A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism

• Main Authors: Julie Siersbæk, Annette Rønholt Larsen, Mads Nybo, Henrik Thybo Christesen
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-02-01
• Series: Frontiers in Endocrinology
• Subjects: hypoglycemia; congenital hyperinsulinism; children; diagnostic performance; immunoassays
• Online Access: https://www.frontiersin.org/articles/10.3389/fendo.2020.614993/full

BackgroundThe diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12–18 pmol/L (2–3 mU/L).ObjectiveTo evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI.MethodsDiagnostic 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.ResultsIn 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.ConclusionsThe 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.