NIH

Zebra of the Week: Insulin autoimmune syndrome

July 28, 2025

Insulin autoimmune syndrome (IAS)—also known as Hirata disease—is a rare autoimmune condition characterized by spontaneous hypoglycemia resulting from the formation of autoantibodies against endogenous insulin. These antibodies bind circulating insulin, interfering with its physiological activity and leading to unpredictable episodes of hypoglycemia.

Although most frequently reported in individuals of East Asian descent, particularly in Japan, IAS has been reported globally. It typically occurs in non-diabetic individuals and is often associated with exposure to medications containing sulfhydryl groups, such as methimazole.

Clinically, patients may present with neuroglycopenic and adrenergic symptoms including dizziness, diaphoresis, palpitations, confusion, and in severe cases, seizures. Diagnosis hinges on the detection of elevated insulin autoantibody titers in the context of hypoglycemia and hyperinsulinemia, in the absence of exogenous insulin administration.

Management strategies include discontinuation of the offending agent, dietary modifications to stabilize glucose levels, and in select cases, immunosuppressive therapy. Notably, IAS often follows a self-limited course, with spontaneous resolution observed in many patients.

Source:

(Accessed July 25, 2025). NIH: Genetic and Rare Diseases Information Center. Insulin autoimmune syndrome. https://rarediseases.info.nih.gov/diseases/10808/insulin-autoimmune-syndrome

Censi S, et al. (2018, Sept). Ann Transl Med. Insulin autoimmune syndrome: from diagnosis to clinical management. https://pubmed.ncbi.nlm.nih.gov/30306074/