Dual Thiol Drug-Induced Insulin Autoimmune Syndrome in a Non-Asian Patient Carrying HLA-DRB1*04:06: A Case Report and...

Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare cause of endogenous hyperinsulinemic hypoglycemia classically linked to high-titer insulin autoantibodies and exposure to sulfhydryl (-SH)-containing drugs. IAS is strongly HLA-associated and is most frequently reported in East Asian populations. We report a case in which simultaneous exposure to two thiol-containing agents unmasked IAS in a non-Asian patient carrying HLA-DRB1*04:06.

A 60-year-old woman developed recurrent autonomic and neuroglycopenic episodes 2-4 hours after meals. Home medications included captopril and over-the-counter α-lipoic acid (ALA). During a symptomatic episode her plasma glucose was 38 mg/dL with markedly elevated serum insulin, C-peptide and proinsulin; mixed-meal testing reproduced a postprandial glucose peak followed by profound hypoglycemia accompanied by paradoxical hyperinsulinemia. Insulin autoantibodies were strongly positive (>150 U/mL) and HLA genotyping revealed DRB1*04:06. A supervised fast was non-diagnostic for insulinoma. Management comprised immediate discontinuation of both captopril and ALA (captopril replaced with losartan) and dietary measures (frequent small low-carbohydrate meals). Hypoglycemic episodes abated within two weeks and resolved by six weeks; fasting glucose, insulin and IAA titers had substantially improved by three months.

To our knowledge, this is the first reported case of IAS temporally associated with concurrent captopril and ALA exposure in a non-Asian carrier of HLA-DRB1*04:06. The case highlights the need to review both prescription drugs and supplements when investigating hyperinsulinemic hypoglycemia, that IAS can occur outside typical ethnic groups when permissive HLA alleles are present, and that prompt withdrawal of offending agents with conservative measures often leads to spontaneous remission.