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

Department of Clinical Biochemistry (D.J.H., M.S., S.O.), Addenbrooke’s Hospital, Cambridge CB2 2QR, United Kingdom; Departments of Haematology-Oncology (M.M.) and Clinical Biochemistry (R.M.-B.), Queen Mary’s Hospital, Sidcup, DA14 6LT, United Kingdom; Department of Clinical Biochemistry (M.N.F.-W.), Southend Hospital, Essex SS0 0RY, United Kingdom; and Clinical Laboratory (R.M.-B., G.W.), Royal Surrey County Hospital, Guildford GU2 7XX, United Kingdom

Address all correspondence and requests for reprints to: David J. Halsall, Department of Clinical Biochemistry, Addenbrooke’s Hospital, Cambridge CB2 2QR, United Kingdom. E-mail: djh44{at}hermes.cam.ac.uk.

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- myeloma in whom frequent hypoglycemia resulted from the ability of the monoclonal IgA- to bind insulin.

Objectives: The aim of this study was to describe the occurrence of profound hypoglycemia in a patient with IgA- 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- 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- 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- 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.