This is trial version www.adultpdf.com Abnormalities in Puberty Scientific and Clinical Advances This is trial version www.adultpdf.com Endocrine Development Vol. 8 Series Editor Martin O. Savage London This is trial version www.adultpdf.com Abnormalities in Puberty Scientific and Clinical Advances Basel · Freiburg · Paris · London · New York · Bangalore · Bangkok · Singapore · Tokyo · Sydney Volume Editor Henriette A. Delemarre-van de Waal Amsterdam 41 figures, 2 in color, and 11 tables, 2005 This is trial version www.adultpdf.com Prof. Dr. Henriette A. Delemarre-van de Waal VU University Medical Center Paediatric Endocrinology PO Box 7057 Amsterdam, The Netherlands Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents ® and Index Medicus. 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 2005 by S. Karger AG, P.O. Box, CH-4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel ISSN 1421–7082 ISBN 3–8055–7867–9 Library of Congress Cataloging-in-Publication Data Abnormalities in puberty : scientific and clinical advances / volume editor, Henriette A. Delemarre-van de Waal. p. ; cm. – (Endocrine development, ISSN 1421-7082 ; v. 8) Includes bibliographical references and indexes. ISBN 3-8055-7867-9 (hard cover : alk. paper) 1. Pediatric endocrinology. 2. Endocrine glands–Diseases. 3. Precocious puberty. 4. Puberty. [DNLM: 1. Puberty, Precocious. 2. Gonadal Disorders. 3. Puberty, Delayed. 4. Puberty. WS 450 A153 2005] I. Delemarre-van de Waal, H. A. (Henriette A.) II. Series. RJ418.A24 2005 618.92Ј4–dc22 2004026715 This is trial version www.adultpdf.com V Contents VII Foreword Savage, M.O. (London) IX Preface Delemarre-van de Waal, H.A. (Amsterdam) 1 Secular Trend of Timing of Puberty Delemarre-van de Waal, H.A. (Amsterdam) 15 Fetal Nutrition and Timing of Puberty van Weissenbruch, M.M.; Engelbregt, M.J.T.; Veening, M.A.; Delemarre-van de Waal, H.A. (Amsterdam) 34 Adrenal Function of Low-Birthweight Children Ong, K. (Cambridge) 54 Puberty and Fertility in Congenital Adrenal Hyperplasia Otten, B.J.; Stikkelbroeck, M.M.L.; Claahsen-van der Grinten, H.L.; Hermus, A.R.M.M. (Nijmegen) 67 Molecular Genetics of Isolated Hypogonadotropic Hypogonadism and Kallmann Syndrome Karges, B. (Ulm); de Roux, N. (Paris) 81 Hypothalamic Hamartoma: A Paradigm/Model for Studying the Onset of Puberty Jung, H.; Parent, A S.; Ojeda, S.R. (Beaverton, Oreg.) This is trial version www.adultpdf.com 94 Gonadotropin-Releasing Hormone Analogue Treatment for Precocious Puberty. Twenty Years of Experience Heger, S.; Sippell, W.G. (Kiel); Partsch, C J. (Esslingen) 126 Very Long-Term Follow-Up of Girls with Early and Late Menarche Johansson, T.; Ritzén, E.M. (Örebro) 137 Polycystic Ovary Syndrome in Adolescence. New Insights in Pathophysiology and Treatment Homburg, R. (Amsterdam) 150 Reversing Sex Steroid Deficiency and Optimizing Skeletal Development in the Adolescent with Gonadal Failure Vanderschueren, D.; Vandenput, L.; Boonen, S. (Leuven) 166 Present and Future Options for the Preservation of Fertility in Female Adolescents with Cancer Beerendonk, C.C.M.; Braat, D.D.M. (Nijmegen) 176 Author Index 177 Subject Index Contents VI This is trial version www.adultpdf.com This is trial version www.adultpdf.com the management of the child with too early onset of puberty, with delayed puberty and other pubertal disorders. Not only the clinical aspects, but also the aspects related to their causes such as early growth, and genetic and develop- mental defects are discussed, which may have consequences on final height, bone development and reproduction. Henriette A. Delemarre-van de Waal Preface X This is trial version www.adultpdf.com Delemarre-van de Waal 2 result of a developing negative feedback as well as due to central inhibiting influences on GnRH release [1]. Gonadotropin levels are low at birth, which is followed by a transient increase during the first months of life, the so-called postnatal peak. Thereafter, levels return into a very low, often undetectable range during the prepubertal phase as a result of the instrinsic restraint. This developmental pattern of the gonadotropin axis appears to be independent of the fetal and child’s own gonadal steroids, since a similar development can be observed in agonadal patients [2]. During the fetal period a sex dimorphism in gonadotropin concentrations is manifest at both the pituitary and peripheral level with higher levels in the female fetus [3]. The sex dimorphism maintains in later life. The high inci- dence of idiopathic central precocious puberty in girls, and the easier response of the pituitary to stimulation with GnRH in girls compared to boys are good examples of this phenomenon [4]. It is assumed that the restraint of GnRH and gonadotropin release is more intense in boys than in girls. The fact that GnRH is not completely suppressed in girls has been confirmed in a study measuring estrogens using ultra-sensitive assays to measure estrogens, showing measur- able and bioactive estrogen levels in the prepubertal girl [5]. Timing of Puberty The clinical signs of puberty are an increase of testicular volume above 3 ml (G2) in boys, and bud-shaped elevation of the areola and papilla (B2) in girls. In girls, this stage is associated with an immediate increase of height velocity, whereas in boys the pubertal spurt occurs in the second half of puberty. Girls experience menarche, a milestone of pubertal development, about 2.3 years after start of breast growth. The appearance of axillary and pubic hair is not a good measure of puberty since it depends on adrenal steroids in girls and at least initially in boys. Improvement of the socioeconomic status appears to advance and shorten pubertal development. In the Netherlands, in the 16th to 18th centuries menar- che was reported to occur at 14–15 years of age and seldom before the age of 13 years [6]. In 1928, a shift to a menarcheal age of 13.7 years was described, and in 1965 it was 13.4 years of age. The growth survey of 1980 showed that most stages of sexual maturation were reached at a younger age and menarche was again advanced to 13.3 years and in 1997 to 13.2 years. In several European countries the trend to an earlier start of pubertal maturation seems to have come to a halt during the last decades. In the Netherlands pubertal onset even tended to be slightly later. In girls the start of This is trial version www.adultpdf.com [...]... ages of 10 .5 and 10 .7 in 19 80 and in 19 97, respectively, whereas in boys testicular development started at the ages of 11 .3 and 11 .4 years in the same studies [7] In contrast to the Dutch data, investigations in the United States have shown an ongoing trend of earlier onset of breast development in girls and genital growth in boys, particularly in the black population [8, 9] These reports resulted in wide... receptor function [28] In conclusion, various genetic abnormalities are described resulting in abnormalities of the hypothalamic-gonadal axis However, whether these genes play a role in the physiologic variations in timing of puberty remains uncertain Nutrition In 19 71, Frisch and Revelle [29] proposed the critical weight hypothesis saying that a minimal weight is needed to achieve menarche In their study,... of glycoprotein hormones consisting of a common ␣-subunit and a hormone specific -subunit The ␣-subunit consists of 92 amino acids and is encoded by one gene localized on chromosome 6q12. 21 For the Timing of Puberty This is trial version www.adultpdf.com 3 FSH -subunit the gene is localized on 11 p13 The gene encoding for the LH -subunit is located on chromosome 19 q13.32, where hCG -subunit genes... that timing of puberty has a familial inheritance The identification of genetic factors involved is still insufficient Over the last decades, gene mutations playing a role in the puberty cascade are identified explaining abnormal pubertal development Mutations in gonadotropin genes and gonadotropin receptors have been found [for review, see 11 , 12 ] LH and FSH, together with TSH and hCG, are part of... function Leptin exerts its effects via the NPY neurons It decreases NPY signalling by acting directly on the NPY-containing perikarya and presumably also at the level of the NPY nerve terminals In the fasting state, leptin levels decline and gonadotropin release is suppressed Such findings suggest that nutrition contributes to pubertal development However, it remains uncertain whether leptin is essential... receptor gene revealed a mutation in the transmembrane domain-encoding exon 10 [24] At the hypothalamic level, GnRH release can be affected by genetic disorders as well The KAL1 gene located in the Xp22.3 region encodes for a protein anosmin that shares homology with molecules involved in neuronal migration and axonal path finding Mutations of the KAL1 gene will result in an arrest of migration of both... development in American girls progresses at a slower pace The earlier onset of puberty in these girls is associated with an increased body mass index, which is more pronounced in white than in black girls [10 ] The reason that overweight children often have an early onset of puberty may be explained by the fact that estrogens are stored in body fat resulting in increased bioactivity Mechanisms The underlying... well Glycoproteins bind to receptors with similar structures These receptors belong to the G protein-coupled receptors with a, for them, characteristic large extracellular hormone-binding domain at the N-terminus The LH receptor is encoded by a gene located at chromosome 2p 21 The FSH receptor gene is located on the same chromosome 2p 21 16 It is evident that mutations in the gonadotropin genes and their... serine at amino acid 10 2, appears to be associated with an increased risk to infertility in both males and females [16 , 17 ] For the FSH gene different inactivating mutations have been described in males and females In males, azoospermia with and without pubertal delay has been described These men have low FSH, increased LH and low testosterone levels DNA sequencing showed among others a homozygous 2-bp... the triggering of pubertal onset Data in the rat have shown that leptin levels remain constant during the pre- and postpubertal stages In addition, leptin gene expression in the hypothalamus does not show any developmental changes These data suggest that leptin itself is not a strong metabolic trigger for the onset of puberty, but that it acts as a permissive signal for the onset of puberty [ 31] The question . variations in timing of puberty remains uncertain. Nutrition In 19 71, Frisch and Revelle [29] proposed the critical weight hypothesis saying that a minimal weight is needed to achieve menarche. In their. bibliographical references and indexes. ISBN 3-8 05 5-7 86 7-9 (hard cover : alk. paper) 1. Pediatric endocrinology. 2. Endocrine glands–Diseases. 3. Precocious puberty. 4. Puberty. [DNLM: 1. Puberty, Precocious Box, CH-4009 Basel (Switzerland) www.karger.com Printed in Switzerland on acid-free paper by Reinhardt Druck, Basel ISSN 14 21 7082 ISBN 3–8055–7867–9 Library of Congress Cataloging -in- Publication