Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis

June 18, 2021

Hashimoto encephalopathy (HE) is a rare disorder characterized by impaired brain function. The exact cause is unknown, but experts believe it to be an immune-mediated disorder or a disorder in which inflammation results from abnormal functioning of the immune system. People with HE have antithyroid antibodies in their bodies. However, it is unclear whether these antibodies play any role in the development of HE or are a coincidental finding. 

Valencia-Sanchez and colleagues at the Mayo Clinic reviewed 144 cases of suspected HE over a 13-year old period to determine the clinical utility of thyroid antibodies in the course of evaluation of those patients. In their experience, the diagnosis of HE/SREAT is assigned to a variety of patients with elevated thyroid antibody values and diverse neuropsychiatric symptomatic presentations, generally without objective demonstration of encephalopathy, CNS inflammation, or objective steroid response. The reliance on subjective responses and outcomes appears to be pervasive, leading to over-diagnosis of autoimmune encephalopathy. Criteria for the diagnosis of HE were proposed in 2016 and were classified within the ‘probable’ autoimmune encephalitis (AE) category because the underlying pathogenic mechanism is unknown.

After completing clinical and testing evaluations, 39 out of 144 patients (27%) were diagnosed with an autoimmune CNS disorder, and the other 105 (73%) were diagnosed with an alternative clinical impairment, such as neurodegenerative disorder, functional neurological disorder, primary psychiatric disorder, and subjective cognitive complaints. None of 105 patients with alternative diagnoses met any of the AE Graus diagnostic criteria. Of the 39 patients with an autoimmune CNS disorder, all but three fulfilled diagnostic criteria for AE (probable HE, 27; probable AE, 4; definite AE, 2; definite limbic encephalitis, 2; and possible AE, 1). 

Almost three-quarters of patients referred to the Mayo Clinic as HE/SREAT in the context of thyroid autoimmunity left Mayo Clinic with an alternative non-autoimmune CNS diagnosis. 

Thyroid antibody values in the patients diagnosed with autoimmune CNS disorders were not significantly different from those in patients with an alternative clinical diagnosis. The proportion of patients with very high concentrations was similar in both groups. They conclude that thyroid antibodies have served their time as diagnostic biomarkers in autoimmune encephalopathy well, but their role in evaluating autoimmune encephalopathy is likely redundant at this point and certainly less specific than a clinical history of autoimmune disease and neural-specific antibodies.