Table Of Content

Pediatric Endocrinology F I F T H E D I T I O N Volume 1 Obesity, Diabetes Mellitus, Insulin Resistance, and Hypoglycemia EDITED BY Fima Lifshitz Pediatric Sunshine Academics, Inc. and Sansum Medical Research Institute Santa Barbara, California, U.S.A. University of Miami Miami, Florida, U.S.A. Health Science Center, State University of New York Brooklyn, New York, U.S.A. New York London DK683x_C000a.indd 3 11/17/06 12:21:13 PM Informa Healthcare USA, Inc. 270 Madison Avenue New York, NY 10016 © 2007 by Informa Healthcare USA, Inc. Informa Healthcare is an Informa business No claim to original U.S. Government works Printed in the United States of America on acid‑free paper 10 9 8 7 6 5 4 3 2 1 International Standard Book Number‑10: 0‑8493‑4068‑3 (Hardcover) International Standard Book Number‑13: 978‑0‑8493‑4068‑0 (Hardcover) This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publish reliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materials or for the consequences of their use. No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any information storage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA 01923, 978‑750‑8400. CCC is a not‑for‑profit organization that provides licenses and registration for a variety of users. For organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation with‑ out intent to infringe. Visit the Informa Web site at www.informa.com and the Informa Healthcare Web site at www.informahealthcare.com DK683x_C000a.indd 4 11/17/06 12:21:14 PM Dedication ‘‘Gracias a la vida que me ha dado tanto’’ and has given me health to enjoy my life and wisdom to do right. FimaLifshitz,M.D. Foreword AsOsleroncesaid,‘‘Readwithtwoobjects:first,toacquaint disorders of carbohydrate metabolism (obesity, T1DM, yourself with the current knowledge on a subject and the T2DM,insulinresistance,andhypoglycemia)in20chapters steps by which it has been reached; and second and more with510pagesandthesecondvolumedealingwith‘‘tradi- important, read to understand and analyze your cases.’’ tional’’ endocrinology (growth, adrenal, sexual, thyroid, The fifth edition of the textbook of Pediatric Endocrinology calcium, and fluid balance) in 33 chapters with 768 pages. providesthereaderwithanopportunitytomeetbothobjec- The increase in the number of chapters and pages devoted tives, combining an update on the latest developments in to obesity and diabetes reflects the increased prevalence of thefieldofpediatricendocrinologywithprovidingpractical these disorders in the pediatric population and is con- information on how this knowledge can be applied to cordant with the patient distribution in many pediatric patient care. endocrine practices. Books area reflection of their times. It is not surpris- Thisbook,therefore,providesanin-depthcoverageof ing,therefore,thattheevolutionofpediatricendocrinology thedisease statesseenintheearly21stcentury.Itprovides over the past two decades is reflected by the changes that thereadershipwithanopportunitytoexplorethewonders have occurred in this textbook since its initial printing in of the science and the clinical breadth of pediatricendocri- 1985. The first edition of Pediatric Endocrinology consisted nology by just turning the pages. Osler wisely said, ‘‘To of 27 chapters with 668 pages; the current edition consists study the phenomena of disease without books is to sail oftwovolumescontaining53chapterswithatotalofmore an uncharted sea, while to study books without patients is than 1300 pages. The expansion in the size of the book tonotgotoseaatall.’’Thisbookprovidesthesail,theboat, reflectstherapidexpansionofknowledgethathasoccurred andtherudder;thecliniciansmustdeterminehowtoapply in the field over the last 22 years. In 1985, only three it to theirpatients. chapters with 60 pages were devoted to the diagnosis and treatment of Type 1 diabetes mellitus and ketoacidosis, Janet H.Silverstein, M.D. while Type 2 diabetes and obesity were not addressed. ProfessorofPediatrics The current edition has been split into two separate UniversityofFlorida but complementary volumes; the first volume covering Gainesville,Florida, U.S.A. The previous four editions of Pediatric Endocrinology, volumetext.Thecollaboration ofmultipleauthorsforeach progressively, have been a dominating educational tool for subsectionpermitsthepresentationofbroaderperspectives subspecialistsinpediatricendocrinology,genetics,nutrition, than ifa single authorhadbeen responsible. etc., and for pediatric generalists. The fifth edition exceeds Ihaveconsideredthepresenceofeachoftheprevious my expectations and will exceed yours. The expansion of foureditionsofPediatricEndocrinologyanecessityonmyshelf thetextintotwovolumescouldbediscouragingtothepro- becauseoftheirhighqualityasadiagnosticandtherapeutic spectiveowner.Itshouldnotbe.Theeducationalleadership toolinthepracticeofpediatricsandpediatricendocrinology. and organizational talent of Dr. Lifshitz have provided us Thefiftheditionsimilarlywillbeanecessaryandwelcomed with a text that now has necessarily expanded into two addition on the shelf reserved for my favorite textbooks. I volumes as the scope of the specialty expanded. The new personallyextendmythanksandcongratulationstoDr.Lif- organization enhances the use of this textbook, permitting shitzandtoeachofhiscontributorsinproducingthisexcel- thereaderinitiallytobeveryfocusedinobtainingtheinfor- lentandtimelytextbook. mation he/she seeks,but it subsequently supplements that informationastimepermitsbygoingtootherchapters,each Robert M.Blizzard, M.D. written by different well-known authors. Examination of DepartmentofPediatrics and Dr. Lifshitz’s preface of this text and the indexed outline Children’s MedicalCenter ofchapterspermits confirmationofmyconclusion. UniversityofVirginia Themultiplecontributingauthorsalsodeservestrong Charlottesville, Virginia,U.S.A. commendations for the excellent content of this two v Foreword Dr.FimaLifshitz’sexpansiveviewofthescopeofpediatric The two volumes complement each other and together endocrinology is reflected in the fifth edition of his classic providecomprehensivecoverageofthecontemporaryprac- textbookPediatricEndocrinology,firstpublishedin1985.Each tice of the expanded scope of pediatric endocrinology and edition has improved upon its predecessor by adding new metabolism. chaptersontopicsrelevanttotherapidlydevelopingscience Dr.Lifshitzhascarefullyselectedpertinenttopicsand andchangingthepracticeofpediatricendocrinology.Unlike superb authors, all experts in their respective fields, who othertextbooksofpediatricendocrinology,whichtendtobe are both investigators and clinicians. As a result, Pediatric largely devoted to classical pediatric endocrine subjects, Endocrinology is characterized by an exceptional blend of Lifshitz’s Pediatric Endocrinology has an expanded scope as rigorous scholarship and pragmatism, which undoubtedly it covers not only these subjects but is equally devoted to contributestoitsbroadappealandwillensureitscontinued what might be referred to as Metabolic Endocrinology success. therebyreflectingthetruepracticeofthespecialty.Thelatter I congratulate Dr. Lifshitz on admirably accomplish- includes thevarious formsofdiabetesmellitus, hypoglyce- ing the monumental task of editing, unassisted, a textbook mia, obesity and its related disorders, insulin resistance, of this magnitude and complexity and ensuring that each lipiddisordersandvariousgeneticdisordersofmetabolism. chaptermeetshisexactingstandardsofscholarship,clinical With 53 fully inclusive chapters, the fifth edition of relevanceandclarityofexposition.Ithasbeenanhonorand PediatricEndocrinologyhasexpandedtotwovolumes.Asub- aprivilegetoserveasacontributortoPediatricEndocrinology stantial portion of volume one is devoted to metabolic andto write this Foreword. endocrinology, whereas volume two contains chapters on all the classical topics in pediatric endocrinology including JosephI.Wolfsdorf, M.B.,B.Ch. growth,adrenal,sexual,thyroid,calcium,andfluidbalance Children’s Hospital and disorders as well as other miscellaneous endocrine altera- Harvard Medical School tions. This textbook also provides valuable information on Boston, Massachusetts, U.S.A. avarietyoftopicsrelevanttopediatricians,pediatricendo- crinologists and academic clinicians throughout the world. In this age of molecular science, our knowledge of the Dr.FimaLifshitzhasagainputtogetheranauthorita- genetic basis of endocrine disorders is rapidly expanding. tive, current and important text to serve the burgeoning As we come to understand the etiology of the disease fieldofpediatricendocrinology.Iknowthatitwillcontinue with pinpoint accuracy, our treatments become more tobeaninvaluable toolfor bothclinicians andresearchers. effectiveandtailoredtoourpatients’needs.Currentmole- cular research impacts treatment when clinicians can use Maria I.New,M.D. such findings to guide their therapies. This textbook ProfessorofPediatrics serves as a crucial bridge between the molecular labora- Director,AdrenalSteroidDisordersProgram tory and the clinical practice, encouraging translational Mount SinaiSchoolofMedicine research. New York, New York, U.S.A. vii Preface Thegoodlifeisoneinspiredbyloveandguidedbyknowl- reflectsthetruestateofthespecialty.Whereaspreviousedi- edge.—BertrandRussell tions of this book already contained chapters dealing with obesity and diabetes in children, long before these entities The fifth edition of Pediatric Endocrinology marks the 22nd attractedthefullattentionofpediatricendocrinologists;other anniversary of this textbook. This edition has built upon textsinthefieldhavebarelyaddressedthesetopics.However the accumulated experience of the previous versions and in this fifth edition of Pediatric Endocrinology, these entities every one of the chapters has been thoroughly updated; are fullyexpandedtoprovidethereaderwitha substantive thereby its content enhances the reputation that Pediatric appraisalofthesubjectsandofthecurrentissues.Themajor Endocrinologyhasenjoyedas‘‘theclassicbookinthefield.’’ publichealthproblemofobesityismostblatantlyvisible;yet Eachofthetopicsofthechaptersofthefiftheditionofthis it is often a neglected disease. In this book, obesity is dis- book addresses one of the many potential alterations of cussed from a pediatric endocrinologist’s perspective, with patientsreferredtothepediatricendocrinologistforevalua- attention given to all aspects of the disease; including the tionandtreatment.Together,theyprovidethemostupdated epidemic and the mechanisms of the illness. The genetics information needed by the physician caring for these and the single gene disorders that are manifested with children, yet written with the detail required by the sub- obesity are reviewed asare theprevention andtreatment of specialist in academic settings. The chapters are written in this disorder and the comorbidities. Included are also the a didactic manner, containing practical information, with chapters that address the current state of knowledge of comprehensivediscussionsthataddressallclinicalsituations. the insulin resistance/metabolic syndrome and the diseases Thereby,thebookservestoincreasetheknowledgeofboththe thatoftenresultfrominsulinresistance,suchashypertension practitionerandthesubspecialist.ThefiftheditionofPediatric and hyperlipidemia. The long-term endocrine alterations Endocrinologyconstitutesastate-of-thearttextbook,writtenby thatfollowthe birthofa small-for-gestational-ageinfantare mature, well-established contributors who transmit their reviewed, with particular detail to the development of knowledge in an erudite manner, covering the theoretical theinsulinresistancesyndrome,appearinglateroninthelife andtheclinicalconsiderationsofeachentity. ofsuchchildren. Since the first edition of Pediatric Endocrinology pub- There was a time when pediatric endocrinologists lished in 1985, the field has grown and has evolved. The were not involved with the care of children with diabetes state of knowledge and the scientific basis of the practice or with the teaching and research of this disorder; that ofthespecialtyaremarkedlydifferentfromthatoftwodec- wasthepast.Currently,thecareforsuchpatientsdemands adesago.Thiseditionencompassesthecurrentstatusofthe theattentionofthespecialist;pediatricendocrinologistsare specialty and the care of patients with pediatric endocrine now intimately involved in providing care and advancing diseases. The ever-increasing scope of the science of endo- the knowledge of the disease through clinical and basic crinology and the rapid acquisition of new knowledge are science research. This is evident in each of the chapters captured and synthesized in each chapter by experts in of this book, which pertain to all aspects of diabetes melli- all aspects of the specialty. The clinical care and practical tus. Included in the book is an update of the new clinical aspects of pediatric endocrinology are written by those multicenter research programs designed to address the whoarecommitted to thepractice ofthe specialty. causes of Type 1 diabetes and chapters dealing with the The fifth edition of Pediatric Endocrinology comprises theoretical and practical aspects of the care of such two volumes—each one dealing with major areas in the patients. Also, there is an expanded chapter dealing with field. The expanded version of the textbook allows a com- Type 2 diabetes mellitus because this disease has become prehensive review of the multiple advances and provides amoreprominentareaforthepediatricendocrinologyspe- the reader the factual information to address all the con- cialty. In the section on hypoglycemia, the disorders that cerns that arise when caring for children with endocrine- produce this alteration are reviewed with attention paid related alterations. Each one of these two books contains to the pathophysiology, its causes and the treatment, both comprehensivechaptersofspecificentitiesthatcontainsuf- inchildrenandinneonates.Theemergenciesthatpediatric ficientdetailedinformationtocoverthetopicinitsentirety. endocrinologists deal when consulted for patients with Thereby,eachvolumeconstitutesabookinitsownright,yet inborn errors of metabolism are thoroughly addressed both complement each other and together they form the and the norms for the assessment of newborn screening resource in the field in an integrated easy-to-read and alterations are provided. Finally, there are new chapters clearlywritten manner. dealing with the current realities in the field, namely the Volume 1 of Pediatric Endocrinology is devoted to obe- private practice of the subspecialty and the performance sity, diabetes mellitus, insulin resistance and hypoglycemia, ofclinicaltrialsbyboththeacademicpediatricendocrinol- with a special section on private practice and clinical ogistand the physician committedto patientcare.Thereis research. Currently, caring for patients with these diseases also a comprehensive reference resource containing fre- constitutes a major part of the pediatric endocrinologist’s quently used charts and tables needed for the assessment time and effort. Thus, the expanded review of these topics of endocrine patients. ix