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Trametinib Toxicities in Patients With Low-grade Gliomas and Diabetes Insipidus

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Egan, Grace MD*; Hamilton, Jill MD; McKeown, Tara NP*; Bouffet, Eric MD*; Tabori, Uri MD*; Dirks, Peter MD; Bartels, Ute MD*

Journal of Pediatric Hematology/Oncology: January 22, 2019 - Volume Publish Ahead of Print - Issue - p
doi: 10.1097/MPH.0000000000001427
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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.

*Division of Haematology/Oncology

Division of Endocrinology, The Hospital for Sick Children

Divison of Neurosurgery, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada

The authors declare no conflict of interest.

Reprints: Grace Egan, MD, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada, M5G1X8 (e-mail: grace.egan@sickkids.ca).

Received September 12, 2018

Accepted December 25, 2018

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