Endocrine Abstracts

Introduction: Prembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, is one of the immune checkpoint inhibitors (ICI) that have revolutionized cancer therapy. However, ICIs can also trigger immune-related adverse events (irAEs) in different organ systems, including endocrine glands. While thyroid dysfunction is among the most common endocrinopathies reported, ICI-induced diabetes mellitus (DM) is extremely rare, with an overall incidence ranging from 0.9 to 2%.

Case report: We report the case of 76 years-old woman, with past history of hypertension and dyslipidemia. She was diagnosed in August/20 with an endometrial adenocarcinoma with peritoneal dissemination. In September/21, due to disease progression, she started treatment with Prembolizumab. A month later she developed a transitory thyrotoxicosis, followed by permanent hypothyroidism, most likely caused by silent inflammatory thyroiditis and is currently being treated with levothyroxine. About 6 months later, her fasting blood glucose levels (108 – 119mg/dl) and her A1c levels started to rise (5.8 - 6.3%). Since she was asymptomatic, she was started on SGLT2 inhibitor treatment. Nevertheless, two months later, she suddenly started to lose weight and complaining of polyuria and polydipsia. At observation, she had a blood glucose level of 477mg/dl, positive ketones (4.5mmol/l) and a metabolic acidosis. A diabetic ketoacidosis (DKA) was admitted, and she was treated accordingly. Her laboratory results at that time revealed an A1c level of 9.6% and a low C-peptide (0.44ng/ml). ICI-induced DM was admitted, and a basal-bolus insulin scheme was started. Prembolizumab treatment was never stopped, and she has been gradually improving her metabolic control.

Conclusion: ICIs are associated with significant endocrine irAEs, that can appear at anytime throughout the course of ICI treatment. In the case reported, two endocrinopathies appeared progressively, with a thyroiditis presenting right after the beginning of ICI treatment and a DM appearing about 6 months later. The majority of patients with ICI-induced DM presents in a fulminant way and DKA is frequent at diagnosis, seen in up to 70% of cases. In the reported case, both the high A1c level at DKA diagnosis and the previous signs of glucose metabolism dysfunction, suggest a slower DM development than what is usually described. Nevertheless, our patient ended up presenting with DKA and will probably need lifelong insulin replacement. Although rare, ICI-induced DM can be life-threatening, and a prompt diagnosis is essential. This reinforces the importance of patient education and regular endocrine dysfunction monitoring as a key to reduce irAEs impact.