MON-111 Plasma Insulin Measured with a Sensitive Immunoassay May Establish the Diagnosis of Congenital Hyperinsulinism Without Further Testing

Background: The diagnosis of congenital hyperinsulinism (CHI) is often hampered by a plasma insulin (p-insulin) detection limit of 2-3 mU/L (14-21 pmol/L) by RIA methods. Objective: To evaluate the diagnostic performance of a sensitive immunoassay for p-insulin and to find the optimal p-insulin cut-off for CHI versus other conditions with hypoglycaemia. Design: Single centre retrospective cohort study. Methods: Diagnostic tests with no medication, no i.v. glucose and under fasting conditions were performed in children with a clinical diagnosis of CHI. P-insulin concentrations determined at simultaneous p-glucose concentrations at least <3.2 mmol/L (57.5 mg/dL) were included in the analysis (n=61). The diagnosis of CHI was either clinical (n=61) or by gold standard criteria: hypoketotic hypoglycaemia plus disease-causing genetic mutations and/or diffuse, focal or atypical pancreatic histopathology (n=57). Samples from 15 children with idiopathic ketotic hypoglycaemia (IKH, diagnosis by exclusion, p-ketones >1.5 mmol/L during hypoglycaemia) were used as controls. P-insulin was measured by the high-sensitive assay (Cobas e411 immunoassay analyzer); lower detection limit 1.4 pmol/L (0.2 mU/L); normal range 18-173 pmol/L (2.57-24.7 mU/L). Concentrations <18 pmol/L were considered suppressed; ≥18 pmol/L un-suppressed. Receiver operating characteristics (ROC) curves with determination of area under the curve (AUC) values were performed for the diagnostic performance of p-insulin in the diagnosis of CHI. Results: In the 61 samples from CHI patients, the median (range) p-insulin was un-suppressed in all diagnostic samples [90; 20-758 pmol/L (12.9; 2.9-109.1 mU/L)], while p-insulin was suppressed in all 15 samples from IKH patients [1.5; 1.5-9 pmol/L (0.21; 0.21-1.3 mU/L)]. The ROC AUC was 1.0 (95%CI. 1.0-1.0) for the diagnosis of CHI defined both by the clinic and by gold standard. The optimal p-insulin cut-off was 14.5 pmol/L (2.1 mU/L) or 12.5 pmol/L (1.8 mU/L), for CHI patients by use of a simultaneous p-glucose cut-off of <3.2 mmol/L (57.5 mg/dL; n=61), or 3.0 mmol/L (55 mg/dL; n=49), respectively. Conclusions: The sensitive insulin assay performed excellent in diagnosing CHI with a ROC AUC of 1.0. The use of a p-insulin cut-off of 13 pmol/L (1.86 mU/L) during a diagnostic hypoketotic hypoglycaemia test may establish the diagnosis of CHI without further diagnostic testing.