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Emily Warmington Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

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Gabrielle Smith Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

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Vasileios Chortis Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK

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Raimunde Liang Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Wuerzburg, Germany
Department of Neurosurgery, Technical University Munich (TMU), Munich, Germany

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Juliane Lippert Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Wuerzburg, Germany

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Sonja Steinhauer Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Wuerzburg, Germany

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Laura-Sophie Landwehr Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Wuerzburg, Germany

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Constanze Hantel Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital Zurich (USZ) and University of Zurich (UZH), Zurich, Switzerland
Medizinische Klinik Und Poliklinik III, University Hospital Carl Gustav Carus, Dresden, Germany

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Katja Kiseljak-Vassiliades Division of Endocrinology Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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Margaret E Wierman Division of Endocrinology Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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Barbara Altieri Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Wuerzburg, Germany

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Paul A Foster Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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Cristina L Ronchi Institute of Metabolism and System Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK

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Adrenocortical carcinoma (ACC) is an aggressive malignancy with limited treatment options. Polo-like kinase 1 (PLK1) is a promising drug target; PLK1 inhibitors (PLK1i) have been investigated in solid cancers and are more effective in TP53-mutated cases. We evaluated PLK1 expression in ACC samples and the efficacy of two PLK1i in ACC cell lines with different genetic backgrounds. PLK1 protein expression was investigated by immunohistochemistry in tissue samples and correlated with clinical data. The efficacy of rigosertib (RGS), targeting RAS/PI3K, CDKs and PLKs, and poloxin (Pol), specifically targeting the PLK1 polo-box domain, was tested in TP53-mutated NCI-H295R, MUC-1, and CU-ACC2 cells and in TP53 wild-type CU-ACC1. Effects on proliferation, apoptosis, and viability were determined. PLK1 immunostaining was stronger in TP53-mutated ACC samples vs wild-type (P = 0.0017). High PLK1 expression together with TP53 mutations correlated with shorter progression-free survival (P= 0.041). NCI-H295R showed a time- and dose-dependent reduction in proliferation with both PLK1i (P< 0.05at 100 nM RGS and 30 µM Pol). In MUC-1, a less pronounced decrease was observed (P< 0.05at 1000 nM RGS and 100 µM Pol). 100 nM RGS increased apoptosis in NCI-H295R (P< 0.001), with no effect on MUC-1. CU-ACC2 apoptosis was induced only at high concentrations (P < 0.05 at 3000 nM RGS and 100 µM Pol), while proliferation decreased at 1000 nM RGS and 30 µM Pol. CU-ACC1 proliferation reduced, and apoptosis increased, only at 100 µM Pol. TP53-mutated ACC cell lines demonstrated better response to PLK1i than wild-type CU-ACC1. These data suggest PLK1i may be a promising targeted treatment of a subset of ACC patients, pre-selected according to tumour genetic signature.

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Henrik Ryberg Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Anna-Karin Norlén Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Andreas Landin Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden
Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Per Johansson Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Zeinab Salman Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Anders Wallin Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden

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Johan Svensson Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Department of Endocrinology, Skaraborg Central Hospital, Skövde, Sweden

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Claes Ohlsson Sahlgrenska Osteoporosis Centre, Center for Bone and Arthritis Research (CBAR), Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

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Objective

Sex steroids exert important biological functions within the CNS, but the underlying mechanisms are poorly understood. The contribution of circulating sex steroids to the levels in CNS tissue and cerebrospinal fluid (CSF) has been sparsely investigated in human and with inconclusive results. This could partly be due to lack of sensitive validated assays. To address this, we validated a gas chromatography–tandem mass spectrometry (GC-MS/MS) assay for quantification of sex steroid hormones/precursors in CSF.

Methods

GC-MS/MS quantification of dihydrotestosterone (DHT, CSF lower limit of quantification, 1.5 pg/mL), testosterone (4.9), estrone (E1, 0.88), estradiol (E2, 0.25), dehydroepiandrosterone (DHEA, 38.4), androstenedione (4D, 22.3), and progesterone (P, 4.2) in CSF, and corresponding serum samples from 47 men.

Results

Analyses of CSF revealed that DHEA was the major sex steroid (73.5 ± 31.7 pg/mL) followed by 4D (61.4 ± 29.6 pg/mL) and testosterone (49.5 ± 18.9 pg/mL). The CSF levels of DHT, E2, and E1 were substantially lower, and P was in general not detectable in CSF. For all sex steroids except E2, strong associations between corresponding CSF and serum levels were observed. We propose that testosteronein CSF is derived from circulating testosterone, DHT in CSF is from local conversion from testosterone, while E2 in CSF is from local conversion from 4D in CNS.

Conclusions

We describe the first thoroughly validated highly sensitive mass spectrometric assay for a broad sex steroid hormone panel suitable for human CSF. This assay constitutes a new tool for investigation of the role of sex steroid hormones in the human CNS.

Significance statement

In this study, a fully validated highly sensitive mass spectrometric assay for sex steroids was applied to human CSF. The results were used to describe the relative contribution of peripheral circulating sex steroids together with locally transformation of sex steroids to the levels in CSF. The results are of importance to understand the biological processes of the human brain.

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Xiaoli Jin Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Jiankang Shen Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Tao Liu Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Ru Zhou Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Xunbo Huang Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Tianxiang Wang Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Weize Wu Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Mingliang Wang Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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Rongli Xie Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Jianming Yuan Department of General Surgery, Ruijin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, Shanghai, China

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Objective

The aim was to explore the effects of preoperative calcium and activated vitamin D3 supplementation on post-thyroidectomy hypocalcemia and hypo-parathyroid hormone-emia (hypo-PTHemia).

Methods

A total of 209 patients were randomly divided into control group (CG) and experimental group (EG). Oral calcium and activated vitamin D3 supplementation were preoperatively administered to EG, whereas a placebo was administered to CG. Data on serum calcium, phosphorus, and PTH concentrations before operation, on postoperative day 1 (POPD1), at postoperative week 3 (POPW3), and on the length of postoperative hospitalization were collected.

Results

The serum calcium, phosphorus, and PTH concentrations, as well as the incidence of postoperative hypocalcemia and hypo-PTHemia, did not significantly differ between EG and CG. Subgroup analysis revealed that the serum calcium concentrations of the experimental bilateral thyroidectomy subgroup (eBTS) on POPD1 and POPW3 were higher than that of the control bilateral thyroidectomy subgroup (cBTS) (P < 0.05); the reduction of serum calcium in eBTS on POPD1 and POPW3 was less than those in cBTS (P < 0.05). However, significant differences were not observed between the unilateral thyroidectomy subgroups (UTS) (P > 0.05). Moreover, the incidence of postoperative hypocalcemia in cBTS on POPD1 was significantly higher than that in eBTS (65.9% vs 41.7%) (P < 0.05). The length of hospitalization in cBTS (3.55 ± 1.89 days) was significantly longer than that (2.79 ± 1.15 days) in eBTS (P < 0.05).

Conclusion

Short-term preoperative prophylactic oral calcium and activated vitamin D3 supplementation could effectively reduce the incidence of postoperative hypocalcemia and decrease the length of postoperative hospitalization in patients who have undergone bilateral thyroidectomy.

Open access
Enrique Pedernera Universidad Nacional Autónoma de México, Facultad de Medicina, Departamento de Embriología y Genética, Ciudad de México, México

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Flavia Morales-Vásquez Instituto Nacional de Cancerología, Ciudad de México, México

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María J Gómora Universidad Nacional Autónoma de México, Facultad de Medicina, Departamento de Embriología y Genética, Ciudad de México, México

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Miguel A Almaraz Universidad Nacional Autónoma de México, Facultad de Medicina, Departamento de Embriología y Genética, Ciudad de México, México

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Esteban Mena Universidad Nacional Autónoma de México, Facultad de Medicina, Secretaría General, Ciudad de México, México
Universidad La Salle, Posgrado de la Facultad de Ciencias Químicas, Ciudad de México, México

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Delia Pérez-Montiel Instituto Nacional de Cancerología, Ciudad de México, México

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Elizabeth Rendon Hospital Militar de Especialidades de la Mujer y Neonatología. Ciudad de México, México

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Horacio López-Basave Instituto Nacional de Cancerología, Ciudad de México, México

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Juan Maldonado-Cubas Universidad La Salle, Posgrado de la Facultad de Ciencias Químicas, Ciudad de México, México

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Carmen Méndez Universidad Nacional Autónoma de México, Facultad de Medicina, Departamento de Embriología y Genética, Ciudad de México, México

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The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan–Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24–0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.

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Adrian J L Clark Editor-in-Chief, Endocrine Connections

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Shuang Wan Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China
Department of Endocrinology, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China

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Chengcheng Zheng Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Tao Chen Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Lu Tan Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Jia Tang Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Haoming Tian Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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Yan Ren Adrenal Center, Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China

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We applied 24-h Holter monitoring to analyze the characteristics of arrhythmias and heart rate variability in Chinese patients with primary aldosteronism (PA) and compared them with age-, sex-, and blood pressure-matched primary hypertension (PH) patients. A total of 216 PA patients and 261 PH patients were enrolled. The nonstudy data were balanced using propensity score matching (PSM), and the risk variables for developing arrhythmias were then analyzed using logistic regression analysis. Before PSM, the proportion of PA patients with combined atrial premature beats and prolonged QT interval was higher than the corresponding proportion in the PH group. After PSM, the PA group had a larger percentage of transient atrial tachycardia and frequent atrial premature beats, and it had higher heart rate variability metrics. The proportion of unilateral PA combined with multiple ventricular premature beats was higher than that of bilateral PA. Older age, grade 3 hypertension, and hypokalemia were independent risk factors for the emergence of arrhythmias in PA patients. PA patients suffer from a greater prevalence of arrhythmias than well-matched PH patients.

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Yanling Cai Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Yan Yang Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Xiao Pang Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Suping Li Department of Nuclear Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan, China

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Purpose

The aim was to investigate the effect of radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC) on male gonadal function.

Methods

PubMed, Embase, Web of Science, OVID, Scopus, and Wanfang databases were searched up to June 10, 2022, to identify published studies related to RAI and male gonadal function. ReviewManager version 5.4.1 software was used to calculate mean differences (MDs) with 95% CIs.

Results

Initially, 1958 articles were retrieved from the databases, and 6 articles were included in the quantitative analysis. The meta-analysis results showed that follicle-stimulating hormone (FSH) increased when the follow-up duration was ≥12 months after RAI, but the difference was not statistically significant (MD = −2.64, 95% CI = (−5.61, 0.33), P = 0.08). But the results of the subgroup analysis showed that when the follow-up time was ≤6 months, FSH levels were significantly higher after RAI (MD = −7.65, 95% CI = (−13.95, −1.34), P = 0.02). The level of inhibin B was significantly lower at ≥12 months and ≤6 months after RAI (MD = 66.38, 95% CI = (8.39, 124.37), P = 0.02) and (MD = 116.27, 95% CI = (43.56, 188.98), P = 0.002). Additionally, luteinizing hormone (LH) and testosterone have similar results – that is, LH and testosterone levels were higher after RAI, but the difference was not statistically significant (MD = –0.87, 95% CI = (−2.04, 0.30), P = 0.15) and (MD = −1.69, 95% CI (−7.29, 3.90), P = 0.55).

Conclusions

Male gonadal function may be temporarily impaired within 6 months after RAI but may return to normal levels afterward.

Open access
S R Ali Developmental Endocrinology Research Group, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK
Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK

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J Bryce Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK

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A L Priego-Zurita Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

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M Cherenko Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

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C Smythe Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK

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T M de Rooij Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

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M Cools Department of Internal Medicine and Paediatrics, Ghent University, Belgium
Department of Paediatric Endocrinology, Ghent University Hospital, Ghent, Belgium

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T Danne Diabetes Center AUF DER BULT, Hannover, Germany

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H Katugampola UCL GOS Institute of Child Health, London

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O M Dekkers Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands
Department of Medicine & Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands

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O Hiort Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, University of Lübeck, Lübeck, Germany

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A Linglart AP-HP, Université Paris Saclay, INSERM, Bicêtre Paris Saclay Hospital, le Kremlin Bicêtre, France

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I Netchine Sorbonne Université, Inserm, Centre de recherche Sainte Antoine, APHP, Hôpital des Enfants Armand Trousseau, Paris, France

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A Nordenstrom Pediatric Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden

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P Attila Clinical Genetics and Endocrinology Laboratory, Department of Laboratory Medicine, Semmelweis University, Budapest, Hungary

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L Persani Department of Endocrine and Metabolic Diseases, Istituto Auxologico Italiano IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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N Reisch Endokrinologie, Medizinische Klinik Innenstadt und Poliklinik IV, Klinikum der Universität München, Munich, Germany

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A Smyth Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK

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Z Sumnik Department of Pediatrics, Motol University Hospital and 2nd Faculty of Medicine, Charles University, Prague, Czech Republic

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D Taruscio National Centre for Rare Diseases, Istituto Superiore di Sanità, Rome, Italy

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W E Visser Erasmus Medical Centre, Department of Internal Medicine, Academic Centre for Thyroid Diseases, Rotterdam, the Netherlands

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A M Pereira Department of Endocrinology and Metabolism, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam, the Netherlands

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N M Appelman-Dijkstra Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

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S F Ahmed Developmental Endocrinology Research Group, School of Medicine, Dentistry & Nursing, University of Glasgow, Glasgow, UK
Office for Rare Conditions, Royal Hospital for Children & Queen Elizabeth University Hospital, Glasgow, UK
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands

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Objective

The European Registries for Rare Endocrine Conditions (EuRRECa, eurreb.eu) includes an e-reporting registry (e-REC) used to perform surveillance of conditions within the European Reference Network (ERN) for rare endocrine conditions (Endo-ERN). The aim of this study was to report the experience of e-REC over the 3.5 years since its launch in 2018.

Methods

Electronic reporting capturing new encounters of Endo-ERN conditions was performed monthly through a bespoke platform by clinicians registered to participate in e-REC from July 2018 to December 2021.

Results

The number of centres reporting on e-REC increased to a total of 61 centres from 22 countries. A median of 29 (range 11, 45) paediatric and 32 (14, 51) adult centres had reported cases monthly. A total of 9715 and 4243 new cases were reported in adults (age ≥18 years) and children, respectively. In children, sex development conditions comprised 40% of all reported conditions and transgender cases were most frequently reported, comprising 58% of sex development conditions. The median number of sex development cases reported per centre per month was 0.6 (0, 38). Amongst adults, pituitary conditions comprised 44% of reported conditions and pituitary adenomas (69% of cases) were most commonly reported. The median number of pituitary cases reported per centre per month was 4 (0.4, 33).

Conclusions

e-REC has gained increasing acceptability over the last 3.5 years for capturing brief information on new encounters of rare conditions and shows wide variations in the rate of presentation of these conditions to centres within a reference network.

Significance statement

Endocrinology includes a very wide range of rare conditions and their occurrence is often difficult to measure. By using an electronic platform that allowed monthly reporting of new clinical encounters of several rare endocrine conditions within a defined network that consisted of several reference centres in Europe, the EuRRECa project shows that a programme of e-surveillance is feasible and acceptable. The data that have been collected by the e-reporting of rare endocrine conditions (e-REC) can allow the continuous monitoring of rare conditions and may be used for clinical benchmarking, designing new studies or recruiting to clinical trials.

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Peiwen Wu Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

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Dongjie He Department of Radiation Oncology, Tangdu Hospital, the Second Affiliated Hospital of Air Force Medical University, Xi’an, China

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Hao Chang Department of Radiation Oncology, Tangdu Hospital, the Second Affiliated Hospital of Air Force Medical University, Xi’an, China

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Xiaozhi Zhang Department of Radiation Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

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Background

Updated epidemiological data of neuroendocrine tumors are currently lacking. Thus, we performed epidemiological and survival analyses on a large cohort of patients with neuroendocrine tumors and developed a new nomogram to predict survival.

Methods

This population-based study examined 112,256 patients with neuroendocrine tumors between 2000 and 2018 using data from the Surveillance, Epidemiology, and End Results program.

Results

The age-adjusted incidence per 100,000 persons of neuroendocrine tumors increased from 4.90 in 2000 to 8.19 in 2018 (annual percentage change, 3.40; 95% confidence interval, 3.13–3.67), with the most significant increases in grade 1, localized stage, and appendix neuroendocrine tumors. The age-adjusted mortality rate increased 3.1-fold from 2000 to 2018 (annual percentage change, 4.14; 95% confidence interval, 3.14–5.15). The 1-, 5-, and 10-year relative survival rates for all neuroendocrine tumors were 80.5%, 68.4%, and 63.5%, respectively. Multivariate analyses showed that male sex; older age; Black, American Indian, and Alaska Native populations; earlier year of diagnosis; lung neuroendocrine tumors; higher grades; and later stage were associated with a worse prognosis and that disease stage and grade were the most important risk factors for prognosis. Furthermore, we established a nomogram to predict the 3-, 5-, and 10-year survival rates, and its discrimination ability was better than that of the TNM classification.

Conclusions

The incidence, prevalence, and mortality rate of neuroendocrine tumors continued to increase over the last two decades. Additionally, the nomogram could accurately quantify the risk of death in patients with neuroendocrine tumors and had good clinical practicability.

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Tao Gao Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China

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Rui Liu Department of Oncology. The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China

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Chunli Li Institute of Life Sciences, Chongqing Medical University, Chongqing, China

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Xinglin Chu Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China

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Qiao Guo Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China

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Dazhi Ke Department of General Practice, The Second Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China

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Background

Fetuin-B, a cytokine that regulates lipid metabolism, has recently been linked to cardiovascular diseases such as coronary heart disease. In this study, we discussed the relationship between fetuin-B and essential hypertension.

Method

A bioinformatics analysis of fetuin-B was performed. A total of 206 with essential hypertension and 180 age- and-sex-matched healthy subjects were enrolled. Plasma fetuin-B, endothelin 1 (ET-1), nitric oxide (NO), and adiponectin (ADI) levels were measured using ELISA kits.

Results

Bioinformatics analysis has revealed that fetuin-B plays an important role in pathways such as lipid metabolism. Compared with healthy subjects, serum fetuin-B levels in patients with essential hypertension were significantly increased. Correlation analysis showed that the serum fetuin-B level was positively correlated with systolic blood pressure (SBP), diastolic blood pressure, body mass index, fat percentage in vivo, waist–hip ratio, intima–media thickness, low-density lipoprotein cholesterol (LDL-C), glutamyltranspeptidase, alanine transaminase, albumin, fasting blood glucose (FBG), glycated hemoglobin, and ET-1 in the overall study subjects (all P < 0.05) and negatively correlated with HDL-C, ADI, and NO (all P < 0.05). Multivariate linear regression analysis showed that SBP, FBG, LDL-C, ADI, and ET-1 were independent factors affecting serum fetuin-B. A binary logistic regression analysis showed that fetuin-B was an independent risk factor for primary hypertension (odds ratio: 1.060, 95% CI: 1.034–1.086, P < 0.001). Receiver operating characteristic curve analysis was used to evaluate the predictive value of fetuin-B for primary hypertension, and the optimal cutoff point was 83.14 μg/mL (sensitivity 77.4%, specificity 63.3%) (area under the curve) = 0.7738, 95% CI 0.7276–0.8200, P < 0.001).

Conclusion

Elevated fetuin-B levels are associated with an increased risk of essential hypertension.

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