(702) An Immunotherapy Paradox: A Rare Case of Hashimoto Encephalopathy Post-Pembrolizumab

Introduction: Hashimoto’s encephalopathy (HE) is a rare condition, occurring in about 2.1 per 100,000 people. This case highlights HE as the likely cause of encephalopathy after immune checkpoint inhibition with pembrolizumab for breast cancer.

Description: A 77-year-old female with a history of hypothyroidism and breast cancer treated with pembrolizumab presented with acute encephalopathy and generalized weakness. Her neurocognitive changes were of chronic insidious onset as she had 6 months of slow cognitive decline and two prior hospitalizations for altered mental status with extensive but unremarkable neurological evaluations, including encephalitis panels, brain MRIs, EEGs, and CSF studies. Her symptoms predominantly consisted of intermittent confusion, myoclonus of her left upper extremity, eyelids and jaw and a decreasing level of consciousness that ultimately led to intubation and ICU admission. Elevated thyroid stimulating hormone prompted treatment for myxedema coma with stress dose steroids, however her mentation remained unchanged. Significantly elevated thyroglobulin and thyroid peroxidase antibody titers were present in serum and EEG revealed severe encephalopathy without epileptiform activity. She was unresponsive to 4 types of standard immunotherapies (intravenous globulin, plasma exchange, hydrocortisone, and rituximab) resulting in treatment switch to 1 g methylprednisolone. The next day after initiation of methylprednisolone, the patient’s mentation improved and she began following commands. She was placed on prolonged steroid taper and improved well with only mild cognitive deficit.

Discussion: HE is also referred to as a steroid-responsive encephalopathy associated with autoimmune thyroiditis, and the mechanism of HE is still unknown. Our patient had a clear, positive response to high-dose steroids, which suggests pembrolizumab as a likely catalyst for the development of HE based on the theory of hidden autoimmunity described in the literature on immune checkpoint inhibitors. This theory relies on a subclinical level of preexisting autoantibodies reaching clinical significance following the inhibition of specific immune checkpoints.