Savage M O, Blair J C, Jorge A J, Street M E, Ranke M B, Camacho-Hübner C
Department of Endocrinology, St Bartholomew's Hospital, London, UK.
Endocr Dev. 2005;9:100-106. doi: 10.1159/000085760.
IGF-I, IGFBP-3 and ALS are GH-dependent peptides and their production is disturbed in states of GH insensitivity. This chapter explores the relative degrees of IGF-I, IGFBP-3 and ALS deficiency across the spectrum of GH insensitivity. In classical GH insensitivity syndrome (GHIS), known as Laron syndrome, due to GH receptor (GHR) deficiency, serum IGF-I, IGFBP-3 and ALS are severely reduced with inability to produce these peptides during an IGF-I generation test. Across the spectrum of severity of GHR defects, some patients have short stature and normal facial appearance, so-called partial or non-classical GH insensitivity. In these cases the IGF-I, IGFBP-3 deficiency is less severe. A positive relationship exists between height SDS and IGFBP-3 SDS (r2 = 0.45, p < 0.001) in patients from the European series with GHIS. In a new series of GHIS cases (n = 36) there was a significant difference in IGFBP-3 and ALS (p < 0.05) between classical (n = 25) and non-classical cases (n = 11). IGF-I, IGFBP-3 and ALS were significantly higher (p < 0.05) in pubertal compared with pre-pubertal subjects in the same series. In idiopathic short stature (ISS), heterozygous mutations of the GHR may have a dominant negative effect. ISS patients have lower IGF-I levels than the normal population. In 21 cases, mean IGF-I SDS was -1.39 (-2.4 to -1.16) and IGFBP-3; -0.45 (-1.13 to 0.38). However, IGF-I and IGFBP-3 responses in the IGF-I generation test were generally normal. In acquired GHI due to chronic illness such as Crohn's disease, juvenile arthritis and cystic fibrosis, IGF-I deficiency is present, although IGFBP-3 is usually normal. In summary, assessment of IGF-I, IGFBP-3 and ALS contributes to diagnosis in GH insensitivity states. In our experience, IGF-I is more sensitive to disturbance of GH action that IGFBP-3, however in severe GHIS cases, IGF-I is usually undetectable and measurement of IGFBP-3 is valuable as a guide to the severity of the biological defect.
胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白-3（IGFBP-3）和酸性不稳定亚基（ALS）是依赖生长激素（GH）的肽类，在GH不敏感状态下它们的产生会受到干扰。本章探讨了在整个GH不敏感范围内IGF-I、IGFBP-3和ALS缺乏的相对程度。在经典的GH不敏感综合征（GHIS），即拉伦综合征中，由于生长激素受体（GHR）缺乏，血清IGF-I、IGFBP-3和ALS严重降低，在IGF-I生成试验中无法产生这些肽类。在GHR缺陷的严重程度范围内，一些患者身材矮小但面容正常，即所谓的部分或非经典GH不敏感。在这些情况下，IGF-I、IGFBP-3缺乏程度较轻。在欧洲的GHIS患者系列中，身高标准差评分（SDS）与IGFBP-3 SDS之间存在正相关（r2 = 0.45，p < 0.001）。在一个新的GHIS病例系列（n = 36）中，经典病例（n = 25）和非经典病例（n = 11）之间的IGFBP-3和ALS存在显著差异（p < 0.05）。在同一系列中，青春期受试者的IGF-I、IGFBP-3和ALS显著高于青春期前受试者（p < 0.05）。在特发性矮小症（ISS）中，GHR的杂合突变可能具有显性负效应。ISS患者的IGF-I水平低于正常人群。在21例患者中，IGF-I SDS的平均值为-1.39（-2.4至-1.16），IGFBP-3为-0.45（-1.13至0.38）。然而，IGF-I生成试验中IGF-I和IGFBP-3的反应通常正常。在因克罗恩病、青少年关节炎和囊性纤维化等慢性疾病导致的获得性GH不敏感（GHI）中，存在IGF-I缺乏，尽管IGFBP-3通常正常。总之，评估IGF-I、IGFBP-3和ALS有助于GH不敏感状态的诊断。根据我们经验，IGF-I对GH作用的干扰比IGFBP-3更敏感，然而在严重的GHIS病例中，IGF-I通常检测不到，测量IGFBP-3对于指导生物缺陷的严重程度很有价值。
