van Doorn J, Ringeling A M, Rikken B, van Buul-Offers S C
Department of Pediatrics, Laboratory of Endocrinology, Wilhelmina Children's Hospital/University Medical Center Utrecht, NL-3508 AB Utrecht, The Netherlands.
Horm Res. 2001;55(3):147-54. doi: 10.1159/000049987.
This study was designed to investigate whether determination of plasma insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2) levels could be of benefit in the evaluation of childhood growth hormone (GH) deficiency (GHD).
A retrospective analysis was performed on 91 prepubertal children referred for investigation of short stature. Maximal GH levels in plasma after provocative stimuli were between 1.0 and 93.0 mU/l, 6 subjects exhibiting peak values of <5 mU/l. Initially a GH peak of 20 mU/l was used as a cutoff limit to define GHD and idiopathic short stature (ISS) patients. The results of GH provocative tests were compared to age- and gender-based standard deviation scores (SDS) of plasma IGFBP-2, IGF-I, IGFBP-3 and the molar ratios of the latter two to IGFBP-2. The respective normative range values for these parameters were determined in plasma samples from 353 healthy children (i.e. 171 girls, 182 boys).
Circulating IGFBP-2 levels did not correlate with height SDS, height velocity SDS or the peak GH levels after provocative stimuli. A weak negative relationship was found between IGFBP-2 and IGF-I. Plasma levels of IGFBP-2 in GHD patients were higher than those of ISS children, who had normal levels. Although at the optimal cutoff point of -0.71 SDS 91.5% of the GHD patients were identified correctly, a substantial proportion (71.9%) of the ISS subjects also had IGFBP-2 levels above this limit. The use of various combinations of IGFBP-2, IGF-I, IGFBP-3 and the derived ratios only slightly improved the diagnostic efficiency as compared to the results of the individual tests. Neither IGFBP-2 nor the IGFBP-3/IGFBP-2 and IGF-I/IGFBP-2 ratios were found to be related to the short- (1 year) or long-term (3 years) growth response to GH therapy.
It is concluded that none of the tests investigated, either alone or in various combinations, are reliable in either predicting the peak GH level after provocative stimuli in prepubertal short children or in predicting their growth response to GH.
本研究旨在调查测定血浆胰岛素样生长因子(IGF)结合蛋白-2(IGFBP-2)水平是否有助于评估儿童生长激素(GH)缺乏症(GHD)。
对91例因身材矮小前来检查的青春期前儿童进行回顾性分析。刺激后血浆中最大GH水平在1.0至93.0 mU/l之间,6例峰值<5 mU/l。最初将GH峰值20 mU/l用作界定GHD和特发性矮小症(ISS)患者的临界值。将GH激发试验结果与基于年龄和性别的血浆IGFBP-2、IGF-I、IGFBP-3标准偏差分数(SDS)以及后两者与IGFBP-2的摩尔比进行比较。这些参数各自的正常范围值是在353名健康儿童(即171名女孩、182名男孩)的血浆样本中确定的。
循环IGFBP-2水平与身高SDS、身高生长速度SDS或刺激后GH峰值水平均无相关性。IGFBP-2与IGF-I之间存在弱负相关。GHD患者的血浆IGFBP-2水平高于ISS儿童,后者水平正常。尽管在最佳临界值-0.71 SDS时,91.5%的GHD患者被正确识别,但相当一部分(71.9%)的ISS受试者IGFBP-2水平也高于此限值。与单项检测结果相比,使用IGFBP-2、IGF-I、IGFBP-3及衍生比值的各种组合仅略微提高了诊断效率。未发现IGFBP-2、IGFBP-3/IGFBP-2和IGF-I/IGFBP-2比值与GH治疗的短期(1年)或长期(3年)生长反应相关。
得出的结论是,所研究的任何检测,无论是单独检测还是各种组合检测,在预测青春期前矮小儿童刺激后GH峰值水平或预测其对GH的生长反应方面均不可靠。