Ali Asif, Hashim Rizwan, Khan Farooq Ahmad, Sattar Abdus, Ijaz Aamir, Manzoor Syed Mohsin, Younas Muhammad
Armed Forces Institute of Pathology, Rawalpindi, Pakistan.
J Ayub Med Coll Abbottabad. 2009 Jul-Sep;21(3):40-5.
Growth Hormone Deficiency (GHD) is conventionally diagnosed and confirmed by diminished peak Growth Hormone (GH) levels to provocative testing. Serum Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are under the influence of GH and reflect the spontaneous endogenous GH secretion. Owing to the absence of a circadian rhythm, it is possible to take individual measurements of IGF-1 and IGFBP-3 at any time of the day for evaluation of GH status instead of subjecting the individual to cumbersome provocative tests. Objectives of this study were to compare IGF-1 and IGFBP-3 assays with Exercise and L-Dopa stimulation tests in the diagnosis of growth hormone deficiency in short stature children using ITT as gold standard.
This validation study was conducted at Department of Chemical Pathology and Endocrinology, AFIP, Rawalpindi, from November 2005 to October 2006. Fifty-two short stature children were included in the study. Basal samples for GH levels and simultaneous IGF-1 and IGFBP-3 measurements were obtained and afterwards all children were subjected to sequential exercise and L-Dopa stimulation tests. Insulin Tolerance Test (ITT) was performed one week later with all the necessary precautionary measures. On the basis of ITT results, children were divided into two groups, i.e., 31 growth hormone deficient and 21 Normal Variant Short Stature (NVSS).
The diagnostic value of exercise stimulation test remained highest with sensitivity 90.3%, specificity 76.0%, Positive Predictive Value (PPV) 84.84%, Negative Predictive Value (NPV) 84.2% and accuracy 84.6%. The conventional L-Dopa stimulation had sensitivity 96.7%, specificity 38.0%, PPV 69.7%, NPV 88.8 % and accuracy 73.0%. The serum IGF-1 and IGFBP-3 levels were positively correlated with post ITT peak GH levels (r = 0.527, r = 0.464 respectively, both p < 0.001). The diagnostic value of IGF-1 had sensitivity 83.87%, specificity 76.2%, PPV 83.87%, NPV 76.2% and accuracy 80.76%. The diagnostic value of IGFBP-3 had sensitivity 54.83%, specificity 90.47%, PPV 89.47%, NPV 57.57% and accuracy 69.23%. With combined use of IGF-1 and IGFBP-3 diagnostic value had sensitivity 69.35%, specificity 83.33% PPV 86%, NPV 64.81% and accuracy 75%.
Growth Hormones provocative tests still remain the most useful investigations for the diagnosis of GHD. Measurements of IGF-1 and IGFBP-3 have shown comparable diagnostic performance with growth hormone stimulation tests and are valuable for patients' convenience and ease of performance and can be useful in the initial workup of short stature.
生长激素缺乏症（GHD）传统上是通过生长激素（GH）激发试验中峰值水平降低来诊断和确认的。血清胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白-3（IGFBP-3）受GH影响，反映内源性GH的自发分泌。由于不存在昼夜节律，因此可以在一天中的任何时间对IGF-1和IGFBP-3进行单独测量，以评估GH状态，而无需让个体进行繁琐的激发试验。本研究的目的是以胰岛素耐量试验（ITT）作为金标准，比较IGF-1和IGFBP-3检测与运动和左旋多巴刺激试验在诊断矮小儿童生长激素缺乏症中的作用。
这项验证性研究于2005年11月至2006年10月在拉瓦尔品第武装部队病理研究所的化学病理学和内分泌科进行。52名矮小儿童被纳入研究。获取GH水平的基础样本以及同时进行的IGF-1和IGFBP-3测量，之后所有儿童依次接受运动和左旋多巴刺激试验。一周后采取所有必要的预防措施进行胰岛素耐量试验（ITT）。根据ITT结果，儿童被分为两组，即31例生长激素缺乏症患儿和21例正常变异型矮小（NVSS）患儿。
运动刺激试验的诊断价值最高，敏感性为90.3%，特异性为76.0%，阳性预测值（PPV）为84.84%，阴性预测值（NPV）为84.2%，准确性为84.6%。传统的左旋多巴刺激试验敏感性为96.7%，特异性为38.0%，PPV为69.7%，NPV为88.8%，准确性为73.0%。血清IGF-1和IGFBP-3水平与ITT后GH峰值水平呈正相关（分别为r = 0.527，r = 0.464，均p < 0.001）。IGF-1的诊断价值敏感性为83.87%，特异性为76.2%，PPV为83.87%，NPV为76.2%，准确性为80.76%。IGFBP-3的诊断价值敏感性为54.83%，特异性为90.47%，PPV为89.47%，NPV为57.57%，准确性为69.23%。联合使用IGF-1和IGFBP-3时，诊断价值敏感性为69.35%，特异性为83.33%，PPV为86%，NPV为64.81%，准确性为75%。
生长激素激发试验仍然是诊断GHD最有用的检查方法。IGF-1和IGFBP-3检测与生长激素刺激试验相比，具有相当的诊断性能，对患者来说方便易行，在矮小症的初步检查中可能有用。
