Egan Grace, Hamilton Jill, McKeown Tara, Bouffet Eric, Tabori Uri, Dirks Peter, Bartels Ute
Division of Haematology/Oncology.
Division of Endocrinology, The Hospital for Sick Children.
J Pediatr Hematol Oncol. 2020 May;42(4):e248-e250. doi: 10.1097/MPH.0000000000001427.
Low-grade gliomas (LGG) represent the most common form of primary central nervous system tumor arising in childhood. There is growing evidence to support the role of the mitogen-activated protein kinase pathway in driving tumor growth and MEK inhibitors are being investigated in clinical trials for refractory and unresectable LGGs. As MEK inhibitors progress through clinical trials, drug toxicities have been identified. We report on 2 pediatric patients with LGG and known diabetes insipidus who developed severe hyponatraemia associated with significant decreases in desmopressin doses after starting trametinib. We review potential mechanisms for this sodium imbalance by examining the interaction between MEK inhibition and aquaporin channel physiology. We recommend close monitoring of serum sodium levels and clinical status in patients with diabetes insipidus who have optic-hypothalamic gliomas and are started on treatment with MEK inhibitors.
低级别胶质瘤（LGG）是儿童期最常见的原发性中枢神经系统肿瘤形式。越来越多的证据支持丝裂原活化蛋白激酶途径在驱动肿瘤生长中的作用，并且MEK抑制剂正在针对难治性和不可切除的LGG进行临床试验研究。随着MEK抑制剂在临床试验中的进展，已发现药物毒性。我们报告了2例患有LGG且已知尿崩症的儿科患者，他们在开始使用曲美替尼后出现严重低钠血症，同时去氨加压素剂量显著降低。我们通过研究MEK抑制与水通道蛋白通道生理学之间的相互作用，来探讨这种钠失衡的潜在机制。我们建议对患有视交叉下丘脑胶质瘤且开始接受MEK抑制剂治疗的尿崩症患者密切监测血清钠水平和临床状况。
