CONCLUSION

Our results show that higher BMI is associated with lower GH secretion. BMI should be measured and GH results appropriately interpreted for all subject undergoing GH stimulation testing. Also, we question the validity of GH measurements as the arbitrary gold standard for the diagnosis of GH deficiency and alternative or complementary approaches should be developed, including IGF-1 and IGFBP3, or auxological parameters.

זט

REFERENCE

1. 2000 Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab 85:3990-3993,2000

2. Albertsson-Wikland K, Rosberg S, Karlberg J, Groth T: Analysis of 24-hour growth hormone profiles in healthy boys and girls of normal stature: relation to puberty. J Clin Endocrinol Metab 78:1195-1201,1994

3. Badaru A, Wilson DM: Alternatives to growth hormone stimulation testing in children. Trends Endocrinol Metab 15:252-258,2004

4. Boquete HR, Sobrado PG, Fideleff HL, Sequera AM, Giaccio AV, Suarez MG, Ruibal GF, Miras M: Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Clin Endocrinol Metab 88:4702-4708,2003

5. Cacciari E, Tassoni P, Cicognani A, Pirazzoli P, Salardi S, Balsamo A, Cassio A, Zucchini S, Colli C, Tassinari D, et al.: Value and limits of pharmacological and physiological tests to diagnose growth hormone (GH) deficiency and predict therapy response: first and second retesting during replacement therapy of patients defined as GH deficient. J Clin Endocrinol Metab 79:1663-1669,1994

6. Carel JC, Tresca JP, Letrait M, Chaussain JL, Lebouc Y, Job JC, Coste J: Growth hormone testing for the diagnosis of growth hormone deficiency in childhood: a

זי

population register-based study. J Clin Endocrinol Metab 82:2117-2121,1997 7. Casanueva FF, Villanueva L, Dieguez C, Diaz Y, Cabranes JA, Szoke B, Scanlon MF,

Schally AV, Fernandez-Cruz A: Free fatty acids block growth hormone (GH)

9. Greulich WW, Pyle SI. (1959) Radiologic atlas of skeletal development of the hand and wrist. Stanford University Press, Standford.

10. Hilczer M, Smyczynska J, Lewinski A: Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature. Endocr Regul 40:69-75,2006a

11. Hilczer M, Smyczynska J, Stawerska R, Lewinski A: Stability of IGF-I concentration despite divergent results of repeated GH stimulating tests indicates poor reproducibility of test results. Endocr Regul 40:37-45,2006b

12. Ho KY, Evans WS, Blizzard RM, Veldhuis JD, Merriam GR, Samojlik E, Furlanetto R, Rogol AD, Kaiser DL, Thorner MO: Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab 64:51-58,1987

13. Iranmanesh A, Lizarralde G, Veldhuis JD: Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory bursts and the half-life of endogenous GH in healthy men. J Clin

חי

14. Kok P, Buijs MM, Kok SW, Van Ierssel IH, Frolich M, Roelfsema F, Voshol PJ, Meinders AE, Pijl H: Acipimox enhances spontaneous growth hormone secretion in obese women. Am J Physiol Regul Integr Comp Physiol 286:R693-698,2004

15. Lee EJ, Nam SY, Kim KR, Lee HC, Cho JH, Nam MS, Song YD, Lim SK, Huh KB:

Acipimox potentiates growth hormone (GH) response to GH-releasing hormone with or without pyridostigmine by lowering serum free fatty acid in normal and obese subjects. J Clin Endocrinol Metab 80:2495-2498,1995

16. Loche S, Bizzarri C, Maghnie M, Faedda A, Tzialla C, Autelli M, Casini MR, Cappa M: Results of early reevaluation of growth hormone secretion in short children with apparent growth hormone deficiency. J Pediatr 140:445-449,2002

17. Maccario M, Procopio M, Loche S, Cappa M, Martina V, Camanni F, Ghigo E: Aimaretti G, Bozzola M: Unreliability of classic provocative tests for the diagnosis of growth hormone deficiency. J Endocrinol Invest 31:159-162,2008

20. Micmacher E, Assumpcao RP, Redorat RG, Spina LD, Cruz IC, Silva CA, Vaisman M, Conceicao FL: Growth hormone secretion in response to glucagon stimulation

טי

test in healthy middle-aged men. Arq Bras Endocrinol Metabol 53:853-858,2009 21. Misra M, Bredella MA, Tsai P, Mendes N, Miller KK, Klibanski A: Lower growth

hormone and higher cortisol are associated with greater visceral adiposity, intramyocellular lipids, and insulin resistance in overweight girls. Am J Physiol Endocrinol Metab 295:E385-392,2008

22. Moon JS, Lee SY, Nam CM, Choi JM, Choe BK, Seo JW, Oh K, Jang MJ, Hwang SS, Yoo MH, Kim YT, Lee CG: 2007 Korean National Growth Charts: review of developmental process and an outlook. . Korean J Pediatr. 51:1-25,2008

23. Ozata M, Dieguez C, Casanueva FF: The inhibition of growth hormone secretion presented in obesity is not mediated by the high leptin levels: a study in human leptin deficiency patients. J Clin Endocrinol Metab 88:312-316,2003

24. Pontiroli AE, Lanzi R, Monti LD, Sandoli E, Pozza G: Growth hormone (GH) autofeedback on GH response to GH-releasing hormone. Role of free fatty acids and somatostatin. J Clin Endocrinol Metab 72:492-495,1991

25. Qu XD, Gaw Gonzalo IT, Al Sayed MY, Cohan P, Christenson PD, Swerdloff RS, Kelly DF, Wang C: Influence of body mass index and gender on growth hormone (GH) responses to GH-releasing hormone plus arginine and insulin tolerance tests. J Clin Endocrinol Metab 90:1563-1569,2005

26. Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, Wollmann HA: Significance of basal IGF-I, IGFBP-3 and IGFBP-2 measurements in the diagnostics of short stature in children. Horm Res 54:60-68,2000

27. Stanley TL, Levitsky LL, Grinspoon SK, Misra M: Effect of body mass index on peak growth hormone response to provocative testing in children with short stature.

כ

28. Tannenbaum GS, Gurd W, Lapointe M: Leptin is a potent stimulator of spontaneous pulsatile growth hormone (GH) secretion and the GH response to GH-releasing hormone. Endocrinology 139:3871-3875,1998

29. Tzanela M, Zianni D, Bilariki K, Vezalis A, Gavalas N, Szabo A, Drimala P, Vassiliadi D, Vassilopoulos C: The effect of body mass index on the diagnosis of GH deficiency in patients at risk due to a pituitary insult. Eur J Endocrinol 162:29-35,2010

30. Van Dam EW, Roelfsema F, Helmerhorst FH, Frolich M, Meinders AE, Veldhuis JD, Pijl H: Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. J Clin Endocrinol Metab 87:4225-4230,2002

31. Vestergaard P, Hoeck HC, Jakobsen PE, Laurberg P: Reproducibility of growth hormone and cortisol responses to the insulin tolerance test and the short ACTH test in normal adults. Horm Metab Res 29:106-110,1997

32. Zadik Z, Chalew SA, Gilula Z, Kowarski AA: Reproducibility of growth hormone testing procedures: a comparison between 24-hour integrated concentration and pharmacological stimulation. J Clin Endocrinol Metab 71:1127-1130,1990

אכ -국문요약-

저신장증 소아에서 체질량 지수가 성장호르몬 자극검사에 미치는 영향

아주대학교 대학원의학과 이 해 상

(지도교수 : 황 진 순)

목적: 소아에서 성장 호르몬 결핍증을 진단하는 성장 호르몬 자극 검사는 결과가 약제간에 변동성이 많고, 약제내에서도 재현성이 낮은 점이 지적 되어 왔다. 또한 비만이 성장 호르몬 자극 검사의 결과에 영향을 미친다 는 보고들이 있어왔다. 본 연구에서는 성장 호르몬 자극 검사에 영향을 미치는 인자에 대해 연구하고, 성장 호르몬 자극 검사의 재현성을 알아보 고자 하였다.

방법: 2003년부터 2010년까지 아주대 병원 소아청소년과에 내원한 신장 이 3 퍼센타일 미만이고, 골연령이 역연령보다 1세이상 지연되어 성장 호 르몬 자극 검사를 시행한 187명의 환아를 대상으로 하였다.

결과: 총 187명의 환아 중 남아가 123명 (65%), 여아가 64명 (34.2%)

בכ

였다. 이 중 66명은 성장호르몬 결핍증으로 진단되었고 121명은 특발성 저신장증으로 진단되었다. 다변량 회귀 분석을 통하여 최대 성장호르몬 수치와 연관있는 인자를 알아보았을 때 체질량지수가 통계학적으로 유의 학게 최대 성장호르몬 수치를 예측할 수 있는 인자였다. 체질량지수가 증 가할수록 최대 성장호르몬 수치는 감소하는 것을 알 수 있었다.

결론: 최대 성장호르몬 수치는 체질량지수가 증가할수록 감소하였다. 저신 장증 환아에서 성장 호르몬 자극 검사를 시행하고 결과를 평가할 때 체질 량지수를 고려하여야 한다.

핵심어: 체질량지수, 성장호르몬, 저신장