Endocrine Abstracts

Insulin autoimmune syndrome (IAS; Hirata syndrome) is a rare cause of hypoglycemia. It seems to be related to specific HLA class II alleles. Rarely, monoclonal antibody acts as an insulin-binding autoantibody: until now 10 cases have been described in association with a myeloproliferative disorder. In June 2015, a 60-year-old patient presented in a local hospital in Mayotte with confusion, sweating and severe hypoglycemia (blood glucose as low as 20 mg/dl). He was suffering of chronic obstructive pulmonary disease and had no history of diabetes neither use of any drug or hypoglycaemic agent. His physical examination revealed obesity: IMC 34 kg/m². Laboratory evaluation showed anemia (Hb 9.2 g/dl). Liver, renal, thyroid and adrenal functions were all normal. Fasting blood sugar was 28 mg/dl with total plasma insulin level of 788 mU/l. He was thus referred to our center in La Reunion, for further investigations: magnetic resonance of the abdomen and ultrasound failed to detect lesions or suspicious masses suggesting insulinoma. A plasma-protein electrophoresis revealed a restricted gammaglobulin band of 1 g/l. Immunoelectrophoresis revealed a monoclonal IgG kappa. But the bone marrow biopsy didn’t show excess of plasma cells (<2%). At 72-h observed fast, there was no hypoglycemia. A 75-gram oral glucose tolerance test caused a severe hypoglycemia after 4 hours (25 mg/dl) with total insulinemia level of 247 (T0) reaching 1722 mU/l (3 h). Concurrently, free insulin level was 10.3 (T0) and reached 63.5 mU/l (3 h) and C-peptide level: 1.12 (T0) and 6.18 μg/l (3 h). These results led to consider an insulin auto-immune syndrome (IAS). Indeed, the dosage of antihuman insulin antibodies (IAA) showed a high level > 50 u/ml. Infectious serologic testing and autoimmune marker were all negative. The serologic typing of HLA alleles was not in favour of HLA DR4. He went back to Mayotte. Despite 2 years treatment (Rituximab-Prednisolone every 2 months), hypoglycaemic events persisted and he was again referred in 2018. High level of insulin antibodies was still found and the IgG level increased to 3.1 g/l (plasma cells < 10% in the marrow). His treatment regimen was changed to bortezomib and high dose of dexamethasone with subsequent remission of hypoglycemia, decrease of IgG level (0.8 g/l) and antihuman insulin antibodies after 8 cycles. In conclusion, the search for paraproteinemia should be undertaken in Hirata syndrome or IAS particularly in case of relapse to immunosuppressive drug.