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胰岛素样生长因子结合蛋白-3评估对生长激素缺乏症的诊断有帮助吗?

Is IGF binding protein-3 assessment helpful for the diagnosis of GH deficiency?

作者信息

Cianfarani S, Boemi S, Spagnoli A, Cappa M, Argirò G, Vaccaro F, Manca Bitti M L, Boscherini B

机构信息

Department of Pediatrics, Università di Tor Vergata, Rome, Italy.

出版信息

Clin Endocrinol (Oxf). 1995 Jul;43(1):43-7. doi: 10.1111/j.1365-2265.1995.tb01891.x.

DOI:10.1111/j.1365-2265.1995.tb01891.x
PMID:7543832
Abstract

OBJECTIVE

The measurement of serum immunoreactive IGFBP-3 levels has been proposed as a screening test to identify children with growth hormone deficiency (GHD). We tested the sensitivity and specificity of the IGFBP-3 assessment in comparison with the measurement of IGF-I.

DESIGN

We assessed the IGFBP-3 and IGF-I circulating levels in normal subjects and patients with GHD or idiopathic short stature (ISS).

PATIENTS

Eighty-two normal subjects, 16 GHD, and 10 children with ISS were studied. Controls were divided into three age groups: group A, 1-4 years (n = 16); group B, 5-9 years (n = 35), and group C, 10-14 years (n = 31).

MEASUREMENTS

All subjects underwent standard anthropometry. In short patients, GH secretory status was assessed by clonidine and arginine stimulation tests. IGFBP-3 and IGF-I circulating levels were measured by radioimmunoassay.

RESULTS

IGFBP-3 and IGF-I levels were closely related (r = 0.51, P < 0.0001) and IGFBP-3 was less age dependent than IGF-I (r = 0.57, P < 0.02 vs r = 0.64, P = 0.0001). Sensitivity (true positive ratio) and specificity (true negative ratio) of IGFBP-3 measurement were 50 and 92% respectively, whereas sensitivity and specificity of IGF-I assessment were 75 and 90% respectively. Below the age of 5 years, sensitivity was 20% for IGFBP-3 and 40% for IGF-I; specificity was 94% for IGFBP-3 and 88% for IGF-I.

CONCLUSIONS

IGFBP-3 measurement had poor sensitivity in detecting growth hormone deficient patients, offering no diagnostic advantage over IGF-I, even in the first years of life, although, due to the high specificity, the finding of subnormal levels of IGFBP-3 was strongly suggestive of growth hormone deficiency. The presence of low IGFBP-3 and IGF-I levels in a short child with normal GH response to provocative tests should prompt further investigations, such as the determination of spontaneous GH secretion or assessment of the GH binding proteins together with an IGF-I and/or IGFBP-3 generation test, in order to identify neurosecretory dysfunction or GH receptor deficiency. Finally, we believe that there is no definitive test for diagnosing or excluding growth hormone deficiency and detailed analysis of the results of endocrine tests, clinical findings and other laboratory and radiological information is necessary to maximize diagnostic accuracy.

摘要

目的

血清免疫反应性胰岛素样生长因子结合蛋白-3(IGFBP-3)水平的测定已被提议作为一种筛查试验,用于识别生长激素缺乏症(GHD)患儿。我们将IGFBP-3评估的敏感性和特异性与胰岛素样生长因子-I(IGF-I)的测量结果进行了比较。

设计

我们评估了正常受试者以及患有GHD或特发性身材矮小(ISS)患者的循环中IGFBP-3和IGF-I水平。

患者

研究了82名正常受试者、16名GHD患者和10名ISS患儿。对照组分为三个年龄组:A组,1 - 4岁(n = 16);B组,5 - 9岁(n = 35),C组,10 - 14岁(n = 31)。

测量

所有受试者均接受标准人体测量。对于身材矮小的患者,通过可乐定和精氨酸刺激试验评估生长激素分泌状态。采用放射免疫分析法测量循环中IGFBP-3和IGF-I水平。

结果

IGFBP-3和IGF-I水平密切相关(r = 0.51,P < 0.0001),且IGFBP-3的年龄依赖性低于IGF-I(r = 0.57,P < 0.02对比r = 0.64,P = 0.0001)。IGFBP-3测量的敏感性(真阳性率)和特异性(真阴性率)分别为50%和92%,而IGF-I评估的敏感性和特异性分别为75%和90%。5岁以下时,IGFBP-3的敏感性为20%,IGF-I为40%;IGFBP-3的特异性为94%,IGF-I为88%。

结论

IGFBP-3测量在检测生长激素缺乏患者方面敏感性较差,即使在生命的最初几年,与IGF-I相比也没有诊断优势,尽管由于高特异性,IGFBP-3水平低于正常强烈提示生长激素缺乏。身材矮小且生长激素对激发试验反应正常的儿童中,若存在低IGFBP-3和IGF-I水平,应促使进一步检查,如测定自发性生长激素分泌或评估生长激素结合蛋白以及进行IGF-I和/或IGFBP-3生成试验,以识别神经分泌功能障碍或生长激素受体缺乏。最后,我们认为不存在用于诊断或排除生长激素缺乏的确定性试验,为使诊断准确性最大化,需要对内分泌检查结果、临床发现以及其他实验室和放射学信息进行详细分析。

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