A Case of Isolated Adrenocorticotropic Hormone Deficiency Followed by the Development of Type 1 Diabetes Mellitus, after the Administration of Atezolizumab

Abstract

An 82-year-old woman was treated with atezolizumab and bevacizumab for hepatocellular carcinoma recurrence after RFA. Four months later, she was brought to our hospital with a complaint of drowsiness. Other than mild hyperammonemia, there were no apparent abnormalities. Her blood glucose level was 170 mg/dL and her HbA1c value was 5.6 %. Drowsiness persisted after treatment for hepatic encephalopathy, and her serum sodium level, which was normal on admission, dropped to 121 mmol/L after 1 week of hospitalization. Her serum cortisol and ACTH levels were both low, and a loading test was performed, resulting in a diagnosis of isolated adrenocorticotropic hormone deficiency. After the administration of hydrocortisone, her fasting blood glucose level was 332 mg/dL, which was managed with multiple daily insulin injections. Although the patient tested positive for anti-GAD antibodies, insulin secretion persisted, and hyperglycemia was considered to be due to hepatic diabetes mellitus and excessive hydrocortisone administration. After discharge from the hospital, the patient's blood glucose level showed significant elevation, and insulin secretion decreased substantially within 6 weeks, leading to a diagnosis of acute-onset type 1 diabetes caused by atezolizumab. This is a rare case in which 2 endocrinologic immune-related adverse events developed successively after anti-PD-L1 antibody treatment, and the course of decline in insulin secretion could be observed.