Endocrine Abstracts

Background: Insulin autoimmune syndrome (Hirata disease) is a very rare cause of hypoglycaemia; approximately 400 cases have been described. The presence of insulin autoantibodies leads to the formation of insulin-Ig complexes, with subsequent dissociation of insulin resulting in episodes of severe hypoglycaemia. The condition can present a diagnostic and management challenge.

Case Report: A 77-year-old man was attended by paramedics with a GCS of 8 and severe hypoglycaemia (capillary blood glucose 1.0 mmol/l) which responded well to initial treatment. He had no history of diabetes or exposure to exogenous insulin or antiglycaemic agents. On transfer to hospital, he had another severe hypoglycaemic episode. Blood samples sent two hours after the second hypoglycaemic episode showed an extremely elevated C-peptide (22,000 pmol/l) and insulin level (>6400 pmol/l). Differential diagnoses included insulinoma, antiglycaemic agent exposure or immune-mediated disease. Cross-sectional imaging did not identify any pancreatic lesions and there was no exposure to antiglycaemic agents; the extremely high C-peptide and insulin levels made these diagnoses less likely. Insulin autoimmune syndrome was confirmed with positive IgG against insulin and polyethylene glycol precipitation of insulin-Ig complexes. The patient was initially managed with regular complex carbohydrate meals, alongside prednisolone at night to reduce nocturnal hypoglycaemic episodes. B-cell depletion using rituximab resulted in reduced frequency of hypoglycaemic episodes and a marked improvement in insulin levels. Prednisolone was able to be discontinued. The patient is now well, with no recent hypoglycaemic episodes on flash glucose monitoring.

Discussion: Insulin autoimmune syndrome is a diagnosis to consider in cases of hypoglycaemia of unclear cause with very elevated insulin and C-peptide levels. Blood sampling during the hypoglycaemic episode is useful to aid the diagnostic process. Management can be challenging, with limited evidence base. This patient had an excellent response to rituximab, with good biochemical and symptomatic outcomes.