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      Treatment of Growth Hormone-Deficient Infants with Recombinant Human Growth Hormone to Near-Adult Height: Patterns of Growth

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          Abstract

          Background/Aims: To determine adult statures and linear growth patterns of children with growth hormone deficiency (GHD) who began treatment with recombinant human growth hormone (rhGH) in infancy. Methods: Forty-seven patients with GHD in whom administration of rhGH was initiated at or before 2 years of age and who had achieved near-adult heights (NAH) were identified in the database of the Genentech National Cooperative Growth Study. Results: After beginning treatment at a mean age of 0.9 years and height of –2.3 SD, these subjects achieved mean statures of –0.6, –0.3, and –0.4 SD at 5 and 10 years of age and at NAH, respectively. In 23 patients whose parental heights were known, mean NAH was comparable to the target height. Patients with uncomplicated courses whose heights were normal or tall when spontaneous puberty occurred or was induced realized the tallest NAHs. Patients with severe prenatal or perinatal, congenital and acquired neurologic insults, sexual precocity, or associated illnesses achieved less optimal NAHs. Conclusion: A normal pattern of linear growth during childhood and adolescence and satisfactory NAHs can be achieved in the majority of patients when treatment of the GHD subject is begun during infancy.

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          Treatment of a pituitary dwarf with human growth hormone.

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            Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database.

            Treatment with GH has been used to correct the growth deficit in children with GH deficiency (GHD). Although successful in increasing height velocity, such treatment often falls short of helping patients achieve full genetic height potential. This study set out to analyze near-final height (FH) data from a cohort of GH-treated children with idiopathic GHD. Of 1258 evaluable patients in the Pfizer International Growth Database (KIGS) with GHD, 980 were of Caucasian origin, and 278 were of Japanese origin; 747 had isolated GHD (IGHD), and 511 had multiple pituitary hormone deficiencies (MPHD). Near-FH, relation to midparental height, and factors predictive of growth outcomes were the main outcome measures. Median height sd scores (SDS) at the start of treatment were -2.4 (IGHD) and -2.9 (MPHD) for Caucasian males and -2.6 (IGHD) and -3.4 (MPHD) for females, respectively; comparable starting heights were -2.9 (IGHD) and -3.6 (MPHD) for Japanese males and -3.3 (IGHD) and -4.0 (MPHD) for females, respectively. Corresponding near-adult height SDS after GH treatment were -0.8 (IGHD) and -0.7 (MPHD) for Caucasian males and -1.0 (IGHD) and -1.1 (MPHD) for females, respectively; and -1.6 (IGHD) and -1.9 (MPHD) for Japanese males and -2.1 (IGHD) and -1.8 (MPHD) for females, respectively. Differences between near-adult height and midparental height ranged between -0.6 and +0.2 SDS for the various groups, with the closest approximation to MPH occurring in Japanese males with MPHD. The first-year increase in height SDS and prepubertal height gain was highly correlated with total height gain, confirming the importance of treatment before pubertal onset. It is possible to achieve FH within the midparental height range in patients with idiopathic GHD treated from an early age with GH, but absolute height outcomes remain in the lower part of the normal range. Patients with MPHD generally had a slightly better long-term height outcome.
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              The mathematical model for total pubertal growth in idiopathic growth hormone (GH) deficiency suggests a moderate role of GH dose.

              The role of GH treatment during total pubertal growth (TPG) is still unclear. We developed a prediction model for TPG (centimeters) through a multiple regression analysis of various prepubertal parameters in 303 adolescents with idiopathic GH deficiency from the KIGS database. Prepubertal catch-up growth and near-adult height were achieved, and GH dose was kept constant at approximately 30 micro g/kg.d. The model was validated on a cohort of 36 patients from one center. Four TPG predictors explained 70% of the variability with an error SD of 4.2 cm: gender (TPG in males was >11.3 cm vs. that in females), age at onset of puberty (negative), height SD score minus midparental height SD score at puberty onset (negative), and mean GH dose during puberty (positive). Our analysis suggests that TPG in idiopathic GH deficiency is only moderately dependent on GH dose. The use of a higher GH dosage at the onset of puberty should thus depend on the individual's height development. The TPG model aids in the planning of individually optimized and cost-effective GH treatment.
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                Author and article information

                Journal
                HRP
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2011
                March 2011
                18 January 2011
                : 75
                : 4
                : 276-283
                Affiliations
                aDepartment of Pediatrics, University of South Florida College of Medicine, Tampa, Fla., and bGenentech, Inc., South San Francisco, Calif., USA
                Author notes
                *Allen W. Root, MD, All Children’s Hospital, 501 Sixth Avenue South, Box 6900, St. Petersburg, FL 33731 (USA), Tel. +1 727 767 4233, Fax +1 727 767 3275, E-Mail roota@allkids.org
                Article
                322881 Horm Res Paediatr 2011;75:276–283
                10.1159/000322881
                21242667
                b4a1e3ad-0103-452f-ba32-c6df348a7e4c
                © 2011 S. Karger AG, Basel

                Copyright: 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. 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 changes 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. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication 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.

                History
                : 09 August 2010
                : 11 September 2010
                Page count
                Figures: 5, Tables: 4, Pages: 8
                Categories
                Original Paper

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Growth patterns,Growth hormone deficiency,Treatment of growth hormone deficiency,Recombinant human growth hormone,Hypopituitarism,Near-adult height

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