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Alessandro Ciresi Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Stefano Radellini Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Valentina Guarnotta Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Maria Grazia Mineo Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Carla Giordano Section of Endocrinology, Biomedical Department of Internal and Specialist Medicine (DIBIMIS), University of Palermo, Palermo, Italy

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Introduction The sexual dimorphism in the mechanisms involved in the regulation of somatotroph axis is well documented, and it might account for some of the sex differences in growth rate and body composition ( 1 ). Indeed, sex hormones are

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Shenglong Le Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Leiting Xu Medical School, Ningbo University, Ningbo, China

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Moritz Schumann Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, Cologne, Germany
The Key Laboratory of Systems Biomedicine, Ministry of Education, and Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

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Na Wu Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Timo Törmäkangas Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland

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Markku Alén Department of Medical Rehabilitation, Oulu University Hospital, Oulu, Finland

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Sulin Cheng Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
The Key Laboratory of Systems Biomedicine, Ministry of Education, and Exercise Translational Medicine Center, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China

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Petri Wiklund Exercise, Health and Technology Centre, Department of Physical Education, Shanghai Jiao Tong University, Shanghai, China
Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Department of Epidemiology and Biostatistics, Centre for Environment and Health, School of Public Health, Imperial College London, London, UK
Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland

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with idiopathic hypoandrogenism and in precocious pubertal girls treated with gonadotropin-releasing hormone analogs ( 4 , 5 ). Some of the variation in circulating SHBG might be related to body composition and insulin sensitivity, both of which change

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Henrik H Thomsen Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Holger J Møller Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Christian Trolle Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Kristian A Groth Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Anne Skakkebæk Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Anders Bojesen Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Christian Høst Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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Claus H Gravholt Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark
Medical Research Laboratories, Departments of Clinical Biochemistry, Molecular Medicine, Department of Clinical Genetics, Department of Endocrinology and Internal Medicine, Clinical Institute, Aarhus University Hospital, Nørrebrogade 44, DK-8000 Aarhus C, Denmark

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variables explain about 35% of the variation in sCD163, with prominent differences between KS and controls. Table 1 Data on KS subjects and controls from the KS cross-sectional study, regarding inflammation markers, body composition, and hormones and insulin

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Yuka Goto Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Yoshie Otsuka Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Kenji Ashida Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Ayako Nagayama Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Nao Hasuzawa Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Shimpei Iwata Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Kento Hara Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Munehisa Tsuruta Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Nobuhiko Wada Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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Seiichi Motomura Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan
Division of Endocrinology and Metabolism, Diabetes Center, Kurume Medical Center, Kokubu-machi, Kurume-city, Fukuoka, Japan

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Yuji Tajiri Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan
Division of Endocrinology and Metabolism, Diabetes Center, Kurume Medical Center, Kokubu-machi, Kurume-city, Fukuoka, Japan

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Masatoshi Nomura Division of Endocrinology and Metabolism, Department of Internal Medicine, Kurume University School of Medicine, Asahi-machi, Kurume-city, Fukuoka, Japan

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the risk of cardiovascular events and mortality in diabetes mellitus ( 1 , 2 ). SGLT2 inhibitors exert glucose-lowering effects, improving insulin sensitivity through the changes in the body composition over long-term treatment ( 3 , 4 ). While

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Sherwin Criseno Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
School of Nursing and Midwifery, Institute of Clinical Sciences, University of Birmingham, UK

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Helena Gleeson Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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Andrew A Toogood Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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Neil Gittoes Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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Anne Topping School of Nursing and Midwifery, Institute of Clinical Sciences, University of Birmingham, UK

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Niki Karavitaki Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

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(AGHD) is associated with a wide range of clinical features, including abnormal body composition, reduced bone mineral density, decreased muscle strength and exercise capacity, adverse metabolic and cardiovascular risk profiles and impaired general well

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Imane Benabbad Endocrinology and Diabetes Unit, Eli Lilly, Neuilly-sur-Seine, France

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Myriam Rosilio Endocrinology and Diabetes Unit, Eli Lilly, Neuilly-sur-Seine, France

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Maité Tauber Department Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France

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Emmanuel Paris BioClinica, Lyon, France

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Anne Paulsen Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France

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Lovisa Berggren Eli Lilly and Company, Bad Homburg, Germany

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Hiren Patel Eli Lilly and Company, Indianapolis, Indiana, USA

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Jean-Claude Carel Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France

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the Phoenix Study Group
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(for calculation of target height (sex-adjusted average of parental heights)) and body composition. Height was determined barefoot using a wall-mounted Harpenden stadiometer. Bone age was determined from a centralised reading of an X-radiograph of the

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Lukas Ochsner Ridder Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark

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Agnethe Berglund Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Clinical Genetics and Clinical Medicine, Aarhus University Hospital, Aarhus, Denmark

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Kirstine Stochholm Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark

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Simon Chang Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
Unit for Thrombosis Research, Hospital of South West Jutland and University of Southern Denmark, Esbjerg, Denmark

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Claus H Gravholt Department of Endocrinology and Internal Medicine and Medical Research Laboratories, Aarhus University Hospital, Aarhus, Denmark
Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
Unit for Thrombosis Research, Hospital of South West Jutland and University of Southern Denmark, Esbjerg, Denmark

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lumbar and femoral BMD in patients with osteoporosis ( 15 ). Studies have found that treated KS patients have higher lumbar BMD than non-treated KS patients and found direct negative effects of age of diagnosis and body composition on the trabecular

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Jeyanthini Risikesan Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Birgitte Nellemann Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway

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Britt Christensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Jens Otto Lunde Jørgensen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark

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Søren Nielsen Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

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[ 3 H]palmitate SA during the same period to calculate plasma palmitate oxidation rates. The plasma 3 H 2 O concentration and body water were determined as described previously ( 12 , 25 , 26 ). Body composition At the end of both metabolic

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Shanlee M Davis Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Rhianna Urban Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA

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Angelo D’Alessandro Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Julie A Reisz Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Christine L Chan Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Megan Kelsey Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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Susan Howell Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Nicole Tartaglia Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Philip Zeitler Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA
eXtraOrdinarY Kids Clinic, Children's Hospital Colorado, Aurora, Colorado, USA

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Peter Baker II Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado, USA

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hypogonadism, a nearly universal finding in adult men with KS, has been implicated as the underlying pathologic mechanism leading to this increased risk ( 2 ). As an anabolic steroid, testosterone has effects on body composition and mitochondrial metabolism

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Charlotte Höybye Department of Endocrinology, Metabolism and Diabetology, Karolinska University Hospital and Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden

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Andreas F H Pfeiffer Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Klinik für Endokrinologie & Stoffwechselmedizin, Berlin, Germany

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Diego Ferone IRCCS AOU San Martino-IST, Università di Genova – Endocrinologia DiMI, Dipartimento di Medicina Interna e Specialità Mediche, & CEBR, Centro di Eccellenza per la Ricerca Biomedica, Genova, Italy

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Jens Sandahl Christiansen Medicinsk Endokrinologist Afd., MEA, NBG, Århus Sygehus, Århus, Denmark

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David Gilfoyle Ascendis Pharma A/S, Hellerup, Denmark

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Eva Dam Christoffersen Ascendis Pharma A/S, Hellerup, Denmark

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Eva Mortensen Ascendis Pharma Inc., Palo Alto, California, USA

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Jonathan A Leff Ascendis Pharma Inc., Palo Alto, California, USA

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Michael Beckert Ascendis Pharma A/S, Hellerup, Denmark

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with insulin-like growth factor 1 (IGF1), leads to abnormal body composition and metabolism as well as psychological impairment ( 1 , 2 ). Left untreated, AGHD is associated with decreased bone mineral density, increased risk of cardiovascular

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