193-LB: A Puzzling Case of Hypoglycemia in a Patient with Type 1 Diabetes Mellitus and Cushing Syndrome

Abstract

Introduction: Exogenous insulin antibodies are common in patients with type 1 diabetes mellitus (T1DM) on insulin. However, they are clinically irrelevant as a cause of hypoglycemia. We report a unique case of exogenous insulin antibody-mediated severe hypoglycemia in a patient with T1DM and Cushing syndrome. Case Report: A 55-year-old woman with T1DM on insulin pump presented with proximal muscle weakness and myalgia. She was diagnosed with Cushing syndrome due to an adrenal adenoma. Despite high serum cortisol, she had severe symptomatic episodic hypoglycemia with glucose levels <10 mg/dL requiring intermittent prolonged suspension of insulin pump. Surprisingly, she did not develop hyperglycemia or ketosis when off the insulin pump. During a witnessed hypoglycemic episode, serum insulin was 20.8 uIU/mL (NRR <19.7 uIU/mL), C-peptide <0.10 ng/mL (NRR 0.80-2.85 ng/mL), glucagon 11 pg/nl (NRR 8-57 pg/nl), and insulin antibody 4.1 U/mL (NRR <0.4/U/mL). She eventually underwent right adrenalectomy and was started on prednisone post-operatively resulting in a marked decrease in frequency of hypoglycemia. She was discharged on prednisone with plan for outpatient taper. Discussion: Our case highlights the complex nature of glycemic dysregulation in insulin antibody-mediated hypoglycemia. Literature review suggests that binding capacity and affinity to insulin, rather than the quantity of insulin antibodies, determines the severity of hypoglycemia. We hypothesize that high binding capacities in our patient resulted in rapid sequestration of exogenous insulin through formation of immunoglobulin-insulin complexes. The low affinity allowed for subsequent rapid release of insulin in a physiologically dyssynchronous manner resulting in hyperinsulinemic hypoglycemia. A distinctive aspect of our patient is the presence of severe hypoglycemia despite endogenous hypercortisolism, although she responded to prednisone. This finding may have implications for future research. Disclosure M. Amini: None. A. H. Khine: None. S. S. Lamba: None. S. Mishra: None. S. Naing: None. V. Babu: None.