Diagnostic pitfalls in endogenous hyperinsulinaemic hypoglycaemia due to insulin autoimmune syndrome

Insulin autoimmune syndrome (IAS) is a rare cause of spontaneous endogenous hyperinsulinaemic hypoglycaemia, mediated by autoantibodies directed against endogenous insulin in the absence of prior exposure to exogenous insulin. An elderly woman presented with recurrent episodes of both fasting and postprandial hypoglycaemia in the absence of diabetes mellitus or prior bariatric surgery. Whipple’s triad was fulfilled, and during documented hypoglycaemia (plasma glucose 2.4 mmol/L), insulin and C-peptide concentrations were markedly elevated, with a negative sulfonylurea screen. A 72-hour supervised fast and a mixed-meal test demonstrated early-onset hypoglycaemia accompanied by elevated insulin and C-peptide levels. Cross-sectional and functional imaging revealed no pancreatic lesion. Insulin IgG antibodies were strongly positive and polyethylene glycol precipitation confirmed significant assay interference, supporting the diagnosis of IAS. This case highlights the diagnostic challenges and clinical course of this rare condition.