The insulin autoimmune syndrome (IAS, Hirata disease) described a syndrome of hypoglycemia secondary to insulin autoantibodies. The syndrome was first described by Hirata in Japan.


Criteria for diagnosis:

(1) multiple episodes of spontaneous hypoglycemia

(2) extremely high insulin levels with elevated C-peptide levels

(3) circulating anti-insulin (possibly anti-insulin receptor) antibodies

(4) no exposure to exogenous insulin

(5) exclusion of other causes


The elevated serum insulin level is partially an artifact of the anti-insulin antibodies, which may interfere with some immunoassays.


Biopsy of the pancreas may show nesidioblastosis, with diffuse hypertrophy and/or hyperplasia of islet cells.



(1) drug-induced insulin antibodies following exposure to:

(1a) methimazole

(1b) alpha-mercaptopropionyl glycine

(1c) glutathione

(1d) possibly antibiotics

(2) autoimmune disease (Grave's disease, etc.)


Differential diagnosis:

(1) factitious hypoglycemia following self-injection of insulin

(2) insulin alloantibodies in a patient with diabetes mellitus

(3) insulinoma


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