Insulin autoimmune syndrome (Hirata disease): clinical features and epidemiology in Japan

Since Hirata et al. first reported a patient with insulin autoimmune syndrome in 1970, 197 cases have been reported in Japan as of December, 1992. The clinical profiles of these 197 cases were as follows; the peak age at onset was 60-69 years and peak duration of hypoglycemic attacks was more than 1 and less than 3 months. There was no gender difference in the peak age of onset or duration of hypoglycemic attacks. Approximately 82% of the IAS patients had spontaneous remission without any positive treatment. Before diagnosis of IAS, 43% of the patients with IAS had been taking medication; methimazole (MTZ) for Graves' disease, alpha-mercaptopropionyl glycine (MPG) for cataracts, liver disease or rheumatoid arthritis, or glutathione for liver disease, all of which are sulfhydryl compounds. After such sulfhydryl compounds were discontinued, the hypoglycemic attacks subsided. Three patients with IAS experienced recurrence of the hypoglycemic attacks after re-administration of MTZ and MPG, although 6 patients who developed IAS without exposure to any drug had recurrent attacks without exposure to any drug around 1 year after the first hypoglycemic attacks had stopped. Thus, hypoglycemia in IAS is mainly transient and the development of IAS may be related to sulfhydryl compounds.