Zaied Ali A, Akturk Halis K, Joseph Richard W, Lee Augustine S
Divisions of Pulmonary and Critical Care Medicine, Mayo Clinic, Jacksonville, Florida, USA.
Divisions of Endocrinology, Mayo Clinic, Jacksonville, Florida, USA.
Endocrinol Diabetes Metab Case Rep. 2018 Mar 28;2018. doi: 10.1530/EDM-17-0174. eCollection 2018.
Nivolumab, a monoclonal antibody against programmed cell death-1 receptor, is increasingly used in advanced cancers. While nivolumab use enhances cancer therapy, it is associated with increased immune-related adverse events. We describe an elderly man who presented in ketoacidosis after receiving nivolumab for metastatic renal cell carcinoma. On presentation, he was hyperpneic and laboratory analyses showed hyperglycemia and anion-gapped metabolic acidosis consistent with diabetic ketoacidosis. No other precipitating factors, besides nivolumab, were identified. Pre-nivolumab blood glucose levels were normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. He was diagnosed with insulin-dependent autoimmune diabetes mellitus secondary to nivolumab. Although nivolumab was stopped, he continued to require multiple insulin injection therapy till his last follow-up 7 months after presentation. Clinicians need to be alerted to the development of diabetes mellitus and diabetic ketoacidosis in patients receiving nivolumab.
Diabetic ketoacidosis should be considered in the differential of patients presenting with metabolic acidosis following treatment with antibodies to programmed cell death-1 receptor (anti-PD-1).Autoimmune islet cell damage is the presumed mechanism for how insulin requiring diabetes mellitus can develop following administration of anti-PD-1.Because anti-PD-1 works by the activation of T-cells and reduction of 'self-tolerance', other autoimmune disorders are likely to be increasingly recognized with increased use of these agents.
纳武单抗是一种抗程序性细胞死亡-1受体的单克隆抗体,越来越多地用于晚期癌症。虽然使用纳武单抗可增强癌症治疗效果,但它与免疫相关不良事件的增加有关。我们描述了一名老年男性,他在接受纳武单抗治疗转移性肾细胞癌后出现酮症酸中毒。就诊时,他呼吸急促,实验室分析显示高血糖和阴离子间隙代谢性酸中毒,符合糖尿病酮症酸中毒。除纳武单抗外,未发现其他诱发因素。纳武单抗治疗前血糖水平正常。患者接受静脉补液、胰岛素和电解质补充治疗后有反应。他被诊断为继发于纳武单抗的胰岛素依赖型自身免疫性糖尿病。尽管停用了纳武单抗,但直到就诊后7个月的最后一次随访时,他仍需要多次注射胰岛素治疗。临床医生需要警惕接受纳武单抗治疗的患者发生糖尿病和糖尿病酮症酸中毒。
对于接受程序性细胞死亡-1受体抗体(抗PD-1)治疗后出现代谢性酸中毒的患者,鉴别诊断时应考虑糖尿病酮症酸中毒。自身免疫性胰岛细胞损伤被认为是使用抗PD-1后发生胰岛素依赖型糖尿病的机制。由于抗PD-1通过激活T细胞和降低“自身耐受性”起作用,随着这些药物使用的增加,其他自身免疫性疾病可能会越来越多地被认识到。