Clinical and Experimental Pediatrics

대한소아청소년과학회 (The Korean Pediatric Society)
권호 표지
DOI QR코드

DOI QR Code

성장호르몬 자극검사가 정상인 성장 장애 소아 환자에게서 성장호르몬 투여에 따른 성장속도의 변화

Growth responses to growth hormone therapy in children with attenuated growth who showed normal growth hormone response to stimulation tests

  • 김재현 (서울대학교 의과대학 소아과학교실) ;
  • 정혜림 (분당서울대학교병원 소아청소년과) ;
  • 이영아 (서울대학교 의과대학 소아과학교실) ;
  • 이선희 (서울대학교 의과대학 소아과학교실) ;
  • 김지현 (서울대학교 의과대학 소아과학교실) ;
  • 신충호 (서울대학교 의과대학 소아과학교실) ;
  • 양세원 (서울대학교 의과대학 소아과학교실)
  • Kim, Jae-Hyun (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Chung, Hye-Rim (Department of Pediatrics, Seoul National University Bundang Hospital) ;
  • Lee, Young-Ah (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Lee, Sun-Hee (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Kim, Ji-Hyun (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Shin, Choong-Ho (Department of Pediatrics, College of Medicine, Seoul National University) ;
  • Yang, Sei-Won (Department of Pediatrics, College of Medicine, Seoul National University)
  • 투고 : 2009.05.23
  • 심사 : 2009.07.17
  • 발행 : 2009.08.15
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

목 적 : 성장 장애는 영아 및 소아에서 성장 속도가 같은 성별, 연령 보다 현저히 작은 경우를 지칭하며 여러 가지 원인에 의해서 발생할 수 있다. 저신장을 주소로 내원한 환자 중 성장 장애를 보이지만 성장호르몬 자극검사가 정상인 환자들의 임상적 특성 및 성장호르몬 치료에 대한 반응을 알아보고자 하였다. 방 법 : 1990년 1월부터 2008년 6월까지 서울대학교 어린이병원 소아청소년과에 내원한 어린이 중에서 성장속도가 연간 4 cm 미만이면서, 2가지 서로 다른 약제로 성장호르몬 자극검사를 시행하였을 때 정상 소견을 보이는 환자를 대상으로 하였다. SGA군과 AGA군으로 나누어 임상적인 특성을 비교하였으며, 성장호르몬 투여군에 대한 분석을 시행하였다. 결 과 : 총 39명의 환자가 연구에 포함되었으며, 남자가 25명(64%), 여자 14명(36%)이었고, SGA군 11명(28%), AGA군 28명(72%), 성장호르몬 투여군 16명(41%), 비 투여군 23명(59%)이었다. SGA군과 AGA군 모두에서 골연령이 역연령에 비하여 지연되어 있었으나(P=0.028), 두 군간의 차이는 없었다. 모든 환자에서 성장호르몬 자극검사 후 성장호르몬의 최고 농도는 10 ng/mL 이상이었고, clonidine을 사용하였을 때 성장호르몬의 최고농도가 30.4 (6.2, 92.0) ng/mL로 다른 약제에 비하여 유의하게 높았다(P=0.03). 성장호르몬 치료받은 환자 16명의 1년간 성장 속도는 7.7 (4.9, 11.1) cm/yr, 치료 받지 않고 추적관찰 된 6명은 3.7 (2.7, 4.5) cm/yr으로 유의한 차이가 있었다(P<0.001). 또한 성장호르몬 투여군에서 치료 1년 동안 신장 SDS는 0.3 (-0.1, 0.9) 증가하였고(P<0.001), 성장 속도의 변화는 4.8 (2.1, 7.7) cm/yr로 의미있게 증가하였다(P<0.001). 성장호르몬으로 치료받은 환자 중, 치료 후 1년간 성장속도는 SGA군에서 7.1 (5.1, 8.5) cm/yr, AGA군에서 8.2 (4.9, 11.1) cm/yr로 두 군 모두에서 성장호르몬 사용 전 1년 간의 성장 속도보다는 유의하게 증가하였다. 성장호르몬 치료를 시작할 때의 신장의 SDS가 -3 이상인 군과 -3 미만인 군으로 나누어 분석해 보았을 때, 성장호르몬 자극검사시의 IGF-I 농도가 SDS가 -3 미만인 군에서 유의하게 낮게 측정되었다(P=0.023). 결 론 : 성장 속도가 연간 4 cm 미만으로 감소하였으나 성장호르몬 자극검사가 정상인 환자들이 단기간의 성장호르몬 투여로 성장 속도의 증가가 있었으나 이들에서의 장기적인 성장호르몬 효과에 대하여는 향후 더 추적관찰이 필요하다. 또한 이들에서 부분적 인 성장호르몬 저항성 증후군의 가능성이 있으므로, 추후 이러한 환자들을 대상으로 IGF-I 생성 검사를 포함한, GH-IGF-I 축에 대한 검사를 시행하여 성장 장애의 원인을 밝혀야 할 것이다.

Purpose : The aim was to investigate the clinical characteristics and responses to growth hormone (GH) therapy in children with attenuated growth who showed normal GH responses to GH stimulation tests (GHST). Methods : The study included 39 patients with height velocity (HV) of less than 4 cm/yr and normal GHST results. Clinical characteristics of patients were analyzed retrospectively. Results : Eleven were born as small for gestational age (SGA) and 28 as appropriate for age (AGA). In the SGA group, the standard deviation score (SDS) of age and height measured at their first visit was significantly low. Sixteen patients were treated with GH and six of 23 without GH therapy were followed for 1 year after GHST. The mean (range) of HV was 7.7 (4.9 to 11.1) cm/yr in patients with GH therapy and 3.7 (2.7 to 4.5) cm/yr in those without GH therapy, which was statistically significant (P<0.001). In the GH-treated group, HV and difference in height SDS during the treatment increased significantly (P<0.001; P< 0.001, respectively). HV increased after 1 year of GH therapy in the SGA and AGA groups (SGA, P=0.043; AGA, P=0.003). The level of Insulin-like growth factor-I was significantly lower in GH-treated patients with height SDS <-3 than those with ${\geq}3$ (P=0.023). Conclusion : In children with growth failure and normal GHST, HV increases significantly by short-term GH therapy. The assessment of long-term effects of GH therapy is necessary. Moreover, further studies should be considered to evaluate the GH-IGF-I axis due to the possibility of GH insensitivity syndrome.

키워드

참고문헌

  1. Mahoney CP. Evaluating the child with short stature. Pediatr Clin North Am 1987;34:825-49
  2. Lee KH. Growth assessment and diagnosis of growth disorders in childhood. Korean J Pediatr 2003;46:1171-7
  3. Consensus statement on the diagnosis and treatment of chil-dren 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. Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, et al. J Clin Endocrinol Metab 2008;93:4210-7 https://doi.org/10.1210/jc.2008-0509
  4. Saenger P. Partial growth hormone insensitivity-idiopathic short stature is not always idiopathic. Acta Paediatr 1999;88 suppl 428:S194-8 https://doi.org/10.1111/j.1651-2227.1999.tb14390.x
  5. Walenkamp MJ, Wit JM. Genetic disorders in the growth hormone-insulin-like growth factor-I axis. Horm Res 2006; 66:221-30 https://doi.org/10.1159/000095161
  6. Baxter L, Bryant J, Cave CB, Milne R. Recombinant growth hormone for children and adolescents with Turner syndrome. Cochrane Database Syst Rev 2007;(1):CD003887
  7. Bryant J, Baxter L, Cave CB, Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev 2007;(3):CD004440
  8. Korea Center for Disease Control and Prevention, The Korean Pediatric Society, The Committee for the Development of Growth Standard for Korean Children and Adolescents. 2007 Korean Children and Adolescents Growth Standard (commentary for the development of 2007 growth charts). [Government report online]. C: Division of Chronic Disease Surveillance; 2007 Nov. Available from: URL://www.cdc.go. kr/webcdc/
  9. Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. California : Standford University Press, 1959:61-183
  10. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969;44:291-303 https://doi.org/10.1136/adc.44.235.291
  11. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in boys. Arch Dis Child 1970;45:13-23 https://doi.org/10.1136/adc.45.239.13
  12. Ranke MB. Diagnosis of growth hormone deficiency and growth hormone stimulation tests. In: Ranke MB, editor. Diagnostics of endocrine function in children and adolescents. 3rd ed. Basel: Karger, 2003:107-28
  13. GH Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab 2000;85:3990-3 https://doi.org/10.1210/jc.85.11.3990
  14. Savage MO, Rosenfeld R. Growth hormone insensitivity: a proposed revised classification. Acta Paediatr 1999;88 suppl 428:S182-4 https://doi.org/10.1111/j.1651-2227.1999.tb14371.x
  15. Laron Z, Pertzelan A, Mannheimer S. Genetic pituitary dwarfism with high serum concentration of growth hormone: a new inborn error of metabolism? Isr J Med Sci 1966;2:152-5
  16. Woods KA, Dastot F, Preece MA, Clark AJ, Postel-Vinay MC, Chatelain PG, et al. Phenotype:genotype relationships in growth hormone insensitivity syndrome. J Clin Endocrinol Metab 1997;82:3529-35 https://doi.org/10.1210/jc.82.11.3529
  17. Rosenfeld RG. Molecular mechanisms of IGF-I deficiency. Horm Res 2006;65 suppl 1:S15-20 https://doi.org/10.1159/000090642
  18. 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. Acta Paediatr 1994;83 suppl 399:S117-24 https://doi.org/10.1111/j.1651-2227.1994.tb13303.x
  19. Rosenfeld RG, Buckway C, Selva K, Pratt KL, Guevara- Aguirre J. Insulin-like growth factor (IGF) parameters and tools for efficacy: the IGF-I generation test in children. Horm Res 2004;62 suppl 1:S37-43 https://doi.org/10.1159/000080757
  20. Zadik Z, Chalew SA, Kowarski A. Assessment of growth hormone secretion in normal stature children using 24-hour integrated concentration of GH and pharmacological stimulation. J Clin Endocrinol Metab 1990;71:932-6 https://doi.org/10.1210/jcem-71-4-932
  21. Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, et al. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab 1996;81:3323-7 https://doi.org/10.1210/jc.81.9.3323
  22. Marin G, Domené HM, Barnes KM, Blackwell BJ, Cassorla FG, Cutler GB Jr. The effects of estrogen priming and puberty on the growth hormone response to standardized treadmill exercise and arginine-insulin in normal girls and boys. J Clin Endocrinol Metab 1994;79:537-41 https://doi.org/10.1210/jc.79.2.537
  23. Saenger P, Czernichow P, Hughes I, Reiter EO. Small for gestational age: short stature and beyond. Endocr Rev 2007; 28:219-51 https://doi.org/10.1210/er.2006-0039
  24. Chatelain P, Carrascosa A, Bona G, Ferrandez-Longas A, Sippell W. Growth hormone therapy for short children born small for gestational age. Horm Res 2007;68:300-9 https://doi.org/10.1159/000107935
  25. Goddard AD, Covello R, Luoh SM, Clackson T, Attie KM, Gesundheit N, et al. Mutations of the growth hormone receptor in children with idiopathic short stature. the growth hormone insensitivity study group. N Engl J Med 1995;333: 1093-8 https://doi.org/10.1056/NEJM199510263331701
  26. Hujeirat Y, Hess O, Shalev S, Tenenbaum-Rakover Y. Growth hormone receptor sequence changes do not play a role in determining height in children with idiopathic short stature. Horm Res 2006;65:210-6
  27. Martinelli CE, Sader Milani S, Previato JK, Figueira M, Rangel Montenegro AP, Miraki-Moud F, et al. Final height in patients with idiopathic short stature and high growth hormone responses to stimulation tests. Horm Res 2007;67: 224-30 https://doi.org/10.1159/000097512