Endocrine Abstracts

Background: Pembrolizumab is a novel anti-cancer drug that targets programmed cell death protein 1 (PD-1) receptor on lymphocytes resulting in their activation against tumor cells. PD-1 receptors are also distributed in endocrine organs and pembrolizumab use has long-been associated with hypophysitis and thyroiditis. We describe a patient with pembrolizumab-induced thyroiditis who developed an uncommon fulminant Type 1 Diabetes Mellitus (FT1D).

Case presentation: A 68-year old Phillipino woman was diagnosed with lung cancer in 2016. She had no response to chemotherapy and subsequently commenced on pembrolizumab in March 2017. There was no history of diabetes or any other endocrinopathy. Blood tests prior to third cycle of pembrolizumab in April 2017 showed thyrotoxicosis (FT4 34 pmol/l (9.0–19.0 pmol/l), TSH 0.03 mIU/l (0.35–4.94 mIU/l). She was managed conservatively and became hypothyroid (TSH 29.4 mIU/l, FT4 9.17 pmol/l) in June 2017 and hence started on thyroxine replacement. In early 2018, she became acutely unwell with hyperglycaemia (plasma glucose- 48.95 mmol/l), ketosis (urine ketones ++++) and severe metabolic acidosis (pH-7.062). She was diagnosed with diabetic ketoacidosis. Eventually, DKA resolved with appropriate treatment and she was commenced on basal-bolus insulin for newly diagnosed diabetes. Subsequent tests revealed lack of autoimmune nature (C-peptide of <33.1 pmol/l (330–1400 pmol/l), negative IA-2 (4.5%, reference<6.5%), GAD-65 (0.01 IU/ml, reference<1 IU/ml) and Zinc-transporter 8 antibodies (2.1 RU/ml, reference<15 RU/ml). Patient was hence diagnosed with pembrolizumab-induced FT1D.

Conclusion: Only recently has type 1 diabetes mellitus been acknowledged as an adverse effect of pembrolizumab. These patients need close monitoring and joint specialist follow-up to mitigate such complications.