Hypoglycaemia in a non-diabetic patient due to alpha-lipoic acid-induced insulin autoimmune syndrome with HLA-DRB1*04:03:01G.

Insulin autoimmune syndrome (IAS), also known as Hirata syndrome, is a rare cause of endogenous hyperinsulinaemic hypoglycaemia characterised by markedly elevated circulating insulin levels and the presence of insulin autoantibodies in individuals without prior exposure to exogenous insulin. IAS is increasingly recognised worldwide, particularly in association with sulfhydryl-containing medications such as alpha-lipoic acid (ALA). We report the case of a woman in her 70s with no history of diabetes who presented with recurrent episodes of palpitations, tremors, sweating and hunger. A random plasma glucose of 2.6 mmol/L was documented during symptoms, with resolution following oral carbohydrate intake and intravenous dextrose administration, fulfilling Whipple's triad. One week before symptom onset, she had been prescribed a multivitamin preparation containing ALA for low back pain. During supervised evaluation, she developed symptomatic hypoglycaemia with a plasma glucose of 2.4 mmol/L. Critical sample analysis revealed markedly elevated insulin 13 890 pmol/L, elevated plasma C-peptide 3.2 nmol/L, suppressed beta-hydroxybutyrate <0.2 mmol/L and strongly positive anti-insulin antibodies >300 U/L, consistent with endogenous hyperinsulinaemic hypoglycaemia due to IAS. High-resolution HLA typing demonstrated homozygosity for the HLA-DRB1*04:03:01G allele. The patient was treated with dietary modification and oral prednisolone, resulting in rapid clinical improvement. Six weeks later, the hypoglycaemic symptoms recurred following inadvertent re-exposure to ALA and resolved after discontinuation of the medication, supporting a causal relationship. This case highlights ALA-induced IAS as an important but often overlooked cause of spontaneous hypoglycaemia. Given the widespread over-the-counter availability of ALA-containing supplements, careful medication history and awareness of this condition are essential to avoid misdiagnosis and unnecessary investigations.