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.