Case Presentation: A 79 y/o obese male with a history of hemochromatosis on scheduled phlebotomies, hypertension, afib, and hyperlipidemia presented to the ED for the third time in a week with chief complaints of nausea, syncope, and diaphoresis. Vitals signs were normal on presentation. Preliminary investigations were unremarkable except for glucose of 48. The patient was given 25g of D50 with a transient improvement of hypoglycemia to 141; shortly thereafter, symptoms re-occurred, and repeat blood glucose was 87. Further history indicated that the patient takes amiodarone, which he has not filled recently, and Berberine prescribed by his naturopath.Broad differentials for recurrent symptomatic hypoglycemia with hyper-adrenergic and neuroglycopenic features were considered, especially given the use of Berberine, pancreatic sufficiency, insulinoma, and liver disease given the history of amiodarone use and hemochromatosis. Further labs showed Hgb A1c of 4.7%, negative UDS, undetectable sulphonyl urea levels, and normal cortisol. Other key lab findings include pro-insulin 77pmol/L, Insulin Qt 1750, and Insulin antibodies of 7.62nmol/L (Reference 0.00-0.02). These were obtained during hypoglycemic episodes. CT abdomen MRI and PET scans were unremarkable.The patient continued to have multiple episodes of hypoglycemia over the course of one week with blood glucose in the low 40s, which necessitated continuous dextrose infusion and octreotide. The patient was started on prednisone 40mg per endocrinology and was subsequently stable off dextrose infusions. The patient was referred to Mayo Clinic endocrinology for further follow-up upon discharge
Discussion: Insulin Autoimmune syndrome (IAS), also known as Hirata’s disease, is a rare medical condition where hypoglycemic episodes occur due to elevated insulin autoantibodies (IAA) levels. It is an immune-mediated phenomenon occurring in genetically predisposed individuals with clustering around HLA DR4, DRB 0406, DRB 0403, and DRB 0407; this was thought to explain the preponderance in some Asian populations and predilection with certain medications. Exact epidemiology is unknown but tends to occur in the 7th to 8th decades of life. The central pathogenetic mechanism involves the binding of insulin-to-insulin autoantibody (IAA), leading to a two-step process. The first of these is mild hyperglycemia due to insulin non-availability, followed by marked hypoglycemia after the dissociation of insulin release back into the blood. Diagnosis is very challenging, with the benchmark being the presence of IAA in the blood. Treatment is usually by immunomodulating agents like steroids and azathioprine, acarbose, somatostatin analogs, intravenous dextrose, and dietary modifications.
Conclusions: IAS is an extremely rare disease requiring a high index of suspicion and careful diagnostic workup, with very limited information available in the literature.