MON-330 Spontaneous Intracranial Hypotension in a Patient with Papillary Thyroid Carcinoma Treated with Dabrafenib and Trametinib: A Case Report

Abstract Disclosure: K. Kaur: None. S.A. Salgado: None. Introduction: Papillary thyroid carcinoma is an endocrine malignancy that, in cases with BRAF mutations, can be effectively managed with targeted therapies like Dabrafenib (a BRAF inhibitor) and Trametinib (a MEK inhibitor). While these therapies demonstrate efficacy, they are associated with notable side effects, including systemic and neurological complications. Here, we report a unique case of spontaneous intracranial hypotension (SIH) presenting with severe postural headaches during treatment with Dabrafenib and Trametinib. Case Description: A 41-year-old female with papillary thyroid carcinoma, with a BRAF mutation, was started on Dabrafenib 150 mg BID and Trametinib 2 mg nightly in May 2024 following surgical intervention due to persistent inoperable disease. Approximately four months into treatment, she began experiencing daily, positional headaches described as severe and splitting, particularly on bending forward. An initial MRI in September 2024 was unremarkable. However, symptoms persisted until therapy was discontinued two months later, leading to rapid resolution of headaches. An MRI brain with and without contrast on October 25, 2024, revealed findings consistent with spontaneous intracranial hypotension. The patient's neurological exam at presentation to the Neurology clinic was unremarkable, with a Karnofsky Performance Scale score of 100. Following discontinuation of therapy, the patient has remained asymptomatic. Discussion: Dabrafenib and Trametinib are known to induce systemic inflammatory responses and, rarely, neurological side effects such as encephalopathy. A potential mechanism may be transient intracranial hypertension with a secondary CSF leak, leading to SIH. The resolution of symptoms following drug discontinuation underscores the role of targeted therapy in the pathophysiology. Conclusion: This case highlights the importance of recognizing intracranial hypotension as a rare but significant side effect of BRAF/MEK inhibition therapy. Early recognition and intervention, including imaging and possible therapy discontinuation, can lead to symptom resolution and prevent long-term complications. Further investigation is warranted to establish the mechanism underlying this association and to optimize management strategies for affected patients. Keywords: Papillary thyroid carcinoma, Dabrafenib, Trametinib, Spontaneous intracranial hypotension, Targeted therapy, Neurological side effects. Presentation: Monday, July 14, 2025