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      Optimizing Growth Hormone Efficacy: An Evidence-Based Analysis

      review-article
      Hormone Research in Paediatrics
      S. Karger AG
      Monitoring, Growth hormone deficiency, Compliance, Puberty

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          Abstract

          For almost two decades, recombinant growth hormone (GH) has been in abundant supply to treat GH-deficient subjects to final height, yet the results continue to be suboptimal. Although there are numerous potential causes for this underachievement, the issues of poor compliance, ineffective dosing and lack of efficacy monitoring have been frequently promulgated to explain the phenomenon. Compliance is tied to knowledge, which is best promoted at the time of diagnosis by hospital-based personnel. GH pens have improved acceptability, but data on improvement in compliance are lacking. No GH device or delivery system has yet been shown to increase final height. Daily (or six times per week) dosing is clearly more effective, but increasing GH dose, especially during puberty, has a tendency to advance bone age and pubertal progression, which mitigates many of the effects. Finally, titration of dose to the insulin-like growth factor (IGF)-I level may prove to be useful in promoting final height; however, the converse is not true, i.e. increments in IGF-I level have not been shown to correlate with increments in height velocity. Thus, these issues with respect to achievement of final height are far from solved.

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          Most cited references19

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          High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature.

          Long term growth hormone (GH) treatment in children with idiopathic short stature (ISS) results in a relatively small mean gain in final height of 3-9 cm, which may not justify the cost of treatment. As it is unknown whether GH treatment during puberty adds to final height gain, we sought to improve the cost-benefit ratio, employing a study design with high dose GH treatment restricted to the prepubertal period. To assess the effect of short term, high dose GH treatment before puberty on growth, bone maturation, and pubertal onset. Five year results of a randomised controlled study are reported. Twenty six boys and nine girls were randomly assigned to a GH treatment group (n = 17) or a control group (n = 18). Inclusion criteria were: no signs of puberty, height less than -2 SDS, age 4-8 years for girls or 4-10 years for boys, GH concentration >10 micro g/l after provocation, and normal body proportions. To assess GH responsiveness, children assigned to the GH treatment group received GH treatment for two periods of three months (1.5 IU/m2/day and 3.0 IU/m2/day), separated by three month washout periods, during the first year of study. High dose GH treatment (6.0 IU/m2/day) was then started and continued for at least two full years. When puberty occurred, GH treatment was discontinued at the end of a complete year's treatment (for example, three or four years of GH treatment). In response to at least two years on high dose GH treatment, mean (SD) height SDS for chronological age increased significantly in GH treated children from -2.6 (0.5) to -1.3 (0.5) after two years and -1.4 (0.5) SDS after five years of study. No changes in height SDS were observed in controls. A rapid rate of bone maturation of 3.6 years/2 years in treated children compared to 2 years/2 years in controls was observed in response to two years high dose GH treatment. Height SDS for bone age was not significantly different between groups during the study period. GH treated children entered into puberty at a significantly earlier age compared to controls. High dose GH treatment before puberty accelerates bone age and induces an earlier onset of puberty. This may limit the potential therapeutic benefit of this regimen in ISS.
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            High Dose Recombinant Human Growth Hormone (GH) Treatment of GH-Deficient Patients in Puberty Increases Near-Final Height: A Randomized, Multicenter Trial

            N Mauras (2000)
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              Unfavorable effects of growth hormone therapy on the final height of boys with short stature not caused by growth hormone deficiency.

              A group of 18 boys with non-growth hormone (GH)-deficient short stature without GH therapy (group A) and another group of 9 boys with non-GH-deficient short stature with GH therapy in doses of 0.5 IU (0.17 mg)/kg per week administered 5 to 6 times weekly (group B) were observed until they reached their final height. The mean duration of GH therapy was 4.2 years (range 3.2 to 5.0 years). These two groups were matched with respect to their standard deviation score (SDS) for bone age at the start of observation. Mean +/- SD of the final height for group A and group B was 162.0 +/- 5.4 cm and 154.2 +/- 4.2 cm, respectively. During the prepubertal period, height SDS for bone age of these two groups was not affected by GH therapy. During the pubertal period, however, height SDS for bone age remained constant for group A but decreased gradually for group B. Our observation indicates that for boys with non-GH-deficient short stature GH therapy does not improve height SDS for bone age during the prepubertal period, and in fact reduces it during the pubertal period, possibly resulting in a shorter final height than might have been attained naturally.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                978-3-8055-7833-2
                978-3-318-01154-8
                1663-2818
                1663-2826
                2004
                October 2004
                17 November 2004
                : 62
                : Suppl 3
                : 93-97
                Affiliations
                Division of Endocrinology, Department of Pediatrics, University of California, San Francisco, Calif., USA
                Article
                80506 Horm Res 2004;62(suppl 3):93–97
                10.1159/000080506
                15539806
                a88adb8b-961c-4467-baad-b05fdd137441
                © 2004 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
                Page count
                References: 28, Pages: 5
                Categories
                Convenience and Compliance

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Puberty,Compliance,Growth hormone deficiency,Monitoring

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