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Eveline Bruinstroop Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands

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Anne H van der Spek Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands

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Anita Boelen Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, the Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, the Netherlands

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Introduction Deiodinases The thyroid produces the thyroid hormone, mainly thyroxine (T4) and to a lesser extent tri-iodothyronine (T3). Within the liver, thyroid hormones are transported across the cell membrane by thyroid hormone

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Giorgio Radetti Marienklinik, Bolzano, Italy

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Franco Rigon Department of Paediatrics, University of Padua, Padua, Italy

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Alessandro Salvatoni Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Irene Campi Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Tiziana De Filippis Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Valentina Cirello Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Silvia Longhi Department of Paediatrics, Regional Hospital of Bolzano, Bolzano, Italy

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Fabiana Guizzardi Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Marco Bonomi Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Luca Persani Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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demonstrated ( 4 , 5 , 6 , 7 ). RTHβ, firstly described by Refetoff in 1967 ( 8 ), is characterized by elevated circulating free thyroxine (fT4) and free tri-iodothyronine (fT3) together with an unsuppressed thyroid-stimulating hormone (TSH). RTHβ is

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Zhongli Chen Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Robin P Peeters Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Wesley Flach Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Linda J de Rooij Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Sena Yildiz Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Alexander Teumer Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany

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Matthias Nauck DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany

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Rosalie B T M Sterenborg Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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Joost H W Rutten Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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Marco Medici Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands
Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

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W Edward Visser Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Marcel E Meima Department of Internal Medicine, Academic Centre for Thyroid Diseases, Erasmus University Medical Center Rotterdam, The Netherlands

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Reagents Nonradioactive 3,3’-diiodothyronine (3,3’-T2), 3,3’,5’-triiodothyronine (rT3), 3,3’,5-triiodothyronine (T3) and thyroxine (T4) were purchased from Sigma-Aldrich (Zwijndrecht, the Netherlands). [ 125 I]-3,3’-T2, [ 125 I]-rT3, [ 125 I]-T3, [ 125 I

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

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Patrice Rodien Service d’Endocrinologie-Diabétologie-Nutrition, Centre de référence des maladies rares de la Thyroïde et des récepteurs hormonaux, CHU d’Angers, Angers, France.

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Carla Moran Institute of Metabolic Science, University of Cambridge, Cambridge, UK
Endocrine Section, Beacon Hospital, Dublin, Ireland.
School of Medicine, University College Dublin, Ireland
Endocrinology Department, St Vincent’s University Hospital, Dublin, Ireland

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W Edward Visser Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands

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Stefan Groeneweg Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands

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Robin Peeters Department of Internal Medicine and Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands

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Samuel Refetoff Departments of Medicine and Paediatrics and Committee on Genetics, The University of Chicago, Chicago, Illinois, USA

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Mark Gurnell Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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Paolo Beck-Peccoz Department of Medical Biotechnology and Translational Medicine, University of Milan, Milano, Italy

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Krishna Chatterjee Institute of Metabolic Science, University of Cambridge, Cambridge, UK

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evaluation of a patient with hyperthyroxinemia and non-suppressed TSH is to exclude potential confounding factors (including intercurrent non-thyroidal physical or psychiatric illness) and medications (e.g. amiodarone, thyroxine). At the same time, the

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Sepehr Torabinejad Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy

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Caterina Miro Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy

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Biagio Barone Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

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Ciro Imbimbo Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

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Felice Crocetto Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II

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Monica Dentice Department of Clinical Medicine and Surgery, University of Naples ’Federico II’, Naples, Italy
CEINGE – Biotecnologie Avanzate Scarl, Naples, Italy

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/inactivation of THs. D1 and D2 catalyze the conversion of the thyroxine (T4) into the tri-iodothyronine (T3), with more affinity than T4 for nuclear receptors, whereas, D1 and D3 inactivate both T4 and T3 ( 33 , 34 ). Notably, THs are involved in the growth

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Sander Barnhoorn Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, The Netherlands

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Marcel E Meima Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Robin P Peeters Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Veerle M Darras Laboratory of Comparative Endocrinology, Biology Department, KU Leuven, Leuven, Belgium

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Selmar Leeuwenburgh Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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Jan H J Hoeijmakers Department of Molecular Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Oncode Institute, Utrecht, The Netherlands
Institute for Genome Stability in Ageing and Disease, CECAD Research Centre, Cologne, Germany

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Wilbert P Vermeij Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands
Oncode Institute, Utrecht, The Netherlands

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W Edward Visser Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands

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.1038/icb.1928.4 ) 9 Ooka H Fujita S & Yoshimoto E . Pituitary-thyroid activity and longevity in neonatally thyroxine-treated rats . Mechanisms of Ageing and Development 1983 22 113 – 120 . ( https://doi.org/10.1016/0047-6374(8390104-5 ) 10

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Yingxin Fang Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Pingping Dang Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Yue Liang Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Defa Zhao Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Ranran Wang Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Yue Xi Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China

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Dan Zhang Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China
Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, People’s Republic of China

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Wei Wang Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Zhongyan Shan Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Weiping Teng Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Xiaochun Teng Department of Endocrinology and Metabolism, Institute of Endocrine, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, Shenyang, People’s Republic of China

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Introduction Thyroid hormones (THs, namely, the prohormone thyroxine T4 and its active form, triiodothyronine T3) play pivotal roles in diverse aspects of life, mainly during development, when they regulate skeletal growth, cardiac function

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Yalan Hu Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands

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Kim Falize Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

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A S Paul van Trotsenburg Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands

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Raoul Hennekam Department of Pediatrics, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

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Eric Fliers Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

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Eveline Bruinstroop Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

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Anita Boelen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands

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differences in serum thyroxine (T4), triiodothyronine (T3) and thyroid-stimulating-hormone (TSH) concentrations were observed between Tbl1xr1 Y446C/Y446C and wild type (WT) mice ( 6 ). There were no serum TH abnormalities reported in Pierpont patients or

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Ángel García-Aldea Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Marina Guillén-Yunta Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Víctor Valcárcel-Hernández Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Ana Montero-Pedrazuela Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Ana Guadaño-Ferraz Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Soledad Bárez-López Instituto de Investigaciones Biomédicas Sols-Morreale, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), Madrid, Spain

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Physiology 2017 7 1197 – 1227 . ( https://doi.org/10.1002/cphy.c160049 ) 18 Deol MS . The role of thyroxine in the differentiation of the organ of Corti . Acta Otolaryngologica 1976 81 429 – 435 . ( https://doi.org/10.3109/00016487609107497 ) 19

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Juan Ren ENS de Lyon, INRAE, CNRS, Institut de Génomique Fonctionnelle de Lyon, Lyon, France

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Frédéric Flamant ENS de Lyon, INRAE, CNRS, Institut de Génomique Fonctionnelle de Lyon, Lyon, France

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Thyroid hormones (THs; including T3, 3, 3′, 5-triiodo- l -thyronine and its less active precursor T4 or thyroxine) exert a broad influence on the development of vertebrate species. The possibility that the developmental function of TH in mammals

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