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      The Effect of Recombinant Growth Hormone Treatment in Children with Idiopathic Short Stature and Low Insulin-Like Growth Factor-1 Levels

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          Abstract

          Objective:

          Idiopathic short stature (ISS) constitutes a heterogeneous group of short stature which is not associated with an endocrine or other identifiable cause. Some ISS patients may have varying degrees of insulin-like growth factor-1 (IGF-1) deficiency. Recombinant growth hormone (rGH) treatment has been used by some authors with variable results. Reports on long-term rGH treatment are limited.

          Methods:

          In this study, 21 slowly growing, non-GH-deficient ISS children who received rGH treatment for 3.62±0.92 years were evaluated at the end of a 5.42±1.67-year follow-up period. The study group included patients with low IGF-1 levels who also responded well to an IGF generation test. The patients were divided into two groups as good responders [height increment >1 standard deviation (SD)] and poor responders (height increment <1 SD) at the end of the follow-up period.

          Results:

          The height of the patients improved from -3.16±0.46 SD score (SDS) to -1.9±0.66 SDS. At the end of the follow-up period, mean height SDS was -1.72. Eleven of the patients showed a good response to treatment. Clinical parameters were essentially similar in the good responders and the poor responders groups. A female preponderance was noted in the good responders group.

          Conclusion:

          rGH treatment can safely be used in ISS children. Long-term GH treatment will ameliorate the height deficit and almost 40% of patients may reach their target height.

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          Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop.

          P. Cohen, A Rogol, C L Deal … (2008)
          Our objective was to summarize important advances in the management of children with idiopathic short stature (ISS). Participants were 32 invited leaders in the field. Evidence was obtained by extensive literature review and from clinical experience. Participants reviewed discussion summaries, voted, and reached a majority decision on each document section. ISS is defined auxologically by a height below -2 sd score (SDS) without findings of disease as evident by a complete evaluation by a pediatric endocrinologist including stimulated GH levels. Magnetic resonance imaging is not necessary in patients with ISS. ISS may be a risk factor for psychosocial problems, but true psychopathology is rare. In the United States and seven other countries, the regulatory authorities approved GH treatment (at doses up to 53 microg/kg.d) for children shorter than -2.25 SDS, whereas in other countries, lower cutoffs are proposed. Aromatase inhibition increases predicted adult height in males with ISS, but adult-height data are not available. Psychological counseling is worthwhile to consider instead of or as an adjunct to hormone treatment. The predicted height may be inaccurate and is not an absolute criterion for GH treatment decisions. The shorter the child, the more consideration should be given to GH. Successful first-year response to GH treatment includes an increase in height SDS of more than 0.3-0.5. The mean increase in adult height in children with ISS attributable to GH therapy (average duration of 4-7 yr) is 3.5-7.5 cm. Responses are highly variable. IGF-I levels may be helpful in assessing compliance and GH sensitivity; levels that are consistently elevated (>2.5 SDS) should prompt consideration of GH dose reduction. GH therapy for children with ISS has a similar safety profile to other GH indications.
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            Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial.

            Jeffrey Baron, Mary Ross, Harry A. Quigley … (2004)
            GH is often used to treat children with idiopathic short stature despite the lack of definitive, long-term studies of efficacy. We performed a randomized, double-blind, placebo-controlled trial to determine the effect of GH on adult height in peripubertal children. Subjects (n = 68; 53 males and 15 females), 9-16 yr old, with marked, idiopathic short stature [height or predicted height < or = -2.5 sd score (SDS)] received either GH (0.074 mg/kg) or placebo sc three times per week until they were near adult height. At study termination, adult height measurements were available for 33 patients after mean treatment duration of 4.4 yr. Adult height was greater in the GH-treated group (-1.81 +/- 0.11 SDS, least squares mean +/- sem) than in the placebo-treated group (-2.32 +/- 0.17 SDS) by 0.51 SDS (3.7 cm; P < 0.02; 95% confidence interval, 0.10-0.92 SDS). A similar GH effect was demonstrated in terms of adult height SDS minus baseline height SDS and adult height SDS minus baseline predicted height SDS. Modified intent-to-treat analysis in 62 patients treated for at least 6 months indicated a similar GH effect on last observed height SDS (0.52 SDS; 3.8 cm; P < 0.001; 95% confidence interval, 0.22-0.82 SDS) and no important dropout bias. In conclusion, GH treatment increases adult height in peripubertal children with marked idiopathic short stature.
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              Growth references for Turkish children aged 6 to 18 years.

              Olcay Neyzi, Rüveyde Bundak, Feyza Darendeliler … (2006)
              To create up-to-date reference standards for Turkish children, and to compare these with growth standards for US children (CDC 2000 Growth Charts) and with previous local data. Height and weight measurements of 1100 boys and 1020 girls were obtained by biannual visits to six schools located in relatively well-off districts of Istanbul city. All children came from well-to-do families and all were healthy. All measurements were made by two trained technicians. The LMS method was used in the analyses. Heights of the boys and girls in all age groups were close to the updated 2000 USA growth references and showed an increase from data on Turkish children born 30 y earlier. Weight values were high compared to reference data on US children and to the older data on Turkish children. These results indicate that height growth in Turkish school-age children of high socio-economic level conforms to the updated growth data on US children. The data also show a secular upward trend in Turkey. Weight-for-age values indicate an increase in obesity. The results also point to the value of collecting and evaluating local growth data periodically.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Clin Res Pediatr Endocrinol
                Journal ID (iso-abbrev): J Clin Res Pediatr Endocrinol
                Journal ID (publisher-id): JCRPE
                Title: Journal of Clinical Research in Pediatric Endocrinology
                Publisher: Galenos Publishing
                ISSN (Print): 1308-5727
                ISSN (Electronic): 1308-5735
                Publication date (Print): December 2015
                Publication date (Electronic): 3 December 2015
                Volume: 7
                Issue: 4
                Pages: 301-306
                Affiliations
                [1 ] Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey
                Author notes
                * Address for Correspondence: Ankara University Faculty of Medicine, Department of Pediatric Endocrinology, Ankara, Turkey Phone: +90 312 319 14 40 E-mail: zeynepsklr@ 123456gmail.com
                Article
                Publisher ID: 1549
                DOI: 10.4274/jcrpe.2111
                PMC ID: 4805225
                PubMed ID: 26777041
                SO-VID: 9800dadc-e675-4c80-a0f9-6154833f7fb3
                Copyright © © Journal of Clinical Research in Pediatric Endocrinology, Published by Galenos Publishing.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 14 May 2015
                Date accepted : 6 September 2015
                Categories
                Subject: Original Article

                ScienceOpen disciplines: Pediatrics
                Keywords: final height,growth hormone treatment,idiopathic short stature,insulin-like growth factor deficiency
                Data availability:
                ScienceOpen disciplines: Pediatrics
                Keywords: final height, growth hormone treatment, idiopathic short stature, insulin-like growth factor deficiency

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