MON-070 Cross-Reactivity of Human Insulin and Insulin Analogues in Human Insulin Immunoassay Complicates Case of Medical Child Abuse

Abstract

Background: Measurement of insulin levels with human insulin immunoassays is important in the investigation of hypoglycemia; however, cross-reactivity with insulin analogues complicates clinical assessment. Clinical Case: A 2-month-old male presented with hypoglycemia. Initial tests were consistent with hyperinsulinemic hypoglycemia: low serum glucose (29 mg/dL, n 70 to 99), elevated insulin (90.1 mU/L, n 3.0 to 19.0), suppressed beta-hydroxybutyrate (0.16 mmol/L, n 0.02 to 0.27), and suppressed free fatty acids (0.27 mmol/L, n 0.50 to 1.60). C-peptide level resulted undetectable (<0.1 ng/mL, n 0.8 to 3.5) raising suspicion for exogenous insulin administration. History revealed an older brother with type 1 diabetes mellitus treated with insulins glargine and lispro. Only one caregiver was present in the hospital, who denied knowledge of exogenous insulin administration. Hypoglycemia persisted despite placement of a continuous 1:1 sitter, high-dose intravenous glucose (glucose infusion rate up to 21.6 mg/kg/min), and treatment with diazoxide. A repeat insulin measurement with the Roche Diagnostics assay specific for human insulin was performed on a critical sample and resulted elevated (13.9 uIU/L, n 2.6 to 24.9), suggestive of endogenous insulin. However, an extensive study of commercial human insulin immunoassays by Heurtault et al., including the Roche Diagnostics assay, has demonstrated cross-reactivity with insulin analogues and their metabolites [1]. Given persistent concern for exogenous insulin administration, the patient’s caregiver was asked to leave the bedside for an extended period of time which resulted in normoglycemia. Diazoxide and dextrose-containing IV fluids were discontinued. Patient maintained normoglycemia for the remainder of the admission and was discharged in the care of child protective services. Conclusions: Cross-reactivity exists in human insulin immunoassays with insulin analogues and their metabolites complicating the determination of endogenous versus exogenous insulin as the cause of hyperinsulinemic hypoglycemia. It is important to know the cross-reactivity of the assay used if a diagnosis of surreptitious insulin administration is suspected. Separation of patient and possible perpetrators and involvement of child protective services is essential in suspected cases of exogenous insulin administration. Evaluation in cases where self-injection of insulin is suspected may be more difficult to decipher, and inclusion of c-peptide measurement at the time of hypoglycemia is critical. Reference: [1] Heurtault B, Reix N, Meyer N, et al. Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification. Clin Chem Lab Med. 2014; 52:355-362.