Hypoinsulinemic Hypoglycemia Followed By The Onset Of Severe Insulin Resistance With Hyperglycemia And Circulating Anti-Insulin Receptor Antibodies In A Patient Suffering Systemic Lupus Erythematosus: A Case Report And Literature Review

ABSTRACT Objective: We report an atypical case of autoimmune hypoglycemia due to anti-insulin receptor antibodies after initiation of human monoclonal antibody denosumab and review the literature on this unusual disorder. Methods: We cite the history of a 30-year-old female treated for systemic lupus erythematosus (SLE) who presented with persistent hypoglycemia. This manifestation first appeared after administration of the anti-osteoporotic drug denosumab. Results: The patient's laboratory evaluation initially showed suppression of insulin and C-peptide levels. After ruling out all possible causes of hypoglycemia with decreased insulin levels, we resolved that the temporal relationship between the administration of denosumab and the occurrence of symptoms suggested the involvement of this drug in the disorder. However, in the course of the disease, laboratory tests showed a switch to hyperglycemia accompanied by markedly elevated insulin and C-peptide levels. A diagnosis of type B insulin resistance was made after a positive anti-insulin receptor antibody test. After immunosuppressive treatment with rituximab, cyclophosphamide, and prednisone, our patient achieved normalization of insulin and C-peptide levels and remission of symptoms. Conclusion: We describe an atypical case of type B insulin resistance in association with SLE, hypoglycemia, and suppressed insulin levels with no clinical or biochemical signs of insulin resistance on initial presentation. Although it has already been described that there are some factors that may induce the appearance of anti-insulin receptor antibodies, this is the first reported case of autoimmune hypoglycemia that may have been triggered by administration of a human monoclonal antibody such as denosumab. Abbreviations: Anti-IRAbs anti-insulin receptor antibodies; SLE systemic lupus erythematosus