Endocrine Abstracts

A 56-year-old woman, recently commenced on immunotherapy as second-line treatment for advanced non-small cell lung cancer, presented at the hospital critically unwell with severe diabetic ketoacidosis (DKA) (glucose 47 mmol/l, blood ketones 7.5 mmol/l, pH 6.95, bicarbonate 6.6 mmol/l). One week prior to presentation, she was clinically well with random glucose of 6.1 mmol/l. Following admission to Intensive Care Unit, she responded well to standard treatment for DKA and discharged on basal bolus insulin regime. Her anti-GAD antibodies were 12 kU/l (0–5 kU/l), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab has been recommenced without the development of other immune-mediated phenomena to date.

Besides metastatic lung adenocarcinoma diagnosed 3 years ago, she had no personal/family history of diabetes mellitus (DM), while venous glucose had been normal at numerous measurements. She was initially treated with Pemetrexed and Cisplatin followed by Pemetrexed as maintenance chemotherapy which was discontinued due to side-effects two months prior to her emergency presentation. At that stage, Nivolumab every 2 weeks was initiated. She has maintained good radiological and clinical response to treatment.

Nivolumab is an anti-PD-1 monoclonal antibody and as a checkpoint inhibitor acts as an immunomodulatory antibody that augments the anticancer immune response through downregulation of T-cell inhibition. Immunotherapy has a beneficial effect in an increasing number of tumour sites, but is associated with immune-mediated endocrinopathies. Development of new-onset type 1 DM after receiving anti-PD-1 antibodies, especially as single agent, is extremely rare.

This patient developed fulminant type 1 DM leading to severe DKA and remains insulin dependent. Both endocrinologists and oncologists need to recognise this potentially life-threatening complication and to monitor patients for hyperglycaemia prior to and periodically during immunotherapy. Further studies examining the pathophysiology and natural history of immunotherapy-associated diabetes are warranted in order to guide optimal patient monitoring and management.