9781405145848_1_pre.qxd 1/31/08 5:35 PM Page i Clinical Endocrine Oncology Clinical Endocrine Oncology, Second Edition. Edited By Ian D. Hay and John A.H. Wass. © 2008 Blackwell Publishing. ISBN: 978-1-4051-4584-8 9781405145848_1_pre.qxd 2/4/08 7:04 PM Page iii Clinical Endocrine Oncology EDITED BY IAN D. HAY, BSc, MB, PhD, FACE, FACP, FRCP, FRCPI (Hon) Professor of Medicine and Dr R.F. Emslander Professor of Endocrinology Research Mayo Clinic College of Medicine; and Consultant in Endocrinology and Internal Medicine Mayo Clinic Rochester, Minnesota, USA JOHN A.H. WASS, MA, MD, FRCP Professor of Endocrinology University of Oxford; and Consultant Physician Churchill Hospital Oxford, UK FOREWORD BY ANTHONY P. WEETMAN, MD, DSc, FRCP, FMedSci Dean of the School of Medicine and Biomedical Sciences University of Sheffield Sheffield, UK SECOND EDITION 9781405145848_1_pre.qxd 1/31/08 5:35 PM Page iv © 2008 by Blackwell Publishing Blackwell Publishing, Inc., 350 Main Street, Malden, Massachusetts 02148-5020, USA Blackwell Publishing Ltd, 9600 Garsington Road, Oxford OX4 2DQ, UK Blackwell Publishing Asia Pty Ltd, 550 Swanston Street, Carlton, Victoria 3053, Australia The right of the Author to be identified as the Author of this Work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. First published 2008 1 2008 Library of Congress Cataloging-in-Publication Data Clinical endocrine oncology/edited by Ian D. Hay, John A. H. Wass.—2nd ed. p. ; cm. Includes bibliographical references and index. ISBN 978-1-4051-4584-8 1. Endocrine glands—Tumors. I. Hay, Ian D. II. Wass, J. A. H. [DNLM: 1. Endocrine Gland Neoplasms. 2. Endocrine System Diseases. 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No warranty may be created or extended by any promotional statements for this work. Neither the publisher nor the author shall be liable for any damages arising herefrom. 9781405145848_1_pre.qxd 1/31/08 5:35 PM Page v Contents List of Contributors, viii Part 2: Thyroid and Parathyroid Tumors Foreword, xiv 13 Assessment of Thyroid Neoplasia, 111 Preface, xv Kristien Boelaert, Jayne A. Franklyn, and Michael Sheppard Endocrinology, the Hertz Brothers, and the History of Cancer, xvi 14 Thyroid and Parathyroid Imaging, 116 Conor J. Heaney and Gregory A. Wiseman Part 1: Endocrine Oncology and Therapeutic 15 Pathogenesis ofThyroid Cancer, 124 Options Jan Zedenius and Theodoros Foukakis 1 Structure and Development of the Endocrine System, 3 16 Papillary Thyroid Carcinoma, 130 John F. Morris Ian D. Hay 2 Epidemiology of Endocrine Tumors, 18 17 Follicular Thyroid Carcinoma, 143 Amanda Nicholson Manisha H. Shah and Matthew D. Ringel 3 Inherited Cancers, Genes, and Chromosomes, 24 18 Anaplastic Thyroid Carcinoma, 155 Emma R. Woodward and Eamonn R. Maher Richard T. Kloos 4 Hormones, Growth Factors, and Tumor Growth, 32 19 Thyroid Lymphoma, 162 Andrew G. Renehan Christopher M. Nutting and Kevin J. Harrington 5 Genetic Counseling and Clinical Cancer Genetics, 41 20 Radiation-induced Thyroid Tumors, 166 Lucy Side David H. Sarne and Arthur Schneider 6 Prospects for Gene Therapy for Endocrine Malignancies, 49 21 Parathyroid Adenomas and Hyperplasia, 172 Christine Spitzweg, Ian D. Hay, and John C. Morris Bart L. Clarke 7 Tumor Targeting, 58 22 Parathyroid Carcinoma, 180 Mona Waterhouse and Ashley B. Grossman Göran Åkerström, Per Hellman, and Peyman Björklund 8 Techniques in Radiation Medicine, 64 P. Nicholas Plowman 9 Interventional Radiology, 70 Part 3: Pituitary and Hypothalamic Lesions Jane Phillips-Hughes and Philip Boardman 23 Molecular Pathogenesis of Pituitary Adenomas, 187 10 Surgical Management of Endocrine Tumors, 78 Ines Donangelo and Shlomo Melmed Gustavo G. Fernandez Ranvier and Orlo H. Clark 11 Endocrine Tumor Markers, 86 24 Functional Assessment of the Pituitary, 194 Stefan K.G. Grebe John S. Bevan 12 General Management of Cancer Patients, 102 25 Imaging of the Pituitary and Hypothalamus, 200 Marcia Hall James V. Byrne v 9781405145848_1_pre.qxd 2/4/08 7:04 PM Page vi Contents 26 Pathology of Tumors of the Pituitary, 215 Part 4: Adrenal and Gonadal Tumors Eva Horvath and Kalman Kovacs 45 Imaging of the Adrenal Glands, 339 27 Surgery for Pituitary Tumors, 222 Anju Sahdev and Rodney H. Reznek Simon A. Cudlip 46 Pheochromocytoma, 354 28 Pituitary Radiotherapy, 231 Andrew Solomon and Pierre Bouloux P. Nicholas Plowman 29 Prolactinomas, 237 47 Peripheral Neuroblastic Tumors, 360 Mary P. Gillam and Mark E. Molitch Bruno De Bernardi, Vito Pistoia, Claudio Gambini, and Claudio Granata 30 Acromegaly, 246 John A.H. Wass 48 Primary Hyperaldosteronism, 370 Mark Sherlock and Paul M. Stewart 31 Cushing’s Disease, 253 John Newell-Price 49 Adrenal Causes of Cushing’s Syndrome, 378 John R. Lindsay and A. Brew Atkinson 32 Non-functioning Pituitary Adenomas and Gonadotropinomas, 262 50 Adrenal Incidentalomas, 384 Maarten O. van Aken, Aart Jan van der Lelij, Maria Verena Cicala, Pierantonio Conton, Anna Patalano, and Steven W.J. Lamberts and Franco Mantero 33 Thyrotropinomas, 268 51 Androgen-secreting Tumors, 390 Paolo Beck-Peccoz and Luca Persani Quirinius Barnor, Tom R. Kurzawinski, and Gerard S. Conway 34 Pituitary Carcinoma, 274 52 Functional Ovarian Tumors, 396 Olaf Ansorge Nia Jane Taylor and Niall Richard Moore 35 Pituitary Incidentalomas, 278 53 Endocrine Aspects of Ovarian Tumors, 404 Karin Bradley John H. Shepherd and Lisa Wong 36 Craniopharyngioma, 282 54 Testicular Germ Cell Cancers, 412 Niki Karavitaki R. Timothy D. Oliver 37 Benign Cysts: Rathke’s Cleft Cysts, Mucoceles, Arachnoid 55 Neoplasia and Intersex States, 421 Cysts, and Dermoid and Epidermoid Cysts, 288 Sabine E. Hannema and Ieuan A. Hughes Niki Karavitaki 56 Gestational Trophoblastic Neoplasia, 430 38 Hypothalamic Hamartomas and Gangliocytomas, 293 Tim Crook and Michael J. Seckl Lawrence A. Frohman 39 Cranial Ependymoma, 298 Part 5: Neuroendocrine Tumors and Silvia Hofer and Michael Brada the Clinical Syndromes 40 Perisellar Tumors including Chordoma, Optic Nerve Glioma, Meningioma, Hemangiopericytoma, and 57 Classification of Neuroendocrine Tumors, 437 Glomus Tumors, 302 Adeel Ansari, Karim Meeran, and Stephen R. Bloom David Choi and Alan Crockard 58 Imaging of Gastrointestinal Neuroendocrine Tumors, 443 41 Pineal Tumors: Germinomas and Non-germinomatous Andrew F. Scarsbrook and Rachel R. Phillips Germ Cell Tumors, 310 Frank Saran and Sharon Peoples 59 Insulinomas and Hypoglycemia, 455 Adrian Vella and F. John Service 42 Cavernous Sinus Hemangiomas, 318 Mark E. Linskey 60 Gastrinomas (Zollinger–Ellison Syndrome), 462 Matthew L. White and Gerard M. Doherty 43 Langerhans’ Cell Histiocytosis, 325 Matthew F. Gorman, Michelle Hermiston, and 61 VIPomas, 469 Katherine K. Matthay Vian Amber and Stephen R. Bloom 44 Pituitary and Hypothalamic Sarcoidosis, 331 62 Glucagonomas, 474 Damian G. Morris and Shern L. Chew Niamh M. Martin, Karim Meeran, and Stephen R. Bloom vi 9781405145848_1_pre.qxd 1/31/08 5:35 PM Page vii Contents 63 Somatostatinomas, 479 76 Syndrome of Inappropriate Antidiuretic Hormone John A.H. Wass Secretion, 556 Rachel K. Crowley and Chris Thompson 64 Lung and Thymic Neuroendocrine Tumors, 482 Dan Granberg and Kjell Öberg 77 Hypercalcemia of Malignancy, 561 Gregory R. Mundy, Babatunde Oyajobi, Susan Padalecki, 65 Carcinoid Syndrome, 488 and Julie A. Sterling Thorvardur R. Halfdanarson and Timothy J. Hobday 78 Syndrome of Ectopic ACTH Secretion, 567 66 Appendiceal and Hindgut Carcinoids, 498 Marie-Laure Raffin-Sanson, Hélène Fierrard, Humphrey J.F. Hodgson and Xavier Bertagna 67 Chemotherapy for Neuroendocrine Tumors, 502 79 Insulin-like Growth Factors and Tumor Hypoglycemia, 576 Rebecca L. Bowen and Maurice L. Slevin Robert C. Baxter 80 Metastatic and Other Extraneous Neoplasms in Part 6: Medical Syndromes and Endocrine Endocrine Organs, 582 Neoplasia Ian D. Buley 81 Endocrine Late Effects of Cancer Therapy, 588 68 Multiple Endocrine Neoplasia Type 1 (MEN 1), 507 Robert D. Murray Cornelis J.M. Lips, Koen M.A. Dreijerink, Gerlof D. Valk, and Jo W.M. Höppener 69 Medullary Thyroid Carcinoma and Associated Multiple Part 7: Endocrine-responsive Tumors Endocrine Neoplasia Type 2, 515 and Female Reproductive Hormone Therapy Clive S. Grant 82 Endocrine-responsive Tumors: Prostate Cancer, 601 70 von Hippel–Lindau Disease, 523 Sarah Ngan, Ana Arance, and Jonathan Waxman Shern L. Chew and Eamonn R. Maher 83 Endocrine Therapy in Breast Cancer Management, 609 71 Neurofibromatosis Type 1, 528 Andrew M. Wardley Vincent M. Riccardi 84 Female Reproductive Hormone Therapy: 72 Carney Complex, 532 Risks and Benefits, 618 Constantine A. Stratakis Toral Gathani, Jane Green, and Valerie Beral 73 McCune–Albright Syndrome, 537 William F. Schwindinger and Michael A. Levine Appendix of conversion units, 623 74 Cowden Syndrome, 545 Index, 627 Ingrid Witters and Jean-Pierre Fryns 75 Paraneoplastic Syndromes, 549 David William Ray Color plate section is found facing p. 364 vii 9781405145848_1_pre.qxd 1/31/08 5:35 PM Page viii List of Contributors Göran Åkerström,MD Robert C. Baxter, PhD, DSc Philip Boardman, MRCP, FRCR Professor, Endocrine Surgery Director, Kolling Institute of Medical Research Consultant Radiologist Department of Surgery University of Sydney Churchill Hospital University Hospital, Uppsala, Sweden Royal North Shore Hospital Oxford, UK St Leonards, NSW, Australia Vian Amber,MBChB, MSc, PhD, Kristien Boelaert, MD, MRCP, PhD MRCPath Paolo Beck-Peccoz, MD Lecturer and MRC Clinician Scientist Department of Metabolic Medicine Department of Medical Sciences Division of Medical Sciences Hammersmith Hospital Campus Fondazione Policlinico IRCCS University of Birmingham Imperial College London Milan, Italy Queen Elizabeth Hospital London, UK Birmingham, UK Valerie Beral, FRSl Adeel Ansari,MD Professor of Epidemiology Pierre-Marc G. Bouloux, BSc, Department of Metabolic Medicine Director, Cancer Epidemiology Unit MBBS(Hons), MRCS, LRCP, MD, FRCP Hammersmith Hospital Campus University of Oxford Professor of Endocrinology Imperial College Oxford, UK Royal Free and University College Medical School London, UK London, UK Xavier Bertagna,MD, PhD Olaf Ansorge,MD, MRCPath Institut Cochin, Université Paris Descartes, Rebecca L. Bowen,BMedSci, Department of Neuropathology CNRS(UMR 8104); BMBS, MRCP John Radcliffe Hospital INSEMR U567; and Specialist Registrar, Medical Oncology Oxford, UK AP-HP, Hôpital Cochin St Bartholomew’s Hospital Paris, France London, UK Ana Arance, MD, PhD Department of Oncology John S. Bevan,MD, FRCPEd Michael Brada The Gary Weston Cancer Centre Consultant Endocrinologist Professor of Clinical Oncology Hammersmith Hospital Department of Endocrinology Academic Unit of Radiotherapy and Oncology London, UK Aberdeen Royal Infirmary The Institute of Cancer Research; and Foresterhill, Aberdeen, Scotland Neuro-Oncology Unit A. Brew Atkinson,DSc, MD, FRCP The Royal Marsden NHS Trust Senior Endocrinologist and Professor Peyman Björklund,MSci London and Sutton, UK of Endocrinology University of Uppsala Regional Centre for Endocrinology Uppsala, Sweden Karin Bradley,BSc, MBBS, MRCP, DPhil and Diabetes Consultant Physician and Endocrinologist Royal Victoria Hospital Stephen R. Bloom,MB ChB, MA, FRCP, Bristol Royal Infirmary Belfast, UK Bristol, UK FRCPath, DSc, MD Professor of Medicine Quirinius Barnor, MRCP Department of Metabolic Medicine Ian D. Buley,FRCPath Department of Endocrinology Imperial College London Consultant Histopathologist University College London Hospitals London, UK Honorary University Fellow Peninsula Medical London, UK School Torbay Hospital Torquay, UK viii 9781405145848_1_pre.qxd 1/31/08 5:35 PM Page ix List of Contributors James V. Byrne,MD, FRCS, FRCR Tim Crook,PhD, MRCP Jayne A. Franklyn,MD, PhD, FRCP, Professor of Neuroradiology Department of Medical Oncology FMedSci Department of Neuroradiology Charing Cross Hospital; and Professor of Medicine University of Oxford Cancer Genetics and Epigenetics Laboratory Department of Medicine John Radcliffe Hospital The Breakthrough Toby Robins Breast Cancer University of Birmingham Oxford, UK Research Centre Birmingham, UK at The Institute of Cancer Research Shern L. Chew,BSc, MBBChir, MD, FRCP London, UK Lawrence A. Frohman,MD Professor of Endocrine Medicine/Consultant Professor Emeritus of Medicine Physician Rachel K. Crowley,MB, MRCPI Section of Endocrinology, Diabetes and St Bartholomew’s Hospital Honorary Lecturer in Endocrinology Metabolism London, UK Academic Department of Diabetes & University of Illinois at Chicago Endocrinology Chicago, lllinois, USA David Choi,MA, MBChB, FRCS(SN), PhD Beaumont Hospital/RCSI Medical School Dublin, Ireland Jean-Pierre Fryns Consultant Neurosurgeon Victor Horsley Department of Neurosurgery Chairman, Genetics Department The National Hospital for Neurology and Simon A. Cudlip,MB,BS, BSc, MD, Center for Human Genetics Neurosurgery FRCS (SN) University Hospital of Leuven London, UK Consultant Neurosurgeon Leuven, Belgium John Radcliffe Hospital Maria Verena Cicala,MD Oxford, UK Claudio Gambini,MD Division of Endocrinology Service of Pathology Department of Medical and Surgical Sciences Bruno De Bernardi,MD Giannina Gaslini Children’s Hospital University of Padua Department of Hematology/Oncology Genova, Italy Padua, Italy Giannina Gaslini Children’s Hospital Genova, Italy Toral Gathani,MRCS(Eng), MBBS(Hons), Orlo H. Clark, MD BSc(Hons) Professor of Surgery Gerard M. Doherty,MD Clinical Research Fellow Department of Surgery NW Thompson Professor of Surgery Cancer Epidemiology Unit University of California, San Francisco Head, Section of General Surgery University of Oxford San Francisco, California, USA Residency Program Director, Surgery Oxford, UK University of Michigan Bart L. Clarke,MD Ann Arbor, Michigan, USA Mary P. Gillam, MD Division of Endocrinology, Metabolism and Division of Endocrinology, Diabetes/ Molecular Medicine Metabolism, and Nutrition Ines Donangelo,MD, PhD Northwestern University Feinberg School Mayo Clinic College of Medicine Cedars-Sinai Research Institute of Medicine Rochester, Minnesota, USA UCLA David Geffen School of Medicine at Chicago, Illinois, USA University of California Los Angeles Pierantonio Conton,MD Los Angeles, California, USA Matthew F. Gorman,MD Division of Endocrinology Clinical Fellow Department of Medical and Surgical Sciences Koen M.A. Dreijerink,MD Department of Pediatrics University of Padua Department of Clinical Endocrinology Division of Hematology/Oncology Padua, Italy University Medical Center University of California, San Francisco Utrecht, The Netherlands UCSF Children’s Hospital Gerard S. Conway,MD, FRCP San Francisco, California, USA Department of Endocrinology Hélène Fierrard University College London Hospitals Unité d’Endocrinologie Claudio Granata,MD London, UK Assistance Publique-Hôpitaux de Paris Service of Radiology Hôpital Ambroise Paré Giannina Gaslini Children’s Hospital Alan Crockard,DSc, FRCS, FDS, Boulogne, France; and Genova, Italy INSERM RCS (Eng), FRCP Victor Horsley Department of Neurosurgery Institut Cochin Dan Granberg,MD, PhD Département Endocrinologie Métabolisme & The National Hospital for Neurology and Department of Medical Sciences and Department Cancer Neurosurgery of Endocrine Oncology Paris, France London, UK University Hospital Uppsala, Sweden Theodoros Foukakis,MD, PhD Department of Oncology Clive S. Grant,MD Karolinska University Hospital Professor of Surgery Stockholm, Sweden Mayo Clinic Rochester, Minnesota, USA ix 9781405145848_1_pre.qxd 2/4/08 7:05 PM Page x List of Contributors Stefan K.G. Grebe, MD, FRACP, DABCC Conor J. Heaney, MD Richard T. Kloos,MD Co-director, Endocrine and Automated Clinical Fellow Divisions of Endocrinology & Nuclear Medicine Immunoassay Laboratories Department of Radiology The Ohio State University Medical Center and Chair, Division of Clinical Biochemistry and Mayo School of Graduate Medical Education Comprehensive Cancer Center Immunology Rochester, Minnesota, USA The Arthur G James Cancer Hospital and Solove Departmental Vice-Chair for Information Research Center Management and Supply Chain Per Hellman, MD Columbus, Ohio, USA Department of Laboratory Medicine & Pathology University of Uppsala Mayo Clinic Uppsala, Sweden Kalman Kovacs, MD, PhD Rochester, Minnesota, USA Professor of Pathology Michelle Hermiston, MD, PhD St. Michael’s Hospital Jane Green, BM BCh, Dphil Assistant Professor Toronto, Ontario, Canada Cancer Epidemiology Unit Pediatric Hematology-Oncology University of Oxford Oxford, UK UCSF School of Medicine Tom R. Kurzawinski, FRCS San Francisco, California, USA Department of Endocrinology University College London Hospitals Ashley B. Grossman, BA, BSc, MD, Timothy J. Hobday, MD London, UK FRCP, FMedSci Assistant Professor of Oncology Professor of Neuroendocrinology Department of Oncology Department of Endocrinology Mayo Clinic Steven W.J. Lamberts, MD, PhD St Bartholomew’s Hospital Rochester, Minnesota, USA Professor of Medicine London, UK Erasmus Medical Center Department of Internal Medicine Humphrey J. F. Hodgson, FRCP, Division of Endocrinology Thorvardur R. Halfdanarson DM, FMedSci Rotterdam, The Netherlands Mayo Clinic College of Medicine Sheila Sherlock Chair of Medicine Department of Oncology Division of Medical Oncology Royal Free and University College School Michael A. Levine, MD of Medicine Rochester, Minnesota, USA Section of Pediatric Endocrinology London, UK Division of Pediatrics Marcia Hall, MBBS, PhD, FRCP Silvia Hofer, MD CLelernveelra Cndo lClelgine iocf C Mheilddirceinn’es oHf oCsapsiet aWl; easntdern Consultant in Medical Oncology Medical Oncology Department Reserve University Department of Medical Oncology University Hospital Zürich Cleveland, Ohio, USA Mount Vernon Cancer Centre Zürich, Switzerland Northwood, Middlesex, UK John R. Lindsay, MD Sabine E. Hannema, MD, PhD Jo W.M. Höppener, PhD Consultant Physician Associate Professor Endocrinology & Diabetes Department of Paediatrics Department of Metabolic and Endocrine Diseases Altnagelvin Area Hospital Juliana Children’s Hospital University Medical Center Utrecht Londonderry The Hague, The Netherlands Utrecht, The Netherlands United Kingdom KTheev Ininsti tJu.t eH oaf rCrainncegr tRoesnea, rFcRhCP, FRCR Eva Horvath, PhD Mark E. Linskey, MD, PhD Department of Laboratory Medicine Targeted Therapy Laboratory Associate Professor and Chairman St. Michael’s Hospital Cancer Research UK Centre for Cell and Molecular Department of Neurological Surgery Toronto, Ontario, Canada Biology University of California, Irvine London, UK UCI Medical Center Ieuan A. Hughes, MA, MD, FRCP, FRCP(C), Orange, California, USA Ian D. Hay, BSc, MB, PhD, FACE, FACP, FRCPCH, FMedSci FRCP, FRCPI (Hon) Department of Paediatrics Cornelis J.M. Lips, MD, PhD University of Cambridge Professor of Medicine and Dr R.F. Emslander Professor of Endocrinology and Internal Medicine Addenbrooke’s Hospital Professor of Endocrinology Research University Medical Center Utrecht Cambridge, UK Mayo Clinic College of Medicine; and Utrecht, The Netherlands Consultant in Endocrinology and Internal Medicine Niki Karavitaki, MBBS, MSc, PhD D. Lynn Loriaux,MD, PhD Mayo Clinic Department of Endocrinology Chair Rochester, Minnesota, USA Oxford Centre for Diabetes, Endocrinology Department of Medicine and Metabolism Oregon Health & Science University Churchill Hospital Portland, Oregon, USA Oxford, UK x 9781405145848_1_pre.qxd 1/31/08 5:35 PM Page xi List of Contributors Eamonn R. Maher,MD, FRCP, FMedSci Niall R. Moore, FRCP, FRCR Christopher M. Nutting, BSc, MRCP, Professor of Medical Genetics Departments of Radiology and Nuffield FRCR, MD Department of Medical and Molecular Genetics Department of Medicine Consultant and Hon. Senior Lecturer in Clinical University of Birmingham School of Medicine; and Oxford Radcliffe Hospital Oncology; and West Midlands Regional Genetics Service University of Oxford Head of Head and Neck Unit Birmingham Women’s Hospital Oxford, UK Royal Marsden Hospital Birmingham, UK London, UK Damian G. Morris, MBBS, PhD, MRCP Eamonn R. Maher, MD, FRCP, FMedSci Consultant Physician Kjell Öberg, MD, PhD Professor of Medical Genetics Department of Diabetes & Endocrinology Professor of Endocrine Oncology Department of Medical and Molecular Genetics The Ipswich Hospital NHS Trust Department of Medical Sciences and Department University of Birmingham School of Medicine; and Ipswich, UK of Endocrine Oncology West Midlands Regional Genetics Service University Hospital Birmingham Women’s Hospital Uppsala, Sweden John C. Morris, MD Birmingham, UK Professor of Medicine R. Timothy D. Oliver, MD, FRCP Division of Endocrinology Franco Mantero, MD Mayo Clinic College of Medicine Professor of Medical Oncology St Bartholomew’s Hospital Professor of Endocrinology Rochester, Minnesota, USA Department of Medical Oncology Division of Endocrinology London, UK Department of Medical and Surgical Sciences John F. Morris, BSc, MB ChB, MD, MA, University of Padua FMedSci Babatunde Oyajobi, MD, PhD Padua, Italy University Lecturer and Professor of Human Assistant Professor Anatomy Department of Cellular and Structural Biology Niamh M. Martin, MBChB PhD MRCP Director of Preclinical Studies Graduate School of Biomedical Sciences Clinical Senior Lecturer Department of Physiology, Anatomy & Genetics University of Texas Health Science Center at Department of Metabolic Medicine University of Oxford San Antonio Imperial College Oxford, UK San Antonio, Texas, USA London, UK Gregory R. Mundy, MD Susan Padalecki, PhD Katherine K. Matthay, MD John A. Oates Chair in Translational Medicine Department of Cellular and Structural Biology Professor of Pediatrics Director, Vanderbilt Center for Bone Biology University of Texas Health Science Center Chief, Pediatric Hematology-Oncology Professor of Medicine, Pharmacology, San Antonio, Texas, USA UCSF School of Medicine Orthopaedics, Cancer Biology San Francisco, CA, USA Nashville, Tennessee, USA Anna Patalano, MD Division of Endocrinology Robert D. Murray, MD, MRCP Karim Meeran, MBBS, MD, FRCP Department of Medical and Surgical Sciences Department of Endocrinology Professor of Endocrinology University of Padua Leeds Teaching Hospitals NHS Trust Department of Metabolic Medicine Padua, Italy Leeds, UK Imperial College London, UK John Newell-Price, MA, PhD, FRCP Sharon Peoples, MBChB, MRCP, FRCR Specialist Registrar Senior Lecturer and Consultant Endocrinologist Shlomo Melmed, MD Academic Unit of Diabetes and Endocrinology Edinburgh Cancer Centre Western General Hospital Cedars-Sinai Research Institute University of Sheffield Edinburgh, UK UCLA David Geffen School of Medicine at Sheffield, UK University of California Los Angeles Los Angeles, California, USA Sarah Ngan, MBBS, MRCP (UK) Luca Persani, MD, PhD Clinical Research Fellow Associate Professor of Endocrinology Mark E. Molitch, MD Department of Oncology Department of Medical Sciences Imperial College University of Milan Professor of Medicine London, UK Istituto Auxologico Italiano IRCCS Division of Endocrinology, Metabolism and Milan, Italy Molecular Medicine Northwestern University Feinberg School of Amanda Nicholson, MBBS, PhD Medicine Clinical Research Fellow Rachel R. Phillips, FRCP, DCH, FRCR Chicago, Illinois, USA Department of Epidemiology and Public Health Consultant Radiologist University College London Honorary Senior Clinical Lecturer in Radiology London, UK University of Oxford Oxford, UK xi