Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense, Denmark.
Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
Front Endocrinol (Lausanne). 2021 Feb 19;11:614993. doi: 10.3389/fendo.2020.614993. eCollection 2020.
The diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12-18 pmol/L (2-3 mU/L).
To evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI.
Diagnostic fasting tests, performed without medication or i.v.-glucose, were investigated in children with a clinical diagnosis of CHI, or idiopathic ketotic hypoglycemia (IKH). The CHI diagnosis was either clinical or by the alternative, p-insulin-free criteria; hypoglycemia plus disease-causing genetic mutations and/or CHI-compatible pancreatic histopathology. We included diagnostic p-insulin samples with simultaneous p-glucose <3.2 mmol/L and used a sensitive insulin assay (Cobas e411 immunoassay analyzer; lower detection limit 1.2 pmol/L; normal range 15.1-147.1 pmol/L). Receiver operating characteristics area under the curve (ROC AUC) values and optimal cut-offs were analyzed for the performance of p-insulin to diagnose CHI.
In 61 CHI patients, the median (range) p-insulin was 76.5 (17-644) pmol/L compared to 1.5 (1.5-7.7) pmol/L in IKH patients (n=15). The ROC AUC was 1.0 for the diagnosis of CHI defined both by the clinical diagnosis (n=61) and by alternative criteria (n=57). The optimal p-insulin cut-offs were 12.3 pmol/L, and 10.6 pmol/L, at p-glucose <3.2 mmol/L (n=61), and <3.0 mmol/L (n=49), respectively.
The sensitive insulin assay performed excellent in diagnosing CHI with optimal p-insulin cut-offs at 12.3 pmol/L (2.0 mU/L), and 10.6 pmol/L (1.8 mU/L), at p-glucose <3.2 mmol/L, and <3.0 mmol/L, respectively. A sensitive insulin assay may serve to simplify the diagnosis of CHI.
诊断先天性高胰岛素血症（CHI）可能会受到血浆（p-）胰岛素检测下限为 12-18 pmol/L（2-3 mU/L）的限制。
评估灵敏胰岛素免疫测定的诊断性能，并找到诊断 CHI 的最佳 p-胰岛素截断值。
对临床诊断为 CHI 或特发性酮症低血糖（IKH）的儿童进行无药物或静脉葡萄糖的诊断性禁食试验。CHI 的诊断依据是临床诊断或替代的、无 p-胰岛素的标准；低血糖加上致病基因突变和/或与 CHI 相符的胰腺组织病理学。我们纳入了同时伴有 p-血糖<3.2 mmol/L 的诊断性 p-胰岛素样本，并使用灵敏的胰岛素测定法（Cobas e411 免疫分析仪；检测下限为 1.2 pmol/L；正常范围为 15.1-147.1 pmol/L）。分析了 p-胰岛素诊断 CHI 的性能的接受者操作特征曲线（ROC AUC）值和最佳截断值。
在 61 例 CHI 患者中，p-胰岛素中位数（范围）为 76.5（17-644）pmol/L，而 IKH 患者（n=15）为 1.5（1.5-7.7）pmol/L。ROC AUC 对于通过临床诊断（n=61）和替代标准（n=57）定义的 CHI 诊断均为 1.0。在 p-血糖<3.2 mmol/L（n=61）和<3.0 mmol/L（n=49）时，最佳的 p-胰岛素截断值分别为 12.3 pmol/L 和 10.6 pmol/L。
灵敏胰岛素测定法在诊断 CHI 时表现出色，最佳的 p-胰岛素截断值分别为 12.3 pmol/L（2.0 mU/L）和 10.6 pmol/L（1.8 mU/L），p-血糖分别为<3.2 mmol/L 和<3.0 mmol/L。灵敏胰岛素测定法可能有助于简化 CHI 的诊断。
