Biomarkers and Diagnostic Thresholds for Congenital Hyperinsulinism

Context Congenital Hyperinsulinism (CHI) is associated with inappropriately high levels of C‐peptide in the context of hypoglycemia. Objective We aimed to better clarify a diagnostic threshold value of C‐peptide for children presenting with CHI. Design This was a retrospective case‐control analysis, examining all hypoglycemia screens, undertaken between 2009 and 2019 at a quaternary paediatrics unit. Plasma C‐peptide, insulin, free fatty acid (FFA) and B‐hydroxybutyrate (BHOB) concentrations in children diagnosed with CHI were compared with concentrations in children diagnosed with other conditions. Patients All patients requiring hypoglycaemic screens at the quaternary children's hospital were analysed. Results Median [C‐peptide] were statistically significantly different between CHI (147) and non‐CHI (72) patients, p < 0.05. The Youden Index indicated that a [C‐peptide] value of 291.5 pmol/L would give the greatest optimization of sensitivity (82%) and specificity (99%) for detecting CHI. Median [insulin] differed significantly between the cohorts with a level of 64 pmol/L for CHI patients compared with 0 pmol/L with non‐CHI patients ( p < 0.01). Median [BOHB] was 0 μmol/L in CHI patients as compared with 2378 μmol/L for non‐CHI patients ( p < 0.01). Median [FFA] levels were 1910 μmol/L in the non‐CHI cohort, compared with 0 in the CHI cohort ( p < 0.01). Conclusions This study suggests that a C‐peptide concentration greater than 291.5 pmol/L is diagnostic of CHI in children. C‐peptide appears to offer the greatest utility as a biochemical diagnostic test for CHI and could be prioritised for laboratory analysis.