Mechanism of hypoglycemia observed in a patient with insulin autoimmune syndrome.
A 21-year-old female patient complaining of frequent hypoglycemic attacks in the presence of a large amount of circulating insulin-binding antibodies without previous known immunization is described. In order to clarify the possible mechanism of the hypoglycemic attacks occurring in this new syndrome, changes in plasma glucose, plasma total and free immunoreactive insulin (IRI), and C peptide immunoreactivity (CPR) levels were investigated in the patient before, during, and after a three-hour glucose infusion. The character of her antibodies were also examined. An abrupt discontinuation of the glucose infusion caused a sharp decline in the plasma glucose level, reaching a nadir of 30 mg./100 nk, at 270 minutes; then she became unconscious. A huge amount of total IRI of 2,834 micron U./ml. was registered at 180 minutes, while the peak value of free IRI of 208 micronU./ml. was observed 45 minutes after the cessation of the glucose infusion. Plasma CPR was increased from high basal level, 19.6 ng./ml., to the maximum level of 29.2 ng./ml. The maximum insulin-binding capacity of IgG in the patient's serum was 6.25 mU./ml. The antibody-combining site was homogeneous, showing one high-affinity site (K: 1.1 X 10(9)M-1). Neither the prolonged fasting nor the administration of tolbutamide induced the hypoglycemic attack in the patient. The hypoglycemia may be explained by an unduly excessive amount of insulin liberated from a large pool of bound insulin irrespective of blood sugar level. The cause of the antibody production is also discussed.
D000328:Adult; D000906:Antibodies; D000941:Antigens; D001327:Autoimmune Diseases / Q000378:metabolism*; D002096:C-Peptide / Q000276:immunology; D002850:Chromatography, Gel; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000502:physiology; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology* / Q000276:immunology; D007263:Infusions, Parenteral; D007328:Insulin / Q000276:immunology* / Q000378:metabolism; D013577:Syndrome
D000906:Antibodies; D000941:Antigens; D002096:C-Peptide; D007328:Insulin; D005947:Glucose