Monoclonal Insulin Autoimmune Syndrome Successfully Treated With Plasma Cell Directed Therapy

•Monoclonal insulin autoimmune syndrome is a very rare disease.•Patients typically present with severe attacks of hypoglycemia.•There is no existing treatment recommendation for the disease.•Plasma cell directed therapy is safe and effective.•It should be regarded as a monoclonal gammopathy of clinical significance. Monoclonal insulin autoimmune syndrome (IAS) is a very rare disease characterized by severe attacks of hypoglycemia caused by circulating anti-insulin antibodies produced by a B-cell clone, usually clonal plasma cells. We present 2 female Norwegian patients with monoclonal IAS. The anti-insulin antibodies were quantified by immune precipitation and characterized using a 3-step manual in-house assay. Both patients received plasma cell directed therapy. The first patient received plasma cell directed therapy for a time-limited period and achieved a sustained clinical remission without detectable anti-insulin antibodies. The second patient receives continuous plasma cell directed therapy and is in clinical remission with low values of detectable anti-insulin antibodies. Plasma cell directed therapy was effective and safe in our 2 cases of monoclonal IAS. We recommend considering plasma cell directed therapy for these patients.