjun Zhang, and Yiqing Song Copyright © 2014 Zhi-Jiang Zhang et al. All rights reserved. Oxidative Stress: A Link between Diabetes Mellitus and Periodontal Disease Sun, 30 Nov 2014 00:10:28 +0000 Objective. To investigate oxidative stress (OS) and histological changes that occur in the periodontium of subjects with type 2 diabetes mellitus without signs of periodontal disease and to establish if oxidative stress is a possible link between diabetes mellitus and periodontal changes. Materials and Methods. Tissue samples from ten adult patients with type 2 diabetes mellitus (T2D) and eight healthy adults were harvested. The specimens were examined by microscope using standard hematoxylin-eosin stain, at various magnifications, and investigated for tissue levels of malondialdehyde (MDA) and glutathione (GSH). Results. Our results showed that periodontal tissues in patients with T2D present significant inflammation, affecting both epithelial and connective tissues. Mean MDA tissue levels were 3.578 ± 0.60 SD in diabetics versus 0.406 ± 0.27 SD in controls (P < 0.0001), while mean GSH tissue levels were 2.48 ± 1.02 SD in diabetics versus 9.7875 ± 2.42 SD in controls (P < 0.0001). Conclusion. Diabetic subjects had higher MDA levels in their periodontal tissues, suggesting an increased lipid peroxidation in T2D, and decreased GSH tissue levels, suggesting an alteration of the local antioxidant defense mechanism. These results are in concordance with the histological changes that we found in periodontal tissues of diabetic subjects, confirming the hypothesis of OS implication, as a correlation between periodontal disease incidence and T2D. Adriana Monea, Tibor Mezei, Sorin Popsor, and Monica Monea Copyright © 2014 Adriana Monea et al. All rights reserved. Prediction of Extrathyroidal Extension Using Ultrasonography and Computed Tomography Thu, 27 Nov 2014 13:15:28 +0000 Objectives. The aim of the present study was to evaluate the value of high-resolution ultrasound (US) and computed tomography (CT) scan for preoperative prediction of the extrathyroidal extension (ETE). Methods. We analyzed the medical records of 377 patients with papillary thyroid carcinoma (PTC) with preoperative US and CT scan to calculate the sensitivity, specificity, and positive and negative predictive values of characteristics imaging features (such as contact and disruption of thyroid capsule) for the presence of ETE in postoperative pathologic examination. We also evaluated the diagnostic power for several combinations of US and CT findings. Results. ETE was present in 174 (46.2%) based on pathologic reports. The frequency of ETE was greater in the patients with greater degrees of tumor contact and disruption of capsule, as revealed by both US and CT scans (positive predictive value of 72.2% and 81.8%, resp.). Considering positive predictive values and AUC of US and CT categories, separately or combined, a combination of US and CT findings was most accurate for predicting ETE (83.0%, 0.744). Conclusions. This study suggests that ETE can be predicted most accurately by a combination of categories based on the findings of US and CT scans. Doh Young Lee, Tack-Kyun Kwon, Myung-Whun Sung, Kwang Hyun Kim, and J. Hun Hah Copyright © 2014 Doh Young Lee et al. All rights reserved. Retrospective Analysis of Cushing’s Disease with or without Hyperprolactinemia Sun, 23 Nov 2014 08:15:53 +0000 Objective. We compared the characteristics of patients with Cushing’s disease alone with those of patients with Cushing’s disease and hyperprolactinemia. Methods. Eighty-four patients were enrolled between 2002 and 2011, in a hospital in China. Clinical, endocrinological, and histopathological data, MRI scans, and surgical outcomes were reviewed throughout the follow-up period. Results. Patients with Cushing’s disease and hyperprolactinemia had a younger age at diagnosis (30.28 ± 14.23 versus 36.08 ± 10.91 years; ) and a larger adenoma maximal diameter (2.44 ± 1.32 versus 1.44 ± 1.05 cm; ) than patients with Cushing’s disease alone. Menstrual disorders () and visual field defects () were more common and progressive obesity () and hypertension () were less common in patients with Cushing’s disease and hyperprolactinemia. The rate of normalization of hormonal levels was lower (41.7% versus 91.7%; ) and the recurrence rate was higher (36.1% versus 8.3%; ) in patients with Cushing’s disease and hyperprolactinemia. Conclusions. Careful long-term follow-up is needed of patients with Cushing’s disease and hyperprolactinemia. Cheng Huan, Chao Lu, Guang-ming Xu, Xin Qu, and Yuan-ming Qu Copyright © 2014 Cheng Huan et al. All rights reserved. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study Sun, 23 Nov 2014 00:00:00 +0000 Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL) ( and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (; , ;  , and ;  ), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels () and free T and DHEA-S declined significantly ( and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction. René Rodríguez-Gutiérrez, Jesús Zacarías Villarreal-Pérez, Felipe Arturo Morales-Martinez, René Rodríguez-Guajardo, Gloria González-Saldivar, Leonardo G. Mancillas-Adame, Neri Alejandro Alvarez-Villalobos, Fernando Javier Lavalle-Gonzalez, and José Gerardo González-González Copyright © 2014 René Rodríguez-Gutiérrez et al. All rights reserved.