Growth Hormone Treatment Indications in Children and Adolescents

Öz

Abstract: Until 1985 growth hormone (GH) was obtained from pituitary extracts, and was available in limited amounts only to treat severe growth hormone deficiency. Recombinant human GH has replaced human pituitary-derived GH, which should no longer be used because of the risk of contamination with the Jakob Creutzfeld prion. Although with some differences between different countries, GH treatment is indicated in children with growth hormone defixiency, Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, deletions/mutations of the SHOX gene, as well as in short children born small for gestational age and with idiopathic short stature. For pediatric patients, guidelines fort he use of GH have been developed by several organizations that have identified specific criteria for initiating GH therapy. In this manuscript, we summarize the growth hormone treatment indications among pediatric and transition patients. 

Anahtar Kelimeler

• growth hormone; turner syndrome,prader-willi syndrome,shox deficiency,small for gestational age

Çocuklarda ve Ergenlerde Büyüme Hormonu Tedavisi Endikasyonları

Öz

Öz: 1985 yılına kadar büyüme hormonu hipofizer ekstrelerinden elde ediliyordu ve çok sınırlı sayıda ciddi büyüme hormonu eksikliği (BHE) olan hastalarda kullanılıyordu. Rekombinant DNA teknolojisi ile BH yeterli miktarda üretilmeye başlandıktan sonra çocuklarda büyüme hormonu tedavi endikasyonları genişleyerek, büyüme hormonu eksikliği olmayan hastalıklara bağlı boy kısalıklarında da kullanılmaya başladı. Ülkeler arasında BH tedavi endikasyonları farklılık göstermekle birlikte, BH tedavi endikasyonları içerisine BHE, Turner sendromu (TS), kronik böbrek yetmezliği (KBY), Prader-Willi sendromu (PWS), SHOX geni delsyonu veya mutasyonu, gestasyon yaşına göre düşük doğum ağırlıklı (SGA) ve boy kısalığı olan çocuklar ve idiopatik boy kısalıkları girmektedir. Pediatrik hastalar için birçaok organizasyon tarafından büyüme hormonu tedavisinin başlanması kriterleri tanımlanmıştır. Biz bu yazıda pediatrik ve adölesan hastalarda büyüme hormonu tedavisi endikasyonlarını özetledik. 

Anahtar Kelimeler

• Büyüme hormonu; boy kısalığı

Kaynakça

1. 1. Wilson TA, Rose SR, Cohen P, Rogol AD, Backeljauw P, Brown R, Hardin DS, Kemp SF, Lawson M, Radovick S, Rosenthal SM, Silverman L, Speiser P; Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee (2003) Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr, 143(4), 415-421.
2. 2. Davenport ML (2010) Approach to the patient with Turner syndrome. J Clin Endocrinol Metab, 95 (4), 1487-1495.
3. 3. Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, Muroya K, Binder G, Kirsch S, Winkelmann M, Nordsiek G, Heinrich U, Breuning MH, Ranke MB, Rosenthal A, Ogata T, Rappold GA (1997) Pseudootosomal deletions encompassing a novel homebox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet, 16 (1), 54-63.
4. 4. Soucek O, Zapletalova J, Zemkova D, Snajderova M, Novotna D, Hirschfeldova K, Plasilova I, Kolouskova S, Rocek M, Hlavka Z, Lebl J, Sumnik Z (2013) Prepubertal girls with Turner syndrome and children with isolated SHOX deficiency have similar bone geometry at the Radius. J Clin Endocrinol Metab, 98 (7), E1241-E1247.
5. 5. Stephure DK; Canadian Growth Hormone Advisory Committee (2005) Impact of growth hormone supplementation on adult height in turner syndrome: results of the Canadian randomized controlled trial. J Clin Endocrinol Metab, 90 (6), 3360-3366.
6. 6. Ross JL, Quigley CA, Cao D, Feuillan P, Kowal K, Chipman JJ, Cutler GB Jr (2011) Growth hormone plus childhood low-dose estrogen in Turner syndrome. N Eng J Med 364 (13), 1230-1242.
7. 7. Davenport ML, Crowe BJ, Travers SH, Davenport ML, Crowe BJ, Travers SH, Rubin K, Ross JL, Fechner PY, Gunther DF, Liu C, Geffner ME, Thrailkill K, Huseman C, Zagar AJ, Quigley CA (2007) Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized controlled, multicenter trial. J Clin Endocrinol Metab, 92(9), 3406-3416.
8. 8. Linglart A, Cabrol S, Berlier P, Linglart A, Cabrol S, Berlier P, Stuckens C, Wagner K, de Kerdanet M, Limoni C, Carel JC, Chaussain JL; French Collaborative Young Turner Study Group (2011) Growth hormone treatment before the age of 4 years prevents short stature in young girls with Turner syndrome. Eur J Endocrinol, 164(6),891-897.

9. 9. Bondy CA; Turner Syndrome Study Group (2007) Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab, 92(1):10-25.
10. 10. Baxter I, Bryant J, Cave CB, Milne R (2007) Recombinant growth hormon for children and adolescents with Turner syndrome. Cochrane Database Syst Rev, (1):CD003887.
11. 11. Menke LA, Sas TC, de Muinck Keizer-Schrama SM, Zandwijken GR, de Ridder MA, Odink RJ, Jansen M, Delemarre-van de Waal HA, Stokvis-Brantsma WH, Waelkens JJ, Westerlaken C, Reeser HM, van Trotsenburg AS, Gevers EF, van Buuren S, Dejonckere PH, Hokken-Koelega AC, Otten BJ, Wit JM (2010) Efficacy and safety of oxandrolone in growth hormone-treated girls with turner syndrome. J Clin Endocrinol Metab, 95(3)1151–1160.
12. 12. Gault EJ, Perry RJ, Cole TJ, Casey S, Paterson WF, Hindmarsh PC, Betts P, Dunger DB, Donaldson MD; British Society for Paediatric Endocrinology and Diabetes (2011) Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial. BMJ, 342:d1980.
13. 13. Quigley CA, Crowe BJ, Anglin DG, Chipman JJ (2002) Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height. J Clin Endocrinol Metab, 87(5), 2033–2041.
14. 14. van Pareren YK, de Muinck Keizer-Schrama SM, Stijnen T, Sas TC, Jansen M, Otten BJ, Hoorweg-Nijman JJ, Vulsma T, Stokvis-Brantsma WH, Rouwé CW, Reeser HM, Gerver WJ, Gosen JJ, Rongen-Westerlaken C, Drop SL (2003) Final height in girls with turner syndrome after long-term growth hormone treatment in three dosages and low dose estrogens. J Clin Endocrinol Metab, 88(3),1119–1125.
15. 15. Clayton PE, Cianfarani S, Czernichow P, Johannsson G, Rapaport R, Rogol A (2007) Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab, 92(3), 804–810.
16. 16. Van Pareren Y, Mulder P, Houdijk M, Jansen M, Reeser M, Hokken-Koelega A (2003) Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose-response GH trial. J Clin Endocrinol Metab, 88(8), 3584–3590.
17. 17. Carel JC, Chatelain P, Rochiccioli P, Chaussain JL (2003) Improvement in adult height after growth hormone treatment in adolescents with short stature born small for gestational age: results of a randomized controlled study. J Clin Endocrinol Metab, 88 (4), 1587–1593.
18. 18. Dahlgren J, Wikland KA (2005) Swedish Study Group for Growth Hormone Treatment. Final height in short children born small for gestational age treated with growth hormone. Pediatr Res, 57(2), 216–222.
19. 19. van Dijk M, Bannink EM, van Pareren YK, Mulder PG, Hokken-Koelega AC (2007) Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (sga) and untreated short SGA controls. J Clin Endocrinol Metab 92 (1), 160–165.
20. 20. Maiorana A, Cianfarani S (2009) Impact of growth hormone therapy on adult height of children born small for gestational age. Pediatrics, 124(3): e519–e531.
21. 21. Willemsen RH, Arends NJ, Bakker-van Waarde WM, Jansen M, van Mil EG, Mulder J, Odink RJ, Reeser M, Rongen-Westerlaken C, Stokvis-Brantsma WH, Waelkens JJ, Hokken-Koelega AC (2007) Long-term effects of growth hormone (GH) treatment on body composition and bone mineral density in short children born smallfor-gestational-age: six-year follow-up of a randomized controlled GH trial. Clin Endocrinol (Oxf), 67(4),485–492.
22. 22. Schweizer R, Martin DD, Schonau E, Ranke MB (2009) Muscle function improves during growth hormone therapy in short children born small for gestational age: results of a peripheral quantitative computed tomography study on body composition. J Clin Endocrinol Metab, 93(8), 2978–2983.
23. 23. Mehls O, Wuhl E, Tonshoff B, Schaefer F, Nissel R, Haffner D (2008) Growth hormone treatment in short children with chronic kidney disease. Acta Paediatr, 97 (9), 1159–1164.
24. 24. Hodson EM, Willis NS, Craig JC (2012) Growth hormone for children with chronic kidney disease. Cochrane Database Syst Rev, 2, CD003264.
25. 25. Haffner D, Schaefer F, Nissel R, Wuhl E, Tonshoff B, Mehls O. German Study Group for Growth Hormone Treatment in Chronic Renal Failure (2000) Effect of growth hormone treatment on the adult height of children with chronic renal failure. N Engl J Med, 343(13),923–930.
26. 26. Nissel R, Lindberg A, Mehls O, Haffner D. Pfizer International Growth Database (KIGS) International Board. Factors predicting the near-final height in growth hormone-treated children and adolescents with chronic kidney disease. J Clin Endocrinol Metab, 93(4), 1359–1365.
27. 27. Cassidy SB, Schwartz S, Miller JL, Driscoll DJ (2012) Prader-Willi syndrome. Genet Med, 14 (1), 10–26.
28. 28. Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M; speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS (2008) Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab, 93(11),4183-4197.
29. 29. Cappa M, Grossi A, Borrelli P, Ghigo E, Bellone J, Benedetti S, Carta D, Loche S (1993) Growth hormone (GH) response to combined pyridostigmine and GH-releasing hormone administration in patients with Prader-Labhard-Willi syndrome. Horm Res, 39(1-2), 51–55.
30. 30. Tauber M, Barbeau C, Jouret B, Pienkowski C, Malzac P, Moncla A, Rochiccioli P (2000) Auxological and endocrine evolution of 28 children with Prader-Willi syndrome: effect of GH therapy in 14 children. Horm Res, 53(6), 279–287.
31. 31. Eiholzer U, Stutz K, Weinmann C, Torresani T, Molinari L, Prader A (1998) Low insulin, IGF-I and IGFBP-3 levels in children with Prader-Labhart-Willi syndrome. Eur J Pediatr, 157 (11), 890–893.
32. 32. Bakker NE, Kuppens RJ, Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, Bindels-de Heus GC, Bocca G, Haring DA, Hoorweg-Nijman JJ, Houdijk EC, Jira PE, Lunshof L, Odink RJ, Oostdijk W, Rotteveel J, Schroor EJ, Van Alfen AA, Van Leeuwen M, Van Pinxteren-Nagler E, Van Wieringen H, Vreuls RC, Zwaveling-Soonawala N, de Ridder MA, Hokken-Koelega AC (2013) Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects. J Clin Endocrinol Metab, 98(10), 4013–4022.
33. 33. Siemensma EP, Tummers-de Lind van Wijngaarden RF, Festen DA, Troeman ZC, van Alfen-van der Velden AA, Otten BJ, Rotteveel J, Odink RJ, Bindels-de Heus GC, van Leeuwen M, Haring DA, Oostdijk W, Bocca G, Mieke Houdijk EC, van Trotsenburg AS, Hoorweg-Nijman JJ, van Wieringen H, Vreuls RC, Jira PE, Schroor EJ, van Pinxteren-Nagler E, Willem Pilon J, Lunshof LB, Hokken-Koelega AC (2012) Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study. J Clin Endocrinol Metab, 97(7), 2307–2314.
34. 34. Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS, 2011 Growth Hormone in Prader-Willi Syndrome Clinical Care Guidelines Workshop Participants. Growth Hormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab, 98(6), E1072–E1087.
35. 35. Festen DA, Wevers M, Lindgren AC, Böhm B, Otten BJ, Wit JM, Duivenvoorden HJ, Hokken-Koelega AC (2008) Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome. Clin Endocrinol (Oxf), 68(6), 919–925.
36. 36. Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA (2010) Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics, 126(4), 746-759.
37. 37. Roberts AE, Allanson JE, Tartaglia M, Gelb BD (2013) Noonan syndrome. Lancet , 81(9863), 333–342.
38. 38. Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA (2010) Noonan syndrome: clinical features, diagnosis, and management guidelines. Pediatrics, 126 (4),746–759.
39. 39. Binder G, Neuer K, Ranke MB, Wittekindt N (2005) PTPN11 mutations are associated with mild growth hormone resistance in individuals with Noonan syndrome. J Clin Endocrinol Metab, 90(9), 5377–5381.
40. 40. Noordam C, Peer PG, Francois I, De Schepper J, van den Burgt I, Otten BJ (2008) Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, nonreceptor-type 11. Eur J Endocrinol, 159(3), 203–208.
41. 41. Romano AA, Dana K, Bakker B, Davis DA, Hunold JJ, Jacobs J (200) Growth response, near-adult height, and patterns of growth and puberty in patients with noonan syndrome treated with growth hormone. J Clin Endocrinol Metab, 94(7), 2338–2344.
42. 42. Munns CJ1, Haase HR, Crowther LM, Hayes MT, Blaschke R, Rappold G, Glass IA, Batch JA (2004) Expression of SHOX in human fetal and childhood growth plate. J Clin Endocrinol Metab, 89(8), 4130–4135.
43. 43. Binder G (2011) Short stature due to SHOX deficiency: genotype, phenotype, and therapy. Horm Res Paediatr, 75:81–89.
44. 44. Rosilio M, Huber-Lequesne C, Sapin H, Carel JC, Blum WF, Cormier-Daire V (2012) Genotypes and phenotypes of children with SHOX deficiency in France. J Clin Endocrinol Metab, 97(7), E1257–E1265.
45. 45. Blum WF1, Crowe BJ, Quigley CA, Jung H, Cao D, Ross JL, Braun L, Rappold G; SHOX Study Group (2007) Growth hormone is effective in treatment of short stature associated with short stature homeobox-containing gene deficiency: two-year results of a randomized, controlled, multicenter trial. J Clin Endocrinol Metab 92(1) 219–228.
46. 46. Blum WF, Ross JL, Zimmermann AG, Quigley CA, Child CJ, Kalifa G, Deal C, Drop SL, Rappold G, Cutler GB Jr (2013) GH treatment to final height produces similar height gains in patients with SHOX deficiency and Turner syndrome: results of a multicenter trial. J Clin Endocrinol Metab, 98(8), E1383–E1392.
47. 47. Cohen P1, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM (2008) 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, 93(11), 4210–4217.
48. 48. Loche S, Casini MR, Ubertini GM, Cappa M (2005) Growth hormone treatment in non-growth hormone-deficient short children. J Endocrinol Invest, 28(2), 193–198.
49. 49. Hindmarsh PC, Brook CG (1987) Effect of growth hormone on short normal children. Br Med J (Clin Res Ed), 295(6598), 573–577.
50. 50. Hopwood NJ, Hintz RL, Gertner JM, Attie KM, Johanson AJ, Baptista J, Kuntze J, Blizzard RM, Cara JF, Chernausek SD (1993) Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy. J Pediatr, 123(2), 215–222.
51. 51. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM; 2007 ISS Consensus Workshop participants (2008) 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 93(11), 4210-4217.
52. 52. Leschek EW, Rose SR, Yanovski JA, Troendle JF, Ross JL, Quigley CA (2001) Effect of growth hormone treatement on the final height of children with non-growth hormone-deficient short stature: a randomized, doubleblind, placebo-controlled trial. Pediatr Res, 49(3), 17A,#OR9-96.
53. 53. Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society (2001). J Clin Endocrinol Metab, 86,1868-1870.
54. 54. Clayton PE, Cowell CT (2000) Safety issues in children and adolescents during growth hormone therapy—a review. Growth Horm IGF Res 10(6), 306-317.
55. 55. Fine RN, Sullivan EK, Kuntze J, Blethen S, Kohaut E (2000) The impact of recombinant human growth hormone treatment during chronic renal insufficiency on renal transplant recipients. J Pediatr, 136 (3), 76-82