Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Serum levels of free insulin-like growth factor-I and clinical value in healthy children

한국 소아 및 청소년에서 혈중 유리 insulin-like growth factor-I 농도치와 임상적 의의

  • Chung, Young Hee (Department of Pediatrics, College of Medicine, Inje University) ;
  • Chung, Woo Yeong (Department of Pediatrics, College of Medicine, Inje University)
  • 정영희 (인제대학교 의과대학 소아과학교실) ;
  • 정우영 (인제대학교 의과대학 소아과학교실)
  • Received : 2007.11.01
  • Accepted : 2007.12.10
  • Published : 2008.01.15
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Abstract

Purpose : The serum levels of total insulin-like growth factor (IGF)-I and IGF binding protein (IGFBP)-3 reflect endogenous growth hormone (GH) secretion in healthy children. Free form of IGF-I which is suggested to have more potent biological action than complex form of IGF-I. The aim of this study is to investigate the serum levels of free IGF-I and its clinical value in healthy children. Methods : Serum levels of total IGF-I and IGFBP-3 were determined in 494 healthy children (248 boys and 246 girls) by RIA and IRMA. Serum level of free IGF-I was determined in 206 healthy children (103 boys and 103 girls) by IRMA. Results : The free IGF-I level increased with age in both sex. The free IGF-I level increased continuously between 7 and 15 years of age in boys, but decrement was noted after 14 years of age in girls. Serum total IGF-I level also increased with age in similar pattern of that of free IGF-I. There were no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age in both sex. And there were significant correlations between the level of free IGF-I and total IGF-I and the ratio of total IGF-I/IGFBP-3, respectively. Conclusion : In healthy children, serum free IGF-I increased with age in both sex and high free IGF-I level may play an important role in pubertal growth spurt. Our results suggest that the increased serum free IGF-I level in puberty may reflect changes in total IGF-I rather than IGFBP-3. But free IGF-I does not have more clinical value than total IGF-I because of no significant differences of mean values of the ratio of free IGF-I/total IGF-I in relation to age.

목 적 : 소아의 성장을 평가하는데 혈중 Insulin like growth factor(IGF)-I과 IGF binding protein(IGFBP)-3가 성장호르몬에 의존적이라는 사실이 확인되면서 선별검사로 널리 이용되고 있다. 그러나 실질적인 생물학적 활성을 가진 유리 IGF-I의 임상적인 유용성과 진단적 의의에 대해서는 국내에서 보고된 예가 거의 없다. 이에 저자들은 한국의 소아 및 청소년을 대상으로 유리 IGF-I의 혈중농도분포 및 총 IGF-I, IGFBP-3 농도와의 상관성을 규명하여 유리 IGF-I의 임상적 의의를 알아보고자 한다. 방 법 : 총 IGF-I과 IGFBP-3의 혈중 농도는 494명(남아 248명, 여아 246명)을 대상으로 하였으며, 이중 무작위로 206명(남아 103명, 여아 103명)을 선택하여 유리 IGF-I의 혈중농도를 측정하였다. 혈중 총 IGF-I는 RIA 방법으로, IGFBP-3와 유리 IGF-I은 IRMA 방법으로 측정하였다. 결 과 : 나이에 따른 혈중 유리 IGF-I 농도는 남아의 경우 7세부터 15세까지 지속적으로 증가하는 경향을 보였으며, 여아에서는 14세 이전까지는 증가하다가 이후 감소하는 양상을 나타냈다. 이는 총 IGF-I 및 IGFBP-3치의 변화와 유사한 양상을 보였다. 혈중 유리 IGF-I/총 IGF-I 농도비, 유리 IGF-I/IGFBP-3 농도비의 변화는 남녀에서 모두 나이에 따른 연령별 차이점은 보이지 않았다. 혈중 유리 IGF-I과 총 IGF-I, IGFBP-3 사이의 상관성 분석에서는 성별에 관계없이 유리 IGF-I과 총 IGF-I 사이에는 매우 유의하였고(r=0.46, P<0.001), 유리 IGF-I과 총 IGF-I/IGFBP-3 농도비 사이에도 유의한 상관관계(r=0.40, P<0.001)를 보였다. 결 론 : 소아 및 청소년에서 혈중 유리 IGF-I 농도는 나이에 따라 증가하였으며, 총 IGF-I과 유사한 양상을 보였고, 혈중 유리 IGF-I과 총 IGF-I 및 총 IGF-I/IGFBP-3 농도비 사이에도 유의한 상관관계가 관찰되어 생물학적 활성을 가진 유리 IGF-I의 측정이 임상적으로 유용하게 사용될 수 있다. 그러나, 유리 IGF-I/총 IGF-I 농도비는 연령별 분포차이를 보이지 않았으며 이는 유리 IGF-I이 총 IGF-I에 비해 사춘기적 성장을 평가하는데 더 유용하다고 보기는 힘들다.

Keywords

References

  1. Shimasaki S, Ling N. Identification and molecular characterization of insulin-like growth factor binding proteins (IGFBP-1, -2, -3, -4, -5, and -6). Prog Growth Factor Res 1991;3:243-66 https://doi.org/10.1016/0955-2235(91)90003-M
  2. Sneppen SB, Lange M, Pedersen LM, Kristensen LO, Main KM, Juul A, et al. Total and free insulin-like growth factor I, insulin-like growth factor binding protein 3 and acid-labile subunit reflect clinical activity in acromegaly. Growth Horm IGF Res 2001;11:384-91 https://doi.org/10.1054/ghir.2001.0254
  3. Lee PDK, Powell D, Baker B, Liu F, Mathew G, Levitsky I, et al. Characterization of a direct, non-extraction immunoradiometric assay for free IGF-I. Program and abstracts, the 76th annual meeting of the Endocrine Society; 1994 June 15-18, Anaheim, Calif, USA: Endocrine Societ
  4. Takada M, Nakanome H, Kishida M, Hirose S, Hasegawa T, Hasegawa Y. Measurement of free insulin-like growth factor-I using immunoradiometric assay. J Immunoassay 1994;15:263-76 https://doi.org/10.1080/15321819408009577
  5. Juul A, Dalgaard P, Blum WF, Bang P, Hall K, Michaelsen KF, et al. Serum levels of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) in healthy infants, children, and adolescents: the relation to IGF-I, IGF-II, IGFBP-1, IGFBP-2, age, sex, body mass index, and pubertal maturation. J Clin Endocrinol Metab 1995;80:2534-42 https://doi.org/10.1210/jc.80.8.2534
  6. Jorgensen JO, Blum WF, Moller N, Ranke MB, Christiansen JS. Circadian patterns of serum insulin-like growth factor (IGF) II and IGF binding protein 3 in growth hormonedeficient patients and age- and sex-matched normal subjects. Acta Endocrinol (Copenh) 1990;123:257-62
  7. Hizuka N, Takano K, Asakawa K, Sukegawa I, Fukuda I, Demura H, et al. Measurement of free form of Insulin-like growth factor I in human plasma. Growth Regul 1991;1:51-5
  8. Frystyk J, Skjaerbaek C, Dinesen B, Orskov H. Free insulinlike growth factors (IGF-I and IGF-II) in human serum. FEBS Lett 1994;348:185-91 https://doi.org/10.1016/0014-5793(94)00602-4
  9. Hasegawa Y, Hasegawa T, Takada M, Tsuchiya Y. Plasma free insulin-like growth factor I concentrations in growth hormone deficiency in children and adolescents. Eur J Endocrinol 1996;134:184-9 https://doi.org/10.1530/eje.0.1340184
  10. Juul A, Flyvbjerg A, Frystyk J, Muller J, Skakkebaek NE. Serum concentrations of free and total insulin-like growth factor-I, IGF binding proteins-1 and -3 and IGFBP-3 protease activity in boys with normal or precocious puberty. Clin Endocrinol (Oxf) 1996;44:515-23 https://doi.org/10.1046/j.1365-2265.1996.711531.x
  11. Hasegawa Y, Hasegawa T, Fujii K, Konii H, Anzo M, Aso T, et al. High ratios of free to total insulin-like growth factor-I in early infancy. J Clin Endocrinol Metab 1997;82:156-8 https://doi.org/10.1210/jc.82.1.156
  12. Nimura A, Katsumata N, Tanaka T. Serum levels of free insulin-like growth factor (IGF)-I in normal children. Clin Pediatr Endocrinol 2004;13:71-8 https://doi.org/10.1297/cpe.13.71
  13. Kawai N, Kanzaki S, Takano-Watou S, Tada C, Yamanaka Y, Miyata T, et al. Serum free insulin-like growth factor I (IGF-I), total IGF-I, and IGF-binding protein-3 concentra-tions in normal children and children with growth hormone deficiency. J Clin Endocrinol Metab 1999;84:82-9 https://doi.org/10.1210/jc.84.1.82
  14. Song AK, Kim HJ, Suk HJ, Hwang JS, Hong CH. Serum IGF-I and IGFBP-3 in 919 healthy Korean children and adolescents: normal values and correlations with age, sex, height, body mass index and bone age. J Korean Soc Pediatr Endocrinol 2005;10:35-41
  15. Juul A, Holm K, Kastrup KW, Pedersen SA, Michaelsen KF, Scheike T, et al. Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab 1997;82:2497-502 https://doi.org/10.1210/jc.82.8.2497
  16. Hasegawa Y, Hasegawa T, Aso T, Kotoh S, Tsuchiya Y, Nose O, et al. Usefulness and limitation of measurement of insulin-like growth factor binding protein-3 (IGFBP-3) for diagnosis of growth hormone deficiency. Endocrinol Jpn 1992;39:585-91 https://doi.org/10.1507/endocrj1954.39.585
  17. Rosenfield RI, Furlanetto R, Bock D. Relationship of somatomedin- C concentrations to pubertal changes. J Pediatr 1983;103:723-8 https://doi.org/10.1016/S0022-3476(83)80465-X
  18. Cara JF, Rosenfield RL, Furlanetto RW. A longitudinal study of the relationship of plasma somatomedin-C concentration to the pubertal growth spurt. Am J Dis Child 1987;141:562-4
  19. Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents and adults; relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab 1994;78:744-52 https://doi.org/10.1210/jc.78.3.744
  20. Rosenfeld RG, Kemp SF, Hintz RL. Constancy of somatomedin response to growth hormone treatment of hypopituitary dwarfism, and lack of correlation with growth rate. J Clin Endocrinol Metab 1981;53:611-7 https://doi.org/10.1210/jcem-53-3-611
  21. Yamada M, Hasegawa T, Hasegawa Y. Increase in free insulin-like growth factor-I levels in precocious and normal puberty. Endocr J 1998;45:407-12 https://doi.org/10.1507/endocrj.45.407
  22. Musolino NR, Da Cunha Neto MB, Marino Junior R, Giannella-Neto D, Bronstein MD. Evaluation of free insulinlike growth factor-I measurement on the diagnosis and follow- up treatment of growth hormone-deficient adult patients. Clin Endocrinol (Oxf) 1999;50:441-9 https://doi.org/10.1046/j.1365-2265.1999.00677.x
  23. Rose SR, Municchi G, Barnes KM, Kamp GA, Uriarte M, Ross JL. Spontaneous growth hormone secretion increases during puberty in normal girls and boys. J Clin Endocrinol Metab 1991;73:428-35 https://doi.org/10.1210/jcem-73-2-428
  24. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science 1998;279:563-6 https://doi.org/10.1126/science.279.5350.563
  25. Manousos O, Souglakos J, Bosetti C, Tzonou A, Chatzidakis V, Trichopoulos D, et al. IGF-I and IGF-II in relation to colorectal cancer. Int J Cancer 1999;83:15-7 https://doi.org/10.1002/(SICI)1097-0215(19990924)83:1<15::AID-IJC4>3.0.CO;2-Y