Hypoglycemia due to an Insulin Binding Antibody in a Patient with an IgA-κ Myeloma

• Published in: The journal of clinical endocrinology and metabolism 2007-06, Vol.92 (6), p.2013-2016
• Main Authors: Halsall, D. J., Mangi, M., Soos, M., Fahie-Wilson, M. N., Wark, G., Mainwaring-Burton, R., O’Rahilly, S.
• Format: Article
• Language: English
• Subjects: Aged; Antibody Specificity; Autoantibodies - blood; Autoantibodies - immunology; Chromatography, Gel; Humans; Hypoglycemia - etiology; Hypoglycemia - immunology; Immunoglobulin A - blood; Immunoglobulin A - immunology; Immunoglobulin kappa-Chains - blood; Immunoglobulin kappa-Chains - immunology; Insulin - blood; Insulin - immunology; Male; Multiple Myeloma - complications; Multiple Myeloma - immunology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2007-0075

Context: Autoantibodies to insulin have been described to cause spontaneous hypoglycemia in nondiabetic subjects. There have been occasional reports of spontaneous hypoglycemia due to monoclonal anti-insulin antibodies. We present the first report of a patient with an IgA-κ myeloma in whom frequent hypoglycemia resulted from the ability of the monoclonal IgA-κ to bind insulin. Objectives: The aim of this study was to describe the occurrence of profound hypoglycemia in a patient with IgA-κ myeloma, characterize biochemically the nature of the IgA:insulin complex present, and place this case in the context of the published literature on hypoglycemia resulting from autoantibodies to insulin. Design: A case study was performed. Patients: A single case of profound hypoglycemia associated with IgA-κ myeloma was studied. Intervention: There were no interventions. Main Outcome Measures: A case study was performed. Results: Polyethylene glycol precipitation and gel filtration chromatography were used to demonstrate high-molecular weight insulin immunoreactivity in the patient’s plasma. This was characterized as an insulin binding IgA-κ paraprotein present at 4200 mg/dl (42 g/liter) with a relatively high insulin dissociation constant of 0.32 μm/liter using radiolabelled insulin binding studies. Conclusions: We present the first case of hypoglycemia due to IgA binding insulin antibodies in a patient with an IgA-κ paraprotein myeloma. The hypoglycemia was associated with high-plasma insulin levels and relatively low C-peptide levels. A plausible mechanism for the hypoglycemia is the delayed clearance of insulin. This case broadens the spectrum of monoclonal gammopathies that have been associated with anti-insulin reactivity and spontaneous hypoglycemia.