-
摘要: 多种抗肿瘤药物如激素类、化疗、靶向药物和免疫检查点抑制剂在发挥抗癌作用的同时对内分泌腺具有毒性作用，其中对肾上腺的影响逐渐受到临床重视。药物治疗相关的肾上腺功能不全若无法及时诊治，可导致肾上腺危象的发生甚至危及生命。本文将就抗肿瘤药物对肾上腺机制影响进行综述，为临床防治肿瘤患者的肾上腺功能异常提供指导。Abstract: Multiple antineoplastic agents, including immune checkpoint inhibitors, chemotherapeutic agents, and hormonal and targeted agents, cause inevitable endocrine toxicity, and clinicians should pay more attention to their effects on the adrenal glands. If adrenal insufficiency related to drug therapy is not identified or treated in time, it may lead to an adrenal crisis and even be life-threatening. This paper reviews the mechanisms and effects of antineoplastic agents with respect to the adrenal glands, and our results may guide the prevention and treatment of adrenal dysfunction in cancer patients.
-
Key words:
- antineoplastic agents /
- adrenal gland /
- hormone /
- targeted agents /
- immune checkpoint inhibitor (ICPi)
-
图 1 抗肿瘤药物对肾上腺影响的可能途径
CRH：促肾上腺皮质激素释放激素；AVP：血管加压素；POMC：阿片黑素促皮质素原；ATP：三磷酸腺苷；cAMP：环磷酸腺苷；PKA：蛋白激酶A；StAR：类固醇激素合成急性调节蛋白；VEGF：血管内皮生长因子；CBG：皮质类固醇结合球蛋白；GR：糖皮质激素受体；（-）：负反馈调节
表 1 抗肿瘤药物的作用机制与分类
-
[1] Lu J, Li L, Lan Y, et al. Immune checkpoint inhibitor-associated pituitary- adrenal dysfunction: A systematic review and meta- analysis [J]. Cancer Med, 2019, 8(18): 7503-7515. doi: 10.1002/cam4.2661 [2] Yanase T, Tajima T, Katabami T, et al. Diagnosis and treatment of adrenal insufficiency including adrenal crisis: a Japan endocrine society clinical practice guideline [Opinion] [J]. Endocr J, 2016, 63(9): 765-784. doi: 10.1507/endocrj.EJ16-0242 [3] Harvey PW. Adrenocortical endocrine disruption[J]. J Steroid Biochem Mol Biol, 2016, 155(Pt B): 199-206. http://www.sciencedirect.com/science/article/pii/S0960076014002441 [4] Oddie PD, Albert BB, Hofman PL, et al. Mitotane in the treatment of childhood adrenocortical carcinoma: a potent endocrine disruptor[J]. Endocrinol Diabetes Metab Case Rep, 2018, 2018: 18. http://www.researchgate.net/publication/327195434_Mitotane_in_the_treatment_of_childhood_adrenocortical_carcinoma_a_potent_endocrine_disruptor [5] Cao Y. VEGF-targeted cancer therapeutics-paradoxical effects in endocrine organs[J]. Nat Rev Endocrinol, 2014, 10(9): 530-539. doi: 10.1038/nrendo.2014.114 [6] Johnson DB, Balko JM, Compton ML, et al. Fulminant myocarditis with combination immune checkpoint blockade[J]. N Engl J Med, 2016, 375(18): 1749-1755. doi: 10.1056/NEJMoa1609214 [7] Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade[J]. N Engl J Med, 2018, 378(2): 158-168. doi: 10.1056/NEJMra1703481 [8] Basile V, Puglisi S, Calabrese A, et al. Unwanted hormonal and metabolic effects of postoperative adjuvant mitotane treatment for adrenocortical cancer[J]. Cancers (Basel), 2020, 12(9): 2615. doi: 10.3390/cancers12092615 [9] Poirier J, Gagnon N, Terzolo M, et al. Recovery of adrenal insufficiency is frequent after adjuvant mitotane therapy in patients with adrenocortical carcinoma[J]. Cancers (Basel), 2020, 12(3): 639. doi: 10.3390/cancers12030639 [10] Han HS, Park JC, Park SY, et al. A prospective multicenter study evaluating secondary adrenal suppression after antiemetic dexamethasone therapy in cancer patients receiving chemotherapy: a Korean south west oncology group study[J]. Oncologist, 2015, 20(12): 1432-1439. doi: 10.1634/theoncologist.2015-0211 [11] Loimijoki T, Lapatto R, Taskinen M. Adrenal function after induction therapy for acute lymphoblastic leukemia in children short: adrenal function in ALL[J]. Eur J Pediatr, 2020, 179(9): 1453-1459. doi: 10.1007/s00431-020-03624-5 [12] Laugesen K, Petersen I, Sørensen HT, et al. Clinical indicators of adrenal insufficiency following discontinuation of oral glucocorticoid therapy: a Danish population-based self-controlled case series analysis[J]. PLoS One, 2019, 14(2): e0212259. doi: 10.1371/journal.pone.0212259 [13] Joseph RM, Hunter AL, Ray DW, et al. Systemic glucocorticoid therapy and adrenal insufficiency in adults: a systematic review[J]. Semin Arthritis Rheum, 2016, 46(1): 133-141. doi: 10.1016/j.semarthrit.2016.03.001 [14] Santen RJ, Jewell CM, Yue W, et al. Glucocorticoid receptor mutations and hypersensitivity to endogenous and exogenous glucocorticoids[J]. J Clin Endocrinol Metab, 2018, 103(10): 3630-3639. doi: 10.1210/jc.2018-00352 [15] de Ruiter RD, Gordijn MS, Gemke RJBJ, et al. Adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia is associated with glucocorticoid receptor polymorphisms ER22/23EK and BclI[J]. Haematologica, 2014, 99(8): e136-e137. doi: 10.3324/haematol.2014.105056 [16] Huang C, Jiang Y, Duan G, et al. Effects of sequential chemotherapy of FOLFIRI/FOLFOX on the endocrine axes of ACTH-cortisol and reninangiotensin-aldosterone[J]. J Neurooncol, 2012, 108(3): 485-490. doi: 10.1007/s11060-012-0845-0 [17] Kawazoe A, Yamaguchi K, Yasui H, et al. Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first- line treatment in patients with advanced gastric/gastroesophageal junction cancer: cohort 1 data from the KEYNOTE-659 phase Ⅱb study [J]. Eur J Cancer, 2020, 129: 97-106. doi: 10.1016/j.ejca.2020.02.002 [18] Owattanapanich W, Sirinvaravong S, Suphadirekkul K, et al. Transient adrenal insufficiency in diffuse large B cell lymphoma patients after chemotherapy with short-course, high-dose corticosteroids[J]. Ann Hematol, 2018, 97(12): 2403-2410. doi: 10.1007/s00277-018-3470-y [19] Patyna S, Arrigoni C, Terron A, et al. Nonclinical safety evaluation of sunitinib: a potent inhibitor of VEGF, PDGF, KIT, FLT3, and RET receptors[J]. Toxicol Pathol, 2008, 36(7): 905-916. doi: 10.1177/0192623308326151 [20] Voss M, Batarfi A, Steidl E, et al. Adrenal insufficiency in patients with corticosteroid- refractory cerebral radiation necrosis treated with bevacizumab[J]. J Clin Med, 2019, 8(10): 1608. doi: 10.3390/jcm8101608 [21] Colombo C, De Leo S, Di Stefano M, et al. Primary adrenal insufficiency during lenvatinib or vandetanib and improvement of fatigue after cortisone acetate therapy[J]. J Clin Endocrinol Metab, 2019, 104(3): 779-784. doi: 10.1210/jc.2018-01836 [22] Lupi I, Brancatella A, Cosottini M, et al. Clinical heterogeneity of hypophysitis secondary to PD-1/PD-L1 blockade: insights from four cases[J]. Endocrinol Diabetes Metab Case Rep, 2019, 2019: 19. http://www.researchgate.net/publication/336564835_Clinical_heterogeneity_of_hypophysitis_secondary_to_PD-1PD-L1_blockade_insights_from_four_cases [23] Min L, Ibrahim N. Ipilimumab- induced autoimmune adrenalitis[J]. Lancet Diabetes Endocrinol, 2013, 1(3): e15. doi: 10.1016/S2213-8587(13)70031-7 [24] Zhai Y, Ye X, Hu F, et al. Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US food and drug administration adverse events reporting system[J]. J Immunother Cancer, 2019, 7(1): 286. doi: 10.1186/s40425-019-0754-2 [25] Paepegaey AC, Lheure C, Ratour C, et al. Polyendocrinopathy resulting from pembrolizumab in a patient with a malignant melanoma [J]. J Endocr Soc, 2017, 1(6): 646-649. doi: 10.1210/js.2017-00170 -
下载:
点击查看大图
图(1) / 表(1)
计量
- 文章访问数: 103
- HTML全文浏览量: 9
- PDF下载量: 18
- 被引次数: 0
