DOI: 10.12890/2021_002756
Hyperosmolar Hyperglycaemic State and Diabetic Ketoacidosis in Nivolumab-Induced Insulin-Dependent Diabetes Mellitus
Authors
asaleh17@hamad.qa
Keywords
DKA, HHS, nivolumab, diabetes mellitus, checkpoint inhibitorsAbstract
Nivolumab is a monoclonal antibody directed against programmed cell death-1 receptor. It has an increasing application in the treatment of various advanced metastatic cancers. The incidence of autoimmune side effects associated with such agents is expected to increase. New-onset autoimmune diabetes mellitus associated with immune checkpoint inhibitor treatment is rare, occurring in less than 1% of patients. Nivolumab-induced diabetes often presents as diabetic ketoacidosis, which could be life-threatening if not recognized and treated promptly. We present the case of a patient who developed severe diabetic ketoacidosis concomitant with hyperosmolar hyperglycaemic state (HHS) after receiving nivolumab for metastatic testicular lymphoma. Pre-nivolumab blood glucose levels were normal, apart from transient hyperglycaemia related to steroids as part of the chemotherapy protocol. The diagnosis was confirmed with extremely low C-peptide in the clinic.
References
- Barroso-Sousa R, Barry WT, Garrido-Castro AC, Hodi FS, Min L, Krop IE, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens. JAMA Oncology 2018;4(2):173.
- Venetsanaki V, Boutis A, Chrisoulidou A, Papakotoulas P. Diabetes mellitus secondary to treatment with immune checkpoint inhibitors. Curr Oncol 2019;26(1):e111–e114.
- Wright JJ, Salem J, Johnson DB, Lebrun-Vignes B, Stamatouli A, Thomas JW, et al. Increased reporting of immune checkpoint inhibitor-associated diabetes. Diabetes Care 2018;41(12):e150–e151.
- Magis Q, Gaudy-Marqueste C, Basire A, Loundou A, Malissen N, Troin L, et al. Diabetes and blood glucose disorders under anti-PD1. J Immunother 2018;41(5):232–240.
- Akturk HK, Kahramangil D, Sarwal A, Hoffecker L, Murad MH, Michels AW. Immune checkpoint inhibitor-induced Type 1 diabetes: a systematic review and meta-analysis. Diabet Med 2019;36(9):1075–1081.
- de Filette JMK, Pen JJ, Decoster L, Vissers T, Bravenboer B, Van der Auwera BJ, et al. Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review. Eur J Endocrinol 2019;181(3):363–374.
- Towns R, Pietropaolo M. GAD65 autoantibodies and its role as biomarker of Type 1 diabetes and Latent Autoimmune Diabetes in Adults (LADA). Drugs Future 2011;36(11):847.
- Higham CE, Olsson-Brown A, Carroll P, Cooksley T, Larkin J, Lorigan P, et al. Society for Endocrinology Endocrine Emergency Guidance: acute management of the endocrine complications of checkpoint inhibitor therapy. Endocr Connect 2018;7(7):G1¬–G7.
- Pu N, Lou W, Yu J. PD-1 immunotherapy in pancreatic cancer. J Pancreatol 2019;2(1):6–10.
- Spiers L, Coupe N, Payne M. Toxicities associated with checkpoint inhibitors–an overview. Rheumatology 2019;58 Suppl 7:vii7–vii16.
- Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, et al. Collateral damage: insulin-dependent diabetes induced with checkpoint inhibitors. Diabetes 2018;67(8):1471–1480.
- Ansari MJ, Salama AD, Chitnis T, Smith RN, Yagita H, Akiba H, et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med 2003;198(1):63–69.
- Fujisawa R, Haseda F, Tsutsumi C, Hiromine Y, Noso S, Kawabata Y, et al. Low programmed cell death-1 (PD-1) expression in peripheral CD4+T cells in Japanese patients with autoimmune type 1 diabetes. Clin Exp Immunol 2015;180(3):452–457.
- Hansen E, Sahasrabudhe D, Sievert L. A case report of insulin-dependent diabetes as immune-related toxicity of pembrolizumab: presentation, management and outcome. Cancer Immunol Immunother 2016;65:765–767.