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

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.

Kaynakça

Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM; 2007 ISS Consensus Workshop participants. 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. J Clin Endocrinol Metab 2008;93:4210-4217. Epub 2008 Sep 9

Collett-Solberg PF. Update in growth hormone therapy of children. J Clin Endocrinol Metab 2011;96:573-579.

Cohen P, Rogol AD, Weng W, Kappelgaard AM, Rosenfeld RG, Germak J; American Norditropin Study Group. Efficacy of IGF-based growth hormone (GH) dosing in nonGH-deficient (nonGHD) short stature children with low IGF-I is not related to basal IGF-I levels. Clin Endocrinol (Oxf) 2013;78:405-414.

Park P, Cohen P. Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS). Growth Horm IGF Res 2005;15(Suppl A):13-20.

Cohen J, Blethen S, Kuntze J, Smith SL, Lomax KG, Mathew PM. Managing the child with severe primary insulin-like growth factor-1 deficiency (IGFD): IGFD diagnosis and management. Drugs R D 2014;14:25-29.

Savage MO, Camacho-Hübner C, David A, Metherell LA, Hwa V, Rosenfeld RG, Clark AJ. Idiopathic short stature: will genetics influence the choice between GH and IGF-I therapy? Eur J Endocrinol 2007:157(Suppl 1):33-37.

Teissier R, Flechtner I, Colmenares A, Lambot-Juhan K, Baujat G, Pauwels C, Samara-Boustani D, Beltrand J, Simon A, Thalassinos C, Crosnier H, Latrech H, Pinto G, Le Merrer M, Cormier-Daire V, Souberbielle JC, Polak M. Characterization and prevalence of severe primary IGF1 deficiency in a large cohort of French children with short stature. Eur J Endocrinol 2014;170:847-854. Epub 2014 Mar 24

Wit JM, Rekers-Mombarg LT; Dutch Growth hormone Advisory Group. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab 2002;87:604-611.

Hintz RL. Growth hormone treatment of idiopathic short stature: clinical studies. Growth Horm IGF Res 2005;15(Suppl A):6-8.

Blum WF, Cotterill AM, Postel-Vinay MC, Ranke MB, Savage MO, Wilton P. Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls. Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes. Acta Paediatr Suppl 1994;399:117-124.

Bundak R, Furman A, Gunoz H, Darendeliler F, Bas F, Neyzi O. Body mass index references for Turkish children. Acta Paediatr 2006;95:194-198.

Neyzi O, Furman A, Bundak R, Gunoz H, Darendeliler F, Bas F. Growth references for Turkish children aged 6-18 years. Acta Paediatr 2006;95:1635-1641.

Bundak R, Darendeliler F, Günöz H, Baş F, Saka N, Neyzi O. Puberty and pubertal growth in healthy Turkish girls: no evidence for secular trend. J Clin Res Pediatr Endocrinol 2008;1:8-14. Epub 2008 Aug 2

Radetti G, D'Addato G, Gatti D, Bozzola M, Adami S. Influence of two different GH dosage regimens on final height, bone geometry and bone strength in GH-deficient children. Eur J Endocrinol 2006;154:479-482.

Pedicelli S, Peschiaroli E, Violi E, Cianfarani S. Controversies in the definition and treatment of idiopathic short stature (ISS). J Clin Res Pediatr Endocrinol 2009;1:105-115. Epub 2009 Feb 1

Edouard T, Grünenwald S, Gennero I, Salles JP, Tauber M. Prevalence of IGF1 deficiency in prepubertal children with isolated short stature. Eur J Endocrinol 2009;161:43-50.Epub 2009 May 5

Leschek EW, Rose SR, Yanovski JA, Troendle JF, Quigley CA, Chipman JJ, Crowe BJ, Ross JL, Cassorla FG, Blum WF, Cutler GB Jr, Baron J; National Institute of Child Health and Human Development-Eli Lilly & Co. Growth Hormone Collaborative Group. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2004;89:3140-3148.

Kemp SF, Kuntze J, Attie KM, Maneatis T, Butler S, Frane J, Lippe B.Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature. J Clin Endocrinol Metab 2005;90:5247-5253. Epub 2005 Jul 5

Albertsson-Wikland K, Aronson AS, Gustafsson J, Hagenäs L, Ivarsson SA, Jonsson B, Kriström B, Marcus C, Nilsson KO, Ritzén EM, Tuvemo T, Westphal O, Aman J. Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency. J Clin Endocrinol Metab 2008;93:4342-4350. Epub 2008 Aug 26

Bryant J, Baxter L, Cave CB, Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev 2007;CD004440.

Cohen P, Germak J, Rogol AD, Weng W, Kappelgaard AM, Rosenfeld RG; American Norditropin Study Group. Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children. J Clin Endocrinol Metab 2010;95:2089-2098. Epub 2010 Mar 5

Rogol AD, Blethen SL, Sy JP, Veldhuis JD. Do growth hormone (GH) serial sampling, insulin-like growth factor-I (IGF-I) or auxological measurements have an advantage over GH stimulation testing in predicting the linear growth response to GH therapy? Clin Endocrinol (Oxf) 2003;58:229- 237.

Elder CJ, Barton JS, Brook CG, Preece MA, Dattani MT, Hindmarsh PC. A randomised study of the effect of two doses of biosynthetic human growth hormone on final height of children with familial short stature. Horm Res 2008;70:89- 92. Epub 2008 Jun 12

Wit JM, van Duyvenvoorde HA, Scheltinga SA, de Bruin S, Hafkenscheid L, Kant SG, Ruivenkamp CA, Gijsbers AC, van Doorn J, Feigerlova E, Noordam C, Walenkamp MJ, Claahsen-van de Grinten H, Stouthart P, Bonapart IE, Pereira AM, Gosen J, Delemarre-van de Waal HA, Hwa V, Breuning MH, Domené HM, Oostdijk W, Losekoot M. Genetic analysis of short children with apparent growth hormone insensitivity. Horm Res Paediatr 2012;77:320-333. Epub 2012 Jun 6

Kaynak Göster