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      Validation of a Mathematical Model Predicting the Response to Growth Hormone Treatment in Prepubertal Children with Idiopathic Growth Hormone Deficiency

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          Abstract

          Objective: To validate a mathematical model developed by Ranke et al. (J Clin Endocrinol Metab 1999;84:1174–7783) to predict the GH response during the first years of GH replacement therapy. Patients and Methods: 38 children with idiopathic GH deficiency (GHD) met all inclusion criteria for the prediction model, but the group differed in some characteristics from the cohort from which the model was derived. Results: Using the model for the 1st year including maximum GH after stimulation and the equation for the 6th year, the predicted value corresponded well with actual height gain. Differences were found when the growth response of the 1st year excluding maximum GH and that of the 2nd–5th year were calculated, resulting in a significant underestimation of actual height gain (–0.63 to –1.07 cm/year). Conclusion: The mathematical prediction model tended to underpredict the growth response to GH treatment in our patients with pronounced GHD. The severity of GHD seems to be an important parameter for the 1st year prediction.

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          Prediction of response to growth hormone treatment in short children born small for gestational age: analysis of data from KIGS (Pharmacia International Growth Database).

          D. Price, Michael B. Ranke, H Reiter … (2002)
          A model was developed that allows physicians to individualize GH treatment in children born short for gestational age (SGA) who fail to show spontaneous catch-up growth. Data from children (n = 613) in a large pharmacoepidemiological survey, the KIGS (Pharmacia International Growth Database), or who had participated in clinical trials were used to develop the model. Another group of similar children (n = 68) from KIGS was used for validation. In the first year of GH treatment, the growth response correlated positively with GH dose, weight at the start of GH treatment, and midparental height SD score and negatively with age at treatment start. Using this model, 52% of the variability of the growth response could be explained, with a mean error SD of 1.3 cm. GH dose was the most important response predictor (35% of variability), followed by age at treatment start. The second year growth response was best predicted by a three-parameter model (height velocity in yr 1 of treatment, age at start of treatment, and GH dose), which accounted for 34% of the variability, with an error SD of 1.1 cm. The first year response to GH treatment was the most important predictor of the second year response, accounting for 29% of the variability. No statistically significant differences between the predicted and observed growth responses were found when the models were applied to the validation groups. In conclusion, using simple variables, we have developed a model that can be used in clinical practice to adjust the GH dose to achieve the desired growth response in patients born SGA. Furthermore, this model can be used to provide patients with a realistic expectation of treatment and may help to identify compliance problems or other underlying causes of treatment failure.
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            Factors predicting the response to growth hormone (GH) therapy in prepubertal children with GH deficiency

            S L Blethen (1993)
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              Growth Response to Recombinant Human Growth Hormone (GH) in Children with Idiopathic Growth Retardation by Level of Maximum GH Peak during GH Stimulation Tests

              Jan Van den Broeck, Nicolette J.T. Arends, Anita Hokken-Koelega (2000)
              Due to their lack of reproducibility, it is unlikely that GH stimulation tests can provide reliable diagnostic information to distinguish partial isolated GH deficiency (GHD) from idiopathic short stature (ISS). We hypothesized that the classical distinction between these groups, essentially based on stimulatory GH peaks, is artificial and that, as a consequence, the average response to GH treatment will not be different between them. The hypothesized lack of prognostic validity of stimulatory GH peaks was studied in 435 prepubertal children with nonorganic growth retardation. Children were categorized as ‘severe GHD’, ‘partial GHD’ or ‘ISS’, if the maximum rise in their serum GH during two GH stimulation tests was 0– 10 mU/l, 10–20 mU/l, or >20 mU/l, respectively. Children with ‘partial GHD’ had short-term (1- and 2-year) and long-term (till final adult height) growth responses similar to those of children with ISS, significantly lower than the response seen in children with ‘severe GHD’. In children with stimulatory GH peaks >10 mU/l, including those currently considered partially GH deficient, the maximum GH peak was not a significant determinant of growth response in the short or the long term. In conclusion, ‘partial GHD’ is ill defined and cannot be distinguished from ISS based on the currently applied auxological or GH stimulation test criteria alone. More research is required for better identification of (all) children who will respond to GH treatment, whether or not GH deficient.
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                Author and article information

                Journal
                Journal ID (publisher-id): HRE
                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: 2004
                Publication date (Print): March 2004
                Publication date (Electronic): 17 March 2004
                Volume: 61
                Issue: 3
                Pages: 143-147
                Affiliations
                aPediatric Department, 3rd Faculty of Medicine, Prague, Czech Republic; bCancer Research Institute, Department of Epidemiology and cPediatric Department, University of Vienna, Austria
                Article
                Publisher ID: 75590 Other ID: Horm Res 2004;61:143–147
                DOI: 10.1159/000075590
                PubMed ID: 14676463
                SO-VID: 1731dc16-21ed-4353-bc78-277a91db9fa1
                Copyright © © 2004 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 : 05 September 2003
                Date accepted : 12 November 2003
                Page count
                Figures: 1, Tables: 3, References: 15, Pages: 5
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Keywords: Short stature,Growth hormone deficiency,Growth response,Height prediction model,Therapy, growth hormone
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes, Neurology, Nutrition & Dietetics, Sexual medicine, Internal medicine, Pharmacology & Pharmaceutical medicine
                Keywords: Short stature, Growth hormone deficiency, Growth response, Height prediction model, Therapy, growth hormone

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