Chrysis D C, Alexandrides T K, Koromantzou E, Georgopoulos N, Vassilakos P, Kiess W, Kratsch J, Beratis N G, Spiliotis B E
Endocrine Unit, Department of Pediatrics, University of Patras School of Medicine, Patras, Greece.
Clin Endocrinol (Oxf). 2001 Feb;54(2):253-9. doi: 10.1046/j.1365-2265.2001.01198.x.
Children with beta-thalassaemia major (beta-thal) frequently have growth retardation in the presence of low serum IGF-I and a normal GH response to pharmacological stimulation suggesting that they have GH insensitivity (GHIS). This study was carried out to study the cause of their growth retardation.
We studied IGF-I and IGFBP-3 generation after exogenous GH administration for four days, in 15 prepubertal controls (C) and 41 prepubertal beta-thal patients divided into three groups according to their growth status: (Group 1) 15 with normal growth (N-thal) (Group 2) 16 with decelerated growth (D-thal) and (Group 3) 10 with short stature (S-thal), in order to determine whether GHIS is the cause of their growth retardation.
IGF-I and IGFBP-3 were measured daily, before and for 4 days after daily administration of 0.1 IU/kg hGH, in 3 groups of prepubertal beta-thal patients and normal controls.
N-thal and C had similar basal serum IGF-I (142 +/- 52 and 196 +/- 56 ng/ml, respectively) and IGFBP-3 concentrations (2.07 +/- 0.49 and 2.66 +/- 0.41 mg/l, respectively) as well as a similar percent increase of IGF-I (101 +/- 23% and 104 +/- 37%, respectively) and IGFBP-3 (52 +/- 36%, and 38 +/- 14%, respectively) during the generation tests. S-thal and D-thal had significantly lower basal IGF-I and IGFBP-3 concentrations (85 +/- 42 and 101 +/- 36 ng/ml; and 1.60 +/- 0.49 and 1.79 +/- 0.52 mg/l, respectively) as compared to N-thal and C (P < 0.001 and P < 0.005, respectively), and a significantly higher percent increase of IGF-I and IGFBP-3 during the generation tests (249 +/- 43 and 161 +/- 76%; and 121 +/- 99 and 73 +/- 35%, respectively) as compared to N-thal and C (P < 0.0001 and P < 0.01, respectively). Twenty-five percent of the growth retarded patients had classic GH deficiency (GHD) and percent increases of IGF-I and IGFBP-3 in the generation tests (164 +/- 86% and 80 +/- 49%, respectively) which were similar to those of the remaining growth-retarded children.
The greater percent increases of IGF-I and IGFBP-3 in the generation tests of the growth retarded beta-thal patients, both with and without GHD, strongly suggest impaired GH secretion rather than GHIS as the cause of their growth retardation. We conclude that the IGF-I and IGFBP-3 generation tests are useful tools for the study not only of GHIS but also of GH secretory disorders in patients with beta-thal and short stature that can easily be performed in an outpatient setting as an initial test to identify the patients that may benefit from GH therapy.
重型β地中海贫血（β-地贫）患儿常伴有生长发育迟缓，其血清胰岛素样生长因子-I（IGF-I）水平较低，对药物刺激的生长激素（GH）反应正常，提示存在GH不敏感（GHIS）。本研究旨在探讨其生长发育迟缓的原因。
我们对外源性GH给药4天后的IGF-I和IGF结合蛋白-3（IGFBP-3）生成情况进行了研究，研究对象为15名青春期前对照儿童（C组）和41名青春期前β-地贫患儿，后者根据生长状况分为三组：（第1组）15名生长正常的患儿（N-地贫组）；（第2组）16名生长减速的患儿（D-地贫组）；（第3组）10名身材矮小的患儿（S-地贫组），以确定GHIS是否为其生长发育迟缓的原因。
在三组青春期前β-地贫患儿和正常对照儿童中，每天测量一次IGF-I和IGFBP-3，给药前及每天给予0.1IU/kg重组人生长激素（hGH）后的4天内也进行测量。
N-地贫组和C组的基础血清IGF-I水平（分别为142±52和196±56ng/ml）及IGFBP-3浓度（分别为2.07±0.49和2.66±0.41mg/l）相似，在生成试验期间IGF-I（分别为101±23%和104±37%）及IGFBP-3（分别为52±36%和38±14%）的增加百分比也相似。与N-地贫组和C组相比，S-地贫组和D-地贫组的基础IGF-I和IGFBP-3浓度显著降低（分别为85±42和101±36ng/ml；1.60±0.49和1.79±0.52mg/l）（P均<0.001），在生成试验期间IGF-I和IGFBP-3的增加百分比显著升高（分别为249±43和161±76%；121±99和73±35%）（P均<0.0001）。25%的生长发育迟缓患儿存在典型的GH缺乏（GHD），其在生成试验中IGF-I和IGFBP-3的增加百分比（分别为164±86%和80±49%）与其余生长发育迟缓儿童相似。
生长发育迟缓的β-地贫患儿，无论有无GHD，在生成试验中IGF-I和IGFBP-3的增加百分比更高，这强烈提示其生长发育迟缓的原因是GH分泌受损而非GHIS。我们得出结论，IGF-I和IGFBP-3生成试验不仅是研究GHIS的有用工具，也是研究β-地贫和身材矮小患者GH分泌障碍的有用工具，该试验可在门诊轻松进行，作为初步检查以识别可能从GH治疗中获益的患者。
