You are looking at 11 - 20 of 813 items for

  • All content x
Clear All
Open access

Jing Zhang, Zhiyong Zhao, Li Dong, Tao Han, Guojin Zhang, Yuntai Cao, and Junlin Zhou

Introduction and aim: It is difficult to distinguish between non-functioning pituitary macroadenomas (NFPMAs) and sellar meningiomas because of their overlapping imaging manifestations on routine magnetic resonance imaging (MRI), especially in cases of meningiomas growing into the saddle. Here, we aimed to differentiate between these two tumors using apparent diffusion coefficient (ADC) values and MRI characteristics.

Methods: A total of 60 NFPMA and 52 sellar meningioma cases confirmed by pathological analysis were retrospectively reviewed. All patients were examined via routine MRI and diffusion weighted imaging (DWI) before undergoing surgery. The clinical, MRI characteristics, and max ADC (ADCmax), average ADC (ADCmean), and minimum ADC (ADCmin) values were compared between the two tumors via Chi-square test and two sample t-tests. Receiver operating characteristic (ROC) curve and binary logistic regression analyses were conducted to determine the discrimination ability.

Results: The ADCmax, ADCmean, and ADCmin values were significantly higher in NFPMAs compared to sellar meningiomas (p < 0.001 for all). Among ADC values, ADCmax demonstrated good performance with an AUC of 0.896 (95% CI, 0.823-0.969) and accuracy of 88.7%. A cut-off value of 0.97 × 10−3 mm2/s was used for ADCmax for differentiation between tumors. A combination of ADCmax values and clinicoradiological features showed the best discrimination ability for differential diagnosis between the two tumors, with an AUC of 0.981 (95% CI, 0.958-1.000) and accuracy of 96.9%.

Conclusion: A combination of ADCmax and clinicoradiological features demonstrates good discrimination ability and high accuracy for differentiation between NFPMAs and sellar meningiomas, and is a potential quantitative tool to aid in the selection of surgical techniques.

Open access

Lina S Silva-Bermudez, Freddy J K Toloza, Maria C Perez-Matos, Russell J de Souza, Laura Banfield, Andrea Vargas-Villanueva, and Carlos O Mendivil


To estimate the effect of oral contraceptives (OC) containing different progestins on parameters of lipid and carbohydrate metabolism through a systematic review and meta-analysis.

Patients and methods

Premenopausal women aged 18 or older, who received oral contraceptives containing chlormadinone, cyproterone, drospirenone, levonorgestrel, desogestrel, dienogest, gestodene or norgestimate, for at least 3 months. Outcome variables were changes in plasma lipids, BMI, insulin resistance and plasma glucose. We searched MEDLINE and EMBASE for randomized trials and estimated the pooled within-group change in each outcome variable using a random-effects model. We performed subgroup analyses by study duration (<12 months vs ≥12 months) and polycystic ovary syndrome (PCOS) status.


Eighty-two clinical trials fulfilled the inclusion criteria. All progestins (except dienogest) increased plasma TG, ranging from 12.1 mg/dL for levonorgestrel (P < 0.001) to 35.1 mg/dL for chlormadinone (P < 0.001). Most progestins also increased HDLc, with the largest effect observed for chlormadinone (+9.6 mg/dL, P < 0.001) and drospirenone (+7.4 mg/dL, P < 0.001). Meanwhile, levonorgestrel decreased HDLc by 4.4 mg/dL (P < 0.001). Levonorgestrel (+6.8 mg/dL, P < 0.001) and norgestimate (+11.5 mg/dL, P = 0.003) increased LDLc, while dienogest decreased it (–7.7 mg/dL, P = 0.04). Cyproterone slightly reduced plasma glucose. None of the progestins affected BMI or HOMA-IR. Similar results were observed in subgroups defined by PCOS or study duration.


Most progestins increase both TG and HDLc, their effect on LDLc varies widely. OC have minor or no effects on BMI, HOMA-IR and glycemia. The antiandrogen progestins dienogest and cyproterone displayed the most favorable metabolic profile, while levonorgestrel displayed the least favorable.

Open access

Jasmin Asberger, Thalia Erbes, Markus Jaeger, Gerta Rücker, Claudia Nöthling, Andrea Ritter, Kai Berner, Ingolf Juhasz-Böss, and Marc Hirschfeld

Breast cancer (BC) represents the most common type of cancer in females worldwide. Endocrine therapy evolved as one of the main concepts in treatment of hormone-receptor positive BC. Current research focuses on the elucidation of tumour resistance mechanisms against endocrine therapy. In a translational in vitro approach, potential regulatory effects of clinically implemented BC anti-estrogens on ERα, its coactivators DDX5, DDX17 and other DEADbox proteins as well as on the proliferation markers cyclin D1 and Ki-67 were investigated on both the RNA and protein level. BC in vitro models for hormone-receptor positive (MCF-7, T-47D) and hormone-receptor negative cells (BT-20) were subjected to endocrine therapy. Anti-estrogen-dependent expression regulation of target genes on the transcriptional and translational level was quantified and statistically assessed. Endocrine therapy decreases the expression levels of Ki-67, cyclin D1 and ERα in hormone-receptor positive cells. In the hormone-receptor negative cells, the three parameters remained stable after endocrine therapy. Endoxifen triggers a downregulation of DDX5 and DDX23 in MCF-7 cells. Fulvestrant treatment downregulates the expression levels of all investigated DEADbox proteins in MCF-7 cells. In T-47D cells, endoxifen and fulvestrant lead to a decrease of all target gene expression levels. Interestingly, endocrine therapy affects DEADbox RNA expression levels in BT-20 cells, too. However, this result could only be confirmed for DDX1, immunocytologically. The investigated DEADbox proteins appear to correlate with the estrogen-dependent tumourigenesis in hormone-receptor positive BC and show expression alterations after endocrine treatment.

Open access

Hauke Thomsen, Xinjun Li, Kristina Sundquist, Jan Sundquist, Asta Försti, and Kari Hemminki

Design: Addison disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, presenting as an isolated AD or part of autoimmune polyendocrine syndromes (APSs) 1 and 2. Although AD patients present with a number of AID co-morbidities, population-based family studies are scarce. We aimed to carry out an unbiased study on AD and related AIDs.

Methods: We collected data on patients diagnosed with AIDs in Swedish hospitals, and calculated standardized incidence ratios (SIRs) in families for concordant AD and for other AIDs, the latter as discordant relative risks.

Results: The number of AD patients was 2852, which accounted for 0.4% of all hospitalized AIDs. A total of 62 persons (3.6%) were diagnosed with familial AD. The SIR for siblings was remarkably high, reaching 909 for singleton siblings diagnosed before age 10 years. It was 32 in those diagnosed past age 29 years and the risk for twins was 323. SIR was 9.44 for offspring of affected parents. AD was associated with 11 other AIDs, including thyroid AIDs and type 1 diabetes, and some rarer AIDs such as Guillain-Barre syndrome, myasthenia gravis, polymyalgia rheumatica and Sjögren syndrome.

Conclusions: The familial risk for AD was very high implicating genetic etiology, which for juvenile siblings may be ascribed to APS-1. The adult part of sibling risk was probably contributed to by recessive polygenic inheritance. AD was associated with many common AIDs; some of these were known co-morbidities in AD patients while some other appeared to more specific for a familial setting.

Open access

Emanuelle Nunes-Souza, Mônica Evelise Silveira, Monalisa Castilho Mendes, Seigo Nagashima, Caroline Busatta Vaz de Paula, Guilherme Vieira Cavalcante da Silva, Giovanna Silva Barbosa, Julia Belgrowicz Martins, Lucia Noronha, Luana Lenzi, José Renato Salles Barbosa, Rayssa Danilow Fachin Donin, Juliana Ferreira de Moura, Gislaine Custódio, Enzo Lalli, Cleber Machado-Souza, and Bonald Cavalcante de Figueiredo

Objective: Adaptive changes in dehydroepiandrosterone (DHEA) and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR.

Materials and methods: DHEAS plasma samples (n=463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9–83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands.

Results: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with similar body-mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis.

Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.

Open access

Catherine Cardot-bauters, Emmanuelle Leteurtre, Bruno Carnaille, Christine Do Cao, Stephanie Espiard, Malo Penven, Evelyne Destailleur, Isabelle Szuster, Tonio Lovecchio, Julie Leclerc, Frederic Frenois, Emmanuel Esquivel, Patricia L. M. Dahia, Emilie Ait-yahya, Michel Crépin, and Pascal Pigny

Objective: We previously described a family in which predisposition to pheochromocytoma (PCC) segregates with a germline heterozygous KIF1B nucleotide variant (c.4442G>A, p.Ser1481Asn) in three generations. During the clinical follow-up, one proband’s brother, negative for the KIF1B nucleotide variant, developed a bilateral PCC at 31 yrs. This prompted us to reconsider the genetic analysis.

Design and Methods: Germline DNA was analyzed by next generation sequencing (NGS) using a multi-gene panel plus MLPA or by whole exome sequencing (WES). Tumor-derived DNA was analyzed by SnapShot, Sanger sequencing or NGS to identify loss-of-heterozygosity (LOH) or additional somatic mutations.

Results: A germline heterozygous variant of unknown significance in MAX (c.145T>C, p.Ser49Pro) was identified in the proband’s brother. Loss of the wild type MAX allele occurred in his PCCs thus demonstrating that this variant was responsible for the bilateral PCC in this patient. The proband and her affected grandfather also carried the MAX variant but no second hit could be found at the somatic level. No other pathogenic mutations were detected in 36 genes predisposing to familial PCC/PGL or familial cancers by WES of the proband germline. Germline variants detected in other genes, TFAP2E and TMEM214, may contribute to the multiple tumors of the proband.

Conclusion: In this family the heritability of PCC is linked to the MAX germline variant and not to the KIF1B germline variant which, however, may have contributed to the occurrence of NB in the proband.

Open access

Caishun Zhang, Junhua Yuan, Qian Lin, Manwen Li, Liuxin Wang, Rui Wang, Xi Chen, Zheng-Yao Jiang, Kun Zhu, Xiaoli Chang, Bin Wang, and Jing Dong

Ghrelin plays a pivotal role in the regulation of food intake, body weight and energy metabolism. However, these effects of ghrelin in the lateral parabrachial nucleus (LPBN) are unexplored. C57BL/6J mice and GHSR-/- mice were implanted with cannula above the right LPBN and ghrelin was microinjected via the cannula to investigate effect of ghrelin in the LPBN. In vivo electrophysiological technique was used to record LPBN glucose sensitive neurons to explore potential underlying mechanisms. Microinjection of ghrelin in LPBN significantly increased food intake in the first 3 hours, while such effect was blocked by [D-Lys3]-GHRP-6 and abolished in GHSR-/- mice. LPBN ghrelin microinjection also significantly increased the firing rate of glucose-excited (GE) neurons and decreased the firing rate of glucose-inhibited (GI) neurons. Additionally, LPBN ghrelin microinjection also significantly increased c-fos expression. Chronic ghrelin administration in the LPBN resulted in significantly increased body weight gain. Meanwhile, no significant changes were observed in both mRNA and protein expression levels of UCP-1 in BAT. These results demonstrated that microinjection of ghrelin in LPBN could increase food intake through the interaction with growth hormone secretagogue receptor (GHSR) in C57BL/6J mice, and its chronic administration could also increase body weight gain. These effects might be associated with altered firing rate in the GS and GI neurons.

Open access

Stephen J Winters, Charles R Scoggins, Duke Appiah, and Dushan T Ghooray

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

Open access

Anastasia Ibba, Francesca Corrias, Chiara Guzzetti, Letizia Casula, Mariacarolina Salerno, Natascia Di Iorgi, Gianluca Tornese, Giuseppa Patti, Giorgio Radetti, Mohamad Maghnie, Marco Cappa, and Sandro Loche

A number of studies have evaluated the role of IGF-I measurement in the diagnosis of growth hormone deficiency (GHD). This study aimed to evaluate the accuracy and the best cut-off of IGF-I SDS in the diagnosis of GHD in a large cohort of short children and adolescents. One-hundred and forty-two children and adolescents with GHD ((63 organic/genetic (OGHD), 79 idiopathic (IGHD)) and 658 short non-GHD children (median age 10.4 y) were included in the analysis. The two groups were subdivided according to age (G1 <6, G2 6<9, G3 9<12, G4 ≥12) and to pubertal status. Serum IGF-I was measured by the same chemiluminescence assay in all samples and expressed as age- and sex-based SDS. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal IGF-I SDS cut-off and the diagnostic accuracy. Median IGF-I SDS was significantly lower in the GHD than in non-GHD patients. The area under the curve (AUC) was 0.69, with the best IGF-I cut-off of -1.5 SDS (sensitivity 67.61%, specificity 62.62%). The AUC was 0.75 for OGHD and 0.63 for IGHD. The accuracy was better in the pubertal (AUC=0.81) than the prepubertal group (AUC=0.64). In our cohort IGF-I measurement has poor accuracy in discriminating GHD from non-GHD. Our findings confirm and reinforce the belief that IGF-I values should not be used alone in the diagnosis of GHD but should be interpreted in combination with other clinical and biochemical parameters.

Open access

Qinglei Yin, Zhou Jin, Yulin Zhou, Dalong Song, Chenyang Fu, Fengjiao Huang, and Shu Wang

Graves’ disease (GD) is a common autoimmune disease that affects the thyroid gland. As a new class of modulators of gene expression, long non-coding RNAs (lncRNAs) have been reported to play a vital role in immune functions and in the development of autoimmunity and autoimmune disease. The aim of this study is to identify lncRNAs in CD4+ T cells as potential biomarkers of GD. lncRNA and mRNA microarrays were performed to identify differentially expressed lncRNAs and mRNAs in GD CD4+ T cells compared with healthy control CD4+ T cells. Quantitative polymerase chain reaction (qPCR) was used to validate the results, and correlation analysis was used to analyze the relationship between these aberrantly expressed lncRNAs and clinical parameters. The microarray identified 164 lncRNAs and 93 mRNAs in GD CD4+ T cells differentially expressed compared to healthy control CD4+ T cells (fold change >2.0 and a P<0.05). Further analysis consistently showed that the expression of HMlincRNA1474 (P<0.01) and TCONS 00012608 (P<0.01) was suppressed, while the expression of AK021954 (P<0.01) and AB075506 (P<0.01) was upregulated from initial GD patients. In addition, their expression levels were recovered in euthyroid GD patients and GD patients in remission. Moreover, these four aberrantly expressed lncRNAs were correlated with GD clinical parameters. Moreover, the areas under the ROC curve were 0.8046, 0.7579, 0.8115 for AK021954, AB075506, HMlincRNA1474, respectively. The present work revealed that differentially expressed lncRNAs were associated with GD, which might serve as novel biomarkers of GD and potential targets for GD treatment.