SAT173 Insulin Autoimmune Syndrome: A Rare Diagnosis With Unique Features

Abstract

Abstract Disclosure: S. Naqvi: None. S. Syed: None. A.R. Kasireddy: None. S. Alshami: None. D. Edem: None. J.A. Henske: None. Introduction: Insulin Autoimmune Syndrome [IAS], or Hirata’s disease, is a rare cause of hypoglycemia. It is characterized by positive insulin autoantibodies in an insulin naïve patient and should be considered in the differential for post-prandial hypoglycemia. Case: A 48-year-old male presented with postprandial tremors, sweating, palpitations and episodes of incoherent speech and loss of consciousness at least 6 months prior to his presentation. He had no history of diabetes, however, was found to have severe symptomatic documented hypoglycemic episodes, with resolution of hypoglycemic symptoms upon treatment; fulfilling the Whipple’s triad. Outpatient workup for causes of his hypoglycemia ruled out insulinoma, use of diabetes medications or insulin, adrenal insufficiency, severe illness, infections, thyroid, liver or kidney dysfunction. He never had gastrointestinal or bariatric surgery. Given his symptoms and severity of hypoglycemic episodes, he was admitted for observation and 72 hour fast. Lab work during hypoglycemic episode revealed inappropriately elevated insulin and low to normal c-peptide levels, undetectable proinsulin, elevated beta-hydroxybutyrate, normal IGF-1, IGF-2, and a negative sulfonylurea screen. Importantly, his insulin: c-peptide ratio was more than 1 and his insulin antibodies were elevated, consistent with IAS. He denied any history of autoimmune disorders or use of any medications with sulfhydryl group. CGM sensor clearly showed the relationship between high glycemic index foods, glucose spikes, and drops in his blood glucose several hours later. Dietary counselling was provided, without much improvement. Trials of Acarbose and Octreotide were not tolerated due to side effects like rash. Prednisone 20 mg bid was started; Diazoxide was titrated to 200 mg tid with much improvement. He has been followed by our clinic, and tapered to prednisone 10 mg bid and Nifedipine 30 mg daily with resolution of his symptoms. Conclusions: Severe hypoglycemia in non-diabetic patients requires investigation utilizing a broad differential diagnosis and biochemical evaluation. The findings of post-prandial hypoglycemia and inappropriately high insulin, with low to normal c-peptide and proinsulin levels with an insulin: C-peptide [ICP] ratio >1 in a non-diabetic patient is consistent with IAS. An ICP ratio >1 is a clue that the half-life of insulin has been increased by circulating antibodies. Mechanistically, post-prandial hyperglycemia cause insulin secretion, however, circulating insulin antibodies neutralize its effect. Ongoing hyperglycemia leads to further high levels of insulin, followed by intermittent spontaneous decoupling of insulin-antibody complex and subsequent post-prandial hypoglycemia. IAS may spontaneously resolve over time but may require indefinite length of treatment and dietary modification until this occurs. Presentation: Saturday, June 17, 2023