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Aldo Bonaventura Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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Fabrizio Montecucco Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy
Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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Franco Dallegri Department of Internal Medicine, Division of Cardiology, Division of Laboratory Medicine, First Clinic of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

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arrhythmias (54) . During nocturnal hypoglycemia there is an eightfold increase in bradycardia and a fourfold increase in atrial ectopy when compared with daytime hypoglycemia. Sleep has been shown to blunt the sympatho-adrenal response to hypoglycemia (55

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Emmi Naskali Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

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Katja Dettmer Institute of Functional Genomics, University of Regensburg, Regensburg, Germany

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Peter J Oefner Institute of Functional Genomics, University of Regensburg, Regensburg, Germany

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Pedro A B Pereira Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Kai Krohn Clinical Research Institute HUCH Ltd, Biomedicum Helsinki 1, Helsinki, Finland

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Petri Auvinen Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Annamari Ranki Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

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Nicolas Kluger Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland

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motility as well as mood, sleep and appetite ( 11 ). APECED patients with circulating TPH-1 Aabs have been shown to have significantly lower serum levels of 5-HT than patients without such Aabs ( 12 ). We have previously reported that severe constipation

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Elinor Chelsom Vogt Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Francisco Gómez Real Department of Clinical Science, University of Bergen, Bergen, Norway
Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway

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Eystein Sverre Husebye Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Sigridur Björnsdottir Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

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Bryndis Benediktsdottir Medical Faculty, University of Iceland, Reykjavik, Iceland
Department of Sleep, Landspitali University Hospital Reykjavík, Reykjavik, Iceland

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Randi Jacobsen Bertelsen Department of Clinical Science, University of Bergen, Bergen, Norway

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Pascal Demoly University Hospital of Montpellier, IDESP, Univ Montpellier-Inserm, Montpellier, France

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Karl Anders Franklin Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden

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Leire Sainz de Aja Gallastegui Unit of Epidemiology and Public Health, Department of Health, Basque Government, Vitoria-Gasteiz, Spain

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Francisco Javier Callejas González Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

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Joachim Heinrich Institute and Clinic for Occupational, Social and Environmental Medicine, University Hospital, LMU Munich, Munich, Germany
Allergy and Lung Health Unit, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria, Australia

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Mathias Holm Occupational and Environmental Medicine, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden

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Nils Oscar Jogi Department of Clinical Science, University of Bergen, Bergen, Norway

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Benedicte Leynaert Université Paris-Saclay, Inserm U1018, Center for Epidemiology and Population Health, Integrative Respiratory Epidemiology Team, Villejuif, France

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Eva Lindberg Department of Medical Sciences, Respiratory, Allergy and Sleep Medicine, Uppsala University, Uppsala, Sweden

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Andrei Malinovschi Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala, Sweden

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Jesús Martínez-Moratalla Pneumology Service of the General University Hospital of Albacete, Albacete, Spain
Albacete Faculty of Medicine, Castilla-La Mancha University, Albacete, Spain

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Raúl Godoy Mayoral Department of Respiratory Medicine, Albacete University Hospital, Albacete, Spain

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Anna Oudin Section of Sustainable Health, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

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Antonio Pereira-Vega Juan Ramón Jiménez University Hospital in Huelva, Huelva, Spain

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Chantal Raherison Semjen INSERM, EpiCene Team U1219, University of Bordeaux, Talence, France

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Vivi Schlünssen Department of Public Health, Environment, Work and Health, Danish Ramazzini Centre, Aarhus University, Aarhus, Denmark
The National Research Center for the Working Environment, Copenhagen, Denmark

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Kai Triebner Department of Clinical Science, University of Bergen, Bergen, Norway

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Marianne Øksnes Department of Clinical Science, University of Bergen, Bergen, Norway
K.G. Jebsen Center for Autoimmune Disorders, University of Bergen, Bergen, Norway
Department of Medicine, Haukeland University Hospital, Bergen, Norway

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Objective

To investigate markers of premature menopause (<40 years) and specifically the prevalence of autoimmune primary ovarian insufficiency (POI) in European women.

Design

Postmenopausal women were categorized according to age at menopause and self-reported reason for menopause in a cross-sectional analysis of 6870 women.

Methods

Variables associated with the timing of menopause and hormone measurements of 17β-estradiol and follicle-stimulating hormone were explored using multivariable logistic regression analysis. Specific immunoprecipitating assays of steroidogenic autoantibodies against 21-hydroxylase (21-OH), side-chain cleavage enzyme (anti-SCC) and 17alpha-hydroxylase (17 OH), as well as NACHT leucine-rich-repeat protein 5 were used to identify women with likely autoimmune POI.

Results

Premature menopause was identified in 2.8% of women, and these women had higher frequencies of nulliparity (37.4% vs 19.7%), obesity (28.7% vs 21.4%), osteoporosis (17.1% vs 11.6%), hormone replacement therapy (59.1% vs 36.9%) and never smokers (60.1% vs 50.9%) (P < 0.05), compared to women with menopause ≥40 years. Iatrogenic causes were found in 91 (47%) and non-ovarian causes in 27 (14%) women, while 77 (39%) women were classified as POI of unknown cause, resulting in a 1.1% prevalence of idiopathic POI. After adjustments nulliparity was the only variable significantly associated with POI (odds ratio 2.46; 95% CI 1.63–3.42). Based on the presence of autoantibodies against 21 OH and SCC, 4.5% of POI cases were of likely autoimmune origin.

Conclusion

Idiopathic POI affects 1.1% of all women and almost half of the women with premature menopause. Autoimmunity explains 4.5% of these cases judged by positive steroidogenic autoantibodies.

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Mohammed S Albreiki Department of Biochemistry and Physiology, Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

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Benita Middleton Department of Biochemistry and Physiology, Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

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Shelagh M Hampton Department of Biochemistry and Physiology, Centre for Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK

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time zones and/or worked night shifts during the month before the study. All participants completed screening questionnaires including Pittsburgh Sleep Quality Index (PSQI), Horne-Östberg (HÖ) and Munich chronotype. Table 1 Participant

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Cheryl M Isherwood Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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M Denise Robertson Section of Metabolic Medicine, Food and Macronutrients, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Debra J Skene Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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Jonathan D Johnston Section of Chronobiology, Faculty of Health and Medical Sciences, University of Surrey, Guildford, United Kingdom

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-prandial responses, glucose homeostasis and insulin sensitivity ( 10 , 11 , 12 ). The SCN clock can synchronise peripheral clocks via a combination of neuronal, endocrine and behavioural pathways (e.g. the overt daily sleep–wake and feed–fast cycles) ( 13 ). Of

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Sun Fei Wuxi Medical College of Jiangnan University, Wuxi, China

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Min Liu Wuxi Maternity and Child Health Care Hospital, Wuxi, China

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Hu Shanshan Wuxi Maternity and Child Health Care Hospital, Wuxi, China

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Ruijie Xie Department of Microsurgery, University of South China, Hengyang, China

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Wu Danni Wuxi Medical College of Jiangnan University, Wuxi, China

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Zhou Ningying Wuxi Medical College of Jiangnan University, Wuxi, China

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, and sleep disorders were also included. Detailed measurement processes of these variables are publicly available at www.cdc.gov/nchs/nhanes/ . Statistical analysis In descriptive analysis, data description and statistical analysis were based

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Jing Wang Tianjin Women’s and Children’s Health Center Tianjin, China
Chronic Disease Epidemiology Laboratory Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

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Leishen Wang Tianjin Women’s and Children’s Health Center Tianjin, China

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Huikun Liu Tianjin Women’s and Children’s Health Center Tianjin, China

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Shuang Zhang Tianjin Women’s and Children’s Health Center Tianjin, China

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Junhong Leng Tianjin Women’s and Children’s Health Center Tianjin, China

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Weiqin Li Tianjin Women’s and Children’s Health Center Tianjin, China

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Tao Zhang Tianjin Women’s and Children’s Health Center Tianjin, China

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Nan Li Tianjin Women’s and Children’s Health Center Tianjin, China

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Wei Li Tianjin Women’s and Children’s Health Center Tianjin, China

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Andrea A Baccarelli Department of Environmental Health Sciences Columbia University Mailman School of Public Health, New York, New York, USA

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Lifang Hou Department of Preventive Medicine Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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Gang Hu Chronic Disease Epidemiology Laboratory Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

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(using a validated food frequency questionnaire (FFQ) ( 18 )) and routine activities (indoor and outdoor activities, screening watching time and sleep duration). All mother–child pairs underwent a physical examination. Using the standardized protocol

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Robert Maidstone Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

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Martin K Rutter Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, NIHR Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester, UK

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Thomas Marjot Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, UK

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David W Ray Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

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Matthew Baxter Oxford Centre for Diabetes, Endocrinology and Metabolism, and Oxford Kavli Centre for Nanoscience Discovery, University of Oxford, Oxford, UK
NIHR Oxford Health Biomedical Research Centre, and NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK

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.87 (74.65) Sleep duration (h) 7.05 (1.02) 6.92 (1.22) 6.69 (1.48) Chronotype (%)  Morning 23.37 24.5 19.39  Intermediate 58.76 56.04 49.65  Evening 7.97 8.66 16.87 Ethnicity

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M von Wolff Division of Gynaecological Endocrinology and Reproductive Medicine, University Women’s Hospital, Bern University Hospital, University of Bern, Bern, Switzerland

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C T Nakas University Institute of Clinical Chemistry, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Laboratory of Biometry, University of Thessaly, Volos, Greece

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M Tobler Division of Gynaecological Endocrinology and Reproductive Medicine, University Women’s Hospital, Bern University Hospital, University of Bern, Bern, Switzerland
Division of Pneumology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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T M Merz Division of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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M P Hilty Intensive Care Unit, University Hospital, Zurich, Switzerland

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J D Veldhuis Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, Centre for Translational Science Activities, Mayo Clinic, Rochester, New York, USA

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A R Huber Centre for Laboratory Medicine, Cantonal Hospital, Aarau, Switzerland

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J Pichler Hefti Division of Pneumology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

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significantly higher cortisol levels or prolactin levels after physical exercise at an altitude of approximately 5000 m. The effect of disturbed sleep due to periodic breathing at high altitudes would also be conceivable in terms of the change in stress axes

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I M A A van Roessel Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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J P de Graaf Dutch Pituitary Foundation, Nijkerk, The Netherlands
Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
Endo-ERN European Reference Network on Rare endocrine conditions

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N R Biermasz Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
Endo-ERN European Reference Network on Rare endocrine conditions

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E Charmandari Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece
Division of Endocrinology and Metabolism, Center for Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

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H M van Santen Department of Pediatric Endocrinology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht, The Netherlands

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heterogeneous between patients ( 10 , 11 ). Children with suprasellar tumors are more prone to develop HD than adults ( 12 ). Chronic fatigue and sleep disorders may both impact school performance and bonding with peers ( 13 ). Since children are still under

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