Background
Insulin autoimmune syndrome (IAS) is characterised by hyperinsulinaemic hypoglycaemia, elevated insulin autoantibodies without prior exposure to insulin, and normal pancreas anatomy.
Case
A 43 year-old Caucasian woman presented with an 8-week history of spontaneous, postprandial hypoglycaemia on a background of a sleeve gastrectomy nine years prior. Past medical history included migraines, insomnia, asthma and post-traumatic stress disorder. She did not take any medications causative of hypoglycaemia and appeared clinically well.
Serum cortisol, thyroid function, hepatic and renal function were normal. Urine drug screen did not detect oral hypoglycaemic agents. Despite multiple low point-of-care blood glucose values, automated biochemistry did not reveal hypoglycaemia despite significantly elevated fasting insulin and c-peptide levels (table 1). Computer tomogram showed a head of pancreas lesion measuring 30mm at largest diameter, magnetic resonance imaging showed a non-specific 9x6mm lesion in the pancreatic body only. 68-Gallium-Exenedin-4 positron emission tomography did not confirm abnormal uptake in the pancreas.
After referral to endocrinology, a modified mixed meal test was performed, which was unremarkable. Insulin and c-peptide were analysed on two alternative platforms and yielded similarly elevated results, therefore the suspicion of abnormally bound insulin was raised. Subsequently, insulin antibodies were measured on two platforms, both yielding significantly elevated results. Further interference testing using polyethylenglycol (PEG) precipitation and affinity chromatography using Protein G columns confirmed abnormally bound insulin: decreasing from 124 mU/L to 29.17 mU/L after PEG, and demonstrating an unbound (free) fraction of 31.70 mU/L after column separation (table 2 & 3).
Conclusion
IAS is rare in insulin-naïve, Caucasian patients. Post gastric bypass hypoglycaemia, insulinoma or nesidioblastosis initially seemed more plausible, and this case highlights the importance of considering a wide range of differentials when investigating hypoglycaemia.