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当激素出现问题时:一例罕见病例及帕博利珠单抗诱导的多内分泌病文献综述

When Hormones are Being Difficult: A Rare Case and the Literature Review of Pembrolizumab-Induced Polyendocrinopathy.

作者信息

Tayyeb Muhammad, Tariq Maham, Khan Ahsan M, Khalid Farhan, Meghal Trishala, Du Doantrang

机构信息

Department of Medicine, Monmouth Medical Center, Long Branch, NJ, USA.

Department of Medicine, Services Institute of Medical Sciences, Lahore, Pakistan.

出版信息

J Community Hosp Intern Med Perspect. 2023 Nov 4;13(6):90-94. doi: 10.55729/2000-9666.1270. eCollection 2023.

Abstract

Immune Checkpoint inhibitors (ICIs) such as nivolumab, pembrolizumab, and ipilimumab are monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA4) or program death (PD)1 and its ligand PDL1. Agents targeting PD1, such as pembrolizumab, have shown widespread efficacy in the past and are also associated with a wide range of immune-related adverse events (irAEs), including endocrine toxicities. A 31-year-old female with a medical history significant for Stage IIb Breast cancer on chemo and immunotherapy (pembrolizumab) presented with nausea, vomiting, and generalized abdominal pain. Laboratory studies showed a blood glucose level of 356 mg/dl, elevated Anion gap 18 meq/L, beta-hydroxybutyrate 46 mg/d, and low C-peptide levels <0.10 ng/ml. The patient was treated for Diabetic Ketoacidosis (DKA). Further testing revealed high Thyroid Stimulating Hormone (TSH) levels along with elevated thyroid peroxidase levels of 38 IU/L. After discharge from the hospital on insulin and levothyroxine therapy, the patient reported increasing fatigue and further testing revealed low cortisol levels <0.5 mcg/dl with elevated ACTH consistent with primary adrenal insufficiency. The patient was started on hydrocortisone therapy with improvement in symptoms. Endocrine toxicities are not uncommon in patients receiving pembrolizumab, but polyendocrinopathy in a relatively rare side effect of pembrolizumab. Only a few cases of pembrolizumab-induced polyendocrinopathy have been reported so far which we have mentioned in this article. While patients are on immunotherapy, close monitoring for clinical signs & symptoms can lead to an early diagnosis, substantially improving morbidity and mortality.

摘要

免疫检查点抑制剂(ICIs),如纳武单抗、帕博利珠单抗和伊匹木单抗,是针对细胞毒性T淋巴细胞抗原4(CTLA4)或程序性死亡(PD)1及其配体PDL1的单克隆抗体。靶向PD1的药物,如帕博利珠单抗,过去已显示出广泛的疗效,并且还与多种免疫相关不良事件(irAEs)相关,包括内分泌毒性。一名31岁女性,有IIb期乳腺癌病史,正在接受化疗和免疫治疗(帕博利珠单抗),出现恶心、呕吐和全腹痛。实验室检查显示血糖水平为356mg/dl,阴离子间隙升高至18meq/L,β-羟丁酸为46mg/d,C肽水平低<0.10ng/ml。该患者接受了糖尿病酮症酸中毒(DKA)治疗。进一步检查发现促甲状腺激素(TSH)水平升高,同时甲状腺过氧化物酶水平升高至38IU/L。出院后接受胰岛素和左甲状腺素治疗,患者报告疲劳加剧,进一步检查发现皮质醇水平低<0.5mcg/dl,促肾上腺皮质激素(ACTH)升高,符合原发性肾上腺功能不全。患者开始接受氢化可的松治疗,症状有所改善。内分泌毒性在接受帕博利珠单抗治疗的患者中并不罕见,但多内分泌病是帕博利珠单抗相对罕见的副作用。迄今为止,仅报道了少数几例帕博利珠单抗诱导的多内分泌病病例,我们在本文中已提及。当患者接受免疫治疗时,密切监测临床体征和症状可实现早期诊断,大幅提高发病率和死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1076/11000850/741126f2b42d/jchim-13-06-090f1.jpg

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