Comprehensive Center for Pediatrics, Division of Pulmology, Allergology and Endocrinology, Medical University of Vienna, Vienna, Austria.
Vienna Bone and Growth Centre, Vienna, Austria.
Horm Res Paediatr. 2020;93(6):371-379. doi: 10.1159/000512336. Epub 2020 Dec 18.
The acid-labile subunit (ALS) is a crucial factor in the tertiary complex. IGF-I and IGFBP-3 are routinely measured during the diagnostic work-up for growth hormone deficiency (GHD). The aim of the study is to evaluate the relevance of serum ALS as an additional biomarker in the diagnosis of GHD.
Ninety-one children undergoing standard diagnostic work-up for GHD were included in this retrospective study. Inclusion criteria were evidence-based auxological cutoffs, IGF-I and IGFBP-3 <-2 SDS at first presentation, at least 1 growth hormone (GH) stimulation test, and IGF-I, IGFBP-3, and ALS measurements on the same day. Statistical analysis was performed by ROC as well as by odds ratio calculations.
Forty-seven of 90 participants presented with peak GH values under the cutoff of 7 ng/mL. AUC from a model containing only IGF-I was 0.76 and 0.68 when using only ALS. A model containing IGF-I, IGFBP-3, and ALS (AUC = 0.77) did not improve the result compared to the combination of IGF-I/IGFBP-3 (0.77) or IGF-I/ALS (0.76). Furthermore, the variation in the outcome (GH peak </≥7) explained by IGF-I only amounts to 20.4%, while that explained by IGFBP-3 and ALS is only 10.6 and 7.8%, respectively. The sensitivity to diagnose GHD at respective concentrations of -2.0 SDS was 48% for IGF-I, 38% for IGFBP-3, and only 8% for ALS.
Determination of serum ALS alone or in combination with IGF-I and IGFBP-3 did not improve definition of biochemical GHD in a cohort of short children and adolescents with suspected growth disorder. However, performance of IGFBP-3 in this context was not statistically superior to ALS.
酸不稳定亚基(ALS)是三级复合物的关键因素。IGF-I 和 IGFBP-3 是生长激素缺乏症(GHD)诊断过程中常规测量的指标。本研究旨在评估血清 ALS 作为 GHD 诊断的附加生物标志物的相关性。
本回顾性研究纳入了 91 名接受 GHD 标准诊断评估的儿童。纳入标准为基于证据的人体测量学截断值、首次就诊时 IGF-I 和 IGFBP-3 <-2 SDS、至少进行了 1 次生长激素(GH)刺激试验,以及 IGF-I、IGFBP-3 和 ALS 同日测量。统计分析采用 ROC 以及优势比计算。
47 名 90 名参与者的峰值 GH 值低于 7ng/mL 的截止值。仅包含 IGF-I 的模型的 AUC 为 0.76,仅包含 ALS 的 AUC 为 0.68。包含 IGF-I、IGFBP-3 和 ALS(AUC = 0.77)的模型与 IGF-I/IGFBP-3(0.77)或 IGF-I/ALS(0.76)的组合相比,并未改善结果。此外,仅由 IGF-I 解释的结果(GH 峰值 </≥7)的变异仅为 20.4%,而由 IGFBP-3 和 ALS 解释的变异仅分别为 10.6%和 7.8%。在各自浓度为-2.0 SDS 时,IGF-I 诊断 GHD 的敏感性为 48%,IGFBP-3 为 38%,而 ALS 仅为 8%。
在疑似生长障碍的短身材儿童和青少年队列中,单独或联合 IGF-I 和 IGFBP-3 测定血清 ALS 并不能改善生化 GHD 的定义。然而,在这种情况下,IGFBP-3 的性能在统计学上并不优于 ALS。