Insulin autoimmune syndrome

Insulin autoimmune syndrome (IAS), a rare cause of reversible autoimmune hypoglycemia

Also known as Hirata’s disease.

Patients are usually adults, experiencing multiple episodes of spontaneous hypoglycemia with neuroglycopenic symptoms.

The cause of IAS is not clearly understood. 

The interaction of disulfide bond in the insulin molecule with sulfhydryl group drugs such as methimazole, carbimazole, captopril, isoniazid, hydralazine, imipenem, and also with lipoic acid has been suggested.

Drug-induced autoimmunization is evidenced by insulin autoantibodies appear a few weeks after the intake of drug containing the sulfhydryl group. 

It has a significant genetic predisposition as its association with specific HLA class has been observed.

Following a meal, glucose concentration provides  a stimulus for insulin secretion. 

Autoantibodies bind to these insulin molecules, rendering them unable to exert their effect, with resultant hyperglycemia promotes further insulin release. 

The glucose concentration eventually falls, insulin secretion also subsides, and the total insulin level decreases. 

The insulin molecules spontaneously dissociate from the autoantibodies, giving rise to a raised free insulin level inappropriate for the glucose concentration, causing hypoglycemia.

Presenting features are multiple episodes of spontaneous hypoglycemia and appearance of insulin autoantibodies without prior history of administration of exogenous insulin.

Laboratory: The insulin level is significantly high, usually up to 100 mIU/L, C-peptide level is markedly elevated, and insulin antibodies are positive.


Frequent, small meals and to avoid simple sugars. 

Sulfhydryl group-containing drugs should be avoided and steroids can be used in resistant cases.

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