Recurrent severe hypoglycaemic episodes in the context of insulin receptor antibodies

Ruth Ronneberger; Afizah Nobeebux; Yuliya Manova; Gill Rumsby; Francis Lam; Gary Woodward; David Isenberg; Michael Ehrenstein; David Halsall; David Church; Robert Semple; Helen Simpson

doi:10.1530/endoabs.55.OC8

We present a 32-year-old woman with recurrent hypoglycaemic episodes and a history of juvenile onset SLE. Over months, she experienced severe hypoglycaemic episodes with unconsciousness, occuring mainly in the early morning resulting in several hospital admissions. The patient had to take precautions like eating snacks between meals and before going to bed, and even setting an alarm clock to eat a bowl of porridge at 0200 h. She was of normal weight, did not present with any hyperpigmentation or acanthosis nigricans and did not have a history of diabetes mellitus. The known juvenile onset SLE had been difficult to control over the years with recurrent flares. Current treatment included prednisolone, hydroxychloroquine and azathioprine. A fasting blood test revealed a blood glucose of 1.8 mmol/l with borderline insulin level of 2.3 mlU/l and undetectable C-peptide, making an insulinoma unlikely. NEFA and 3-hydroxybutyrate were inappropriately low, suggestive of hyperinsulinaemia or action via the insulin receptor. Drug-induced hypoglycaemia and sulfonylurea abuse was excluded, the ongoing prednisolone treatment contradicted an underlying hypocortisolism. Insulin antibodies were found to be negative on two separate samples. A random insulin study was performed, showing hyperinsulinaemia (3,504 pmol/l), elevated C-peptide (3,240 pmol/l) and raised adiponectin concentration (27.1 μg/ml), consistent with an insulin receptor dysfunction. In fact, insulin receptor antibodies were found to be weakly positive, giving diagnosis a type B insulin resistance syndrome. In view of another flare of her SLE and the newly diagnosed type B insulin resistance, our patient was commenced on Rituximab which helped control her hypoglycaemia. After two doses, she did not have any more hypoglycaemic episodes. Type B insulin resistance with insulin receptor antibodies is a very rare condition, commonly associated with other autoimmune diseases. The history of SLE in our patient, severe fasting hypoglycaemia, hyperinsulinaemia and raised adiponectin concentration were suggestive of the underlying insulin receptor dysfunction. The most common symptom of type B insulin resistance is hyperglycaemia with extremely high insulin need while some patients seem to suffer both from hyper- and hypoglycaemic episodes, possibly due to fluctuating antibody titers. Our patient presented purely with hypoglycaemic episodes. Treatment for this condition is not yet standardised, and the production of autoantibodies may even remit spontaneously. Different therapeutic approaches in the past achieved very mixed outcomes, and although our patient showed a great improvement on Rituximab, the duration of remission and possible long term treatment remains unknown.

Endocrine Abstracts

OC8