Endocrine Abstracts

Introduction: The immune checkpoint inhibitors (ICI) are increasingly being used in the treatment of several malignancies. ICI are monoclonal antibodies that inhibit immune checkpoints, thus stimulating the action of the immune cells to attack the tumour cells. The overstimulation of the immune system can lead to several endocrinopathies, such as autoimmune diabetes, known as ICI-associated diabetes mellitus (ICIDM).

Case Report: In September 2023, a 62-year-old male presented to the emergency department with diabetic ketoacidosis (DKA). He had no prior diagnosis of diabetes mellitus. The patient was diagnosed with clear cell renal cell carcinoma in November 2022 and underwent right nephrectomy in January 2023. In May 2023 there were detected pulmonary metastases, initiating immunotherapy with nivolumab and ipilimumab one month after, which led us to suspect of autoimmune diabetes secondary to ICI. In admission, the patient presented with polyuria, polydipsia, and loss of 3 kg in the past week, and a biochemical evaluation that revealed DKA with a glycemia of 590 mg/dl, a ketonemia of 6.2mmol/l, and arterial pH of 7.303. The autoimmunity study with anti-GAD, anti-ICA, anti-insulin and anti-IA2 was negative, the C-peptide was low (0.26 ng/ml) and the HbA1C was 6.5%. Abdominopelvic CT was performed and did not show neoplastic lesions or sins of pancreatitis. Furthermore, the study of other endocrinopathies potentially associated with ICI was negative. Glycaemic control was achieved with insulin perfusion followed by intensive insulin therapy. The patient was then discharged, monitored with a continuous glucose monitoring device and under intensive insulin therapy, which he currently maintains, with good control of glycaemic profile.

Discussion: ICIDM presents as an acute symptomatic and severe hyperglycaemia with a high prevalence of DKA (in approximately 70% of the cases), a near-normal HbA1C and an undetectable C-peptide, suggesting a rapid progression of beta-cell destruction. In this case report, approximately 3 months after starting an ICI, the patient presented with DKA, a HbA1C of 6.5%, and a low C-peptide which indicated rapid progression to insulin insufficiency. Roughly 60% of the cases of ICIDM described in the literature don´t have diabetes autoantibodies, as occurred in this case report. In accordance with other endocrinopathies associated with ICI, ICIDM requires lifelong treatment with the deficient hormone, in this case insulin.

Conclusion: This case report is in line with other case studies available in literature and not only alert us to this unusual diagnosis, but also for the need to screen these patients for endocrinopathies associated with ICI.