HYPOGLYCEMIA CAUSED BY ATYPICAL INSULIN-ANTIBODIES IN A PATIENT WITH BENIGN MONOCLONAL GAMMOPATHY

We describe a 48-year-old woman with recurrent severe hypoglycaemia ap parently caused by a paraprotein with insulin-binding capacity. Very h igh fasting values were found for serum insulin (170 and > 250 mU l-1) as well as for proinsulin 125 pmol l-1 and an insulinoma was suspecte d. Hypoglycaemia developed after an oral glucose tolerance (OGTT) test but not during fasting for 48 h. Free insulin and C-peptide were norm al during OGTT whereas serum insulin was very high. I-125-insulin bind ing to serum, determined with a polyethylene glycol (PEG) precipitatio n method was high (40%), and equally high after addition of 1.7 x 10(- 5) mol l-1 cold insulin to estimate non-specific binding. By adding ve ry high concentrations of cold insulin, displacement of I-125-insulin bound to serum was found (50% displacement at 4 x 10(-5) mol l-1). No immunoglobulin G (IgG) insulin antibodies were detected by radio-immun oelectrophoresis. On agarose electrophoresis a small paraprotein (4 g l-1) in the gamma-globulin fraction was detected. I-125-insulin bindin g to this paraprotein was demonstrated. We conclude that if insulin au toantibodies are suspected as a cause of hypoglycaemia screening for i nsulin antibodies should always be done with a PEG-precipitation metho d.