Not Your Typical DKA: Severe Insulin Resistance after Brentuximab Treatment

Presentation Number: SAT 610
Date of Presentation: April 1st, 2017

Janet M. Chiang*1, Robert J Rushakoff1, Wint Lwin2, Andrew R Lai2 and Mark Stuart Anderson3
1University of California, San Francisco, San Francisco, CA, 2University of California, San Francisco, 3University of California at San Francisco, San Francisco, CA

Abstract

Background:

Extreme insulin resistance (requiring up to 18,000 units/day) is rare. Patients usually have a history of autoantibodies to the insulin receptor associated with autoimmune disease, acanthosis, and weight loss. Previously, no cases of severe insulin resistance with DKA have been reported following initiation of targeted immunotherapy.

Clinical case:

A 54-year-old man with human immunodeficiency virus (HIV) and Hodgkin’s lymphoma, without history of diabetes, (glucose 107-135 mg/dL in the month prior to admission), received his first dose of brentuximab for treatment of lymphoma. One week later, the patient presented to the emergency room with fatigue, polydipsia, and polyuria. He had an initial glucose of 460 mg/dL (70-199 mg/dL), bicarbonate of 7 mmol/L (22-32 mmol/L), and ketones of 11.2 mmol/L (0.02-0.27 mmol/L), and was diagnosed with DKA. He did not have acanthosis nigricans or signs of cortisol excess on physical exam. HgbA1c was 5.9% prior to admission. C-peptide was 15.1 ng/mL (0.8-3.1 ng/mL) prior to IV insulin administration. GAD-65 antibody and insulin autoantibody were negative. Standard DKA protocol treatment was initiated with IV hydration and IV insulin. Within 12 hours of admission, the IV insulin had been titrated to >600 units/hour with only minor decreases in glucose to 394 mg/dL and ketones to 7.35 mmol/L. The patient received 1748 units of IV insulin in the first 24 hours of admission and 10,725 units in the following 24 hours. He developed cardiovascular, respiratory, and renal failure, and due to the severity of his illness, he was treated for suspected type B insulin resistance and cytokine storm with two doses of IV methylprednisolone 1 g followed by plasmapheresis. Following plasmapheresis, the patient’s insulin requirements decreased over the next 12 hours from 600 units/hour to 75 units/hour. Unfortunately, the patient ultimately died from multiple organ failure approximately 72 hours after admission. Autopsy revealed a normal-appearing pancreas, a known malignant abdominal mass, and no infectious source or major emboli as explanations of death.

Discussion:

Brentuximab is an anti-CD30 monoclonal antibody approved for use in Hodgkin’s lymphoma. CD30 is expressed in Hodgkin’s cells but also found on T-regulatory cells and on activated T-cells producing Th2-type cytokines. We hypothesize that the combination of abnormal T-cell function in HIV and the possible attenuation of T-cell regulation via the CD30 receptor led to an “unleashing” of a severe autoimmune response that included antibodies to the insulin receptor and a cytokine cascade, which ultimately resulted in the patient’s death.

 

Nothing to Disclose: JMC, RJR, WL, ARL, MSA