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      Comparison of Body Surface Area versus Weight-Based Growth Hormone Dosing for Girls with Turner Syndrome

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          Abstract

          Background/Aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m<sup>2</sup> BSA in comparison with dosing per kg BW in girls with Turner syndrome (TS). Methods: Serum IGF-I, GH dose, and adult height gain (AHG) from girls participating in two Dutch and five Swedish studies on the efficacy of GH were analyzed, and the cumulative GH dose and costs were calculated for both dose adjustment methods. Additional medication included estrogens (if no spontaneous puberty occurred) and oxandrolone in some studies. Results: At each GH dose, the serum IGF-I standard deviation score remained stable over time after an initial increase after the start of treatment. On a high dose (at 1 m<sup>2</sup> equivalent to 0.056-0.067 mg/kg/day), AHG was at least equal on GH dosed per m<sup>2</sup> BSA compared with dosing per kg BW. The cumulative dose and cost were significantly lower if the GH dose was adjusted for m<sup>2</sup> BSA. Conclusion: Dosing GH per m<sup>2</sup> BSA is at least as efficacious as dosing per kg BW, and is more cost-effective.

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          Body index measurements in 1996-7 compared with 1980.

          S P Verloove-Vanhorick, Nicolai S C van Oers, A M Fredriks … (2000)
          To compare the distribution of body mass index (BMI) in a national representative study in The Netherlands in 1996-7 with that from a study in 1980. Cross sectional data on height, weight, and demographics of 14 500 boys and girls of Dutch origin, aged 0-21 years, were collected from 1996 to 1997. BMI references were derived using the LMS method. The 90th, 50th, and 10th BMI centiles of the 1980 study were used as baseline. Association of demographic variables with BMI-SDS was assessed by ANOVA. BMI age reference charts were constructed. From 3 years of age onwards 14-22% of the children exceeded the 90th centile of 1980, 52-60% the 50th centile, and 92-95% the 10th centile. BMI was related to region, educational level of parents (negatively) and family size (negatively). The -0.9, +1.1, and +2.3 SD lines in 1996-7 corresponded to the adult cut off points of 20, 25, and 30 kg/m(2) recommended by the World Health Organisation/European childhood obesity group. BMI age references have increased in the past 17 years. Therefore, strategies to prevent obesity in childhood should be a priority in child public health.
          Article 0 comments Cited 137 times – based on 0 reviews     Review now
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            Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations.

            Carin M. A. Rademaker, Alfred Schobben, Niek van Wieringen … (2005)
            The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that are currently available. In addition, dosage adjustments based on practical problems, such as child-friendly formulations and feeding regimens, disease state, genetic make-up and environmental influences are presented. Modification of a dosage based on absorption, depends on the route of absorption, the physico chemical properties of the drug and the age of the child. For oral drug absorption, a distinction should be made between the very young and children over a few weeks old. In the latter case, it is likely that practical considerations, like appropriate formulations, have much greater relevance to oral drug absorption. The volume of distribution (V(d)) may be altered in children. Hydrophilic drugs with a high V(d) in adults should be normalised to bodyweight in young children (age <2 years), whereas hydrophilic drugs with a low V(d) in adults should be normalised to body surface area (BSA) in these children. For drugs that are metabolised by the liver, the effect of the V(d) becomes apparent in children <2 months of age. In general, only the first dose should be based on the V(d); subsequent doses should be determined by the clearance. Pharmacokinetic studies on renal and liver function clarify that a distinction should be made between maturation and growth of the organs. After the maturation process has finished, the main influences on the clearance of drugs are growth and changes in blood flow of the liver and kidney. Drugs that are primarily metabolised by the liver should be administered with extreme care until the age of 2 months. Modification of dosing should be based on response and on therapeutic drug monitoring. At the age of 2-6 months, a general guideline based on bodyweight may be used. After 6 months of age, BSA is a good marker as a basis for drug dosing. However, even at this age, drugs that are primarily metabolised by cytochrome P450 2D6 and uridine diphosphate glucuronosyltransferase should be normalised to bodyweight. In the first 2 years of life, the renal excretion rate should be determined by markers of renal function, such as serum creatinine and p-aminohippuric acid clearance. A dosage guideline for drugs that are significantly excreted by the kidney should be based on the determination of renal function in first 2 years of life. After maturation, the dose should be normalised to BSA. These guidelines are intended to be used in clinical practice and to form a basis for more research. The integration of these guidelines, and combining them with pharmacodynamic effects, should be considered and could form a basis for further study.
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              Recommendations for the diagnosis and management of Turner syndrome.

              P Saenger, K Wikland, G S Conway … (2001)
              Comprehensive recommendations on the diagnosis of Turner syndrome (TS) and the care of affected individuals were published in 1994. In the light of recent advances in diagnosis and treatment of TS, an international multidisciplinary workshop was convened in March 2000, in Naples, Italy, in conjunction with the Fifth International Symposium on Turner Syndrome to update these recommendations. The present paper details the outcome from this workshop. The genetics and diagnosis of the syndrome are described, and practical treatment guidelines are presented.
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                Author and article information

                Journal
                Journal ID (publisher-id): HRP
                Journal ID (nlm-ta): Horm Res Paediatr
                Journal ID (doi): 10.1159/issn.1663-2818
                Title: Hormone Research in Paediatrics
                Publisher: S. Karger AG
                ISSN (Print): 1663-2818
                ISSN (Electronic): 1663-2826
                Publication date Subscription-year: 2014
                Publication date (Print): June 2014
                Publication date (Electronic): 23 April 2014
                Volume: 81
                Issue: 5
                Pages: 319-330
                Affiliations
                aCentre for Human Drug Research, and bDepartment of Pediatrics, Leiden University Medical Center, Leiden, cDepartment of Pediatrics, Albert Schweitzer Hospital, Dordrecht, dErasmus Medical Center, Rotterdam, and eDepartment of Pediatrics, University Medical Center Nijmegen St. Radboud, Nijmegen, The Netherlands; fInstitute of Clinical Science, Department of Pediatrics, Umeå University, Umeå, and gGöteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden
                Author notes
                *J.M. Wit, MD, PhD, Department of Pediatrics, Leiden University Medical Center, Albinusdreef 2, NL-2333 ZA Leiden (The Netherlands), E-Mail j.m.wit@lumc.nl
                Article
                Publisher ID: 357844 Other ID: Horm Res Paediatr 2014;81:319-330
                DOI: 10.1159/000357844
                PubMed ID: 24776754
                SO-VID: 0c5d8c75-0dae-4cde-8184-41313596c9e5
                Copyright © © 2014 S. Karger AG, Basel
                License:

                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
                Date received : 18 October 2013
                Date accepted : 09 December 2013
                Page count
                Figures: 4, Tables: 2, Pages: 12
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Turner syndrome,Body weight,Adult height,Cost-effectiveness,Body surface area,Growth hormone therapy
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Turner syndrome, Body weight, Adult height, Cost-effectiveness, Body surface area, Growth hormone therapy

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