Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review

Am J Med. 1992 Jun;92(6):681-5. doi: 10.1016/0002-9343(92)90787-c.


Recurrent episodes of postprandial hypoglycemic symptoms culminated in hypoglycemic coma in a hypertensive but otherwise healthy man while he was taking hydralazine. The patient was found to have an extreme elevation in the immunoreactive insulin level, leading to the discovery of insulin antibodies in the absence of prior exposure to exogenous insulin. Negative results of an anatomic study of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast helped to exclude insulinoma. In contrast, symptomatic hypoglycemia developed in response to oral glucose loading and was associated with an elevation in total and free insulin as well as C-peptide levels. The patient was diagnosed with insulin autoimmune syndrome, which, although a common source of hypoglycemia in Japan, has been well documented in only 15 cases from other countries. HLA typing revealed the patient to be positive for groups Cw4 and DR4, a combination that has been preliminarily associated with insulin autoimmune syndrome in Japan. Unlike the majority of cases previously reported, this patient had no clinical or serologic evidence of an underlying autoimmune disorder and had not been exposed to drugs containing sulfhydryl groups. This case adds to the world literature on insulin autoimmune syndrome, lends support to a postulated HLA association, and documents the presence of insulin autoantibodies in the absence of another underlying autoimmune disorder.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Autoimmune Diseases / complications*
  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / genetics
  • Blood Glucose / analysis
  • Child, Preschool
  • Coma / blood
  • Coma / etiology*
  • Diagnosis, Differential
  • Ethnic Groups
  • Female
  • Glucose Tolerance Test
  • HLA-C Antigens / blood
  • HLA-DR4 Antigen / blood
  • Histocompatibility Testing
  • Humans
  • Hydralazine / therapeutic use
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypoglycemia / blood
  • Hypoglycemia / etiology*
  • Insulin / blood
  • Insulin Antibodies / blood*
  • Male
  • Middle Aged


  • Blood Glucose
  • HLA-C Antigens
  • HLA-C*04 antigen
  • HLA-DR4 Antigen
  • Insulin
  • Insulin Antibodies
  • Hydralazine