Diagnostics of Endocrine Function in Children and Adolescents 4th, revised and extended edition
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1 Diagnostics of Endocrine Function in Children and Adolescents 4th, revised and extended edition
2 Diagnostics of Endocrine Function in Children and Adolescents 4th, revised and extended edition Editors Michael B. Ranke Tübingen Primus-E. Mullis Bern 109 figures and 80 tables, 2011 Basel Freiburg Paris London New York Bangalore Bangkok Shanghai Singapore Tokyo Sydney
3 Michael B. Ranke, MD Pediatric Endocrinology Section University Children s Hospital University of Tübingen Tübingen, Germany Primus-E. Mullis, MD Pediatric Endocrinology, Diabetology & Metabolism University Children s Hospital Inselspital Bern, Switzerland Library of Congress Cataloging-in-Publication Data Diagnostics of endocrine function in children and adolescents / editors, Michael B. Ranke, Primus-E. Mullis. -- 4th, rev. and extended ed. p. ; cm. Includes bibliographical references and indexes. ISBN (hard cover : alk. paper) -- ISBN (E-ISBN) 1. Pediatric endocrinology. I. Ranke, Michael B. II. Mullis, P.-E. [DNLM: 1. Endocrine System Diseases--diagnosis. 2. Adolescent. 3. Child. 4. Hormones -- analysis. WS 330] RJ418.D '4--dc st edition published in 1992 as Functional Endocrinologic Diagnostics in Children and Adolescents by J & J Verlag, Mannheim 2nd edition published in 1996 as Diagnostics of Endocrine Function in Children and Adolescents by Barth Verlag (Edtion J & J), Heidelberg 3rd edition published in 2003 as Diagnostics of Endocrine Function in Children and Adolescents 3rd revised and extended edition by S. Karger Publishers, Basel Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents and Index Medicus. Disclaimer. The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the book is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements. Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Copyright 2011 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISBN e-isbn
4 Section Title Contents VII Preface ; Mullis, P.-E.(Bern) VIII Preface to the Third Edition IX Preface to the Second Edition X Preface to the First Edition XI Before Using This Book 1 Laboratory Measurements of Hormones and Related Biomarkers: Technologies, Quality Management and Validation Elmlinger, M.W. (Konstanz) 32 Molecular Genetics and Bioinformatics Methods for Diagnosis of Endocrine Disorders Pandey, A.V.; Mullis, P.-E. (Bern) 53 Sonographic Measurement of Endocrine Tissue Haber, H.P.; Neu, A. (Tübingen) 68 In vivo Diagnostic Methods of Imaging and Testing of Endocrine Function with Radionuclides Reiners, C.; Farahati, J.; Lassmann, M. (Würzburg) 85 Diagnostic Tests of Thyroid Function in Children and Adolescents Krude, H.; Grüters, A. (Berlin) 102 Growth Hormone Deficiency: Diagnostic Principles and Practice 138 Methods of Evaluating Spontaneous Growth Hormone Secretion Albertsson-Wikland, K.; Rosberg, S. (Göteborg) 157 Insulin-Like Growth Factors and Their Binding Proteins Blum, W.F. (Bad Homburg); Böttcher, C.; Wudy, S.A. (Giessen) 183 Diagnosis of Growth Hormone Excess and Hyperprolactinemia Riedl, S.; Frisch, H. (Vienna) 194 Testing Water Regulation Czernichow, P.; Polak, M. (Paris) V
5 210 Diagnostic Investigations in Inherited Endocrine Disorders of Sodium Regulation Ferrari, P. (Perth, W.A.); Bianchetti, M.G. (Bellinzona) 235 Investigation of Calcium Disorders in Children Perry, L.; Allgrove, J. (London) 260 Hyperinsulinism, Neonatal Hypoglycemia, New Mechanisms Valayannopoulos, V.; de Lonlay, P.; Polak, M. (Paris) 273 Hypoglycaemia in Infants and Children Hussain, K. (London) 294 Insulin Resistance in Childhood and Adolescence Ehehalt, S.; Neu, A. (Tübingen) 310 Endocrine Function of the Testis Holterhus, P.-M. (Kiel); Honour, J.W.; Savage, M.O. (London) 331 Normal Ovarian Function and Assessment of Ovarian Reserve in Children and Young People Johnston, R.J.; Wallace, W.H.B. (Edinburgh) 350 Assessing the Function of the Human Adrenal Cortex Flück, C.E. (Bern) 379 Mass Spectrometry in the Diagnosis of Steroid-Related Disorders: Clinical Applications Wudy, S.A.; Hartmann, M.F. (Giessen) 402 Assessing Endocrine Function in the Newborn Baby Ogilvy-Stuart, A.L. (Cambridge) 429 Bone Metabolites Crofton, P.M. (Edinburgh) 448 Quantification of Densitometric Bone Parameters and Muscle Function Schoenau, E.; Fricke, O. (Cologne) 465 Body Composition Assessment in Children and Adolescents Wells, J.C.K. (London) 483 Effect of Body Weight on Endocrine Parameters and Fat Hormones Wabitsch, M.; Reinehr, T.; Fischer-Posovszky, P. (Ulm) 499 Diagnostics: Appendix A 502 Appendix B 523 Author Index 524 Subject Index VI Contents
6 Section Title Preface Since the first appearance of the first edition of this book in 1992, there have been a multitude of new developments which have influenced the diagnostic approach in children and adolescents with endocrine disorders. The encouraging response to the first three editions of this book encouraged us to adhere to the original format of the chapters, which are a combination of in- depth discussion of the diagnostic process, practical conclusions, and expert advice based on extensive experience. The new developments, as considered by the authors of this volume, refer to practically all the traditional areas of pediatric endocrinology not only the rapidly advancing field of molecular genetics and steroid metabolism. Several chapters have been revised completely and all have been updated by authors who had contributed to the previous editions as well as a large number of new authors. In addition, new chapters dealing with the muscle- bone unit and bone metabolism have also been incorporated, since the editors felt that this emerging field will broaden our understanding of the links between growth, hormones and metabolism. It was also considered that this major new area of pediatric endocrinology is related to physiological changes and disorders occurring during the neonatal phase of term and preterm babies. We hope that this 4th revised edition on the diagnostics of endocrine function will continue to support clinicians in their attempts to reach evidence- based, rapid diagnostic solutions as the basis of advice and therapy for their patients. We thank the contributing authors for their devotion to this project. The editors are particularly grateful to Thomas Nold (Karger Publishers) who has encouraged us throughout the complex process of the production of this 4th edition. Michael B. Ranke, Tübingen Primus- E. Mullis, Bern VII
7 Preface to the Third Edition When the first edition of this volume appeared in 1992, it soon became clear that a second edition would follow in order to incorporate the new developments in pediatric endocrinology. The second edition was published in 1996, and further, significant expansions in knowledge have made this new edition necessary. These include the discoveries in molecular genetics which dominated the biosciences in the past decade. It cannot be denied, however, that the prime professional challenges for the physician are to identify clinical symptoms, arrive at a definite diagnosis, and select the most appropriate treatment for each individual patient. The encouraging response to the first two editions of this book and the readers' appreciation of its value at various stages of the diagnostic process have led to our decision to adhere to the original format of the chapters, which are a combination of in-depth discussion of the diagnostic process, succinct, practical conclusions, and expert advice deriving from extensive experience. One unique feature of this third edition is that, in light of the wealth of new information and recent discoveries in some fields, most of the contributors offer the readers completely revised chapters. Thus, this edition incorporates several aspects which could not be dealt with previously, such as new information on congenital hyperinsulinaemic states, steroid analysis by GCMS, specific elements in the prematurely born and the neonate, bone development, and the influence of weight changes on the diagnostic process. This edition also offers improved flow charts which illustrate the differential diagnoses of frequently-encountered disorders that, understandably, continue to be the subject of debate. It is my sincere hope that the new information, coupled with all of the improvements and revisions, will enhance the value of this book as a guide and reference work in the field of endocrine diagnostics in children and adolescents. I would like to thank all the contributing authors for their co-operation, thoroughness and patience. I am also grateful to Priscilla Herrmann (University Children's Hospital, Tubingen, Germany) and Thomas Nold (Karger Publishers, Basel, Switzerland) for their support of this project, without which the production of this third edition would not have been possible. Michael B. Ranke, Tübingen, June 2003 VIII
8 Preface to the Second Edition The first edition of this volume received a favorable response from readers, who also provided many constructive suggestions for improvements. These and the many new developments in pediatric and adolescent endocrinology have led to a completely revised and expanded second edition. New chapters relating to molecular genetics, imaging methods using radionuclides, sequential hormone measurements, and the measurement and diagnostic relevance of urinary growth hormone have also been added to expand the coverage of areas that were not exhaustively treated in the first edition. An appendix of flow charts illustrating the differential diagnosis of frequently encountered hormonal and metabolic disorders has also been included at the end of the volume to provide physicians with quick guidance on how to deal with complex diagnostic situations. It is my hope that these revisions will further enhance the value of the book as a practical guide and reference to the diagnosis of endocrine and metabolic disorders in pediatric and adolescent patients. My thanks go to the contributing authors for their collaboration in this project, as well as to Dr. Susan Kentner of Edition.J & J for her tireless editorial support, without which the production of this second edition would not have been possible. Michael B. Ranke, Tübingen, July 1996 IX
9 Preface to the First Edition In terms of sheer numbers, hormonal disorders in children and adolescents occupy a significant place in pediatrics. Research in pediatric endocrinology has progressed to the point where it is now possible to arrive at a precise diagnosis of the most important endocrine disorders, classify them exactly according to pathophysiology, and provide treatment based on rational criteria. New molecular genetic techniques have increased our understanding of a variety of pathologic conditions, and the ability to produce hormones biosynthetically has rapidly broadened the spectrum of therapeutic methods at our disposal. In light of these developments, it seems particularly important for the physician to be able to proceed from the observation of clinical symptoms to the correct diagnosis and the appropriate therapy by following a series of rational diagnostic steps. In most textbooks of pediatrics, methods of diagnosing endocrine disorders in children and adolescents are given little space with no mention of specific details. The objective of this volume is therefore to describe in depth methods for the functional diagnosis of the most important hormonal disorders occurring in pediatric age groups. Special emphasis is placed on evaluating the methods discussed in terms of their clinical relevance. Normal values for hormonal parameters and test results are presented, together with a discussion of methodologic problems and more recent techniques that have not yet become firmly established diagnostic procedures. The intention is to provide a judicious mixture comprising not only knowledge based on long-established diagnostic procedures and confirmed test results, but also reflecting the personal experience of the contributing authors with a variety of newly developed and less well-established test procedures. This combination provides a picture of the problems associated with functional endocrinologic diagnostics that is at once extremely varied, but always relevant to actual clinical practice. I thank all the authors for contributing their knowledge and expertise to realize this volume. Special thanks also go to Dr. Susan Kentner, who has guided the publication of the volume with experience and patience. Michael B. Ranke, Tübingen, January 1992 X
10 Before Using This Book The pediatrician is frequently confronted with disorders of endocrine function and deviations from normal growth patterns. Diagnosing such conditions often demands detailed knowledge of childhood developmental processes, profound clinical experience, and an understanding of the intricate interaction of metabolic and endocrine factors. At the same time, we are fortunate in having a diverse and well-validated arsenal of diagnostic methods at our disposal. This volume presents the diagnostic approaches, test procedures, and normative data required to establish diagnoses for a broad spectrum of endocrine disorders. It is hoped that the reader will use this book to obtain reference values for various diagnostic parameters. In this regard, however, it is appropriate to provide a few preliminary words of caution on how to evaluate the information presented in this volume: (1) The diagnostic approaches outlined here are based on the profound experience of the authors and reflect the state of the art. Nevertheless, other diagnostic paths not discussed in this volume, that are based on different traditions and experience, may also be useful. (2) Test results may depend on a variety of circumstances related to the individual tested and the test modalities. With regard to the latter, for example, the time of day at which a test is administered may be of particular importance. Specific normative data need to be established for procedures performed at special times during the day owing to circumstances within a particular clinical setting. In special situations, certain requirements (e.g., fasting state) must be fulfilled. (3) Standard hormone measurements are performed today in many laboratories, and often a multitude of assays are available for the same hormone. Assay performance and the quality of the results obtained can therefore vary considerably depending on the laboratory and the assay used. Reference data are therefore only valid for the method used and for the laboratory that has established them. The data published in this volume can thus only be taken as guidelines for normative data when different methods are employed. (4) In general, it is important that those interpreting the results of hormone measurements be familiar with the methods used, the conditions under which they are employed, and the quality of the results obtained with them. If the clinician has no XI
11 control over the characteristics of a particular assay (e.g., because an outside laboratory is performing it), he or she should obtain the relevant information from the laboratory. In particular, it should be kept in mind that an assay that works well for adults may not be appropriate for children, e.g., because of differences in the relevant range of concentrations or because of other interfering factors specific to the child's developmental stage. (5) Each investigator should make an effort to establish normative data with the methodology at his or her disposal. As a minimal requirement, investigators should acquire sufficient experience to develop a 'feeling' for the results of a given method in order to be able to judiciously evaluate the figures supplied by the laboratory performing the assay. The latest fashions in methodology may not necessarily serve the needs of either the investigator or the patients neither do shortcuts imposed by economic considerations. The reader is therefore urged to study not only the tables included in this book, but also the methodological analyses presented by each author in order to gain the critical confidence required to counsel and treat patients XII Before Using This Book
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