A Case of Antibody-Mediated Recurrent Hypoglycemia in a Patient With Mixed Connective Tissue Disease

Insulin Autoimmune Syndrome (IAS) is a rare autoimmune condition in which the body produces antibodies to insulin, leading to recurrent episodes of severe hypoglycemia accompanied by elevated serum insulin and insulin antibody levels. Hypoglycemia can mimic neurological conditions such as stroke. Also known as Hirata's disease, IAS occurs in patients with autoimmune conditions or a genetic predisposition. IAS is typically treated with immunosuppressive agents, including steroids and rituximab, and patients often undergo thorough evaluations to rule out more common causes of hypoglycemia. Here, we present a case of a patient with pulmonary arterial hypertension (type 1) and mixed connective tissue disease who experienced persistent and recurrent symptomatic hypoglycemia, with glucose levels as low as 35 mg/dL (1.94 mmol/L). C-peptide, a marker of endogenous insulin production, was within normal limits at 2.9 ng/mL (0.96 nmol/L) while the patient was hypoglycemic (glucose <60 mg/dL (3.3 mmol/L)), indicating inappropriate insulin secretion. Total insulin levels were markedly elevated at 7,000 µU/mL (48,615.00 pmol/L), and free insulin levels were elevated at 24 µU/mL (166.68 pmol/L), which initially raised concern for an insulinoma. However, insulin antibodies were evaluated and found to be significantly elevated at >625 µU/mL (>4,340.63 pmol/L), confirming the diagnosis of Hirata's disease. The patient improved following dietary modifications, initiation of prednisone, and discontinuation of home hydroxychloroquine.