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ENCYCLOPEDIA OF
ENDOCRINE DISEASES
SECOND EDITION
EDITORS IN CHIEF
Ilpo Huhtaniemi
Imperial College London
London, United Kingdom
Luciano Martini
University of Milan
Milan, Italy
VOLUME 1
GENERAL PRINCIPLES, DIABETES, METABOLISM, OBESITY, GASTROINTESTINAL
HORMONES, AGING, ENDOCRINE TOXICOLOGY
AMSTERDAM BOSTON HEIDELBERG LONDON NEW YORK OXFORD ACADEMIC

PARIS SAN DIEGO SAN FRANCISCO SINGAPORE SYDNEY TOKYO PRESS
Academic Press is an imprint of Elsevier
The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK
50 Hampshire St, 5th Floor, Cambridge, MA 02139, USA
Copyright r 2019 Elsevier Inc.. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including
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the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted
herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in
research methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers may always rely on their own experience and knowledge in evaluating and using any information, methods,
compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the
safety of others, including parties for whom they have a professional responsibility.
To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or
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products, instructions, or ideas contained in the material herein.
Library of Congress Cataloging-in-Publication Data

A catalog record for this book is available from the Library of Congress
British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library
ISBN 978-0-12-812199-3
For information on all publications visit our

website at http://store.elsevier.com
Publisher: Oliver Walter

Acquisition Editor: Blerina Osmanaj
Content Project Manager: Kate Miklaszewska-Gorczyca
Designer: Miles Hitchen
Printed and bound in the United States

DEDICATION
Professor Luciano Martini, 1927–2017

The other Editor in Chief of the Encyclopedia, Professor Luciano Martini, passed away on July 13th, 2017. He was an
internationally acclaimed authority in the field of endocrinology, in particular neuroendocrinology, a brilliant and imaginative
scientist, and an impressive and erudite scholar.
Luciano achieved the venerable age of 90, and his long career was full of outstanding scientific achievements, leadership
positions in academia and in scientific societies, academies, and committees.
Luciano received his MD degree from the University of Milan in 1950. He then rapidly progressed through junior academic
ranks up to the position of Professor and Chairman of the Department of Pharmacology at the University of Perugia in 1968, and
subsequently, in 1972, he returned to his alma mater, the University of Milan, as full Professor and Chairman of the Department of
Endocrinology, a post he held until 2001. He served in Milan as director of the training and research program entitled Physiology
of Reproduction for nearly 20 years and attracted to his team top-class Italian and foreign scientists to address his main research
interests of neuroendocrine regulation of reproductive functions.
Scientific severity, ethical integrity, fine perception, and deep farsightedness describe best Luciano’s character as a scientist. He
created in his institute a scientific research group devoted to experimental endocrinology, which grew over the years in size and
visibility and became widely recognized internationally. Luciano published more than 400 peer-reviewed and highly cited papers
mainly in the fields of neuroendocrinology, endocrine oncology, physiology of reproduction, and steroid and energy metabolisms.
Luciano was a prolific editor of scientific books and journals, which include the two volumes of Neuroendocrinology and the nine
biennial volumes of Frontiers in Neuroendocrinology. He was Editor in Chief of Comprehensive Endocrinology published in 12 volumes
and the first Edition of Encyclopedia of Endocrine Diseases. He served as President in many national and international scientific
societies including the International Society of Neuroendocrinology, the Italian Society of Endocrinology, the International Society
of Endocrinology, and the European Federation of Endocrine Societies. For his scientific achievements Luciano received honorary
doctorates in the universities of Liège, Santiago de Compostela, Pécs, and Milan, and he was the recipient of numerous scientific
awards and invited academy memberships.
Luciano’s portrait could not be complete if one forgets to mention his life-time passion for music. He was a well-trained and
accomplished pianist, a passionate music listener, and an enthusiastic connoisseur of all types of music. He also was an amateur in
visual arts and deeply interested in history.
All of us who knew Professor Luciano Martini deeply mourn the loss of a great scientist and friend, the real “Il Maestro”,
teacher, colleague, and pioneer of modern neuroendocrinology. I trust Luciano would have been proud of this new edition of the
Encyclopedia of Endocrine Diseases, and all of us having worked on its production would like to dedicate it to his memory.
Ilpo Huhtaniemi
Editor in Chief
Encyclopedia of Endocrine Diseases, 2nd edition
v
EDITORS IN CHIEF
Ilpo Huhtaniemi received his MD and PhD at University of Helsinki, Finland, did postdoctoral
training in United States (UC San Francisco and NIH, Bethesda), and has been on sabbatical
leave in Germany, United States and Scotland. In 1986–2002 he held the post of Professor and
Chairman of Physiology at University of Turku, Finland. He moved in 2002 to UK to a Chair in
Reproductive Endocrinology at Imperial College London, from which position he retired in
2015. He has received several national and international honors, amongst them a fellowship of
The Academy of Medical Sciences, United Kingdom, and a Doctor Honoris Causa at the
Medical University Łódź, Poland, and University of Szeged, Hungary. He was the Chief
Managing Editor of Molecular and Cellular Endocrinology 1999-2017, has served in the Editorial
Board of Endocrinology and Endocrine Reviews and is/has been the Editor or Editorial Board
Member of several other scientific journals (e.g., European Journal of Endocrinology, Clinical
Endocrinology, Human Reproduction Update, Journal of Endocrinology, Molecular Human Reproduc-
tion, Reproduction, Asian Journal of Andrology). He has extensive experience as Official of inter-
national scientific organizations (e.g., Past President of International Society of Andrology).
His research interests include clinical and basic reproductive endocrinology, in particular the function of gonadotrophins and male
reproductive endocrinology. He also has long-term interests in development of male contraception, hormone-dependent cancer,
and the endocrinology of aging. He has authored about 700 peer-reviewed research articles and reviews, and his H-factor is 78.
Luciano Martini was born on May 14, 1927, in Milan, Italy. He obtained the degree of Medical
Doctor "summa cum laude" on November 24, 1950, from the Faculty of Medicine of the
University of Milan, Italy. He was Emeritus Professor of Pharmacology of the University of
Perugia, Italy, and Emeritus Professor of Endocrinology of the University of Milan, Italy. He
was Doctor Honoris Causa in Medicine of the Universities of Liège, Belgium, Santiago de
Compostela, Spain, and Pécs, Hungary, and Doctor Honoris Causa in Biotechnological Sci-
ences of the University of Milan, Italy. He was an author of more than 400 peer-reviewed
scientific publications in the fields of endocrinology, neuroendocrinology, pharmacology,
physiology of reproduction, steroid biochemistry, and basic oncology. He was elected member
of the Accademia Nazionale dei Lincei (Italian National Academy) and of the American
Academy of Arts and Sciences (Honorary Foreign Member).
Luciano Martini acted as Editor in Chief of the journal Frontiers in Neuroendocrinology from
1990 to 2001, and was a Member of the Editorial Board of Endocrinology (Foreign Consulting
Editor, 1961–65), as well as of several other speciality journals, such as Experimental and
Clinical Endocrinology, Biochemistry, and Steroids. He has acted as Editor of several textbooks
(e.g., Neuroendocrinology, a textbook in 2 volumes, Academic Press, New York, 1966–67, and Clinical Neuroendocrinology, a textbook
in 2 volumes, Academic Press, New York, 1977–82) as well of a series of books under the name Comprehensive Endocrinology
(13 volumes), Raven Press, New York, 1979–84. He acted as Editor in Chief for the first edition of Encyclopedia of Endocrine Diseases
(4 volumes), Academic Press-Elsevier, San Diego, 2004.
vii
EDITORIAL BOARD
Jean-Jacques Body Jean Marc Kaufman

CHU Brugmann, Free University of Brussels (ULB), Brussels, Department of Endocrinology, Ghent University Hospital,
Belgium Ghent, Belgium
Felipe F. Casanueva André Lacroix

Department of Medicine, Santiago de Compostela University, Endocrine Division and Research Center, Centre hospitalier de
Complejo Hospitalario Universitario de Santiago (CHUS), l'Université de Montréal (CHUM), Montreal, QC, Canada
Santiago de Compostela, Spain
Franco Mantero
CIBER de Fisiopatologia Obesidad y Nutricion (CIBERobn),
University of Padua Medical School, Padua, Italy
Carlos III Health Institute, Santiago de Compostela, Spain
Jorma Toppari
Jean-Louis Chiasson
Institute of Biomedicine, Research Center for Integrative
Department of Medicine, Division of Endocrinology,
Physiology and Pharmacology, University of Turku, Turku,
Cardiometabolic Axis, CRCHUM, Montreal, QC, Canada
Finland
Sophie Christin-Maitre Department of Pediatrics, Turku University Hospital, Turku,
Hospital Saint-Antoine, Assistance-Publique Hôpitaux de Paris, Finland
Paris, France
Jacquetta Trasler
Sorbonne University, Medical University, Paris, France
Research Institute, McGill University Health Center, Montreal,
Richard N Clayton QC, Canada
Keele University, Newcastle under Lyme, United Kingdom
Christina Wang
Nuffield Hospital, Derriford, Plymouth, United Kingdom
David Geffen School of Medicine at UCLA, Los Angeles, CA,
Ulla Feldt-Rasmussen United States
Department of Medical Endocrinology and Metabolism Department of Medicine, Harbor-UCLA Medical Center, Torrance,
Rigshospitalet, National University Hospital, CA, United States
Copenhagen University, Copenhagen, Denmark Los Angeles Biomedical Research Institute (LA BioMed),
Torrance, CA, United States
Wouter W. de Herder
Department of Internal Medicine—Sector of Endocrinology Martin O. Weickert
Erasmus MC - University Hospital Rotterdam, Rotterdam, The The ARDEN NET Centre, ENETS Centre of Excellence,
Netherlands Coventry, United Kingdom
University Hospitals Coventry and Warwickshire NHS Trust,
Ieuan Hughes Coventry, United Kingdom
Department of Pediatrics, University of Cambridge, Clinical Research Network (CRN) West Midlands, Coventry,
Cambridge, United Kingdom United Kingdom
Cambridge University Hospitals NHS Foundation Trust and
Cambridge Biomedical Campus, Cambridge, United Kingdom
Gregory Kaltsas
National and Kapodistrian University of Athens, Athens,
Greece
ix
SECTION EDITORS
Professor Jean-Jacques Body has been trained as an endocrinologist and a medical oncologist.
He was Head of the Department of Medicine at University Hospital Brugmann in Brussels and
Full Professor of Medicine (Internal Medicine) at the Free University of Brussels, (ULB),
Brussels, Belgium. He was previously Head of the Internal Medicine Clinic at Institute J. Bordet
(Cancer Center of ULB). He has also developed the “Supportive Care Dept” at the same
Institute. His particular research interests are osteoporosis and bone metastases. He has a long-
standing interest for bone metabolism and turnover in osteoporosis and tumor bone diseases.
He has authored or co-authored more than 250 international peer-reviewed papers and he
counts more than 200 invited lectures for international meetings.
Felipe F. Casanueva is Professor of Medicine at University of Santiago de Compostela and

Head of Department of Endocrinology and Nutrition at University Hospital Santiago. He has
been President of the scientific societes, such as: European Federation of Endocrine Societies
(EFES), The Pituitary Society, International Society of Endocrinology (ISE) and, Sociedad
Española para el Estudio de la Obesidad (SEEDO). Has written more than 50 chapters in
international books and published more than 700 papers in international journals. He has
received several awards for research at national and international level, such as: Rey Jaime I to
the Medical Research, Geoffrey Harris Prize in Neuroendocrinology, Fundación Lilly of Bio-
medical Research Clinic, Fundacion Danone – Professional Career – Dr Carlos Martí Hennberg,
European Hormone Medal by the European Society for Endocrinology (ESE); he has been
named Honorary Doctorate in Medicine of the University of Łódź, Erciyes, and Belgrade, and
Honorary Member of the European Society of Endocrinology.
Dr. Jean-Louis Chiasson is currently Full Professor of Medicine at the University of Montreal.
He is Head of the Research Group on Diabetes and Metabolic Regulation at the Research
Center of the Centre hospitalier de l’Université de Montréal (CRCHUM).
Dr. Chiasson obtained his MD at Laval University in Quebec City in 1967. He did his specialty
training in Internal Medicine at Laval Univesity and in Endocrinology at McGill University. He
then did a research Fellowship in Diabetes at Vanderbilt University in Nashville, Tennessee. In
1974–76 and 1978–80, he was appointed Assistant Professor in the Department of Medicine
and Physiology respectively at Vanderbilt University. In 1980, he returned to Montreal as
Assistant Professor in the Department of Medicine at the University of Montreal and as
Endocrinologist at Hotel-Dieu Hospital, now merged into the Centre hospitalier de l’Université
de Montréal.
Dr. Chiasson’s research interests include the regulation of carbohydrate metabolism in health
and diabetes, as well as the development and evaluation of new strategies for the treatment and
prevention of diabetes and its vascular complications. He has contributed over 250 scientific
publications and lectures nationally and internationally on various topics on diabetes mellitus,
its pathogenesis, its treatment, and its prevention. His scientific contribution puts him in the
prestigious club of the 100 most cited publications in the world in the field of diabetes.
xi
xii Section Editors
Sophie Christin-Maitre received her MD at University of Paris XI and her PhD at University
Paris VI, Pierre and Marie Curie, France. She did a postdoctoral training in United States
(Massachusetts General Hospital, Harvard University, Boston); she specialized in reproductive
medicine. She holds the post of Professor of Endocrinology at University of Sorbonne, Paris,
France. She has been the head of the Adult Endocrine Unit, in Hôpital Saint-Antoine, Assis-
tance-Publique Hôpitaux de Paris, since 2011. She is a member of the INSERM research unit
UMR S_933, specialized in identifying new genes in reproductive disorders. Her interests
include clinical and basic reproductive endocrinology, in particular the management of
patients with Turner syndrome, patients with primary ovarian insufficiency, patients with
hypogonadisms, and patients with abnormalities of sex development. She has authored
approximately 150 peer-reviewed research articles and reviews.
Ulla Feldt-Rasmussen is Professor at Copenhagen University and Chief of Medical Endocri-

nology, National University Hospital. Her research interests involve the thyroid gland and
autoimmunity, as well as pituitary and adrenal dysfunction.
She has published more than 410 papers in peer-reviewed journals on e.g., thyroid hormones
and body composition, thyroid autoimmunity and cancer, cytokines as regulators of endocrine
cells, influence of thyroid disrupting chemicals on thyroid cells, growth hormone deficiency
related to body composition, bone metabolism and other pituitary axes, and transition from
adolescent to adult care, as well as several aspects of Fabry disease. In recent years her group
has embarked on studies on pituitary function after traumatic brain injury in a nationwide
setting, and focusing on diagnostic accuracy of pituitary testing procedures. She has further
authored numerous proceedings, textbook chapters, and other publications; as well as orga-
nized numerous international meetings and postgraduate courses, and has led several Eur-
opean projects and other collaborations within many areas of endocrinology.
Professor Feldt-Rasmussen reviews for international journals, and is an editorial board
member of several endocrine journals. She belongs to many international professional orga-
nizations, including the Endocrine Society, ETA, ATA, ENEA, and GRS; she has served as Secretary-Treasurer of ETA and as
President of the ETA Cancer Research Network.
Professor Feldt-Rasmussen serves on the advisory boards of several ad hoc endocrine committees, and has received many pres-
tigious prizes including the Mayo Clinic’s Haynes Lecturer's Award and ETA’s Pinchera Research Prize.
Wouter W. de Herder M.D. Ph.D. (1960) is Professor of Endocrine Oncology at the Erasmus
MC in Rotterdam, the Netherlands. In this University Hospital he is chairman of a multi-
disciplinary group for endocrine oncology (tumorwerkgroep endocriene tumoren) and he is
head of the ENETS centre of excellence for neuroendocrine tumors. His major research interests
are neuroendocrine and endocrine tumors.
Professor de Herder received his M.D. in 1985 and his Ph.D. in 1990 from the Erasmus
University in Rotterdam, the Netherlands.
He is a member of several international and Dutch national societies, such as the Dutch Society
for Endocrinology (NVE), the Endocrine Society (USA), the European Society of Endocrinol-
ogy (ESE), European Neuroendocrine Tumor Society (ENETS) and the North American Neu-
roendocrine Tumor Society (NANETS). He served as a board member of the Dutch Society for
Endocrinology (NVE) (2009–14). He served as chairman (2006–08) and vice-chairman of
ENETS (2008–10) (European Neuroendocrine Tumour Society). He is member of the advisory
boards of ENETS and NANETS.
Professor de Herder has (co-)published over 400 peer-reviewed papers and book chapters and
is a reviewer for many international journals.
He is a member of the editorial boards of Neuroendocrinology; Endocrinology, Diabetes &
Metabolism Case Reports; Clinical Endocrinology, and Endocrine-Related Cancer.
Professor de Herder has given over 200 invited presentations at Dutch national and international meetings.
Section Editors xiii
Ieuan Hughes is currently Emeritus Professor of Pediatrics at the University of Cambridge and
Honorary Consultant Pediatrician at Cambridge University Hospitals NHS Foundation Trust
and Cambridge Biomedical Campus. He is the author of more than 300 papers and chapters
across the whole range of paediatric endocrinology. His particular expertise is in disorders of
sex development for which he coordinated the International Consensus on the approach to the
investigation and management of this broad topic. Research interests focus on steroid enzyme
deficiencies and molecular mechanisms of androgen action.
Professor Hughes has served on the editorial boards of several journals, including Clinical
Endocrinology, Journal of Clinical Endocrinology, and Metabolism and Archives of Disease in Child-
hood where he was also the Associate Editor. He is Past-Secretary and President of the European
Society for Pediatric Endocrinology and a recipient of the highest award of the Society, the
Andrea Prader Prize. Professor Hughes is a James Spence Medallist of the Royal College of
Pediatrics and Child Health for outstanding contributions to paediatric knowledge. He is a
Fellow of the Academy of Medical Sciences, a Council Member of the Learned Society of Wales
and a Trustee of two charities. The chapter on Disorders of Sex Development in Williams
Textbook of Endocrinology (now in its 14e) by Hughes and co-authors is considered to be a
definitive and up to date regular review of this topic, specific and key to pediatric endocrinology.
Dr. Gregory Kaltsas MD FRCP (Lon) is Professor in General Medicine and Endocrinology at
the National and Kapodistrian University of Athens, Greece. He was trained in General Med-
icine in Athens, Greece and London, UK, and in Endocrinology at the Middlesex and St
Bartholomew’s Hospital, London, UK. He developed a particular interest in neuroendocri-
nology (pituitary and neuroendocrine tumors) and adrenal physiology and diseases. Upon
returning to Greece he established a neuroendocrine network and he is currently running the
European Neuroendocrine Tumor Society (ENETS) Center of Excellence at Laiko Hospital in
Athens, Greece. He has served as a member of the advisory board of ENETS and of the
Executive Committee of the European Neuroendocrine Association (ENEA) and he has been
elected in the Executive Committee of the International Society of Endocrinology. He has
recently been elected as a representative of the European Society of Endocrinology in the ExCo
of the International Society of Endocrinology. He has published more than 300 original
papers, reviews, and chapters and serves on editorial boards and as associate editor in several
endocrine journals.
Jean-Marc Kaufman obtained his MD and PhD degrees at the Ghent University, Belgium. He
was a Senior Postdoctoral Research Fellow (1982–84) in reproductive physiology at the Uni-
versity of Texas Medical School at Houston. He is board certified in Endocrinology and in
Nuclear Medicine. In 1985 he joined the staff of the Ghent University Hospital; he headed the
department of Endocrinology from 2003 to 2014 and the Laboratory for Hormonology from
1995 to 2014. He was appointed in 1993 Professor of Medicine at the Ghent University (1993)
and is past Chair of the Department of Internal Medicine at the Ghent University (2010–14).
From October 1st 2014 he is Professor Emeritus at the Ghent University where he is pursuing clinical and research activities. Main
research interests are in the assessment, regulation, and action of sex steroids with focus on their role in health, disease, and aging in
men, and in osteoporosis in men. He is (co)author of over 300 publications in international peer-reviewed journals.
xiv Section Editors
André Lacroix, MD FCAHS is Professor of Medicine, Division of Endocrinology at Centre

hospitalier de l’Université de Montréal (CHUM). His areas of interest include the mechanisms
of adrenal Cushing syndrome, primary aldosteronism, adrenal tumorigenesis, the role of
aberrant adrenal hormone receptors in adrenal overfunction, as well as new drugs in the
therapy of Cushing disease, primary aldosteronism and adrenocortical cancer.
He was trained at the University of Montreal followed by fellowships in Endocrinology and
research at Vanderebilt University and National Institutes of Health, USA. He was Chairman of
Medicine and Director of Academic Affairs at CHUM. Former President of the Canadian
Society of Endocrinology and Metabolism, he is currently chairperson of the International
Society of Endocrinology (2016–20), Editor, Adrenal Section of UpToDate and Encyclopedia of
Endocrinology, Senior Editor of the European Journal of Endocrinology. Fellow of the Canadian
Academy of Health Sciences since 2008 and Foreign member of the National Academy of
Medicine of France since 2016.
Franco Mantero received his MD at the University of Padua, Italy, did postdoctoral training in
Switzerland (Clinique Medicale Therapeutique, Hopital Cantonal, University of Geneva) and
in United States (University of California, San Francisco), and has been on sabbatical leave in
United Kingdom, United States, and France. He held a post of Associate Professor in Medicine
at the Institute of Semeiotica Medica, University of Padua (1981–86). In 1986 he moved to the
University of Catania to the Chair of Andrology and Endocrinology, in 1992 to the University
of Ancona, and in 2000 to the University of Padua to the Chair of Endocrinology and Chief of
the Endocrinology Unit of the Department of Medicine. He has received national and inter-
national honors, including a Doctor Honoris Causa at the Semmelweis University, Budapest,
Hungary.
He has been Editorial Board Member of several scientific journals (e.g., Clinical Endocrinology,
Endocrinology, Journal of Hypertension, Journal of Endocrinology Investigation Steroids)
He has served as Member of the Council of several international scientific societies (including International Society of Endocri-
nology, International Aldosterone Conference, Journee Klotz d’Endocrinologie Clinique, ENS@T) and one of the founders of the
European Network for the Study of Adrenal Tumors. His research interests include clinical and basic endocrinology of the adrenal
gland and endocrinology of hypertension, in particular pathophysiology of mineralocorticoids and primary aldosteronism. He has
authored approximately 500 peer–reviewed articles and edited several books and proceedings.
Jorma Toppari, MD, PhD, is Professor of Physiology at the University of Turku and Chief
Physician of Pediatric Endocrinology at Turku University Hospital, Turku, Finland. He is also
Adjunct Professor in the Department of Growth and Reproduction at the University of
Copenhagen, Denmark. He has served as chief editor of International Journal of Andrology
(2001–09), and has been on editorial boards of several endocrinological journals, including
currently Endocrinology and Journal of Clinical Endocrinology and Metabolism. He is the past
President of the European Academy of Andrology. He has made numerous contributions to the
studies on endocrine disruption in the past 20 years. He has published approximately 400
articles on endocrinology.
Section Editors xv
Jacquetta Trasler is a James McGill Professor in the Departments of Pediatrics, Human

Genetics, and Pharmacology and Therapeutics at McGill University and a Senior Scientist at the
Research Institute of the McGill University Health Centre (RI-MUHC). She received her MD
and PhD degrees from McGill University followed by postdoctoral training in reproductive
molecular biology at Tufts University in Boston. She has served as Director of the McGill
University MD-PhD Program, Scientific Director of the Montreal Children’s Hospital Research
Institute (and simultaneously as Deputy Director/CSO of the RI-MUHC), President of the
Canadian Fertility and Andrology Society, Member of the Institute Advisory Board for the
Canadian Institutes of Health Research (CIHR) Institute of Genetics and currently serves on the
CIHR Stem Cell Oversight Committee and College of Reviewers. Her research focuses on
epigenetics and epigenomics to better understand the molecular and cellular targets for drug
effects on germ cells with implications for the resulting offspring. She has been involved in
scientific program organization for numerous meetings in the field of reproductive biology and medicine and is collaborating with
national and international colleagues in clinical studies to examine how assisted reproductive technologies, infertility, drug
treatment, and folate deficiency and supplementation impact the human epigenome including that of future generations.
Christina Wang, MD is Professor of Medicine, Assistant Dean at the David Geffen School of
Medicine at UCLA, and Associate Director for Clinical and Translational Science Institute and a
faculty member of the Division of Endocrinology, Department of Medicine, Harbor-UCLA
Medical Center and Los Angeles Biomedical Research Institute, Torrance, California.
Dr. Wang has been involved in many funded basic and clinical research studies. Her current
clinical research studies include androgen replacement therapy, hormonal male contraceptive
development, late onset hypogonadism, accurate assessment of serum androgens, and diet and
androgen metabolism. Her basic research studies focus on the regulation of spermatogenesis
and mitochondrial derived peptides in spermatogenesis.
She has authored over 300 peer-reviewed publications, 67 chapters and reviews mainly on
male reproductive biology including characterization of the pharmacokinetics and efficacy of
androgens in men, trials of hormonal male contraceptive, regulation of germ cell apoptosis,
and reproductive aging. Dr. Wang served on the Executive Council, several committees and was the President of the American
Society of Andrology (2006–07). She also served the International Society of Andrology as Secretary (2001–05) and Chair of the
Program Organizing Committee (2005–09). She was President of the International Society of Andrology (2009–13). She is a
member of the Research Group on Methods for the Regulation of Male Fertility of the World Health Organization since 1984 and
Chairperson (1991–2002).
She has mentored many physician and scientist and is an advocate of young investigators. Dr. Wang has been invited speaker and
distinguished lecturer at many national and international endocrinology, reproductive endocrinology, and andrology conferences.
LIST OF CONTRIBUTORS
Bo Abrahamsen R.G. Allen

University of Southern Denmark, Odense, Denmark; The Sally Balin Medical Center, Media, PA, United
and Holbæk Hospital, Holbæk, Denmark States
Catarina Abreu Jeremy Allgrove

Hospital of Santa Maria, Lisbon, Portugal Great Ormond Street Hospital NHS Foundation Trust,
O. Addison
University of Maryland School of Medicine, Baltimore, Paloma Alonso-Magdalena
MD, United States Miguel Hernan ́ dez University of Elche and CIBERDEM,
Alicante, Spain
Zaida Agü era
Carlos III Institute of Health, Madrid, Spain; and Mazen Alsahli
University Hospital of Bellvitge-IDIBELL, Barcelona, Southlake Regional Health Center, Newmarket, ON,
Spain Canada; and University of Toronto Faculty of Medicine,
Toronto, ON, Canada
Enrico Agabiti-Rosei
University of Brescia, Brescia, Italy Laurence Amar
Hop̂ ital Européen Georges Pompidou, Paris, France;
Carlo Aggiusti INSERM, UMR970, Paris, France; and Université Paris
Department of Clinical and Experimental Sciences, Descartes, Paris, France
University of Brescia, ASST Spedali Civili di Brescia and
L. Amar
Società Italiana dell'Ipertensione, Brescia, Italy
Hop̂ ital Européen Georges Pompidou, Paris, France; and
Veena Agrawal Paris Descartes University, Paris, France
University of Colorado, Aurora, CO, United States
Gisah Amaral de Carvalho
James Ahlquist Federal University of Parana,́ Curitiba, Brazil
Southend Hospital, Westcliff on Sea, United Kingdom Ravinder Anand-Ivell
Syed Faisal Ahmed University of Nottingham, Nottingham, United Kingdom
Royal Hospital for Children, Glasgow, United Kingdom Dana K. Andersen
National Institutes of Health, Bethesda, MD, United
Oluwaseun A. Akinseye
States
University of Tennessee Health Science Center,
Memphis, TN, United States Niels H. Andersen
Aalborg University Hospital, Aalborg C, Denmark
Adriana Albani
Ludwig Maximilian University of Munich, Munich, Mikkel Andreassen
Germany; and University of Messina, Messina, Italy ENETS NET CoE, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark
Maria Alevizaki
National and Kapodistrian University of Athens, Athens, Di Vincenzo Angelo
Greece Center for the Study and the Integrated Treatment of
Obesity – Bariatric Unit, University of Padua, Padua,
Kristallenia Alexandraki Italy
Greece Jean-Marie Antoine
Tenon Hospital, Paris, France; and Pierre et Marie
Ahmad Alkhatib Curie University, Paris, France
Dasman Diabetes Institute, Dasman, Kuwait
Athanasios Antoniou-Tsigkos
Stefano Allasia National and Kapodistrian University of Athens, Athens,
University of Turin, Turin, Italy Greece
xvii
xviii List of Contributors
Victor Appay Diabetes and Associated Metabolic Disorders, ISCIII,

INSERM Centre d'Immunologie et des Maladies Madrid, Spain
Infectieuses (CIMI-Paris), Paris, France
Guillaume Assié
David Araújo-Vilar Paris Descartes University, Paris, France; and Cochin
UETeM, IDIS-CIMUS, University of Santiago de Hospital, Paris, France
Compostela, Santiago de Compostela, Spain; and
Mohamed G. Atta
University Clinical Hospital of Santiago de Compostela,
Johns Hopkins University, Baltimore, MD, United States
Santiago de Compostela, Spain
A.A. Aubdool
Sheryl E. Arambula
King's College London, London, United Kingdom
North Carolina State University, Raleigh, NC, United
States Richard J. Auchus
University of Michigan, Ann Arbor, MI, United States
Jesús A. Araujo
University of California Los Angeles, Los Angeles, CA, Alain Audebert
United States Bordeaux, France
Leonardo Tadeu Araujo Maria Christina W. Avellar
University of Sao Paulo, Sao Paulo, Brazil Federal University of São Paulo, Paulista School of
Medicine, São Paulo, Brazil
Teresa Arcidiacono
IRCCS San Raffaele Scientific Institute, Milan, Italy M. Azizi
Hop̂ ital Européen Georges Pompidou, Paris, France; and
Josephine Arendt
Paris Descartes University, Paris, France
University of Surrey, Guildford, United Kingdom
Stéphanie Bécourt
Jesús Argente Hop̂ ital Saint-Louis, Paris
Autonomous University of Madrid, Madrid, Spain;
University Hospital Niñ o Jesús, Institute of Investigation Anne Bachelot
La Princesa, Madrid, Spain; and Center for Biomedical Sorbonne University, Paris, France
Research in Network on the Pathophysiology of Obesity
Lina Badimon
and Nutrition (CIBEROBN), Carlos III Health Institute,
Cardiovascular Research Center, CSIC-ICCC Hospital
Madrid, Spain; and Madrid Institutes for Advanced
Santa Creu I Sant Pau, Barcelona, Spain
Studies (IMDEA), Campus of International Excellence,
Autonomous University of Madrid (CEIUAM), Madrid, Stefan Bagheri-Fam
Spain The University of Melbourne, Parkville, VIC, Australia
Decio Armanini Preeti Bajpai
University of Padua, Padova, Italy Integral University, Lucknow, India
David G. Armstrong Vania Balderrama
Manchester Royal Infirmary, Manchester, United University of São Paulo, São Paulo, Brazil
Kingdom; and Southern Arizona Veterans Affairs
Medical Center, Tucson, AZ, United States A.K. Balin
The Sally Balin Medical Center, Media, PA, United
Wilbert S. Aronow States
New York Medical College, Valhalla, NY, United States
Indraneel Banerjee
Pablo Arriagada Royal Manchester Children's Hospital, Manchester,
Gedeon Richter/Preglem S.A., Geneva, Switzerland United Kingdom; and University of Manchester,
Manchester, United Kingdom
Sylvia L. Asa
University Health Network, Toronto, ON, Canada; Kanthi Bangalore Krishna
University of Toronto, Toronto, ON, Canada; and Penn State Hershey Medical Center, Hershey, PA,
Princess Margaret Cancer Centre, Toronto, ON, Canada United States
Juan F. Ascaso María-José Barahona
University of Valencia, Valencia, Spain; and Hospital Universitari Mútua de Terrassa, Terrassa,
CIBERDEM-Spanish Biomedical Research Centre in Spain; and Centro de Investigacioń Biomédica en Red de
List of Contributors xix
Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII, Pierre J.M. Bergmann

Barcelona, Spain Department of Nuclear Medicine, Centre Hospitalier
Universitaire Brugmann, Free University of Brussels,
Pedro N. Barri Brussels, Belgium
́ Dexeus, Barcelona, Spain
University Hospital Quiron
Odilia I. Bermudez
Luigi Bartalena Tufts School of Medicine, Boston, MA, United States
University of Insubria, Varese, Italy
Margaux Bernard
Anu Bashamboo INSERM, Faculty of Medicine Lyon East, Lyon, France
Institut Pasteur, Paris, France
Alfredo Berruti
Spyridon P. Basourakos University of Brescia, Brescia, Italy
New York Presbyterian Hospital/Weill Cornell Medical
Center, New York, NY, United States Fabio Bertacchini
Department of Clinical and Experimental Sciences,
Rafael L. Batista University of Brescia, ASST Spedali Civili di Brescia and
University of São Paulo, São Paulo, Brazil Società Italiana dell'Ipertensione, Brescia, Italy
Gerhard Baumann Jérô me Bertherat
Northwestern University Feinberg School of Medicine, Reference Center for Rare Adrenal Diseases, Cochin
Chicago, IL, United States Hospital, Assistance Publique – Hopitaux de Paris, Paris,
France
Kathryn Beardsall
University of Cambridge, Cambridge, United Kingdom Virginie Bertrand-Lehouillier
University of Montreal, Montreal, QC, Canada
Albert Beckers
University Hospital Center of Lieg̀ e, Lieg̀ e, Belgium Shalender Bhasin
Harvard Medical School, Boston, MA, United States;
P. Beck-Peccoz Research Program in Men's Health: Aging and
University of Milan, Milan, Italy Metabolism, Boston, MA, United States; Boston Claude
My-Thanh Beedle D. Pepper Older Americans Independence Center,
Washington State University, Pullman, WA, United Boston, MA, United States; and Brigham and Women's
States Hospital, Boston, MA, United States
Alicia Belgorosky Antonio Bianchi

Hospital de Pediatría Garrahan, Buenos Aires, Pituitary Unit, Catholic University of Sacred Heart,
Argentina; and Consejo Nacional de Investigaciones Rome, Italy
Científicas y Técnicas (CONICET), Argentina Andreas Bikfalvi
Julie Benard University of Bordeaux, Pessac, France
Service de Médecine de la Reproduction et Préservation Beverly M.K. Biller
de la Fertilité, Jean Verdier Hospital, Bondy, France; Massachusetts General and Harvard Medical School,
and University Paris XIII, Bobigny, France Boston, MA, United States
Alexandra Benoit Emma O. Billington
Service de Médecine de la Reproduction et Préservation University of Calgary, Calgary, AB, Canada
de la Fertilité, Jean Verdier Hospital, Bondy, France
Bernadette Biondi
Salvatore Benvenga University of Naples Federico II, Naples, Italy
University of Messina, Messina, Italy; and University
Hospital Policlinico Universitario G. Martino, Messina, Nick Bishop
Italy Sheffield Children's NHS FT and University of Sheffield,
Sheffield, United Kingdom
Sarah L. Berga
Division of Reproductive Endocrinology and Infertility, Joanne C. Blair
University of Utah School of Medicine, Salt Lake City, Alder Hey Children's Hospital, Liverpool, United
UT, United States Kingdom
xx List of Contributors
Sofie Bliddal Janet Brown

Copenhagen University Hospital (Rigshospitalet), University of Sheffield, Sheffield, United Kingdom
Copenhagen, Denmark
Thierry Brue
Floyd E. Bloom Reference Center for Rare Pituitary Diseases, Assistance
The Scripps Research Institute, La Jolla, CA, United Publique Hopitaux de Marseille, La Conception Hospital,
States Marseille Cedex 05, France; and INSERM UMR-U910,
Aix Marseille University, Marseille Cedex 05, France
Bruce Blumberg
University of California Irvine, Irvine, CA, United States Antonio Bruni
University of Alberta, Edmonton, AB, Canada
Fausto Bogazzi
University of Pisa, Pisa, Italy Rosa Maria Bruno
Marco Bonomi University of Pisa, Pisa, Italy
University of Milan, Milan, Italy; and IRCCS Italian Aude Bruyneel
Auxological Institute, Milan, Italy Free University of Brussels, Brussels, Belgium
Julia K. Bosdou Michael Buchfelder
Aristotle University of Thessaloniki, Thessaloniki, Greece University Hospital Erlangen, Erlangen, Germany
Anja Bosy-Westphal Krupali Bulsari
University of Kiel, Kiel, Germany Princess Alexandra Hospital, Brisbane, QLD, Australia;
Philippe Bouchard and University of Queensland, Brisbane, QLD, Australia
Sorbonne University, Paris, France Peter Burckhardt
Roger Bouillon Hirslanden Clinic, Lausanne, Switzerland
Laboratory of Clinical and Experimental Endocrinology, Albert G. Burger
KU Leuven, Leuven, Belgium; and University Hospitals, University of Bern, Bern, Switzerland; and University of
Leuven, Belgium Geneva, Geneva, Switzerland
Isabelle Bourdeau Alexander S. Busch
Centre hospitalier de l'Université de Montréal (CHUM), University of Copenhagen, Copenhagen, Denmark
Montréal, QC, Canada
Luca Busetto
Jean-Pierre Bourguignon University of Padua, Padua, Italy
University of Lieg̀ e, Lieg̀ e, Belgium; and CHU de Lieg̀ e,
Chen̂ ée, Belgium Gary Butler
University College London Hospital NHS Trust, London,
Mary L. Bouxsein United Kingdom; and UCL Great Ormond Street
Beth Israel Deaconess Medical Center, Boston, MA, Institute of Child Health, London, United Kingdom
United States; Harvard Medical School, Boston, MA,
United States; and Massachusetts General Hospital, Véronique Cadoret
Boston, MA, United States PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly,
France; and CHRU Bretonneau, Medicine and Biology
Elvira V. Bräuner of Reproduction, CECOS, Tours, France
University of Copenhagen, Copenhagen, Denmark
Lorenzo A. Calò
S.D. Brain University of Padua, Padua, Italy
Irene Campi
Glenn D. Braunstein
University of Milan, Milan, Italy
Cedars-Sinai Medical Center, Los Angeles, CA, United
States; and University of California Los Angeles, Los Biagio Cangiano
Angeles, CA, United States University of Milan, Milan, Italy; and IRCCS Italian
Auxological Institute, Milan, Italy
Ralph Brecheisen
Maastricht University, Maastricht, The Netherlands Letizia Canu
University of Florence, Florence, Italy
Claire Briet
University Hospital of Angers, Angers, France; and Perrine Capmas
University of Angers, Angers, France Bicetre Hospital, Le Kremlin Bicetre, France
List of Contributors xxi
Carlo Cappelli Sophie Catteau-Jonard

University of Brescia, Brescia, Italy; and Endocrine and Department of Endocrine Gynecology and Reproductive
Metabolic Medicine Unit, ASST Spedali Civili di Medicine, Lille University Hospital, Lille, France
Brescia, Brescia, Italy
Anne Caufriez
Marta Caretto Free University of Brussels, Brussels, Belgium
University of Pisa, Pisa, Italy
Isadora Pontes Cavalcante
Robert M. Carey University of São Paulo, São Paulo, Brazil
University of Virginia Health System, Charlottesville,
VA, United States Etienne Cavalier
University of Lieg̀ e, Lieg̀ e, Belgium
Rafael Carmena
University of Valencia, Valencia, Spain Jonas Č eponis
Lithuanian University of Health Sciences, Kaunas,
Nancy Carrasco Lithuania
Yale School of Medicine, New Haven, CT, United States
Filomena Cetani
Olivera Casar-Borota University of Pisa, Pisa, Italy; and University Hospital of
Uppsala University, Uppsala, Sweden Pisa, Pisa, Italy
Livio Casarini Nathalie Chabbert-Buffet
University of Modena and Reggio Emilia, Modena, Italy Sorbonne University, Paris, France
James Casella-Mariolo Alan Chait
Sapienza University of Rome, Rome, Italy University of Washington, Seattle, WA, United States
C. Casellini Peter T. Chan
Eastern Virginia Medical School, Norfolk, VA, United McGill University Health Center, Royal Victoria
States Hospital, Montreal, QC, Canada
Lidia Castagneto-Gissey Philippe Chanson
Sapienza University of Rome, Rome, Italy Assistance Publique-Hop̂ itaux de Paris, Service
d'Endocrinologie et des Maladies de la Reproduction and
Maurizio Castellano Centre de Référence des Maladies Hypophysaires Rares,
University of Brescia, Brescia, Italy; and Endocrine and Bicet̂ re Hospital, Le Kremlin-Bicet̂ re, France; Université
Metabolic Medicine Unit, ASST Spedali Civili di Paris-Sud, Le Kremlin-Bicet̂ re, France; and Institut
Brescia, Brescia, Italy National de la Santé et de la Recherche Médicale
Frederic Castinetti (INSERM) U1185, Le Kremlin-Bicet̂ re, France
Reference Center for Rare Pituitary Diseases, Assistance Karen E. Chapman
Publique Hopitaux de Marseille, La Conception Hospital, University of Edinburgh, Edinburgh, United Kingdom
Marseille Cedex 05, France; and INSERM UMR-U910,
Aix Marseille University, Marseille Cedex 05, France Helaine Laiz Silva Charchar
University of São Paulo, São Paulo, Brazil
Frederic Castinetti
Aix Marseille University, Marseille, France F. Charles Brunicardi
University of California Los Angeles, Los Angeles, CA,
́
Victoria Catalan United States
University of Navarra, Pamplona, Spain; CIBEROBN,
ISCIII, Pamplona, Spain; and IdiSNA, Pamplona, Spain Evangelia Charmandari
National and Kapodistrian University of Athens Medical
Victoria Catalan ́
School, Athens, Greece; and Biomedical Research
Metabolic Research Laboratory, University of Navarra, Foundation of the Academy of Athens, Athens, Greece
Pamplona, Spain; CIBEROBN, Carlos III Health
Institute, Pamplona, Spain; and Instituto de Sumana Chatterjee
Investigacioń Sanitaria de Navarra (IdiSNA) Pamplona, Barts and the London School of Medicine and Dentistry,
Spain London, United Kingdom
Richard L. Cate Eleftherios Chatzellis
Boston University, Boston, MA, United States 251 Hellenic Air Force and VA Hospital, Athens, Greece
xxii List of Contributors
Tim Cheetham Laurie E. Cohen

Newcastle University, Newcastle-upon-Tyne, United Harvard Medical School, Boston, MA, United States;
Kingdom and Dana-Farber/Boston Children's Hospital Cancer and
Blood Disorders Center, Boston, MA, United States
Wassim Chemaitilly
St. Jude Children's Research Hospital, Memphis, TN, Annamaria Colao
United States University of Naples Federico II, Naples, Italy
H. Chen Annamaria Colao
University of Alabama at Birmingham, Birmingham, Federico II University of Naples, Naples, Italy
AL, United States
Robert Coleman
Sabrina Chiloiro
University of Sheffield, Sheffield, United Kingdom
Pituitary Unit, Catholic University of Sacred Heart,
Rome, Italy James J. Colt
Luca Chiovato Weill Cornell Medicine, New York, NY, United States
University of Pavia, Pavia, Italy Oscar Coltell
E.R. Christ Carlos III Health Institute, Madrid, Spain; and
University of Bern, Bern, Switzerland; and University of University Jaume I, Castelloń , Spain
Geneva, Geneva, Switzerland
Robert V. Considine
Mirjam Christ-Crain Indiana University School of Medicine, Indianapolis, IN,
University Hospital Basel, Basel, Switzerland United States
Sophie Christin-Maitre Lindsay S. Cooley
Hospital Saint-Antoine, Assistance-Publique Hôpitaux de University of Bordeaux, Pessac, France
Paris, Paris, France; and Sorbonne University, Paris,
France Martine Cools
Ghent University Hospital, Ghent, Belgium
George P. Chrousos
National and Kapodistrian University of Athens Medical Cyrus Cooper
School, Athens, Greece; and Biomedical Research MRC Lifecourse Epidemiology Unit, Southampton
Foundation of the Academy of Athens, Athens, Greece General Hospital, Southampton, United Kingdom
Janet S. Chuang Cyrus Cooper
Cincinnati Children's Hospital Medical Center, University of Southampton, Southampton, United
Cincinnati, OH, United States Kingdom; University of Southampton and University
Maria Verena Cicala Hospital Southampton NHS Foundation Trust,
South Tyrolian Academy of General Practice, Bolzano, Southampton, United Kingdom; WHO Collaborating
Italy Centre for Public Health Aspects of Musculoskeletal
Health and Aging, Lieg̀ e, Belgium; and University of
Francesca Cioppi Oxford, Oxford, United Kingdom
Georges Copinschi
Frédérique Clément Free University of Brussels, Brussels, Belgium
Project-team Mycenae, Inria Center of Paris, Paris,
France F. Coppedè
Philippe Clézardin
INSERM, Faculty of Medicine Lyon East, Lyon, France Claire Cordroch
Hedi L. Claahsen van de Grinten University Hospital of Bordeaux, Bordeaux, France
Radboud University Medical Center, Nijmegen, the Dolores Corella
Netherlands University of Valencia, Valeǹ cia, Spain; and Carlos III
Mélanie Claps Institute of Health, Madrid, Spain
University of Brescia, Brescia, Italy
Isabel M. Cornejo-Pareja
Bart L. Clarke Virgen de la Victoria Universitary Hospital (IBIMA),
Mayo Clinic, Rochester, MN, United States Malaga, Spain
List of Contributors xxiii
Giovanni Corona A.H. Jan Danser

University of Florence, Florence, Italy; and Bologna Erasmus MC, Rotterdam, The Netherlands
Maggiore-Bellaria Hospital, Bologna, Italy
Jessica Daolio
Dalila B. Corry Arcispedale Santa Maria Nuova of Reggio Emilia,
David Geffen UCLA School of Medicine, Los Angeles, Reggio Emilia, Italy
CA, United States
Emile Daraï
Karen E. Cosgrove Sorbonne University, Paris, France
University of Manchester, Manchester, United Kingdom
Mehul T. Dattani
Maria Manuel Costa Great Ormond Street Hospital for Children NHS
Centro Hospitalar São João, Porto, Portugal; and Queen Foundation Trust, London, United Kingdom; and UCL
Mary University of London, London, United Kingdom Institute of Child Health, London, United Kingdom
Luís Costa Justin H. Davies
Hospital of Santa Maria, Institute of Molecular Southampton Children's Hospital, Southampton, United
Medicine, Faculty of Medicine, University of Lisbon, Kingdom
Lisbon, Portugal
Stephen N. Davis
Mariana Costanzo University of Maryland School of Medicine, Baltimore,
Hospital de Pediatría Garrahan, Buenos Aires, Argentina MD, United States
Carine Courtillot Shanlee M. Davis

Sorbonne University, Paris, France University of Colorado, Boulder, CO, United States
Rafael Coveñ as Adolfo J. de Bold

University of Salamanca, Salamanca, Spain University of Ottawa, Ottawa, ON, Canada
Danila Covelli Giuseppina De Filpo

University of Milan, Milan, Italy University of Florence, Florence, Italy
Laura E. Cowen K. De Gendt

Georgetown University Medical Center, Washington, Catholic University of Leuven, Leuven, Belgium
DC, United States Wouter W. de Herder
Brittany Croft Department of Internal MedicineF Sector of
Murdoch Children's Research Institute, Melbourne, VIC, Endocrinology, Erasmus MC - University Hospital
Australia Rotterdam, Rotterdam, The Netherlands
William C. Cushman Frank H. de Jong

University of Tennessee Health Science Center, Erasmus University Medical Center, Rotterdam, The
Memphis, TN, United States Netherlands
Daniele Cusi Frank H. de Jong

Bio4Dreams, Milan, Italy Erasmus University Medical Centre, Rotterdam, The
Netherlands
Lanfranco D'Elia
Federico II University of Naples, Naples, Italy Peter W. de Leeuw
Maastricht University Medical Center, Maastricht, The
Stella D'Oronzo Netherlands
Laura De Marinis
Catherine Dacou-Voutetakis Pituitary Unit, Catholic University of Sacred Heart,
University of Athens, Athens, Greece Rome, Italy
Rozenn Dalbies-Tran Maria Cristina De Martino
PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly, University of Naples Federico II, Naples, Italy
France
Sabine M.P.F. de Muinck Keizer-Schrama
Adrian F. Daly Erasmus Medical Center – Sophia Children's Hospital,
University Hospital Center of Lieg̀ e, Lieg̀ e, Belgium Rotterdam, The Netherlands
xxiv List of Contributors
Beatriz Marinho de Paula Mariani S. Dizon

University of São Paulo, São Paulo, Brazil Queen's University, Kingston, ON, Canada
Jean De Schepper Graham J. Dockray
Free University of Brussels, Brussels, Belgium University of Liverpool, Liverpool, United Kingdom
Miguel Debono Marie-Madeleine Dolmans
The University of Sheffield, Sheffield, United Kingdom Pol̂ e de Recherche en Gynécologie, Institut de Recherche
Expérimentale et Clinique (IREC), Catholic University
Peter A. Deddish of Leuven, Brussels, Belgium; and Cliniques
University of Illinois College of Medicine, Chicago, IL, Universitaires Saint Luc, Brussels, Belgium
United States
G.A. Donnan
Asma Deeb University of Melbourne, Melbourne, VIC, Australia
Mafraq Hospital, Abu Dhabi, United Arab Emirates
Jacques Donnez
Olaf M. Dekkers Society for Research into Infertility (SRI, Société de
Leiden University Medical Centre, Leiden, The Recherche pour l'Infertilité), Brussels, Belgium; and
Netherlands Catholic University of Leuven, Leuven, Belgium
Rita Del Pinto Olivier Donnez
University of L'Aquila, L'Aquila, Italy Institut du Sein et de Chirurgie Gynécologique d'Avignon
Anne Delbaere (ICA), Polyclinique Urbain V, Avignon, France
Free University of Brussels, Brussels, Belgium Robert M. Dores
University of Denver, Denver, CO, United States
Elaine M Dennison
MRC Lifecourse Epidemiology Unit, Southampton Maria Dracopoulou
General Hospital, Southampton, United Kingdom University of Athens, Athens, Greece
Didier Dewailly A. Drexler
Department of Endocrine Gynecology and Reproductive UCLA School of Medicine, Los Angeles, CA, United
Medicine, Lille University Hospital, Lille, France States
Nathalie di Clemente Stenvert L.S Drop
Pierre and Marie Curie University, Paris, France Erasmus Medical Center-Sophia Children's Hospital,
Rotterdam, The Netherlands
Guido Di Dalmazi
Alma Mater Studiorum University of Bologna, Bologna, Ludivine Drougat
Italy Eunice Kennedy Shriver National Institute of Child
Health and Human Development, National Institutes of
N. Di Iorgi Health, Bethesda, MD, United States
University of Genoa, Genoa, Italy
Jérô me Dulon
Paola Di Mauro Sorbonne University, Paris, France
INSERM, Faculty of Medicine Lyon East, Lyon, France
Agathe Dumont
Chantal Diaz-Latoud Department of Endocrine Gynecology and Reproductive
INSERM, Faculty of Medicine Lyon East, Lyon, France Medicine, Lille University Hospital, Lille, France
Michael DiMattina Typhanie Dumontet
Dominion Fertility, Arlington, VA, United States CNRS, INSERM, Clermont Auvergne University,
Georgios K. Dimitriadis Clermont-Ferrand, France
University of Warwick Medical School, Coventry, United Leo Dunkel
Kingdom; and Imperial College London, London, United Queen Mary University of London, London, United
Kingdom Kingdom
Na Ding Mark J. Dunne
Anhui Medical University, Hefei, China University of Manchester, Manchester, United Kingdom
Maria R. Dionísio Leonidas H. Duntas
Hospital of Santa Maria, Lisbon, Portugal University of Athens, Athens, Greece
List of Contributors xxv
Richard Eastell Jane Evanson

University of Sheffield, Sheffield, United Kingdom Barts Health NHS Trust, London, United Kingdom
Camilla Eckert-Lind Shereen Ezzat
University of Copenhagen, Copenhagen, Denmark University Health Network, Toronto, ON, Canada;
University of Toronto, Toronto, ON, Canada; and
Grigoris Effraimidis
Princess Margaret Cancer Centre, Toronto, ON, Canada
Copenhagen University Hospital (Rigshospitalet),
Copenhagen, Denmark Patrick Fénichel
Urs Eiholzer University of Nice-Sophia-Antipolis, Nice, France
Paediatric Endocrine Center Zurich (PEZZ), Zurich, Stéphane Fabre
Switzerland PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly,
Graeme Eisenhofer France
Technical University Dresden, Dresden, Germany Henrik Falhammar
Jean-Marie Ekoe Karolinska University Hospital, Stockholm, Sweden;
CHUM University of Montreal, Montreal, QC, Canada Karolinska Institute, Stockholm, Sweden; and Menzies
School of Health Research and Royal Darwin Hospital,
Mustapha El Lakis Darwin, NT, Australia
National Cancer Institute, Bethesda, MD, United States
Renato Fanchin
Sébastien Elis Hospital Foch, University Paris-Ouest, Suresnes, France
PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly,
France Maritza Farrant
University of Washington, Seattle, WA, United States
Rossella Elisei
University of Pisa, Pisa, Italy Aitak Farzi
Medical University of Graz, Graz, Austria
Gregory R. Emkey
Pennsylvania Regional Center for Arthritis & Patricia Fauque
Osteoporosis Research, Wyomissing, PA, United States Laboratoire de Biologie de la Reproduction, Dijon,
France
Klaus Engelke
University of Erlangen-Nürnberg, Erlangen, Germany Birgitte Federspiel
T. Erbas ENETS NET CoE, Rigshospitalet, University of
Hacettepe University, Ankara, Turkey Copenhagen, Copenhagen, Denmark
Ervin G. Erdö s Richard A. Feelders

University of Illinois College of Medicine, Chicago, IL, Erasmus Medical Center, Rotterdam, The Netherlands
United States Ulla Feldt-Rasmussen
Héctor F. Escobar-Morreale Copenhagen University Hospital (Rigshospitalet),
University Hospital Ramon ́ y Cajal, Madrid, Spain; Copenhagen, Denmark
University of Alcala,́ Madrid, Spain; Ramoń y Cajal Fernando Fernan ́ dez-Aranda
Institute for Health Research IRYCIS, Madrid, Spain; Carlos III Health Institute, Madrid, Spain; University
and Biomedical Research Network Center in Diabetes Hospital of Bellvitge-IDIBELL, Barcelona, Spain; and
and Related Metabolic Diseases CIBERDEM, Madrid, University of Barcelona, Barcelona, Spain
Spain
Fabio L. Fernandes-Rosa
Marc Espié
INSERM, UMRS_970, Paris Cardiovascular Research
Saint-Louis Hospital, Paris
Center, Paris, France; Paris Descartes University, Paris,
Stéphanie Espiard France; and Assistance Publique-Hop̂ itaux de Paris,
Claude Huriez Hospital, Lille University Hospital, Lille, Hop̂ ital Européen Georges Pompidou, Genetics
France Department, Paris, France
Erica A. Eugster Uxía Fernandez
Riley Hospital for Children at Indiana University CIMUS, USC, IDIS, Santiago de Compostela, Spain;
Health, Indianapolis, IN, United States and Carlos III Health Institute, Madrid, Spain
xxvi List of Contributors
Hervé Fernandez Julie Fudvoye

Bicetre Hospital, Le Kremlin Bicetre, France University of Lieg̀ e, Lieg̀ e, Belgium; and CHU de Lieg̀ e,
Chen̂ ée, Belgium
Amanda Meneses Ferreira
University of São Paulo, São Paulo, Brazil Laura Fugazzola
University of Milan, Milan, Italy; and IRCCS Italian
Claudio Ferri
Auxological Institute, Milan, Italy
University of L'Aquila, L'Aquila, Italy
Amandine Ferriere Nicholas R Fuggle
University Hospital of Bordeaux, Bordeaux, France MRC Lifecourse Epidemiology Unit, Southampton
General Hospital, Southampton, United Kingdom
Alison Fildes
University of Leeds, Leeds, United Kingdom Seiji Fukumoto
Tokushima University, Tokushima, Japan
D. Fink
New York University Medical Center, New York, NY, Peter J. Fuller
United States Hudson Institute of Medical Research, Clayton, VIC,
Australia
Alessandra D. Fisher
University of Florence, Florence, Italy; and VU Medical John W. Funder
Center, Amsterdam, The Netherlands Hudson Institute of Medical Research, Clayton, VIC,
Australia; and Monash University, Clayton, VIC,
Christa E. Flü ck Australia
University of Bern, Bern, Switzerland
Ferruccio Galletti
P.E. Fort
University of Naples Federico II, Naples, Italy
Anissa Gamble
Ashley M. Fortress
University of Alberta, Edmonton, AB, Canada
VA Pittsburgh Healthcare System, Pittsburgh, PA,
United States Alan J. Garber
Athanasios Fountas Baylor College of Medicine, Houston, TX, United States
Institute of Metabolism and Systems Research, College of Silvia Garelli
Medical and Dental Sciences, University of Birmingham, Alma Mater Studiorum University of Bologna, Bologna,
Birmingham, United Kingdom; Centre for Italy
Endocrinology, Diabetes and Metabolism, Birmingham
Health Partners, Birmingham, United Kingdom; and Jameson Garland
University Hospital of Ioannina, Ioannina, Greece University of Uppsala, Uppsala, Sweden
Maria Candida Barisson Villares Fragoso E.F. Garner
University of São Paulo, São Paulo, Brazil University of Alabama at Birmingham, Birmingham,
AL, United States
Stephen Franks
Imperial College, London, United Kingdom; and Aoife Garrahy
Hammersmith Hospital, London, United Kingdom Beaumont Hospital/RCSI Medical School, Dublin,
Ireland
Ellen Marie Freel
Queen Elizabeth University Hospital, Glasgow, United Paul J. Gately
Kingdom Leeds Beckett University, Leeds, United Kingdom
Karyn M. Frick Maria Gavriatopoulou
University of Wisconsin-Milwaukee, Milwaukee, WI, National and Kapodistrian University of Athens, Athens,
United States Greece
Gema Frü hbeck Ashley Gearhardt
Metabolic Research Laboratory, University of Navarra, University of Michigan, Ann Arbor, MI, United States
Pamplona, Spain; CIBEROBN, Carlos III Health
́
Institute, Pamplona, Spain; Instituto de Investigacion Nori Geary
Sanitaria de Navarra (IdiSNA) Pamplona, Spain;and Weil Medical College of Cornell University, New York,
University of Navarra Clinic, Pamplona, Spain NY, United States
List of Contributors xxvii
Corinna Geisler Andrea Giustina

Universty of Kiel, Kiel, Germany San Raffaele Vita-Salute University, Milan, Italy
Andrea R. Genazzani Nathalia L. Gomes
University of Pisa, Pisa, Italy University of São Paulo, São Paulo, Brazil
John E. Gerich Anne Gompel
University of Rochester School of Medicine, Rochester, Paris Descartes University, Port Royal, Paris
NY, United States
Louis Gooren
Willem J.M. Gerver University of Florence, Florence, Italy; and VU Medical
Maastricht University, Maastricht, The Netherlands Center, Amsterdam, The Netherlands
Sana A. Ghaznavi Daniela-Brindusa Gorduza
Memorial Sloan Kettering Cancer Centre, New York, Hop̂ ital Mer̀ e-Enfant – Claude-Bernard University,
NY, United States Lyon, France
Ezio Ghigo Monserrat Graell
University of Turin, Turin, Italy University Hospital Niñ o Jesús, Institute of Investigation
Mara Giacchè La Princesa, Madrid, Spain
Endocrine and Metabolic Medicine Unit, ASST Spedali Guido Grassi
Civili di Brescia, Brescia, Italy University Milano-Bicocca, Monza, Italy
Antonella Giampietro
Claus H. Gravholt
Pituitary Unit, Catholic University of Sacred Heart,
Aarhus University Hospital, Aarhus C, Denmark
Rome, Italy
J.R. Grider
J. Gianfortoni
Virginia Commonwealth University, Richmond, VA,
Life Source Fertility Center, Richmond, VA, United
United States
States
Andrea Giannini Michael D. Griswold
University of Pisa, Pisa, Italy Washington State University, Pullman, WA, United
States
Evelien Gielen
Center for Metabolic Bone Diseases, UZ Leuven, Leuven, Virginie Grouthier
Belgium Sorbonne University, Paris, France
Céline Gillet Simona Grozinsky-Glasberg

Free University of Brussels, Brussels, Belgium Hadassah-Hebrew University Medical Center, Jerusalem,
Israel
Anne-Paule Gimenez-Roqueplo
Hop̂ ital Européen Georges Pompidou, Paris, France; Michael Grynberg
INSERM, UMR970, Paris, France; and Paris Descartes Service de Médecine de la Reproduction et Préservation
University, Paris, France de la Fertilité, Jean Verdier Hospital, Bondy, France;
University Paris XIII, Bobigny, France; and Unité Inserm
Véronique Gingras U1133, Paris-Diderot University, Paris, France
Montreal Clinical Research Institute, Montreal, QC,
Canada; and University of Montreal, Montréal, QC, Federica Guaraldi
Canada IRCCS, Istituto Scienze Neurologiche di Bologna,
Bologna, Italy; and University of Bologna, Bologna, Italy
Luca Giovanella
Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Gabriela Guercio
and Oncology Institute of Southern Switzerland, Hospital de Pediatría Garrahan, Buenos Aires,
Bellinzona, Switzerland Argentina; and Consejo Nacional de Investigaciones
Científicas y Técnicas (CONICET), Argentina
Marta Giralt
University of Barcelona, Barcelona, Catalonia, Spain; Jenny E. Gunton
Sant Joan de Déu Research Institute, Esplugues de Westmead Hospital, Sydney, NSW, Australia; The
Llobregat, Spain; and CIBER Fisitopatología de la Westmead Institute for Medical Research, The University
Obesidad y Nutricioń , Spain of Sydney, Sydney, NSW, Australia; and Garvan
xxviii List of Contributors
Institute of Medical Research, University of New South Nicholas C.W. Harvey

Wales, Darlinghurst, NSW, Australia University of Southampton, Southampton, United
Kingdom; University of Southampton and University
Mark Gurnell
Hospital Southampton NHS Foundation Trust,
University of Cambridge, Cambridge, United Kingdom;
Southampton, United Kingdom; and WHO
and National Institute for Health Research Cambridge
Collaborating Centre for Public Health Aspects of
Biomedical Research Centre, Cambridge, United
Musculoskeletal Health and Aging, Lieg̀ e, Belgium
Kingdom
Annik Hauri-Hohl
Wolfgang Hö gler Paediatric Endocrine Center Zurich (PEZZ), Zurich,
Birmingham Women's and Children's NHS Foundation Switzerland
Trust, Birmingham, United Kingdom; and IMSR,
University of Birmingham, Birmingham, United L. Haynes
Kingdom University of Connecticut Health Center, Farmington,
CT, United States
Abdelhadi Habeb
Prince Mohammed bin Abdulaziz Hospital for National Anthony P. Heaney
Guard & Taibah University, Al-Madinah, Kingdom of University of California Los Angeles, Los Angeles, CA,
Saudi Arabia United States
Joel F. Habener Maka S. Hedrington

Massachusetts General Hospital, Boston, MA, United University of Maryland School of Medicine, Baltimore,
States; and Harvard University, Boston, MA, United MD, United States
States Laszlo Hegedü s
Béla Halaś z Odense University Hospital, Odense, Denmark
Hungarian Academy of Sciences and Semmelweis J.M. Hershman
University, Budapest, Hungary Division of Endocrinology, VA Greater Los Angeles
Geoffrey L. Hammond Healthcare System, Los Angeles, CA United States
Life Sciences Center, Vancouver, BC, Canada Lesley A. Hill
Daria Handkiewicz-Junak Life Sciences Center, Vancouver, BC, Canada
Maria Sklodowska-Curie Memorial Institute–Cancer Barry T. Hinton
Center, Gliwice, Poland University of Virginia School of Medicine,
Markolf Hanefeld Charlottesville, VA, United States
Technical University Dresden, Dresden, Germany Angelica Lindén Hirschberg
Fady Hannah-Shmouni Karolinska Institutet, Stockholm, Sweden; and
National Institutes of Health, Bethesda, MD, United Karolinska University Hospital, Stockholm, Sweden
States Rikke Hjortebjerg
Sabine E. Hannema Aarhus University, Aarhus C, Denmark
Leiden University Medical Centre, Leiden, The Johannes Hofland
Netherlands Erasmus University Medical Center, Rotterdam, The
Anne Marie Hannon Netherlands
RCSI Medical School, Dublin, Ireland; and Beaumont David W. Hogg
Hospital, Dublin, Ireland University of Toronto, Toronto, ON, Canada
Carsten Palnæs Hansen Paul-Martin Holterhus
ENETS NET CoE, Rigshospitalet, University of Christian-Albrechts University of Kiel (CAU), Kiel,
Copenhagen, Copenhagen, Denmark Germany; and University Hospital of Schleswig-Holstein
(UKSH), Kiel, Germany
Inga Harbuz-Miller
University of Missouri, Columbia, MO, United States Peter Holzer
Medical University of Graz, Graz, Austria
Yenal I. Harper
University of Tennessee Health Science Center, John W. Honour
Memphis, TN, United States University College London, London, United Kingdom
List of Contributors xxix
Nadine Hornig Martin B. Jørgensen

Christian-Albrechts University of Kiel (CAU), Kiel, University of Copenhagen, Copenhagen, Denmark
Germany; and University Hospital of Schleswig-Holstein
(UKSH), Kiel, Germany Marie-Lise Jaffrain-Rea
University of L'Aquila, L'Aquila, Italy; and IRCCS
Christopher Houk Neuromed, Pozzilli, Italy
Augusta University Health Sciences, Augusta, GA,
United States Ashish Jain
Montreal Diabetes Research Center, Montreal, QC,
Sasha Howard Canada; and CHUM-Research Center (CRCHUM),
Queen Mary University of London, London, United Montreal, QC, Canada
Kingdom
Andrzej Januszewicz
Ieuan Hughes Institute of Cardiology, Warsaw, Poland
Department of Pediatrics, University of Cambridge,
Cambridge, United Kingdom Barbara Jarząb
Cambridge University Hospitals NHS Foundation Trust and Maria Sklodowska-Curie Memorial Institute-Cancer
Cambridge Biomedical Campus, Cambridge, United Kingdom Center, Gliwice, Poland
Mia Husic Ravi Jasuja
University of Toronto, Toronto, ON, Canada Translational Research and Discovery, Boston, MA,
Vivian Hwa United States; Research Program in Men's Health: Aging
Cincinnati Children's Hospital Medical Center, and Metabolism, Boston, MA, United States; Boston
Cincinnati, OH, United States of America Claude D. Pepper Older Americans Independence
Center, Boston, MA, United States; and Brigham and
Guido Iaccarino Women's Hospital, Boston, MA, United States
University of Salerno, Baronissi, SA, Italy
Rebecca L. Jaworski
Davide Iacuaniello
University of California San Diego, San Diego, CA,
United States
Antonio Ieni
University of Messina, Messina, Italy Robert T. Jensen
National Institutes of Health/National Institute of
I. Ilie Diabetes and Digestive and Kidney Diseases, Bethesda,
Ìuliu Hatieganu' University of Medicine and Pharmacy, MD, United States
Cluj Napoca, Romania
Susana Jiménez-Murcia
E.A. Iliescu University Hospital of Bellvitge-IDIBELL, Barcelona,
Queen's University, Kingston, ON, Canada Spain
Frédéric Illouz Dipesalema Joel
University Hospital of Angers, Angers, France University of Botswana, Gaborone, Botswana
Frediano Inzani
Fjola Johannesdottir
Catholic University – IRCCS Fondazione Policlinico
Beth Israel Deaconess Medical Center, Boston, MA,
Universitario A. Gemelli, Roma, Italy
United States; and Harvard Medical School, Boston,
Richard Ivell MA, United States
University of Nottingham, Nottingham, United Kingdom
Anders H. Johnsen
Maitane Izaguirre Copenhagen University Hospital, Copenhagen, Denmark
Metabolic Research Laboratory, University of Navarra,
Pamplona, Spain Pamela Jones
Massachusetts General Hospital, Boston, MA, United
Jarmo Jääskeläinen States
University of Eastern Finland and Kuopio University
Hospital, Kuopio, Finland Nathalie Josso
Pierre and Marie Curie University, Paris, France
Niklas Rye Jørgensen
Rigshospitalet, Glostrup, Denmark; and University of Emmanuel Jouanneau
Southern Denmark, Odense, Denmark Groupement Hospitalier Est, Bron, France
xxx List of Contributors
Anne Jouinot Elena Kaschina

Paris Descartes University, Paris, France CharitéF Medicine University Berlin, Berlin, Germany;
and Berlin Institute of Health, Berlin, Germany
Anders Juul
University of Copenhagen, Copenhagen, Denmark Rachel R. Kaspari
Yale School of Medicine, New Haven, CT, United States
Josef Kö hrle
Charité–Medicine University Berlin, Berlin, Humboldt Claudia Katschnig
University of Berlin, Berlin, Germany; Berlin Institute of Pediatric Endocrine Center Zurich (PEZZ), Zurich,
Health, Institute of Experimental Endocrinology, Berlin, Switzerland
Germany Harshini Katugampola
Great Ormond Street Hospital for Children NHS
Agnė Kadusauskienė
Foundation Trust, London, United Kingdom
Lithuania Electron Kebebew
National Cancer Institute, Bethesda, MD, United States;
Gregory Kaltsas and The George Washington University, Washington,
National and Kapodistrian University of Athens, Athens, DC, United States
Greece
Daniel M. Kemp
Archana Kamalakar Massachusetts General Hospital, Boston, MA, United
Emory University, Atlanta, GA, United States; University States; and Harvard University, Boston, MA, United
of Arkansas for Medical Sciences, Little Rock, AR, States
United States; and Texas A& M University, College
Ivana Kholová
Station, TX, United States
Tampere University, Tampere, Finland
Chen Kan Wieland Kiess
Anhui Medical University, Hefei, China University of Leipzig, Leipzig, Germany
Lixin Kan John Paul Kilday
Anhui Medical University, Hefei, China; and Royal Manchester Children's Hospital, Manchester,
Northwestern University, Chicago, IL, United States United Kingdom
John A. Kanis Andreas Kjær
University of Sheffield Medical School, Sheffield, United Nuclear Medicine & PET, ENETS NET CoE,
Kingdom; and Catholic University of Australia, Rigshospitalet, University of Copenhagen, Copenhagen,
Melbourne, VIC, Australia Denmark
Vijayarangan G. Kannian Marianne Klose

Oxford University Hospitals NHS Foundation Trust, Copenhagen University Hospital, Copenhagen, Denmark
Oxford, England Ulrich Knigge
ENETS NET Center of Excellence (CoE), Rigshospitalet,
V. Kantorovich
University of Copenhagen, Copenhagen, Denmark
University of Connecticut Health Center, Farmington,
CT, United States; and National Institutes of Health, Christian A. Koch
Bethesda, MD, United States Technical University of Dresden, Dresden, Germany;
and Medicover MVZ Oldenburg, Oldenburg, Germany
Kung-Ting Kao
Royal Hospital for Children, Glasgow, United Kingdom X. Kodji
Niki Karavitaki
Institute of Metabolism and Systems Research, College of Kamila Kolanska
Medical and Dental Sciences, University of Birmingham, Sorbonne University, Paris, France
Birmingham, United Kingdom; and Centre for Efstratios M. Kolibianakis
Endocrinology, Diabetes and Metabolism, Birmingham Aristotle University of Thessaloniki, Thessaloniki, Greece
Health Partners, Birmingham, United Kingdom
Anne-Sophie C.A.M. Koning
Gerard Karsenty Leiden University Medical Center, Leiden, The
Columbia University, New York, NY, United States Netherlands
List of Contributors xxxi
George Kontogeorgos André Lacroix

``George Gennimatas'' General Hospital of Athens, Endocrine Division and Research Center, Centre
Athens, Greece; National and Kapodistrian University of hospitalier de l'Université de Montréal (CHUM),
Athens, Athens, Greece; and University of Toronto, Montreal, QC, Canada
Toronto, ON, Canada
Svetlana Lajic
John J. Kopchick Karolinska Institute at Karolinska University Hospital,
Ohio University, Athens, OH, United States Stockholm, Sweden
Maŕ ta Korbonits Elizabeth M. Lamos

Queen Mary University of London, London, United University of Maryland School of Medicine, Baltimore,
Kingdom MD, United States
Olympia Koulouri Fabio Lanfranco

University of Cambridge, Cambridge, United Kingdom; University of Turin, Turin, Italy
and National Institute for Health Research Cambridge
Bente L. Langdahl
Biomedical Research Centre, Cambridge, United
Aarhus University Hospital, Aarhus, Denmark
Kingdom
Seppo W. Langer
Stavroula Kousteni ENETS NET CoE, Rigshospitalet, University of
Columbia University, New York, NY, United States Copenhagen, Copenhagen, Denmark
Jolanta Krajewska A. Lania
Maria Sklodowska-Curie Memorial Institute-Cancer University of Milan, Milan, Italy
Center, Gliwice, Poland
E. Laspa
Csilla Krausz University Hospital of Ioannina, Ioannina, Greece
Guido Lastra
Berit Kriströ m University of Missouri, Columbia, MO, United States
Umeå University, Umeå, Sweden
Ana Claudia Latronico
Helen Kroening University of São Paulo, São Paulo, Brazil
Vincent Laudet
Abraham A Kroon Sorbonne University, Banyuls-sur-Mer, France
Maastricht University Medical Center, Maastricht, The
Netherlands S. Lauhon
Heiko Krude
Charité–Medicine University, Berlin, Germany; and Michaël R. Laurent
Institute of Experimental Pediatric Endocrinology, Berlin, University Hospitals Leuven, Leuven, Belgium
Germany Fabio Lauria
National Research Council of Italy, Avellino, Italy
George A. Kuchel
University of Connecticut Health Center, Farmington, John H. Lazarus
CT, United States Institute of Molecular and Experimental Medicine,
Cardiff University, Cardiff, United Kingdom; and
Alexandra Kulle
University Hospital of Wales, Cardiff, United Kingdom
Christian-Albrechts University of Kiel (CAU), Kiel,
Germany; and University Hospital of Schleswig-Holstein Albert Lecube
(UKSH), Kiel, Germany University Hospital Arnau de Vilanova, Lleida, Spain;
Obesity, Diabetes and Metabolism Research Group
Ioannis Kyrou (ODIM), Lleida Biomedical Research Institute
Harokopio University, Athens, Greece; Aston University, (IRBLleida), Lleida, Spain; and University of Lleida,
Birmingham, United Kingdom; University of Warwick, Lleida, Spain
Coventry, United Kingdom; and University Hospitals
Coventry and Warwickshire NHS Trust, Coventry, Benjamin Z. Leder
United Kingdom Harvard Medical School, Boston, MA, United States
xxxii List of Contributors
E.C.-H. Lee V. Llorente-Cortés

University of Connecticut, Storrs, CT, United States Cardiovascular Research Center, CSIC-ICCC Hospital
Santa Creu I Sant Pau, Barcelona, Spain
Peter Lee
Penn State Hershey Medical Center, Hershey, PA, Jay S. Loeffler
United States Massachusetts General and Harvard Medical School,
Boston, MA, United States
Christoph Lees
Queen Charlotte's and Chelsea Hospital, London, United Marc Lombes̀
Kingdom; and Imperial College London, London, United University Paris-Sud, University of Paris-Saclay, Le
Kingdom Kremlin-Bicet̂ re, France; and Bicet̂ re Hospital, Le
Kremlin Bicet̂ re, France
̀ vre
Pierre J. Lefeb
University of Lieg̀ e, Lieg̀ e, Belgium Lindsey A. Loomba-Albrecht
University of California Davis, Davis, CA, United States
Lisa-Marie Legault
University of Montreal, Montreal, QC, Canada Miguel Ló pez
́ , Carlos III
CIBER Fisiopatología Obesidad y Nutricion
Jacques W.M. Lenders Health Institute, Madrid, Spain; and University of
Radboud University Medical Center, Nijmegen, The Santiago de Compostela (USC), Santiago de
Netherlands; and Technical University Dresden, Compostela, Spain
Dresden, Germany
Carolina López-Cano
Livia Lenzini University Hospital Arnau de Vilanova, Lleida, Spain;
University of Padua, Padua, Italy Obesity, Diabetes and Metabolism Research Group
A.M. Leung (ODIM), Lleida Biomedical Research Institute
Division of Endocrinology, UCLA David Geffen School (IRBLleida), Lleida, Spain; and University of Lleida,
of Medicine, Los Angeles, CA United States Lleida, Spain
Stafford Lightman Isabel Losano

University of Bristol, Bristol, United Kingdom University of Turin, Turin, Italy
Padiporn Limumpornpetch David A. Lovejoy

University of Leeds, Leeds, United Kingdom; and Prince University of Toronto, Toronto, ON, Canada
of Songkla University, Songkhla, Thailand María Lozano-Madrid
M. Link Carlos III Health Institute, Madrid, Spain; and
University of Utah, Salt Lake City, UT University Hospital of Bellvitge-IDIBELL, Barcelona,
Spain
Benjamin A. Lipsky
University of Washington, Seattle, WA, United States; Gertrud Lund
and Veterans Affairs Puget Sound Health Care System, CINVESTAV Irapuato Unit, Irapuato, Gto, Mexico
Seattle, WA, United States Elena Lundberg
Saúl Lira-Albarran Umeå University, Umeå, Sweden
National Institute of Medical Sciences and Nutrition SZ Aldons J. Lusis
(INCMNSZ), Mexico City, Mexico University of California Los Angeles, Los Angeles, CA,
United States
Kirstie Lithgow
University of Calgary, Calgary, AB, Canada Lorenza Macrina
IRCCS San Raffaele Scientific Institute, Milan, Italy
Peter Y. Liu
Clinical and Translation Science Institute, Harbor-UCLA Filippo Maffezzoni
Medical Center and Los Angeles Biomedical Research University of Brescia, Brescia, Italy
Institute, Torrance, CA, United States
Mario Maggi
Sarantis Livadas University of Florence, Florence, Italy; and Istituto
University of Athens, Athens, Greece Nazionale Biostrutture e Biosistemi, Rome, Italy
Clare H. Llewellyn M. Maghnie
University College London, London, United Kingdom University of Genova, Genova, Italy
List of Contributors xxxiii
Amita Mahajan Roxana Marino

University of Calgary, Calgary, AB, Canada Hospital de Pediatría Garrahan, Buenos Aires, Argentina
Eamonn R. Maher Gabriel V. Markov
Cambridge Biomedical Campus, Cambridge, United Sorbonne University, Banyuls-sur-Mer, France
Kingdom
Laura Marroquí
Virginie Maillard Miguel Hernan ́ dez University of Elche and CIBERDEM,
PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly, Alicante, Spain
France
Gary R. Marshall
Katharina M. Main University of Pittsburgh School of Medicine, Pittsburgh,
University of Copenhagen, Copenhagen, Denmark PA, United States
Gabriel M. Makhlouf Ritzén E. Martin
Virginia Commonwealth University, Richmond, VA, Karolinska Institute, Stockholm, Sweden
United States
Laetitia Martinerie
Konstantinos Makris
University Paris-Sud, University of Paris-Saclay, Le
KAT General Hospital, Athens, Greece; and University of
Kremlin-Bicet̂ re, France; Service d'Endocrinologie
Athens, Athens, Greece
Pédiatrique, Hop̂ ital Robert Debré, Paris, France; and
Willy J. Malaisse Paris Diderot University, Paris, France
Free University of Brussels, Brussels, Belgium
Antoine Martinez
J. Maletkovic CNRS, INSERM, Clermont Auvergne University,
UCLA School of Medicine, Los Angeles, CA, United Clermont-Ferrand, France
States
Daniel B. Martinez-Arguelles
Federico Mallo Ferrer McGill University, Montreal, QC, Canada
Biomedical Research Center (CINBIO), University of
Vigo, Vigo, Spain Sergio Martinez-Hervas
University of Valencia, Valencia, Spain; and
Nú ria Mallorquí-Bagué CIBERDEM-Spanish Biomedical Research Centre in
Carlos III Health Institute, Madrid, Spain; and Diabetes and Associated Metabolic Disorders, ISCIII,
University Hospital of Bellvitge-IDIBELL, Barcelona, Madrid, Spain
Spain
Enio Martino
Meera Mallya University of Pisa, Pisa, Italy
Cambridge University Hospitals NHS Foundation Trust,
Cambridge, United Kingdom Katia Maruca
Giuseppe Mancia
University of Milan-Bicocca, Monza, Italy George Mastorakos
National and Kapodistrian University of Athens,
Jacqueline Mandelbaum Aretaieion Hospital, Athens, Greece
Tenon Hospital, Paris, France; and Pierre and Marie
Curie University, Paris, France Yuji Matsuzawa
Sumitomo Hospital, Osaka, Japan
Massimo Mannelli
University of Florence, Florence, Italy Gherardo Mazziotti
Carlo Poma Hospital, Mantova, Italy
Franco Mantero
University of Padua, Padua, Italy Eugene V. McCloskey
Paolo Manunta MRC Arthritis Research UK Centre for Integrated
University Vita-Salute San Raffaele, Milan, Italy Research in Musculoskeletal Aging, Metabolic Bone
Center, Northern General Hospital, Sheffield, United
Claudio Marcocci Kingdom; University of Sheffield, Sheffield, United
University of Pisa, Pisa, Italy; and University Hospital of Kingdom; and University of Sheffield Medical School,
Pisa, Pisa, Italy Sheffield, United Kingdom
xxxiv List of Contributors
Timothy McClure Katrina M. Mirabito Colafella

Lefrak Center for Robotic Surgery, Weill Cornell Erasmus MC, Rotterdam, The Netherlands; and Monash
Medicine, New York, NY, United States University, Melbourne, VIC, Australia
Ken McElreavey Alexander D. Miras
Institut Pasteur, Paris, France Imperial College London, London, United Kingdom
Bruce S. McEwen Philippe Monget
Rockefeller University, New York, NY, United States PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly,
France
Serge McGraw
University of Montreal, Montreal, QC, Canada Danielle Monniaux
PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly,
Christian Meier
France
University Hospital Basel, Basel, Switzerland
Onno C. Meijer Silvia Monticone
Leiden University Medical Center, Leiden, The University of Turin, Turin, Italy
Netherlands Rebecca J. Moon
Berenice B. Mendonca Southampton Children's Hospital, Southampton, United
University of São Paulo, São Paulo, Brazil Kingdom
Gabriele Mertes Stefano Mora

Mü lheim, Germany IRCCS San Raffaele Scientific Institute, Milan, Italy
Gemma Mestre-Bach G. Morana

University Hospital of Bellvitge-IDIBELL, Barcelona, University of Genoa, Genoa, Italy
Spain Rachel C. Morgan
Boyd E. Metzger Indiana University School of Medicine, Indianapolis, IN,
Northwestern University Feinberg School of Medicine, United States
Chicago, IL, United States Alberto Morganti
Ralph G. Meyer Centro Fisiologia Clinica e Ipertensione, Policlinico
Utah State University, Logan, UT, United States Hospital, Milan, Italy; and University of Milan, Milan,
Italy
Heino F.L. Meyer-Bahlburg
New York State Psychiatric Institute, New York, NY, Luigi Mori
United States; and College of Physicians & Surgeons of University of Brescia, Brescia, Italy
Columbia University, New York, NY, United States A. Ross Morton
Mirella L. Meyer-Ficca Queen's University, Kingston, ON, Canada
Utah State University, Logan, UT, United States Howard A. Morris
Dragan Micic University of South Australia, Adelaide, SA, Australia
University of Belgrade, Belgrade, Serbia
Giovanna Motta
Jesús E. Millan
́ Nú ñ ez-Cortes University of Turin, Turin, Italy
Gregorio Marañ on University General Hospital, Madrid,
Pierre Mouriquand
Spain; and Complutense University of Madrid, Madrid,
Hop̂ ital Mer̀ e-Enfant – Claude-Bernard University,
Spain
Lyon, France
́ Pérez
Joaquín J. Millan
Miguel Muñ oz
Complutense University of Madrid, Madrid, Spain
Virgen del Rocío University Hospital, Sevilla, Spain
Paul D. Miller
Maria Teresa Muñ oz
University of Colorado Health Sciences Center, Denver,
University Hospital Niñ o Jesús, Institute of Investigation
CO, United States
La Princesa, Madrid, Spain; and Center for Biomedical
Geltrude Mingrone Research in Network on the Pathophysiology of Obesity
Catholic University, Rome, Italy; and Guy's Campus, and Nutrition (CIBEROBN), Carlos III Health Institute,
King's College London, London, United Kingdom Madrid, Spain
List of Contributors xxxv
Araceli Muñ oz-Garach Atossas Niakan

Virgen de la Victoria Universitary Hospital (IBIMA), University of Tennessee Health Science Center,
Malaga, Spain Memphis, TN, United States
Maria Lorenza Muiesan Nicolas C. Nicolaides
Department of Clinical and Experimental Sciences, National and Kapodistrian University of Athens Medical
University of Brescia, ASST Spedali Civili di Brescia and School, Athens, Greece; and Biomedical Research
Società Italiana dell'Ipertensione, Brescia, Italy Foundation of the Academy of Athens, Athens, Greece
Dick Mul Claus H. Nielsen
Diabeter, Center for Pediatric and Adolescent Diabetes Copenhagen University Hospital (Rigshospitalet),
Care and Research, Rotterdam, The Netherlands Copenhagen, Denmark
Manfred J. Mü ller Henriette S. Nielsen
University of Kiel, Kiel, Germany Copenhagen University Hospital (Rigshospitalet),
Copenhagen, Denmark
Beat Mü ller
Medical University Clinic, Kantonsspital Aarau, Aarau, Lynnette K. Nieman
Switzerland; and University Hospital Basel, Basel, National Institutes of Health (NIH), Bethesda, MD,
Switzerland United States
Paolo Mulatero Sarah M Nikkel
University of Turin, Turin, Italy University of British Columbia, Vancouver, BC, Canada
Tayane Muniz Fighera Charlotte M. Niznik

Federal University of Rio Grande do Sul, Porto Alegre, Northwestern University Feinberg School of Medicine,
Brazil Chicago, IL, United States
K.S. Murthy James D. Nobles

Virginia Commonwealth University, Richmond, VA, Leeds Beckett University, Leeds, United Kingdom
United States Pavel Nockel
Marina Muzza National Cancer Institute, Bethesda, MD, United States
University of Milan, Milan, Italy; and IRCCS Italian Ruben Nogueiras
Auxological Institute, Milan, Italy CIMUS, USC, IDIS, Santiago de Compostela, Spain;
Angel Nadal and Carlos III Health Institute, Madrid, Spain
Miguel Hernan ́ dez University of Elche and CIBERDEM, Ruben Nogueiras
Alicante, Spain ́ , Carlos III
CIBER Fisiopatología Obesidad y Nutricion
Y. Nagayama Health Institute, Madrid, Spain; and University of
Nagasaki University, Nagasaki, Japan Santiago de Compostela (USC), Santiago de
Compostela, Spain
Bimota Nambam
Louisiana State University, Shreveport, LA, United States Anna Nordenströ m
Karolinska Institute at Karolinska University Hospital,
Ruta Navardauskaite Stockholm, Sweden
Lithuania M. Nowak
Medical University of Lublin, Lublin, Poland
M.-L. Névoret
Tsuneo Ogawa
Impeto Medical, San Diego, CA, United States
University of Ottawa, Ottawa, ON, Canada
Markella Nezi
Onyebuchi Okosieme
National and Kapodistrian University of Athens,
Cardiff University, Cardiff, United Kingdom
Aretaieion Hospital, Athens, Greece
Wilma Oostdijk
Brian T. Nguyen
Leiden University Medical Center, Leiden, The
Keck School of Medicine of University of Southern
Netherlands
California, Los Angeles, CA, United States; and Los
Angeles Biomedical Research Institute and Harbor-UCLA Jacques Orgiazzi
Medical Center, Torrance, CA, United States Lyon 1-Claude Bernard University, Lyon, France
xxxvi List of Contributors
Andrés E. Ortiz-Flores Ralf Paschke

University Hospital Ramon ́ y Cajal, Madrid, Spain; University of Calgary, Calgary, AB, Canada
University of Alcala,́ Madrid, Spain; Ramoń y Cajal
Leena Patel
Institute for Health Research IRYCIS, Madrid, Spain;
The University of Manchester, Manchester, United
and Biomedical Research Network Center in Diabetes
Kingdom; and Royal Manchester Children's Hospital,
and Related Metabolic Diseases CIBERDEM, Madrid,
Manchester University Hospitals NHS Trust, Manchester
Spain
Academic Health Science Centre, Manchester, United
Nantia Othonos Kingdom
University of Oxford, Oxford, United Kingdom Heather B. Patisaul
Susan M. Ott North Carolina State University, Raleigh, NC, United
University of Washington, Seattle, WA, United States States
Karel Pacak G. Patti

University of Connecticut Health Center, Farmington, University of Genova, Genova, Italy
CT, United States; and National Institutes of Health, Michael A. Patton
Bethesda, MD, United States St Georges University of London, London, United
Stephanie T. Page Kingdom
University of Washington, Seattle, WA, United States L.J. Pelliniemi
University of Turku, Turku, Finland
Uberto Pagotto
Alma Mater Studiorum University of Bologna, Bologna, Bas Penders
Italy Maastricht University, Maastricht, The Netherlands
Anna Paini Alberto M. Pereira
Department of Clinical and Experimental Sciences, Leiden University Medical Center, Leiden, The
University of Brescia, ASST Spedali Civili di Brescia and Netherlands
Società Italiana dell'Ipertensione, Brescia, Italy Paola Perotti
Stefano Palomba University of Turin, Turin, Italy
Grande Ospedale Metropolitano of Reggio Calabria, Luca Persani
Reggio Calabria, Italy University of Milan, Milan, Italy
George Paltoglou Luca Persani
Great Ormond Street Hospital for Children NHS University of Milan, Milan, Italy; and IRCCS Italian
Foundation Trust, London, United Kingdom Auxological Institute, Milan, Italy
Alessandra Panarotto Panagiota Pervanidou
University of Brescia, Brescia, Italy National and Kapodistrian University of Athens Medical
School, Athens, Greece
Amit V. Pandey
University of Bern, Bern, Switzerland Felice Petraglia
University of Florence, Careggi University Hospital,
Vassilios Papadopoulos Florence, Italy
University of Southern California, Los Angeles, CA,
United States Cindy Pham
Harbor-UCLA Medical Center and Los Angeles
Ralph Papas Biomedical Research Institute, Torrance, CA, United
University of Balamand, Beirut, Lebanon States
Theodora Pappa Eliana Piantanida
National and Kapodistrian University, Athens, Greece University of Insubria, Varese, Italy
Anne-Simone Parent Jean-Yves Picard
University of Lieg̀ e, Lieg̀ e, Belgium; and CHU de Lieg̀ e, Pierre and Marie Curie University, Paris, France
̂ ée, Belgium
Chen
Marie-Eve Piché
Gabriele Parenti Quebec Heart and Lung Institute, Quebec City, QC,
Endocrine Unit, Careggi Hospital, Florence, Italy Canada; Laval University, Quebec City, QC, Canada;
List of Contributors xxxvii
and Oxford Centre for Diabetes, Endocrinology and Soraya Puglisi

Metabolism, University of Oxford, Oxford, United University of Turin, Turin, Italy
Kingdom
Shrey Purohit
Axelle Pintiaux Duke University, Durham, NC, United States
Free University of Brussels (ULB), Brussels, Belgium
Lechosław T. Putowski
Rosario Pivonello Medical University of Lublin, Lublin, Poland
Ivan Quesada
Rosario Pivonello Miguel Hernan ́ dez University of Elche and CIBERDEM,
Federico II University of Naples, Naples, Italy Alicante, Spain
T.M. Plant Ingrid Quevedo Wanichi
University of Pittsburgh School of Medicine, Pittsburgh, University of São Paulo, São Paulo, Brazil
PA, United States; and Magee-Womens Research
Institute, Pittsburgh, PA, United States Rémi Rabasa-Lhoret
Montreal Clinical Research Institute, Montreal, QC,
P-F. Plouin Canada; University of Montreal, Montréal, QC,
Hop̂ ital Européen Georges Pompidou, Paris, France; and Canada; and Montreal Diabetes Research Center,
Paris-Descartes University, Paris, France Montréal, QC, Canada
Genevieve Plu-Bureau Naila Rabbani
Paris-Descartes University, Paris, France University of Warwick, Coventry, United Kingdom
Paul Poirier Jacob Rajfer
Quebec Heart and Lung Institute, Quebec City, QC, David Geffen School of Medicine, Los Angeles, CA,
Canada; and Laval University, Quebec City, QC, United States
Canada
Ewa Rajpert-De Meyts
Snezana Polovina Copenhagen University Hospital (Rigshospitalet),
University Business Academy, Novi Sad, Serbia Copenhagen, Denmark
Constantin Polychronakos Stuart H. Ralston
Research Institute of the McGill University Health University of Edinburgh, Edinburgh, United Kingdom
Centre, Montréal, QC, Canada
S. Ramaswamy
Maguelonne Pons University of Pittsburgh School of Medicine, Pittsburgh,
Hop̂ ital Mer̀ e-Enfant – Claude-Bernard University, PA, United States; and Magee-Womens Research
Lyon, France Institute, Pittsburgh, PA, United States
Giulia M. Pontesilli Amarnath Rambhatla
Alma Mater Studiorum University of Bologna, Bologna, Wayne State University, Detroit, MI, United States
Italy
Oliver J. Rando
Callum Potts University of Massachusetts Medical School, Worcester,
Inova Fairfax Hospital, Falls Church, VA, United States MA, United States
Aleksander Prejbisz Elena Rapizzi
Institute of Cardiology, Warsaw, Poland University of Florence, Florence, Italy
Lakdasa D.K.E. Premawardhana
Å se Krogh Rasmussen
Cardiff University, Cardiff, United Kingdom; and
Copenhagen University Hospital (Rigshospitalet),
University Hospital of Wales, Cardiff, United Kingdom Copenhagen, Denmark
Morton P. Printz
Joanne Rasschaert
University of California San Diego, San Diego, CA,
United States
Giulia Rastrelli
Tomas Prior
Queen Charlotte's and Chelsea Hospital, London, United
Kingdom; and Imperial College London, London, United Verdiana Ravarotto
Kingdom University of Padua, Padova, Italy
xxxviii List of Contributors
Gérald Raverot Bernard Robaire

Groupement Hospitalier Est, Bron, France McGill University, Montréal, QC, Canada
José T. Real Vettor Roberto
University of Valencia, Valencia, Spain; and Center for the Study and the Integrated Treatment of
CIBERDEM-Spanish Biomedical Research Centre in Obesity – Bariatric Unit, University of Padua, Padua,
Diabetes and Associated Metabolic Disorders, ISCIII, Italy
Madrid, Spain
Gary. L. Robertson
Dafydd Aled Rees Northwestern University, Chicago, IL, United States
University Hospital of Wales, Cardiff, United Kingdom;
and Cardiff University, Cardiff, United Kingdom Geoffroy Robin
Department of Endocrine Gynecology and Reproductive
Jean-Yves Reginster Medicine, Lille University Hospital, Lille, France
WHO Collaborating Center for Public Health Aspects of
Musculoskeletal Health and Aging, Lieg̀ e, Belgium; and Elisa Roca
University of Lieg̀ e, Lieg̀ e, Belgium University of Brescia, Brescia, Italy
Ian R. Reid Roberto Rocchi
University of Auckland, Auckland, New Zealand University of Pisa, Pisa, Italy
Giuseppe Reimondo Patrice Rodien
University of Turin, Turin, Italy University Hospital of Angers, Angers, France; and
Martin Reincke University of Angers, Angers, France
Ludwig Maximilian University of Munich, Munich, B. Rogina
Germany University of Connecticut Health Center, Farmington,
Rodolfo A. Rey CT, United States
R. Gutierrez Children's Hospital, Buenos Aires,
Alan D. Rogol
Argentina
University of Virginia, Charlottesville, VA, United States
Caroline Reynaud
INSERM, Faculty of Medicine Lyon East, Lyon, France Russell D. Romeo
Rockefeller University, New York, NY, United States
Luigi Ricciardiello
Alma Mater Studiorum University of Bologna, Bologna, Susan R. Rose
Italy Cincinnati Children's Hospital Medical Center,
Cincinnati, OH, United States
Guido Rindi
Catholic University – IRCCS Fondazione Policlinico Claudia Agabiti Rosei
Universitario A. Gemelli, Roma, Italy Department of Clinical and Experimental Sciences,
University of Brescia, ASST Spedali Civili di Brescia and
Scott A. Rivkees Società Italiana dell'Ipertensione, Brescia, Italy
University of Florida College of Medicine, Gainesville,
FL, United States Richard Ross
William B. Rizzo
University of Nebraska Medical Center, Omaha, NE, Judith L. Ross
United States Thomas Jefferson University, Philadelphia, PA, United
States
René Rizzoli
WHO Collaborating Center for Public Health Aspects of Marco Rossato
Musculoskeletal Health and Aging, Lieg̀ e, Belgium; and University of Padua, Padua, Italy
Geneva University Hospitals and Faculty of Medicine,
Geneva, Switzerland Gian Paolo Rossi
University of Padua, Padua, Italy
Carolina De Ciuceis Damiano Rizzoni
Department of Clinical and Experimental Sciences, Ermanno Rossi
University of Brescia, ASST Spedali Civili di Brescia and Department of Internal Medicine, IRCCS Santa Maria
Società Italiana dell'Ipertensione, Brescia, Italy Nuova Hospital, Reggio Emilia, Italy
List of Contributors xxxix
Giovanni Maria Rossi Katerina Saltiki

Nephrology Unit, Department of Clinical and National and Kapodistrian University of Athens, Athens,
Experimental Medicine, Parma University Hospital, Greece
Parma, Italy
Massimo Salvetti
Liliya Rostomyan Department of Clinical and Experimental Sciences,
University Hospital Center of Lieg̀ e, Lieg̀ e, Belgium University of Brescia, ASST Spedali Civili di Brescia and
Società Italiana dell'Ipertensione, Brescia, Italy
Katherine Rotker
University of Massachusetts Medical School, Worcester, Mario Salvi
MA, United States Graves' Orbitopathy Center, Fondazione IRCCS Cà
Granda, Milan, Italy; and University of Milan, Milan,
Charlotte Rougier Italy
University of Nice-Sophia-Antipolis, Nice, France
Susan L. Samson
Phillip W. Round Baylor College of Medicine, Houston, TX, United States
Life Sciences Center, Vancouver, BC, Canada
Jaspreet S. Sandhu
Serge Rozenberg Memorial Sloan Kettering Cancer Center, New York,
Free University of Brussels, Brussels, Belgium; and Vrije NY, United States
Universiteit Brussel, Brussels, Belgium
Darleen A. Sandoval
Speranza Rubattu University of Michigan, Ann Arbor, MI, United States;
Sapienza University, Rome, Italy; and IRCCS and University of Cincinnati School of Medicine,
Neuromed, Pozzilli, Italy Cincinnati, OH, United States
Nadia Rucci Daniele Santi

University of L'Aquila, L'Aquila, Italy University of Modena and Reggio Emilia, Modena, Italy
Paola Russo Nora Saraco

National Research Council of Italy, Avellino, Italy Hospital de Pediatría Garrahan, Buenos Aires,
Argentina; and Consejo Nacional de Investigaciones
A.S. Ryan Científicas y Técnicas (CONICET), Argentina
University of Maryland School of Medicine, Baltimore,
MD, United States Robert M. Sargis
University of Illinois at Chicago, Chicago, IL, United
Fiona J. Ryan States
Oxford University Hospitals NHS Foundation Trust,
Theo C.J. Sas
Oxford, England
Erasmus Medical Center – Sophia Children's Hospital
Lars Sävendahl and Diabeter, Rotterdam, The Netherlands
Karolinska Institutet, Stockholm, Sweden
Martin O. Savage
Chiara Sabbadin Barts and the London School of Medicine and Dentistry,
University of Padua, Padua, Italy London, United Kingdom
Azeez Salawu Mesut Savas

University of Sheffield, Sheffield, United Kingdom Erasmus MC, University Medical Center Rotterdam,
Rotterdam, The Netherlands
Salem A. Salem
University of Tennessee Health Science Center, Camilla Schalin-Jäntti
Memphis, TN, United States Endocrinology, Helsinki University and Helsinki
University Hospital, Helsinki, Finland
Nicola Salituro
Desmond Schatz
Alma Mater Studiorum University of Bologna, Bologna,
University of Florida, Gainesville, FL, United States
Italy
André J. Scheen
Maria Salomon Estebanez
University of Lieg̀ e, Lieg̀ e, Belgium
Royal Manchester Children's Hospital, Manchester,
United Kingdom; and University of Manchester, Jens M. Scherpe
Manchester, United Kingdom University of Cambridge, Cambridge, United Kingdom
xl List of Contributors
Stefan Schlatt Rebecca A. Simmons

Institute of Reproductive and Regenerative Biology, University of Pennsylvania, Philadelphia, PA, United
Mü nster, Germany States
Peter N. Schlegel Tommaso Simoncini
Weill Cornell Medicine, New York, NY, United States University of Pisa, Pisa, Italy
Nadia Schoenmakers Manuela Simoni

University of Cambridge Metabolic Research University of Modena and Reggio Emilia, Modena, Italy
Laboratories, Cambridge, United Kingdom Marco Simonini
Anna Scholz University Vita-Salute San Raffaele, Milan, Italy
University Hospital of Wales, Cardiff, United Kingdom Andrew Sinclair
Murdoch Children's Research Institute, Melbourne, VIC,
R.K. Semple
Australia
University of Cambridge Metabolic Research
Laboratories, Cambridge, United Kingdom Randal A. Skidgel
University of Illinois College of Medicine, Chicago, IL,
Luisa M. Seoane United States
Complejo Hospitalario Universitario de Santiago de
Compostela (CHUS/SERGAS), A Coruñ a, Spain; and Enrico Solcia
CIBER Fisiopatología Obesidad y Nutricioń , Carlos III University of Pavia – IRCCS Fondazione Policlinico San
Health Institute, Madrid, Spain Matteo, Pavia, Italy
Gino Seravalle Charlotte Sonigo

Italian Auxological Institute, IRCCS, Milan, Italy Service de Médecine de la Reproduction et Préservation
de la Fertilité, Jean Verdier Hospital, Bondy, France;
Muhammad Shahreyar University Paris XIII, Bobigny, France; and Unité Inserm
University of Tennessee Health Science Center, U1185, University Paris-Sud, Le Kremlin-Bicet̂ re, France
Memphis, TN, United States
Daniela Sorriento
E. Shane University of Naples, Napoli, Italy
Columbia University Medical Center, New York, NY,
Delphine Spruyt
United States
A.M. James Shapiro Rajini Sreenivasan
University of Alberta, Edmonton, AB, Canada Murdoch Children's Research Institute, Melbourne, VIC,
Swati Sharma Australia
Institute of Reproductive and Regenerative Biology, Ashok K. Srivastava
Mü nster, Germany Montreal Diabetes Research Center, Montreal, QC,
A. Shulkes Canada; CHUM-Research Center (CRCHUM),
University of Melbourne, Melbourne, VIC, Australia Montreal, QC, Canada; and University of Montreal,
Montreal, QC, Canada
Alfonso Siani
Ulrike M. Steckelings
National Research Council of Italy, Avellino, Italy
University of Southern Denmark, Odense, Denmark
Mark Sigman M.S. Stem
Warren Alpert School of Medicine of Brown University, University of Michigan, Ann Arbor, MI, United States
Providence, RI, United States
Andreas Stengel
Joana C. Silva Medical University Hospital Tübingen, Tü bingen,
Hospital of Santa Maria, Lisbon, Portugal Germany
Leticia F. Silveira Alexandra Stephenson
Universidade Federal de Minas Gerais, Belo Horizonte, University of Calgary, Calgary, AB, Canada
Brazil
Trevor Steward
Chiara Simeoli University Hospital of Bellvitge-IDIBELL, Barcelona,
University of Naples Federico II, Naples, Italy Spain
List of Contributors xli
Paul M. Stewart Emily D. Szmuilowicz

University of Leeds, Leeds, United Kingdom Northwestern University Feinberg School of Medicine,
Chicago, IL, United States
Kirstine Stochholm
Aarhus University Hospital, Aarhus C, Denmark Antoine Tabarin
S.D. Stocker University Hospital of Bordeaux, Bordeaux, France
Penn State University College of Medicine, Hershey, PA, Vafa Tabatabaie
United States Albert Einstein College of Medicine, Bronx, NY, United
Helen L. Storr States
Barts and the London School of Medicine and Dentistry,
Stefano Taddei
Michael Stowasser
University of Queensland Diamantina Institute, Rieko Tadokoro-Cuccaro
Brisbane, QLD, Australia University of Cambridge, Cambridge, United Kingdom
Constantine A. Stratakis Nadine Taleb

Eunice Kennedy Shriver National Institute of Child Montreal Clinical Research Institute, Montreal, QC,
Health and Human Development, National Institutes of Canada; and University of Montreal, Montréal, QC,
Health, Bethesda, MD, United States Canada
Pasquale Strazzullo Timothy Shao Ern Tan

University of Naples Federico II, Naples, Italy Singapore General Hospital, Singapore
E.M. Stricker Maria L. Tanda
University of Pittsburgh, Pittsburgh, PA, United States University of Insubria, Varese, Italy
Dennis M. Styne Basil C. Tarlatzis
University of California Davis, Davis, CA, United States Aristotle University of Thessaloniki, Thessaloniki, Greece
Savitha Subramanian Peter Taylor
University of Washington, Seattle, WA, United States Cardiff University, Cardiff, United Kingdom
Yao Sun
Evangelos Terpos
University of Tennessee Health Science Center,
Memphis, TN, United States
Greece
Martin I. Surks
Albert Einstein College of Medicine, Bronx, NY, United Massimo Terzolo
States University of Turin, Turin, Italy
Larry J. Suva Anna Teti

Emory University, Atlanta, GA, United States; University University of L'Aquila, L'Aquila, Italy
of Arkansas for Medical Sciences, Little Rock, AR, Martina Tetti
United States; and Texas A& M University, College University of Turin, Turin, Italy
Ajay Thankamony
A.F. Sved
Cambridge University Hospitals NHS Foundation Trust,
University of Pittsburgh, Pittsburgh, PA, United States
Cambridge, United Kingdom
T. Svingen
Technical University of Denmark, Søborg, Denmark Marily Theodoropoulou
Ludwig Maximilian University of Munich, Munich,
Brooke Swearingen Germany
Massachusetts General Hospital, Boston, MA, United
States Christopher J. Thompson
RCSI Medical School, Dublin, Ireland; and Beaumont
Ronald Swerdloff Hospital, Dublin, Ireland
Clinical and Translation Science Institute, Harbor-UCLA
Medical Center and Los Angeles Biomedical Research Paul J. Thornalley
Institute, Torrance, CA, United States University of Warwick, Coventry, United Kingdom
xlii List of Contributors
Francisco J. Tinahones Giovanni Tuccari

Virgen de la Victoria Universitary Hospital (IBIMA), University of Messina, Messina, Italy
Malaga, Spain
Michael L. Tuck
Jeremy Tomlinson David Geffen UCLA School of Medicine, Los Angeles,
University of Oxford, Oxford, United Kingdom CA, United States
M. Tonacchera Eva Tudurí
University of Pisa, Pisa, Italy Miguel Hernan ́ dez University of Elche and CIBERDEM,
Jorma Toppari Alicante, Spain
Institute of Biomedicine, Research Center for Integrative
Jaakko Tuomilehto
Physiology and Pharmacology, University of Turku,
Dasman Diabetes Institute, Dasman, Kuwait
Turku, Finland; and Department of Pediatrics, Turku
University Hospital, Turku, Finland Adina F. Turcu
Keith Tornheim University of Michigan, Ann Arbor, MI, United States
Boston University School of Medicine, Boston, MA, Jennifer J. Tuscher
United States University of Wisconsin-Milwaukee, Milwaukee, WI,
Stephanie Toth-Manikowski United States
Johns Hopkins University, Baltimore, MD, United States
Suma Uday
Philippe Touraine Birmingham Women's and Children's NHS Foundation
Sorbonne University, Paris, France Trust, Birmingham, United Kingdom; and IMSR,
University of Birmingham, Birmingham, United
Giorgio Treglia
Kingdom
Ente Ospedaliero Cantonale, Bellinzona, Switzerland;
and Oncology Institute of Southern Switzerland, Estrellita Uijl
Bellinzona, Switzerland Erasmus MC, University Medical Center Rotterdam,
Pierpaolo Trimboli Rotterdam, The Netherlands
Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Alfredo Ulloa-Aguirre
and Oncology Institute of Southern Switzerland, National University of Mexico (UNAM-CIC), Mexico
Bellinzona, Switzerland City, Mexico; and National Institute of Medical Sciences
Nicholas A. Tritos and Nutrition SZ (INCMNSZ), Mexico City, Mexico
Massachusetts General and Harvard Medical School,
Xabier Unamuno
Boston, MA, United States
University of Navarra, Pamplona, Spain
Jacqueline Trouillas
Groupement Hospitalier Est, Bron, France; and Claude Thomas Unger
Bernard University, Lyon, France Maastricht University, Maastricht, The Netherlands
Jacqueline Trouillas Thomas J. Upton

Groupement Hospitalier Est, Bron, France University of Otago, Dunedin, New Zealand; and
University of Bristol, Bristol, United Kingdom
Joy N. Tsai
Harvard Medical School, Boston, MA, United States Inbal Uri
Hadassah-Hebrew University Medical Center, Jerusalem,
A. Tsatsoulis
Israel
University Hospital of Ioannina, Ioannina, Greece
Constantine Tsigos Svetlana Uzbekova
Harokopio University, Athens, Greece PRC, CNRS, IFCE, INRA, University of Tours, Nouzilly,
France
Apostolos V. Tsolakis
Karolinska Institute, Stockholm, Sweden; and Karolinska Daniel Vaiman
University Hospital, Stockholm, Sweden Paris-Descartes University, Paris, France
Marina Tsoli Janielle A.E.M. van Alfen-van der Velden
National and Kapodistrian University of Athens, Athens, Radboud University Medical Center – Amalia Children's
Greece Hospital, Nijmegen, The Netherlands
List of Contributors xliii
Diana van Heemst Helena E. Virtanen

Leiden University Medical Center, Leiden, The University of Turku, Turku, Finland
Netherlands
Roberto Vita
Elisabeth F.C. van Rossum University of Messina, Messina, Italy
Erasmus MC, University Medical Center Rotterdam,
Rotterdam, The Netherlands Mette Viuff
Aarhus University Hospital, Aarhus C, Denmark
Mark P.J. Vanderpump
The Physicians' Clinic, London, United Kingdom Massimo Volpe
Sapienza University, Rome, Italy; and IRCCS
Guia Vannucchi Neuromed, Pozzilli (Is), Italy
Fondazione IRCCS Cà Granda, Milan, Italy; and
University of Milan, Milan, Italy Antonis Voutetakis
University of Athens, Athens, Greece
Silvia Vannuccini
University of Florence, Careggi University Hospital, P.C.A.J. Vroomen
Florence, Italy; and University of Siena, Siena, Italy University Medical Centre Groningen, Groningen, The
Netherlands
Samuel Vasikaran
Fiona Stanley Hospital, Murdoch, WA, Australia Christina Wang
Alexandre Vasiljevic David Geffen School of Medicine at UCLA, Los Angeles,
Groupement Hospitalier Est, Bron, France CA, United States; Department of Medicine, Harbor-
UCLA Medical Center, Torrance, CA, United States;
Franco Veglio and Los Angeles Biomedical Research Institute (LA
University of Turin, Turin, Italy BioMed), Torrance, CA, United States
Joseph G. Verbalis Leanne Ward
Georgetown University Medical Center, Washington, University of Ottawa, Ottawa, ON, Canada; and
DC, United States Children's Hospital of Eastern Ontario, Ottawa, ON,
Rasa Verkauskiene Canada
Leonard Wartofsky
Lithuania
MedStar Washington Hospital Center, Georgetown
Peter Vestergaard University School of Medicine, Washington, DC, United
Aalborg University Hospital, Aalborg, Denmark; and States
Steno Diabetes Center North Jutland, Aalborg, Denmark
Charity L. Washam
Roberto Vettor Emory University, Atlanta, GA, United States; University
University of Padua, Padua, Italy of Arkansas for Medical Sciences, Little Rock, AR,
United States; and Texas A& M University, College
Giuseppe Vezzoli
Valentina Vicennati Ari J. Wassner
Alma Mater Studiorum University of Bologna, Bologna, Boston Children's Hospital, Boston, MA, United States
Italy Yui Watanabe
Say Viengchareun University of Miami Miller School of Medicine, Miami,
University of Paris-Sud, University of Paris-Saclay, Le FL, United States
Kremlin-Bicet̂ re, France Torquil Watt
Francesc Villarroya Copenhagen University Hospital, Copenhagen, Denmark
University of Barcelona, Barcelona, Catalonia, Spain;
Susan M. Webb
Sant Joan de Déu Research Institute, Esplugues de
Centro de Investigacioń Biomédica en Red de
Llobregat, Catalonia, Spain; and CIBER Fisitopatología
Enfermedades Raras (CIBER-ER, Unidad 747), ISCIII,
de la Obesidad y Nutricioń , Spain
Barcelona, Spain; Research Center for Pituitary Diseases,
A.I. Vinik Hospital Sant Pau, IIB-Sant Pau, Barcelona, Spain; and
Eastern Virginia Medical School, Norfolk, VA, United Autonomous University of Barcelona (UAB), Barcelona,
States Spain
xliv List of Contributors
Karl T. Weber Bu B. Yeap

University of Tennessee Health Science Center, University of Western Australia, Perth, WA, Australia;
Memphis, TN, United States and Fiona Stanley Hospital, Perth, WA, Australia
Roy E. Weiss Jacques Young
University of Miami Miller School of Medicine, Miami, University of Paris-Sud and Bicet̂ re Hospital, Le
FL, United States Kremlin-Bicet̂ re, France
Margaret E. Wierman Morag J. Young
University of Colorado Anschutz Medical Center and Hudson Institute of Medical Research, Clayton, VIC,
Eastern Colorado Veterans Affairs Health Care System, Australia
Aurora, CO, United States
Lisa Younk
Dagmar Wilhelm University of Maryland School of Medicine, Baltimore,
University of Melbourne, Parkville, VIC, Australia MD, United States
Ingrid C.E. Wilkinson
Fiona Yuen
Barts and the London School of Medicine and Dentistry,
Clinical and Translation Science Institute, Harbor-UCLA
Medical Center and Los Angeles Biomedical Research
Sigal A. Willner Institute, Torrance, CA, United States
University of California Irvine, Irvine, CA, United States
Silvio Zaina
Sunil J. Wimalawansa University of Guanajuato, Leoń , Mexico
Cardio Metabolic Institute, New Jersey, NJ, United
States Wouter T. Zandee
Erasmus Medical Center, Rotterdam, The Netherlands
William Winter
University of Florida, Gainesville, FL, United States Sofia Zanin
University of Padua, Padua, Italy
Bettina F. Winzeler
University Hospital Basel, Basel, Switzerland Evangelia Zapanti
Alexandra Hospital, Athens, Greece
Selma F. Witchel
Children's Hospital of Pittsburgh, UPMC, Pittsburgh, ́
Teresa Zariñ an
PA, United States National University of Mexico (UNAM-CIC), Mexico
City, Mexico; and National Institute of Medical Sciences
Sze Choong Wong
and Nutrition SZ (INCMNSZ), Mexico City, Mexico
Royal Hospital for Children, Glasgow, United Kingdom
Steven Wood Marco Zavattaro
University of Sheffield, Sheffield, United Kingdom University of Turin, Turin, Italy
Ryan Woodman Dongyun Zhang

University of Missouri, Columbia, MO, United States University of California Los Angeles, Los Angeles, CA,
United States
Frederick CW Wu
University of Manchester, Manchester, United Kingdom Yining Zhao
University Hospital Erlangen, Erlangen, Germany
Shizuya Yamashita
Rinku General Medical Center, Osaka, Japan; and Stephan Zipfel
Osaka University Graduate School of Medicine, Osaka, Medical University Hospital Tübingen, Tü bingen,
Japan Germany
PREFACE
The first Edition of the Encyclopedia of Endocrine Diseases was published in 2004. Because of the enormous development in the field
it was found important to produce a completely revised and updated Second Edition of the Encyclopedia. The new Edition is a
must-have one-stop reference covering every aspect of the physiological background, pathogenesis, clinical diagnostics, and
therapeutic aspects of the wide array of endocrine and related metabolic diseases.
The functional balance of the body (homeostasis) is maintained by two regulatory circuits, i.e., the nervous and the endocrine
systems. Among the most complex constructs in the body, the endocrine system comprises a group of glands that secrete
hormones directly into the bloodstream, where they reach their specific receptors in other parts of the body, evoking specific
intracellular signaling pathways leading to their biological effect. Many classically non-endocrine organs (e.g., the heart) have also
turned out to have endocrine functions. The endocrine system maintains and regulates the body’s homeostasis by using hormones
to control metabolism, temperature, biological cycles, internal fluid volume, reproduction, growth, body composition, and
development. The system is a marvel when functioning optimally, i.e., maintaining the body homeostasis. Unfortunately, there is
a myriad of ways these processes, actions, and functions can go awry, resulting in various endocrine and metabolic diseases, which
form the over-arching theme of the Encyclopedia.
The Encyclopedia is not meant as a primer on the subject of endocrinology, but instead intended to provide a comprehensive
reference work on the extensive spectrum of diseases and disorders that can occur within the endocrine and metabolic system. The
updated version of this groundbreaking encyclopedia is especially timely, as it covers the dramatic discoveries in the field of
endocrinology and metabolism over the past 10 years, particularly with respect to novel diagnostic techniques and treatment
approaches. In particular, there have been tremendous advancements in our understanding of the molecular basis of endocrine
and metabolic diseases (mutations, epigenetics, signaling), as well as pathogenesis and therapy of the common forms of these
diseases (e.g., diabetes, obesity, and endocrine malignancies).
The Encyclopedia offers a unique source of up-to-date information for the physicians and basic scientists working in the field. It
is an essential resource for every clinician diagnosing and treating endocrine patients. The Encyclopedia also offers the prime
source of information for students of medicine and science around the world, as well as basic research workers in academia, the
pharma industry, and in other areas in need of information on endocrinology and metabolism. It also offers useful information
for the lay public about normal and abnormal functions of hormones.
The Encyclopedia is intended to serve as a useful and comprehensive source of information spanning the many and varied
aspects of the endocrine and metabolic system. The chapters have been written to be accessible to both clinical and nonclinical
readers. The articles have been formatted in similar fashion and each is intended as a stand-alone presentation. Each article begins
with a glossary list defining key terms that may be unfamiliar to the reader and are important for understanding the article. The
body of the article begins with a brief introduction to the subject under discussion, bold headings lead the reader through the text,
and figures and tables explain and illuminate most articles. The main text is followed by referenced citations to provide the reader
with access to additional information on the topic, and cross-references lead the reader to related entries in the encyclopedia. The
relatively short stand-alone articles have allowed us to recruit the best experts available for each topic.
Unlike the first Edition, where the articles were arranged in alphabetical order, the 2nd Edition is arranged in organ-based
thematic order, where each organ-based group of diseases is presented as cluster of articles in the first four volumes. The fifth
volume is a stand-alone compilation of all articles on pediatric endocrinology. The thematic organization gives the reader a better
general view of the coverage of articles on a specific endocrine organ or disease type.
The Second Edition of the Encyclopedia builds of the first edition. Nevertheless, to bring a major reference work with such a
broad scope from initial conception to final publication involved a great deal of planning and organization, together with the
efforts of innumerable individuals. The authors of the first edition were invited to update their earlier texts. If this was not possible,
the Section Editors invited another expert in the topic either to update the previous text or to write a de novo text; the latter
happened in most of these cases. Hence, the Second Edition contains to a large extent totally new information, or at least the
fluency of all texts has been scrutinized. Furthermore, all manuscripts have undergone peer-review arranged by the Section Editors.
Assembling a large volume of articles with the purpose to cover all essential topics of endocrine diseases posed multiple
challenges. Coverage was a significant problem: on one hand some redundancy of the topics was almost impossible to avoid in
places while, on the other, there were inevitable gaps. Some of these arose from late cancellations; others from oversights on our
part. We can only promise to fill these gaps in future editions. We also note that as can be expected for a large multi-author
compilation the individual articles do differ in detail and approach. We considered it more important to allow our experts
substantial latitude in deciding how to present their topics than to apply rigid guidelines.
Most of the editing work of the Encyclopedia has been carried out by a highly competent board of 16 Section Editors, each of
them internationally renowned experts in their respective field within clinical endocrinology. First, the broadest possible list of
topics was compiled, aiming at the best possible coverage. Throughout the editorial process, the Section Editors supervised their
subject area of expertise, recommended and corresponded with fellow editors and article contributors, reviewed the manuscripts,
and continuously helped to refine the final list of topics. This has made the task of the Editor in Chief easy, mainly entailing the
supervision of smooth progress of the project.
Encyclopedia of Endocrine Diseases, Second Edition, Volume 00 doi:10.1016/B978-0-12-812199-3.09005-8 xlv

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