Severe Hypoglycemic Coma due to Insulin Autoimmune Syndrome

Insulin autoimmune syndrome, characterized by the presence of insulin-binding autoantibodies and fasting or late postprandial hypoglycemia, is a rare cause of hypoglycemia. We report a patient with pulmonary tuberculosis who developed recurrent spontaneously post-absorptive hyperinsulinemic hypoglycemia after treatment with anti-tuberculous drugs. Imaging studies of the pancreas were unremarkable, and selective intra-arterial calcium stimulation with hepatic venous sampling for insulin failed to show a gradient, thus almost completely excluding the possibility of occult insulinoma or nesidioblastosis. Examinations of sera, however, disclosed a high titer of polyclonal insulin-binding autoantibodies containing at least 2 classes of binding sites, 1 with high affinity but low capacity, and the other with low affinity but high capacity. An oral glucose tolerance test revealed high serum levels of total insulin associated with relatively low levels of free insulin, but not of C-peptide, suggesting binding of the released insulin to autoantibodies. Regretfully, shortly after the withdrawal of isoniazid, the patient died of respiratory failure unrelated to hypoglycemia, and whether these antibodies were induced by isoniazid remains unknown. We recommend that insulin autoimmune syndrome be one of the differential diagnoses in patients with hyperinsulinemic hypoglycemia.