ODP581 Rapid Onset Autoimmune (non-type 1) Lean Diabetes Causing Severe Insulin Resistance and Pseudo-Cushing State

Jeronimo Berardo, Jessica L Hwang
2022 Journal of the Endocrine Society  
Introduction Type B insulin resistance syndrome (TBIRS) is a rare life-threatening disorder caused by autoantibodies to the insulin receptor. Suggestive clinical features include profound insulin resistance, concurrent autoimmune disease, acanthosis nigricans in lean individuals. Clinical Case 59 year old male (BMI = 21) diagnosed with diabetes 1 year prior (A1c was 8%) presents to the hospital in DKA (A1c 16.7%, pH 7.17, bicarb 8, anion gap 21, +++ketones). GAD, IA2, Islet cell, insulin
more » ... ies were negative. Prior to admission his doctor increased his insulin (Detemir 30 units twice daily and Lispro 15 units with meals), notably high for his 60 kg frame. In the ICU an insulin drip at 8 units/h for 20 hours closed the anion gap. Glucose remained >250 mg/dL the entire time so dextrose was never required. After aggressive attempts at increasing his insulin doses over 10 days, he was discharged home on metformin, pioglitazone, U500 concentrated insulin 450 units per day (divided amongst 3 meals) and close follow up. 12 months after presentation his U500 dose peaked to 660 units per day. Spontaneously, 6 months later hypoglycemia ensued, A1c improved to 10.2%, weight increased and insulin doses were reduced. Interestingly, because he endorsed hyperpigmentation and weight loss, ACTH (RR= 6-50 pg/mL) and cortisol (RR 6-22 ug/dL) were checked and were high-normal at 8AM (53, 17.3, respectively). 8AM cortisol (RR <1.8 ug/dL) after low dose dexamethasone was not suppressed at 9.44 and 24 hour urine free cortisol (RR <50) was elevated to 114. 8AM ACTH and cortisol were trended at 6 months and peaked at 65 and 20. However, a year after his initial presentation, they spontaneously normalized to 30 and 8 as his insulin requirements decreased suggesting resolution of Pseudo-Cushings due to uncontrolled diabetes. Workup for TBIRS included: fasting insulin level (RR 1.9-23) before his AM dose = 685 uIU/mL, fasting triglycerides = 91 mg/dL, +ANA, +Ribonucleoprotein/Smith, adiponectin 34 u/mL (high), mild pancytopenia. Because of 2 grams of proteinuria after only 1 year with diabetes renal biopsy was performed which demonstrated membranous glomerulonephropathy. Proteinuria improved as A1c decreased. Patient declined immunosuppression because he wanted to see if he would continue to improve spontaneously. Discussion The prevalence of TBIRS is unknown because confirmation testing for antibodies to the insulin receptor is limited to select research laboratories (none that we are aware of in the United States). To avoid delaying treatment, diagnosis can be made clinically on the basis of high fasting insulin levels, extremely high insulin doses with refractory hyperglycemia, autoimmunity, normal triglycerides, high adiponectin and hyperpigmentation. The mortality rate is high because of sporadic hypoglycemia that develops during treatment or as spontaneous remission occurs. Close follow up and counseling can decrease morbidity and morality. Presentation: No date and time listed
doi:10.1210/jendso/bvac150.712 fatcat:45wmbd6b4rhrjmcuadwhjy2rzy