Endocrine Abstracts

JOINT1614

Introduction: Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enhancing the immune system’s ability to recognize and destroy cancer cells. These drugs target regulatory pathways in T-cells, particularly programmed cell death protein 1 (PD-1) and its ligand PD-L1, which can allow cancer cells to evade immune detection. While ICIs have demonstrated significant success in improving survival rates across various cancers, their use is often associated with autoimmune adverse events (AIAEs). Among these, endocrinopathies are particularly common, as the heightened immune response can sometimes attack healthy endocrine organs, leading to conditions such as thyroiditis and diabetes mellitus.

Materials and Methods: In 2018, at the age of 33, Patient T. underwent surgical excision of melanoma in the right subclavian region. Disease progression led to further surgeries in May 2021, including right-sided axillary-subscapular-subclavian lymphadenectomy, left kidney resection, and liver biopsy. In December 2022, the patient was prescribed prolgolimab, a human monoclonal antibody that binds specifically to PD-1, inhibiting its interaction with PD-L1 and PD-L2 to prevent tumor cells from evading the immune system. In January 2023, while undergoing oncoimmunotherapy, the patient reported symptoms of severe thirst, frequent urination, and hyperglycemia, with initial blood glucose levels reaching 40.9mmol/l. He was promptly hospitalized in intensive care, where a diagnosis of mixed-genesis ketoacidosis with cerebral edema was made. Basal-bolus insulin therapy was initiated to manage blood glucose levels. Further evaluation at the National Medical Research Center of Endocrinology in June 2023 revealed significant endocrine findings: C-peptide levels at 7.0pmol/l (reference range: 100–1100), insulin autoantibodies at 3.4IU/mL (0–10), GAD autoantibodies at 0.1U/mL (0–10), and pancreatic beta cell autoantibodies at 0.35 (0–1). Insulin therapy was adjusted to optimize glycemic control, and the patient’s glucose levels were stabilized within individually targeted ranges. Approximately one year after the diabetes mellitus diagnosis, and following three courses of immune checkpoint therapy (nivolumab + ipilimumab), the patient developed destructive thyroiditis in its hypothyroid phase. Laboratory values indicated TSH at 56.9mU/l (0.27–4.2), free T4 at 2.71pmol/l (12–22), and free T3 at 1.65pmol/l (3.1–6.8). Levothyroxine sodium was initiated at 75mg/day, with gradual titration to 112.5mg/day to achieve targeted hypothyroidism compensation.

Results: This case highlights the complex immune response triggered by ICIs, as evidenced by the sequential onset of two significant autoimmune endocrinopathies-diabetes mellitus and thyroiditis. The varied timing of these events underscores the need for diligent monitoring for endocrine disorders throughout different phases of ICI therapy.