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Aled Daffyd Rees Cardiff University, Cardiff, United Kingdom

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Deborah P Merke National Institutes of Health Clinical Center and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, USA

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Wiebke Arlt MRC LMS, London, United Kingdom

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Aude Brac De La Perriere Hospices Civils de Lyon - GHE - Endocrinologie, Bron, France

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Angelica Linden Hirschberg Karolinska Institute, Solna, Sweden

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark, and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

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John Newell-Price The University of Sheffield, Sheffield, United Kingdom

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Alessandro Prete University of Birmingham, Birmingham, United Kingdom

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Nicole Reisch Endokrinologie, Nephrologie und weitere Sektionen - Medizinische Klinik und Poliklinik IV - Campus Innenstadt, München, Germany

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Nike M Stikkelbroeck Radboud University Nijmegen, Nijmegen, Netherlands

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Philippe A Touraine University Hospitals Pitié Salpêtrière - Charles Foix, Paris, France

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Alex Lewis Neurocrine Biosciences Inc, London, United Kingdom

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John Porter Neurocrine Biosciences Inc, London, United Kingdom

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Helen Coope Neurocrine Biosciences Inc, London, United Kingdom

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Richard J Ross The University of Sheffield, Sheffield, United Kingdom

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Background

Prednisolone and prednisone are recommended treatment options for adults with congenital adrenal hyperplasia (CAH); however, there is no randomised comparison of prednis(ol)one with hydrocortisone.

Design

Six-month open-label randomised phase 3 study and interim analysis of a single-arm extension study was the design of the study.

Methods

The method of the study was hydrocortisone dose equivalent and 09:00-h 17-hydroxyprogesterone (17OHP) from 48 patients taking prednis(ol)one at baseline.

Results

At baseline, the median hydrocortisone dose equivalent was 30 mg/day and 17OHP was < 36 nmol/L (3× upper limit of normal) in 56% of patients. Patients were randomised to continue prednis(ol)one or switch to modified-release hydrocortisone capsule (MRHC) at the same hydrocortisone-equivalent dose. At 4 weeks, 94% on MRHC and 71% on prednis(ol)one had 17OHP < 36 nmol/L. At 18 months in the extension study of MRHC, the median MRHC dose was 20 mg/day and 82% had 17OHP < 36 nmol/L. The per cent of patients with 17OHP < 36 nmol/L on a hydrocortisone dose equivalent ≤ 25 mg/day was greater at 18 months in the extension study on MRHC than while on prednis(ol)one at baseline: 57% vs 27%, P = 0.04. In the randomised study, no patients had an adrenal crisis on MRHC and one on prednisolone. In the extension study (221 patient years), there were 12 adrenal crises in 5 patients (5.4/100 patient years).

Conclusion

MRHC reduces 17OHP at 09:00 h compared to prednis(ol)one and the dose of MRHC can be down-titrated over time in the majority of patients.

Open access
Clara Lundetoft Clausen Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark

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Trine Holm Johannsen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Niels Erik Skakkebæk Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Hanne Frederiksen Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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Thomas Benfield Center of Research & Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

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In the context of severe coronavirus disease 2019 (COVID-19) illness, we examined endogenous glucocorticoid concentrations, steroidogenic enzyme activity, and their correlation with inflammation and patient outcomes. This observational study included 125 hospitalized COVID-19 patients and 101 healthy individuals as a reference group. We utilized LC-MS to assess serum concentrations of 11-deoxycortisol, cortisol, and cortisone, as well as activities of steroidogenic enzymes (11β-hydroxylase and 11β-hydroxysteroid-dehydrogenase type 1). Cox proportional hazards regression analysis and competing risk analysis were employed to analyze associations between glucocorticoid concentrations and outcomes, adjusting for relevant factors. In patients with COVID-19, cortisol concentrations were higher and cortisone concentrations were lower compared to the reference group, while 11-deoxycortisol concentrations were similar. Steroidogenic enzyme activity favored cortisol production. Correlations between glucocorticoid concentrations and inflammatory markers were low. A doubling in concentrations cortisol, was associated with increased 90-day mortality and mechanical ventilation (HR: 2.40 95% CI: (1.03–5.59) , P = 0.042 and HR: 3.83 (1.19–12.31), P = 0.024). A doubling in concentrations of 11-deoxycortisol was also associated to mortality (HR: 1.32 (1.05–1.67), P = 0.018), whereas concentrations of cortisone were associated with mechanical ventilation (HR: 5.09 (1.49–17.40), P = 0.009). In conclusion, serum concentrations of glucocorticoid metabolites were altered in patients hospitalized with severe COVID-19, and steroidogenic enzyme activity resulting in the conversion of cortisone to biologically active cortisol was preserved, thus not favoring critical-illness-related corticosteroid insufficiency at the enzymatic level. Glucocorticoid release did not counterbalance the hyperinflammatory state in patients with severe COVID-19. High serum concentrations of 11-deoxycortisol and cortisol were associated with 90-day mortality, and high serum concentrations of cortisol and cortisone were associated with mechanical ventilation.

Open access
Julia Beckhaus Department of Pediatrics and Pediatric Hematology/Oncology, University Children’s Hospital, Carl von Ossietzky Universität, Klinikum Oldenburg AöR, Oldenburg, Germany
Division of Epidemiology and Biometry, Carl von Ossietzky Universität, Oldenburg, Germany

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Maria Eveslage Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany

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Brigitte Bison Diagnostic and Interventional Neuroradiology, Faculty of Medicine, University of Augsburg, Augsburg, Germany

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Carsten Friedrich Department of Pediatrics and Pediatric Hematology/Oncology, University Children’s Hospital, Carl von Ossietzky Universität, Klinikum Oldenburg AöR, Oldenburg, Germany

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Hermann L Müller Department of Pediatrics and Pediatric Hematology/Oncology, University Children’s Hospital, Carl von Ossietzky Universität, Klinikum Oldenburg AöR, Oldenburg, Germany

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Objective

It is well known that both genetic background and lifestyle influence the development of ‘general’ obesity. However, the role of parental body mass index (BMI) on the development of obesity in long-term survivors of childhood-onset craniopharyngioma (CP) is not well understood. This study analyzed the correlation of patients’ BMI at diagnosis and last visit and parental BMI at CP diagnosis and further explored potential risk factors for obesity in CP patients.

Design

This is a registry-based retrospective cohort study.

Methods

In total,291 CP patients and their parents recruited in the German KRANIOPHARYNGEOM studies were included. Correlations between patient’s BMI SDS at CP diagnosis and last visit and parental BMI at CP diagnosis were analyzed. The associations between hypothalamic damage, maternal/paternal BMI and CP patients’ obesity at last visit were analyzed by multivariable logistic regression.

Results

At follow-up, 52% of CP patients developed obesity (BMI > 3SDS). Patient’s BMI SDS at last visit was moderately correlated with BMI-SDS at CP diagnosis (r = 0.48, 95% CI: 0.38–0.58, P < 0.001), and also with maternal BMI at diagnosis (r = 0.28, 95% CI: 0.17–0.38, P < 0.001) and paternal BMI at diagnosis (r = 0.3, 95% CI: 0.19–0.41, P < 0.001). However, the contributing role of parental BMI to the pathogenesis of obesity was small compared to the impact of hypothalamic damage.

Conclusion

We conclude that besides hypothalamic damage, parental disposition for obesity is associated with the development of obesity in patients after CP. Our results indicate that also the family situation could have an influence on the development of obesity after CP and might be a therapeutic target.

Significance statement

Survivors of childhood-onset craniopharyngioma are at risk of developing morbid obesity. So far, patients with posterior hypothalamic involvement and lesion were identified as a high risk group. With this study, the influence of parental body mass index on the risk of obesity was investigated. Patient’s body-mass-index at last visit was correlated with maternal and paternal body mass index at diagnosis. With increasing maternal or paternal body mass index, the likelihood of obesity in individuals with CP increased. Nevertheless, the parents’ weight had only a small effect on the development of patients’ obesity compared to hypothalamic damage.

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Lei Gao Department of Geriatrics, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

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Wenxia Cui Department of Geriatrics, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

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Dinghuang Mu Department of Geriatrics, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, China

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Shaoping Li Department of Health Management Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

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Nan Li Department of Geriatrics, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

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Weihong Zhou Department of Health Management Center, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

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Yun Hu Department of Geriatrics, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

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Objective

To create a nomogram-based model to estimate the Chinese population's 5-year risk of metabolic dysfunction-associated steatotic liver disease (MASLD).

Methods

We randomly divided 7582 participants into two groups in a 7:3 ratio: one group was assigned to work with the training set, which consisted of 5307 cases, and the other group was assigned to validate the model using 2275 cases. The least absolute shrinkage and selection operator model was employed to ascertain the variables with the highest correlation among all potential variables. A logistic model was constructed by incorporating these selected variables, which were subsequently visualized using a nomogram. The discriminatory ability, calibration, and clinical utility of the model were assessed using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).

Results

During the 5-year follow-up, 1034 (13.64%) total participants were newly diagnosed with MASLD. Using eight variables (gender, body mass index, waist, hemoglobin, alanine aminotransferase, uric acid, triglycerides, and high-density lipoprotein), we built a 5-year MASLD risk prediction model. The nomogram showed an area under the ROC of 0.795 (95% CI: 0.779–0.811) in the training set and 0.785 (95% CI: 0.760–0.810) in the validation set. The calibration curves revealed a 5-year period of agreement between the observed and predicted MASLD risks. DCA curves illustrated the practicality of this nomogram over threshold probability profiles ranging from 5% to 50%.

Conclusion

We created and tested a nomogram to forecast the risk of MASLD prevalence over the next 5 years.

Open access
Hsiao-Yun Yeh Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Hung-Ta Hondar Wu Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Musculoskeletal Section, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

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Hsiao-Chin Shen Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

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Tzu-Hao Li Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Foundation, Taipei, Taiwan
School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan

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Ying-Ying Yang Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Kuei-Chuan Lee Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Yi-Hsuan Lin Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Department of Family Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Chia-Chang Huang Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan
Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan

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Ming-Chih Hou Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

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Objective

Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes.

Methods

This retrospective cohort study, spanning from 2011 to 2019, enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes and the effect of different ranges of BMI (18.5–24, 24–27, and ≥27 kg/m2) on the risk of future fracture events in FL patients.

Results

The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors of osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24–27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5–24 kg/m2.

Conclusion

The protective effect of a higher BMI against future fractures in middle-aged and elderly female and male patients with FL is not uniform and diminishes beyond certain BMI ranges.

Open access
M Guftar Shaikh Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK
Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Timothy G Barrett Department of Endocrinology, Birmingham Womens and Children’s Hospital, Birmingham, UK
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

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Nicola Bridges Department of Paediatric Endocrinology, Chelsea and Westminster Hospital, London, UK

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Robin Chung Research Working Group, Prader-Willi Syndrome Association, Northampton, UK

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Evelien F Gevers Department of Paediatric Endocrinology, Barts Health NHS Trust, Royal London Hospital, London, UK
Centre for Endocrinology, William Harvey Research Institute, Barts and The London Medical School, Queen Mary University of London, London, UK

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Anthony P Goldstone PsychoNeuroEndocrinologyResearch Group, Division of Psychiatry, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK
Department of Endocrinology, Imperial College Healthcare NHS Trust, Hammersmith Hospital, London, UK

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Anthony Holland Department of Psychiatry, University of Cambridge, Cambridge, UK

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Shankar Kanumakala Royal Alexandra Children’s Hospital, Brighton, UK

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Ruth Krone Department of Endocrinology, Birmingham Womens and Children’s Hospital, Birmingham, UK

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Andreas Kyriakou Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK
Department of Paediatric Endocrinology, Makarios Children's Hospital, Nicosia, Cyprus

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E Anne Livesey Royal Alexandra Children’s Hospital, Brighton, UK
Sussex Community NHS Trust, Brighton, UK

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Angela K Lucas-Herald Department of Paediatric Endocrinology, Royal Hospital for Children, Glasgow, UK
Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Christina Meade CHI at Tallaght University Hospital, Dublin, Republic of Ireland

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Susan Passmore Prader-Willi Syndrome Association, Northampton, UK

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Edna Roche CHI at Tallaght University Hospital, Dublin, Republic of Ireland
The University of Dublin, Trinity College Dublin, Dublin, Republic of Ireland

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Chris Smith Royal Alexandra Children’s Hospital, Brighton, UK

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Sarita Soni Learning Disability Psychiatry, NHS Greater Glasgow and Clyde, Glasgow, UK

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Prader–Willi syndrome (PWS) is a rare orphan disease and complex genetic neurodevelopmental disorder, with a birth incidence of approximately 1 in 10,000–30,000. Management of people with PWS requires a multi-disciplinary approach, ideally through a multi-disciplinary team (MDT) clinic with community support. Hypotonia, poor feeding and faltering growth are characteristic features in the neonatal period, followed by hyperphagia and risk of rapid weight gain later in childhood. Children and adolescents (CA) with PWS usually display developmental delay and mild learning disability and can develop endocrinopathies, scoliosis, respiratory difficulties (both central and obstructive sleep apnoea), challenging behaviours, skin picking, and mental health issues, especially into adulthood. This consensus statement is intended to be a reference document for clinicians managing children and adolescents (up to 18 years of age) with PWS. It considers the bio-psycho-social domains of diagnosis, clinical assessment, and management in the paediatric setting as well as during and after transition to adult services. The guidance has been developed from information gathered from peer-reviewed scientific reports and from the expertise of a range of experienced clinicians in the United Kingdom and Ireland involved in the care of patients with PWS.

Open access
Camila Aparecida Moma Endocrinology Division, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

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Icléia Siqueira Barreto Department of Pathology, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

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Ligia Vera Montali Assumpção Endocrinology Division, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

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Denise Engelbrecht Zantut-Wittmann Endocrinology Division, Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, São Paulo, Brazil

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Background

Papillary thyroid carcinoma has become increasingly prevalent over the years. Avoiding unnecessary treatments and the risk of complications is essential, as well as understanding the mechanisms of tumor progression and the conditions that indicate a worse prognosis. Assessment of the tumor microenvironment can allow us understand how the immune system organizes itself to contain neoplastic progression.

Methods

We compared characteristics related to the lymphocytic subpopulations in the thyroid tumor microenvironment and lymph nodes in two groups, with and without lymph node metastatic involvement.

Results

Of the 400 cases followed up at a thyroid cancer reference service, 32 were selected, of which, 13 cases did not present lymph node metastasis (N0 group) and 19 had lymph node involvement (N1 group). Clinical data were collected, and immunohistochemical reactions were performed for markers CD4, CD8, FoxP3, CD25, and CD20 in lymph nodes and peritumoral infiltrate. We found that the N1 group had larger tumor sizes, higher risk staging, higher frequency of extrathyroidal extension, shorter disease-free times, and higher expression of CD4+ T lymphocytes in lymph nodes; however, there was no difference in the expression of other markers or in the pattern of lymphocyte distribution in the lymph node.

Conclusion

In cervical lymph nodes, the higher frequency of CD4+ T lymphocytes is related to the presence of metastasis. However, there were no differences in lymphocytic subpopulations in the thyroid tumor microenvironment. The absence of changes in unaffected lymph nodes could not predict any tumor behavior.

Open access
Qing Zhou Department of Endocrinology, Fujian Maternity and Child Health Hospital, Fujian Children’s Hospital, Fuzhou, China

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Li Yong Zhang Department of Thyroid Surgery, Minimal Invasive Center, Fujian Medical University Union Hospital, Fuzhou, China

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Mei Feng Dai Department of Clinical Lab, Fujian Maternity and Child Health Hospital, Fuzhou, China

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Zhen Li Department of Endocrinology, Fujian Maternity and Child Health Hospital, Fujian Children’s Hospital, Fuzhou, China

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Chao Chun Zou Department of Endocrinology, The Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, China

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Hui Liu Department of Endocrinology, Fujian Maternity and Child Health Hospital, Fujian Children’s Hospital, Fuzhou, China

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Graphical abstract

Abstract

Subclinical hypothyroidism (SCH) is closely related to insulin resistance, and thyroid-stimulating hormone (TSH) level is an independent factor for insulin resistance associated with subclinical hypothyroidism. This study aims to explore the effects of TSH levels on insulin signal transduction in adipocytes and to establish the role of endoplasmic reticulum (ER) stress in this process. In this study, the SCH mouse model was established, and 3T3-L1 adipocytes were treated with TSH or tunicamycin (TM), with or without 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress. Subclinical hypothyroidism mice exhibited impaired glucose tolerance, inactivation of the IRS-1/AKT pathway, and activation of the IRE1/JNK pathway in adipose tissue, which can all be alleviated by 4-PBA. Supplementation with levothyroxine restored the TSH to normal, alongside alleviated ER stress and insulin resistance in SCH mice, which is characterized by improved glucose tolerance, decreased mRNA expression of IRE1, and decreased phosphorylation of JNK in adipose tissue. In 3T3-L1 adipocytes, TSH induces insulin resistance, leading to a decrease in glucose uptake. This effect is mediated by the downregulation of IRS-1 tyrosine phosphorylation, reduced AKT phosphorylation, and inhibited GLUT4 protein expression. Notably, all these effects can be effectively reversed by 4-PBA. Moreover, TSH induced TNF-α and IL-6 production and upregulated the expression of ER stress markers. Similarly, these changes can be recovered by 4-PBA. These findings indicate that TSH has the capability to induce insulin resistance in adipocytes. The mechanism through which TSH disrupts insulin signal transduction appears to involve the ER stress–JNK pathway.

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Shams Ali Baig College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Kashish Malhotra Department of Surgery, Rama Medical College Hospital and Research Centre, Hapur, Uttar Pradesh, India
Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK

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Anagh Josh Banerjee College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Mukunth Kowsik College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Khushi Kumar College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Fazna Rahman College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Syeda Sabbah Batul College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Mohammed Faraaz Saiyed College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Vardhan Venkatesh College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Pranav Viswanath Iyer College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom

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Punith Kempegowda Institute of Applied Health Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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YouTube® is one of the leading platforms for health information. However, the lack of regulation of content and quality raises concerns about accuracy and reliability. CoMICs (Concise Medical Information Cines) are evidence-based short videos created by medical students and junior doctors and reviewed by experts to ensure clinical accuracy. We performed a systematic review to understand the impact of videos on knowledge and awareness about diabetes and PCOS. We then evaluated the quality of YouTube® videos about diabetes and PCOS using various validated quality assessment tools and compared these with CoMICs videos on the same topics. Quality assessment tools like DISCERN, JAMA benchmark criteria, and global quality scale (GQS) score were employed. Some of the authors of this study also co-authored the creation of some of the CoMICs evaluated. Our study revealed that while videos effectively improve understanding of diabetes and PCOS, there are notable differences in quality and reliability of the videos on YouTube®. For diabetes, CoMICs videos had higher DISCERN scores (CoMICs vs YouTube®: 2.4 vs 1.6), superior reliability (P < 0.01), and treatment quality (P < 0.01) and met JAMA criteria for authorship (100% vs 30.6%) and currency (100% vs 53.1%). For PCOS, CoMICs had higher DISCERN scores (2.9 vs 1.9), reliability (P < 0.01), and treatment quality (P < 0.01); met JAMA criteria for authorship (100% vs 34.0%) and currency (100% vs 54.0%); and had higher GQS scores (4.0 vs 3.0). In conclusion, CoMICs outperformed other similar sources on YouTube® in providing reliable evidence-based medical information which may be used for patient education.

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Carlijn A Hoekx Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Borja Martinez-Tellez Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands
Department of Nursing Physiotherapy and Medicine, SPORT Research Group (CTS-1024), CERNEP Research Center, University of Almería, Almería, Spain
Biomedical Research Unit, Torrecárdenas University Hospital, Almería, Spain
CIBER de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Granada, Spain

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Maaike E Straat Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Magdalena M A Verkleij Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Mirjam Kemmeren Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Sander Kooijman Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Martin Uhrbom Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca Gothenburg, Sweden
Department of Medicine, Huddinge, Karolinska Institutet Campus Flemingsberg, Neo Building, Huddinge, Sweden

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Saskia C A de Jager Laboratory of Experimental Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands

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Patrick C N Rensen Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Mariëtte R Boon Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands

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Objectives

Cold exposure is linked to cardiometabolic benefits. Cold activates brown adipose tissue (BAT), increases energy expenditure, and induces secretion of the hormones fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15). The cold-induced increase in energy expenditure exhibits a diurnal rhythm in men. Therefore, we aimed to investigate the effect of cold exposure on serum FGF21 and GDF15 levels in humans and whether cold-induced changes in FGF21 and GDF15 levels differ between morning and evening in males and females.

Method

In this randomized cross-over study, serum FGF21 and GDF15 levels were measured in healthy lean males (n = 12) and females (n = 12) before, during, and after 90 min of stable cold exposure in the morning (07:45 h) and evening (19:45 h) with a 1-day washout period in between.

Results

Cold exposure increased FGF21 levels in the evening compared to the morning both in males (+61% vs −13%; P < 0.001) and in females (+58% vs +8%; P < 0.001). In contrast, cold exposure did not significantly modify serum GDF15 levels, and no diurnal variation was found. Changes in FGF21 and GDF15 levels did not correlate with changes in cold-induced energy expenditure in the morning and evening.

Conclusion

Cold exposure increased serum FGF21 levels in the evening, but not in the morning, in both males and females. GDF15 levels were not affected by cold exposure. Thus, this study suggests that the timing of cold exposure may influence cold-induced changes in FGF21 levels but not GDF15 levels and seems to be independent of changes in energy expenditure.

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