Disorders of the Human Adrenal Cortex

Disorders of the Human Adrenal Cortex

Endocrine Development Vol. 13 Series Editor P. Mullis Bern

Disorders of the Human Adrenal Cortex Volume Editors Christa E. Flück Bern Walter L. Miller San Francisco, Calif. 39 figures, 7 in color, and 8 tables, 2008 Basel Freiburg Paris London New York Bangalore Bangkok Shanghai Singapore Tokyo Sydney

Christa E. Flück Pediatric Endocrinology and Diabetology University Children s Hospital Inselspital Bern, Switzerland Walter L. Miller Department of Pediatrics University of California San Francisco, Calif., USA Library of Congress Cataloging-in-Publication Data Disorders of the human adrenal cortex / volume editors, C.E. Flück, Walter L. Miller. p. ; cm. (Endocrine development, ISSN 1421 7082 ; v. 13) Includes bibliographical references and index. ISBN 978-3-8055-8580-4 (hard cover : alk. paper) 1. Adrenal cortex Diseases. I. Flück, C.E. (Christa E.) II. Miller, Walter L. III. Series. [DNLM: 1. Adrenal Cortex Diseases. W1 EN3635 v.13 2008/WK 760 D612 2008] RC659.D57 2008 616.4 5 dc22 2008017636 Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents Disclaimer. The statements, options 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 2008 by S. Karger AG, P.O. Box, CH 4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel ISSN 1421 7082 ISBN 978 3 8055 8580 4

Contents VII Preface Flück, C.E. (Bern); Miller, W.L. (San Francisco, Calif.) 1 Steroidogenic Enzymes Miller, W.L. (San Francisco, Calif.) 19 Disorders of Adrenal Development Ferraz-de-Souza, B.; Achermann, J.C. (London) 33 Adrenal Androgens in Humans and Nonhuman Primates: Production, Zonation and Regulation Nguyen, A.D.; Conley, A.J. (Davis, Calif.) 55 Clinical Implications of Androgen Synthesis via 5 -Reduced Precursors Ghayee, H.K.; Auchus, R.J. (Dallas, Tex.) 67 P450 Oxidoreductase Deficiency A New Form of Congenital Adrenal Hyperplasia Flück, C.E.; Pandey, A.V. (Bern); Huang, N.; Agrawal, V.; Miller, W.L. (San Francisco, Calif.) 82 Long-Term Outcome of Prenatal Treatment of Congenital Adrenal Hyperplasia Lajic, S.; Nordenström, A.; Hirvikoski, T. (Stockholm) 99 Adrenocorticotropin Resistance Syndromes Cooray, S.N.; Chan, L.; Metherell, L.; Storr, H.; Clark, A.J.L. (London) 117 Cushing Syndrome Caused by Adrenocortical Tumors and Hyperplasias (Corticotropin-Independent Cushing Syndrome) Stratakis, C.A. (Bethesda, Md.) 133 The Role of Adrenal Steroidogenesis in Arterial Hypertension Mohaupt, M.G. (Bern)

145 Fetal Programming of Adrenal Androgen Excess: Lessons from a Nonhuman Primate Model of Polycystic Ovary Syndrome Abbott, D.H.; Zhou, R.; Bird, I.M. (Madison, Wisc.); Dumesic, D.A. (Madison, Wisc./Woodbury, Minn.); Conley, A.J. (Davis, Calif.) 159 Author Index 160 Subject Index VI Contents

Preface The human adrenals are large and relatively unimportant during fetal life but small and important postnatally. During development, the adrenal cortex undergoes morphological and functional changes that are still not fully understood and may lead to adrenal disease when disordered. In this volume, the series Endocrine Development covers diseases of the human adrenal cortex for the second time. In 2000, volume 2 of this series, edited by Ieuan A. Hughes and Adrian J.L. Clark, brought together a group of experts reviewing clinical and molecular aspects in the volume Adrenal Disease in Childhood. Substantial further advances in our understanding of adrenal development, steroid biosynthesis and adrenocortical disorders now necessitate another look at this small but complex organ. Studies of families with adrenal hypoplasia congenita have broadened our knowledge on specific factors involved in the adrenal development. Novel insights into the zonation of the adrenal cortex and adrenal androgen production throughout life have been gained from studies of nonhuman primates. Detailed studies of steroidogenesis in the tammar wallaby pouch young revealed an alternate ( backdoor ) pathway to dihydrotestosterone production that is relevant to P450 oxidoreductase deficiency, polycystic ovarian disease, and congenital adrenal hyperplasia (CAH). Finding that mutations in the gene for P450 oxidoreductase cause a complex defect of 17 -hydroxylase and 21-hydroxylase deficiency has defined a new form of CAH and highlighted the pivotal role of electron transfer partners in the activities of steroidogenic enzymes. Critical review of the long-term outcome of prenatal dexamethasone treatment of fetuses at risk for CAH has revealed a potential risk for adverse effects on metabolism, cognitive functions and behavior in later life. Genetic studies of ACTH resistance syndromes and adrenal Cushing s syndrome have determined the causes in some more patients, but have also shown us that there are many more unsolved cases that apparently represent disorders in unknown genes. Finally, showing

that adrenal steroidogenesis is widely important, two experts summarize novel aspects of adrenal steroid production in arterial hypertension and the polycystic ovary syndrome. This book combines ten review chapters written by basic, translational and clinical scientists. Although we tried to cover the newest information gained in the past 5 10 years, there certainly are other developing areas of research concerning the human adrenal cortex. The series Endocrine Development does not intend to replace standard endocrine textbooks, and allows the editors to pick a limited number of topics and permits the authors to express their personal opinions. We thank Primus E. Mullis for inviting us to design this new book on the development and disorders of the human adrenal cortex. Also, we would like to thank all the co-authors for their enthusiasm and effort in sharing their invaluable expertise. Finally, we thank Karger Publishers for bringing this book to the community. Christa E. Flück Walter L. Miller VIII Preface