Severe Fasting Hypoglycemia Mimicking Insulinoma in Three Patients With Insulin Autoimmune Syndrome

Abstract

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia characterized by the presence of insulin autoantibodies (IAA) in patients without prior exposure to exogenous insulin. Differential diagnosis with other causes of hypoglycemia may be complex. We report three IAS cases with severe fasting hypoglycemia, referred to our Unit for the diagnostic workup of insulinoma. All three patients (two women and a man, age 66, 44, and 50 years) had history of severe fasting hypoglycemia leading to loss of consciousness along with weight gain. Both insulin and C-peptide were high, but their levels varied greatly among patients, ranging from 24 to 1500 μU/ml (n.v. <16.3) and from 11 to 27 ng/mL (n.v. < 4,2), respectively. Imaging studies for insulinoma were negative. In all patients, evidence of elevated IAA (ranging from 310 to 660 UA, n.v. < 5) allowed diagnosis of IAS. Two patients were taking alpha lipoic acid, a sulphydryl compound consistently associated to IAS, while in the other the HLA-DRB1*0403 haplotype, conferring susceptibility to IAS, was detected. Continuous monitoring glucose (CGM) (iPro2; Medtronic Diabetes, CA, USA) showed in all patients the presence of prolonged hypoglycemia (with time spent with blood glucose below 54 mg/dL ranging from 9 to 20% of total monitoring time), and in one case the coexistence of high glucose levels after meals. One patient responded well to diazoxide treatment, while the others required both chronic steroid therapy and the use of plasmaphereses. Conclusion: Clinical manifestations of IAS vary widely among patients, without a direct correlation between symptoms severity and levels of both insulin and IAA; prandial hyperglycemia may also be present, leading to increases in glycated hemoglobin. Our patients displayed severe fasting hypoglycemic attacks that initially posed the suspicion of insulinoma. The assessment of IAA is thus mandatory in cases of fasting hypoglycemia, before proceeding to more expensive and probably unnecessary diagnostic and therapeutic procedures. CGM is a useful tool in evaluation and management of IAS, allowing the assessment of hypoglycemia duration and the detection of the wide glycemic variability secondary to the complex mechanism of insulin binding to IAA.