Pediatric growth hormone therapy in Greece: analysis of the Hellenic cohort of the GeNeSIS study
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To describe the data from the Greek cohort of the Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS).
GeNeSIS was a prospective, open-label, multinational, observational study collecting information on clinical outcomes and treatment safety of children with growth disorders treated with growth hormone (GH), according to national indications. After informed consent, 305 patients (143 females), including 255 patients with growth hormone deficiency (GHD) and 30 with Turner syndrome (TS), from eight investigational sites, were enrolled in Greece. Demographic data, treatment efficacy, and adverse events were reported at the discretion of attending physicians.
Treatment with GH was undertaken for 247/255 patients with GHD and 29/30 with TS. The majority of patients treated with GHD (73.7%) and TS (84%) with recorded Tanner stage were prepubertal at enrolment. Among patients treated with GHD and TS, 70.45% and 55% were GH-naïve at study entry, respectively. Height standard deviation score (SDS), height velocity SDS, and height SDS-target height SDS numerically improved during the 4-year observation period. The effect of GH treatment was more prominent in the first year of treatment, especially in the GHD group.
In the Greek cohort of GeNeSIS, GHD is the most frequent indication for GH treatment, followed by TS. While the latter is diagnosed somewhat earlier, GH treatment is not as efficacious as for patients with GHD. No major safety issues were reported during follow-up. The results, which are in accordance with the international literature, should be interpreted in the context of observational studies.
KeywordsGrowth hormone Turner syndrome Children Growth hormone treatment Height velocity
The authors would like to thank Christopher Jeremy Child, Research Advisor, for the help in the preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
A.K and D.E. are employed by Pharmaserve Lilly SACI. The GeNeSIS study was sponsored by Eli-Lilly.
- 2.Grimberg A, DiVall SA, Polychronakos C et al (2016) Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr 19104:361–397. https://doi.org/10.1159/000452150 CrossRefGoogle Scholar
- 3.Gravholt CH, Andersen NH, Conway GS et al (2017) Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol 177:G1–G70. https://doi.org/10.1530/EJE-17-0430 CrossRefPubMedGoogle Scholar
- 7.Raman S, Grimberg A, Waguespack SG et al (2015) Risk of neoplasia in pediatric patients receiving growth hormone therapy--a report from the Pediatric Endocrine Society Drug and Therapeutics Committee. J Clin Endocrinol Metab 100:2192–2203. https://doi.org/10.1210/jc.2015-1002 CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Ranke MB, Lindberg A, Tanaka T et al (2017) Baseline characteristics and gender differences in prepubertal children treated with growth hormone in Europe, USA, and Japan: 25 years’ KIGS® experience (1987-2012) and review. Horm Res Paediatr 87:30–41. https://doi.org/10.1159/000452887 CrossRefPubMedGoogle Scholar
- 9.Kaplowitz PB, Shulman DI, Frane JW et al (2013) Characteristics of children with the best and poorest first- and second-year growth during rhGH therapy: data from 25 years of the Genentech national cooperative growth study (NCGS). Int J Pediatr Endocrinol 2013:9. https://doi.org/10.1186/1687-9856-2013-9 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Swerdlow AJ, Cooke R, Albertsson-Wikland K et al (2015) Description of the SAGhE cohort: a large European study of mortality and cancer incidence risks after childhood treatment with recombinant growth hormone. Horm Res Paediatr 84:172–183. https://doi.org/10.1159/000435856 CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Humatrope 6mg powder and solvent for solution for injection - Summary of Product Characteristics (SmPC) - (eMC). https://www.medicines.org.uk/emc/product/3780/smpc. Accessed 14 Jul 2019
- 16.Preece MA (1994) Evaluation of growth and development. In: Holliday M, Barratt T, Avner E, Kogan B (eds) Pediatric nephrology, 3rd edn. Williams & Wilkins, Baltimore, pp 378–396Google Scholar
- 20.Deal C, Hasselmann C, Pfäffle RW et al (2013) Associations between pituitary imaging abnormalities and clinical and biochemical phenotypes in children with congenital growth hormone deficiency: data from an international observational study. Horm Res Paediatr 79:283–292. https://doi.org/10.1159/000350829 CrossRefPubMedGoogle Scholar
- 24.Ranke MB, Lindberg A, Chatelain P et al (1999) Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. KIGS International Board. Kabi Pharmacia International Growth Study. J Clin Endocrinol Metab 84:1174–1183. https://doi.org/10.1210/jcem.84.4.5634 CrossRefPubMedGoogle Scholar
- 25.Pfäffle R, Land C, Schönau E et al (2018) Growth hormone treatment for short stature in the USA, Germany and France: 15 years of surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS). Horm Res Paediatr 90:169–180. https://doi.org/10.1159/000492397 CrossRefPubMedGoogle Scholar
- 27.Sas TC, de Muinck Keizer-Schrama SM, Stijnen T et al (1999) Normalization of height in girls with Turner syndrome after long-term growth hormone treatment: results of a randomized dose-response trial. J Clin Endocrinol Metab 84:4607–4612. https://doi.org/10.1210/jcem.84.12.6241 CrossRefPubMedGoogle Scholar
- 31.Polak M, Blair JC, Kotnik P, et al (2017) Early growth hormone treatment start in childhood growth hormone deficiency improves near adult height: analysis from NordiNet(®) International Outcome Study. Eur J Endocrinol EJE-16-1024. https://doi.org/10.1530/EJE-16-1024
- 36.Ranke M, Lindberg A, Chatelain P et al (1999) Predicting the response to recombinant human growth hormone in Turner syndrome: KIGS models. Acta Paediatr 88:122–125. https://doi.org/10.1111/j.1651-2227.1999.tb14420.x CrossRefGoogle Scholar
- 39.Witbreuk M, van Kemenade FJ, van der Sluijs JA et al (2013) Slipped capital femoral epiphysis and its association with endocrine, metabolic and chronic diseases: a systematic review of the literature. J Child Orthop 7:213–223. https://doi.org/10.1007/s11832-013-0493-8 CrossRefPubMedPubMedCentralGoogle Scholar
- 45.Baxter L, Bryant J, Cave CB, Milne R (2007) Recombinant growth hormone for children and adolescents with Turner syndrome. In: Bryant J (ed) Cochrane database of systematic reviews. John Wiley & Sons, Ltd, Chichester, p CD003887Google Scholar
- 47.Quigley CA, Child CJ, Zimmermann AG et al (2017) Mortality in children receiving growth hormone treatment for growth disorders: data from the GeNeSIS observational program. J Clin Endocrinol Metab. https://doi.org/10.1210/jc.2017-00214