Response to growth hormone therapy in Turner syndrome

Abstract

Aim: Short stature a common feature of Turner syndrome may be treated effectively by recombinant human growth hormone rhGH In this study we aimed to evaluate response to rhGH in the first three years of therapy Material and Method: Medical records of 46 girls with Turner syndrome treated with rhGH were evaluated retrospectively Karyotypes age of admission to the hospital age of the beginning of rhGH therapy the height of the mother and father were recorded Data including height and weight growth velocity dose of rhGH therapy bone age and predicted height of subjects at the beginning after first second and thirds years of rhGH therapy were recorded Difference between target height Z score and height Z score is defined as delta Z score Results: Age of admission to hospital age of beginning of rhGH therapy target height were 10 2 plusmn;3 8 years 11 54 plusmn;3 03 years and 157 0 plusmn;6 0 cm respectively Height Z score at the beginning at the end of first second and thirds year of therapy were 3 76 plusmn;1 00 3 37 plusmn; 1 01 2 99 plusmn;0 97 2 82 plusmn;1 01 respectively and growth velocity were 3 24 plusmn;1 05 6 53 plusmn;1 52 5 77 plusmn;1 53 5 19 plusmn;1 25 cm per year respectively Bivariate correlation analyzes have revealed that at the first year of therapy growth velocity was correlated negatively with chronologic and bone age of beginning to GH therapy delta Z score and father rsquo;s height and positively with rhGH dose Conclusions: Major factors to affect response to rhGH therapy were age rhGH dose and delta Z score As the major predictor of the growth velocity is age at the beginning of the therapy these girls must be treated with rhGH as soon as possible after diagnosis Turk Arch Ped 2013; 48: 294 8

Keywords

• Growth hormone, treatment, Turner syndrome

Turner sendromlu hastalarda büyüme hormonu tedavisine yanıt

Öz

Amaç: Turner sendromlu hastalarda boy kısalığı büyüme hormonu ile tedavi edilebilmektedir Bu çalışmada Turner sendromlu Türk çocuklarında üç yıllık büyüme hormonu tedavisine yanıtı ve tedavi sırasında büyümeye etki edebilecek etmenlerin değerlendirilmesi amaçlanmıştır Gereç ve Yöntem: Büyüme hormonu tedavisi almış 46 Turner sendromlu hastanın tıbbi kayıtları geriye dönük olarak incelendi Karyotip hastaneye başvuru yaşı büyüme hormonu tedavisi başlama yaşı anne ve baba boyları ayrıca tedavinin başlangıcında birinci ikinci ve üçüncü yıllarında çocuğun boy ağırlık yıllık büyüme hızı büyüme hormonu dozu kemik yaşı ve öngörülen boy değerleri kaydedildi Hedef boy Z skoru ve var olan boy Z skoru arasındaki fark delta Z skor olarak ifade edildi Bulgular: Hastaneye başvuru yaşı 10 2 plusmn;3 8 yıl tedavi başlangıç yaşı 11 54 plusmn;3 03 yıl ve hedef boy 157 0 plusmn;6 0 cm idi Tedavinin başlangıcında birinci ikinci ve üçüncü yılında boy Z skoru sırasıyla 3 76 plusmn;1 00 3 37 plusmn;1 01 2 99 plusmn;0 97 2 82 plusmn;1 01 olarak saptandı yıllık büyüme hızı ise yine sırasıyla 3 24 plusmn;1 05 6 53 plusmn;1 52 5 77 plusmn;1 53 5 19 plusmn;1 25 cm idi Birinci yıl büyüme hızı ile tedavi başlangıcındaki kronolojik ve kemik yaşı delta Z skor ve baba boyu ile negatif ilişki büyüme hormonu dozu ile arasında ise pozitif ilişki saptandı Çoklu regresyon analizlerinde birinci yıl büyüme hızına etki eden en önemli etmenin tedavi başlangıç yaşı ve büyüme hormonu dozu olduğu görüldü Çıkarımlar: Birinci yıl büyüme hızını etkileyen etmenler; tedavi başlangıç yaşı büyüme hormonu dozu ve delta Z skor olarak saptandı Bu çalışma tanı sonrası çok kısa bir sürede tedavi başlanmasının önemli olduğunu göstermektedir Türk Ped Arfl 2013; 48: 294 8

Anahtar Kelimeler

• Büyüme hormonu, tedavi, Turner sendromu

Kaynakça

1. Spiliotis BE. Recombinant human growth hormone in the treatment of Turner syndrome. Ther Clin Risk Manag 2008; 4(6): 1177Bereket A, Turan S, Elçioğlu N, et al. Adult height in Turkish patients with Turner syndrome without growth hormone treatment. Turk J Pediatr 2008; 50: 415-7.
2. Tanner JM, Whitehouse RH, Hughes PC, Vince FP. Effect of human growth hormone treatment for 1 to 7 years on growth of 100 children, with growth hormone deficiency, low birthweight, inherited smallness, Turner’s syndrome, and other complaints. Arch Dis Child 1971; 46: 745-82.
3. Rosenfeld RG, Frane J, Attie KM, et al. Six-year results of a randomized, prospective trial of human growth hormone and oxandrolone in Turner syndrome. J Pediatr 1992; 121: 49-55.
4. Sas TC, de Muinck Keizer-Schrama SM, Stijnen T, et al. Normalization of height in girls with Turner syndrome after longterm growth hormone treatment: results of a randomized doseresponse trial. J Clin Endocrinol Metab 1999; 84: 4607-12.
5. Van den Broeck J, Massa GG, Attanasio A, et al. Final height after long-term growth hormone treatment in Turner syndrome. European Study Group. J Pediatr 1995; 127: 729-35. Özgen ve ark.
6. Turner sendromu ve büyüme hormonu tedavisi / Turner syndrome and growth hormone therapy Braz AF, Costalonga EF, Montenegro LR, et al. The interactive effect of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms on rhGH responsiveness and treatment outcomes in patients with Turner syndrome. J Clin Endocrinol Metab 2012; 97: 671-7.
7. Ranke MB, Lindberg A, Chatelain P, et al. Prediction of longterm response to recombinant human growth hormone in Turner syndrome: development and validation of mathematical models. KIGS International Board. Kabi International Growth Study. J Clin Endocrinol Metab 2000; 85: 4212-8.
8. Neyzi O, Furman A, Bundak R, Gunoz H, Darendeliler F, Bas F. Growth references for Turkish children aged 6 to 18 years. Acta Paediatr 2006; 95: 1635-41.

9. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr 1952; 40: 423-41.
10. Cole TJ. The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990; 44: 45-60.
11. Linglart A, Cabrol S, Berlier P, et al. Growth hormone treatment before the age of 4 years prevents short stature in young girls with Turner syndrome. Eur J Endocrinol 2011; 164: 891-7.
12. Ross J, Lee PA, Gut R, Germak J. Impact of age and duration of growth hormone therapy in children with Turner syndrome. Horm Res Paediatr 2011; 76: 392-9.
13. Schonhoff P, Körner A, Kratzsch J, Pfäffle R, Kiess W. Long term clinical management of girls with Turner syndrome at a center of pediatric endocrinology. Exp Clin Endocrinol Diabetes 2011; 119: 327Elleuch M, Mnif Feki M, Kammoun M, et al. Descriptive analyses of Turner syndrome: 49 cases in Tunisia. Ann Endocrinol (Paris) 2010; 71: 111-6.
14. Bakker B, Frane J, Anhalt H, Lippe B, Rosenfeld RG. Height velocity targets from the national cooperative growth study for first-year growth hormone responses in short children. J Clin Endocrinol Metab 2008; 93: 352-7. van Pareren YK, de Muinck Keizer-Schrama SM, Stijnen T, et al. Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens. J Clin Endocrinol Metab 2003; 88: 1119-25.
15. Reh CS, Geffner ME. Somatotropin in the treatment of growth hormone deficiency and Turner syndrome in pediatric patients: a review. Clin Pharmacol 2010; 2: 111-22.
16. Bannink EM, van Doorn J, Stijnen T, et al. Free dissociable insulin-like growth factor I (IGF-I), total IGF-I and their binding proteins in girls with Turner syndrome during long-term growth hormone treatment. Clin Endocrinol (Oxf) 2006; 65: 310Ranke MB, Lindberg A, Brosz M, et al. Accurate long-term prediction of height during the first four years of growth hormone treatment in prepubertal children with growth hormone deficiency or Turner Syndrome. Horm Res Paediatr 2012; 78: 8-17.
17. Geffner ME, Dunger DB. Future directions: growth prediction models. Horm Res 2007; 68(Suppl 5): 51-6.