Juul A, Holm K, Kastrup K W, Pedersen S A, Michaelsen K F, Scheike T, Rasmussen S, Müller J, Skakkebaek N E
Department of Growth and Reproduction, National University Hospital, Copenhagen, Denmark.
J Clin Endocrinol Metab. 1997 Aug;82(8):2497-502. doi: 10.1210/jcem.82.8.4137.
Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect endogenous GH secretion in healthy children, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. Only a minor fraction of the total IGF-I circulates in its free form, which is believed to be the biologically active form. However, our knowledge of the clinical or physiological value of determination of free IGF-I in serum is limited at present. In adults, the diagnostic value of total IGF-I and IGFBP-3 determinations in patients suspected of GHD has only been reported in a few studies, whereas no previous reports on the diagnostic value of free IGF-I levels in adults suspected of GHD exist. Serum levels of free IGF-I were determined in 1430 healthy children, adolescents, and adults by a newly developed, commercially available immunoradiometric assay (Diagnostic Systems Laboratories) to establish valid normative data for this analysis. We studied the diagnostic value of free IGF-I in relation to total IGF-I and IGFBP-3 determinations in adults who were suspected of GHD. A GH provocative test, using oral clonidine, was performed in 108 adult patients who had previously been treated with GH in childhood. In healthy subjects, free IGF-I levels increased during childhood, with the highest mean values during puberty. After puberty, a subsequent decline in serum levels of free IGF-I was apparent. We found, unmeasurable free IGF-I values in 34 of the prepubertal children (3.3%). All individuals over 8 yr of age had measurable free IGF-I levels that amounted to approximately 1% of the total IGF-I concentrations. Free IGF-I levels were below--2 SD in 56 of 79 GHD patients (sensitivity, 71%) and above--2 SD in 24 of 29 patients with a normal GH response (specificity, 83%). Multiple linear regression analysis demonstrated that free IGF-I was significantly dependent on peak GH levels, duration of the disease, and number of other pituitary axes affected. We conclude that free IGF-I serum levels increase during childhood with a peak in puberty, whereafter free IGF-I levels return to prepubertal levels. Three percent of healthy prepubertal children had unmeasurable free IGF-I levels using this assay. We found that determination of the free IGF-I serum concentration may predict the outcome of a GH provocative test in adults suspected of GHD, but that a single determination of free IGF-I offered no significant advantage compared to determination of total IGF-I or IGFBP-3 serum levels.
血清总胰岛素样生长因子I（IGF-I）和IGF结合蛋白-3（IGFBP-3）水平反映健康儿童的内源性生长激素（GH）分泌情况，这使得它们成为筛查矮小儿童生长激素缺乏症（GHD）的良好诊断标志物，尽管仍存在一些争议。循环中的总IGF-I只有一小部分以游离形式存在，而游离形式被认为是具有生物活性的形式。然而，目前我们对测定血清中游离IGF-I的临床或生理价值的了解有限。在成年人中，仅有少数研究报道了怀疑患有GHD的患者中总IGF-I和IGFBP-3测定的诊断价值，而此前尚无关于怀疑患有GHD的成年人中游离IGF-I水平诊断价值的报道。采用一种新开发的、可商购的免疫放射分析方法（Diagnostic Systems Laboratories）测定了1430名健康儿童、青少年和成年人的血清游离IGF-I水平，以建立该分析的有效标准数据。我们研究了游离IGF-I相对于怀疑患有GHD的成年人中总IGF-I和IGFBP-3测定的诊断价值。对108名童年期曾接受过GH治疗的成年患者进行了口服可乐定的GH激发试验。在健康受试者中，游离IGF-I水平在儿童期升高，在青春期达到最高平均值。青春期后，血清游离IGF-I水平明显下降。我们发现，34名青春期前儿童（3.3%）的游离IGF-I值无法测出。所有8岁以上个体的游离IGF-I水平均可测出，约占总IGF-I浓度的1%。79名GHD患者中有56名（敏感性为71%）的游离IGF-I水平低于-2标准差，而在GH反应正常的29名患者中有24名（特异性为83%）高于-2标准差。多元线性回归分析表明，游离IGF-I显著依赖于GH峰值水平、疾病持续时间以及受影响的其他垂体轴数量。我们得出结论，血清游离IGF-I水平在儿童期升高，在青春期达到峰值，此后游离IGF-I水平恢复到青春期前水平。使用该检测方法，3%的健康青春期前儿童的游离IGF-I水平无法测出。我们发现，测定血清游离IGF-I浓度可能预测怀疑患有GHD的成年人GH激发试验的结果，但与测定总IGF-I或血清IGFBP-3水平相比，单次测定游离IGF-I并无显著优势。
