Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Horm Res 2008;70:89–92 DOI: 10.1159/000139150 A Randomised Study of the Effect of Two Doses of Biosynthetic Human Growth Hormone on Final Height of Children with Familial Short Stature C.J. Elder J.S. Barton C.G.D. Brook M.A. Preece M.T. Dattani P.C. Hindmarsh Great Ormond Street Hospital for Children NHS Trust and University College Hospital, London, UK Introduction Short-term growth acceleration has been observed with the use of recombinant human growth hormone (r-hGH) administered to children with idiopathic short stature [1–3]. Whether this increase in height velocity translates to an increase in adult height remains unclear with increases ranging from 3 to 7 cm depending on the patient cohort studied [4–10]. As a result of the lack of clar- ity on efficacy it has not been possible to move on to con- sider whether such interventions show clinical benefit, are cost-effective or serve to improve psychological outcome. Idiopathic short stature describes a group of children in whom there is no demonstrable pathology, who are 2.5 or more standard deviations (SD) below the mean height for their age and sex, have a normal or reduced growth rate and normal growth hormone (GH) secretion on stimulation testing [2]. Included in this population are children with familial short stature (FSS). Despite the lack of demonstrable pathology GH treatment has been con- sidered in this group of children. Although two ran- domised, double-blinded, placebo controlled trials have suggested improvements of 6 cm or more [4, 5], more rig- orous meta-analysis has suggested gains of only 4 cm [3]. Further, a Cochrane review [2] concluded that there was a paucity of data to support an effect on adult height mainly because of the lack of randomised control trials in this area. Notwithstanding these observations the Food and Drug Administration in the United States of Ameri- ca approved r-hGH therapy for this group of children. We have previously reported the effect of r-hGH in a group of FSS children noting that the overall effect on Key Words Recombinant human growth hormone  Idiopathic short stature  Short normal  Dose effect  Adult height Abstract Background/Aims: The effects of biosynthetic human growth hormone (r-hGH) in children with familial short stat- ure (FSS) are varied. We determined whether responsivity to r-hGH in FSS is dose-dependent. Method: Randomised trial of two doses (20 or 40 IU/m 2 body surface area/week by dai- ly subcutaneous injection) of r-hGH in 29 (24 male, 5 female) FSS children with assessment at adult height. Results: Age range at presentation was 5.1–10.5 years, height less than 1.5 standard deviation scores (SDS) below the mean, height ve- locity SDS greater than –1.5 and peak growth hormone re- sponse to provocative testing over 13.5 mU/l. Adult height data (SDS) at 16.5 8 2.1 years for the low-dose group and 16.1 8 1.1 years for the high-dose group (p = 0.62) were sim- ilar [low dose –1.06 (SD 0.75), high dose –1.02 (SD 0.83); p = 0.88]. The incremental effect of both doses on stature was minimal [low-dose difference in height actual-predicted 0.79 (SD 0.94), high dose 1.27 (SD 0.88); p = 0.12]. Conclusion: Using this r-hGH dosing schedule there were little short- or long-term effects on height in children with FSS. Copyright © 2008 S. Karger AG, Basel Received: May 14, 2007 Accepted: October 2, 2007 Published online: June 12, 2008 HORMONE RESEARCH Prof. Peter Hindmarsh Developmental Endocrinology Research Group, Molecular Genetics Unit Institute of Child Health, University College London 30 Guilford Street, London WC1N 1EH (UK) Tel. +20 7405 9200, ext. 2612, Fax +20 7905 2838, E-Mail p.hindmarsh@ucl.ac.uk © 2008 S. Karger AG, Basel 0301–0163/08/0702–0089$24.50/0 Accessible online at: www.karger.com/hre The study was conceived by P.C.H., M.T.D., M.A.P. and C.G.D.B. and conducted and analysed by C.J.E. and J.S.B.