Endocrine Abstracts

Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare cause of spontaneous hypoglycemia mediated by insulin autoantibodies (IAA). We report a 76 year old Caucasian male with hypertension, ischemic heart disease, and benign prostatic hyperplasia who experienced recurrent syncope and seizure like episodes over two months, leading to three hospital admissions. Initial investigations including CT/MRI brain, EEG, echocardiogram, and Holter monitoring were unremarkable. During the third admission, profound hypoglycemia was documented (serum glucose 2.2 mmol/l), accompanied by markedly elevated insulin (>6945 pmol/l), C-peptide (2.48 nmol/l), and IAA titers (75%, normal < 5.5%). Pancreatic imaging and endoscopic ultrasound excluded insulinoma or other neuroendocrine tumors, and a negative sulfonylurea screen confirmed IAS. Management comprised two days of intravenous hydrocortisone, transition to oral prednisolone, frequent low-carbohydrate meals guided by dietary counselling, and continuous glucose monitoring. Rituximab was considered but not administered due to rapid clinical and serological improvement. Follow up at five months demonstrated declining IAA titers and no further hypoglycemic episodes. Historically most prevalent in Japan (0.017/100,000), IAS is associated with HLA-DR4 (DRB1*0406) and triggers such as sulphhydryl drugs or viral infections. Rising reports among Caucasians likely reflect wider medication use and availability of IAA assays. The pathophysiology involves high capacity, low affinity IAA forming insulin antibody complexes that cause unpredictable glycemic swings. Clinical manifestations range from mild neuroglycopenic symptoms to severe seizures and syncope. Management is challenging but often successful, with an overall spontaneous remission rate of approximately 82% and recurrence in fewer than 5% of cases. This case underscores the importance of considering IAS in patients presenting with unexplained hypoglycemia and highlights the effectiveness of corticosteroids and dietary strategies.