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Frequently Asked Questions 

Question:

My TPO thyroid antibodies are out of range. Is this finding indicative of AE?

 

Answer:

 

No. Out of range TPO indicates the patient has a thyroid condition unrelated to autoimmune encephalitis. About 13% of healthy women have out of range TPO.

AE experts have concluded that thyroid antibodies have served their time as diagnostic biomarkers in autoimmune encephalopathy well, but their role in the evaluation of autoimmune encephalopathy is likely redundant at this point, and certainly less specific than a clinical history of autoimmune disease and neural-specific antibodies. Experience indicates that a diagnosis of HE/SREAT is often given to patients presenting with cognitive symptoms and a variety of neurological and non-neurological complaints, in the setting of elevated thyroid antibodies in serum without objective cognitive abnormalities. The utility of testing for thyroid antibodies seems questionable in the modern era which has brought availability of validated clinical criteria and advanced neuroimmunologic diagnostics. Over diagnosis of autoimmune encephalopathy brings undesired consequences such as iatrogenic harm, cost of unnecessary immunosuppressive therapies and delayed diagnosis of the correct neurological disorder. As always, test results need to be interpreted in the context of detailed clinical history and examination.

The history of when out of range TPO was used as a marker for HE/AE began in 1966 with the identification of Hashimoto’s Encephalitis/SREAT.  As research progressed in 1991, 2003, 2006, 2016, 2019 to 2021 we have learned more with each piece of evidence learned.

 

Hashimoto encephalopathy (HE) was first described in 1966 in a 49-year-old man who presented with stroke-like episodes and sub-acute encephalopathy months after the onset of Hashimoto thyroiditis (Brain et al., 1966). Over the ensuing four decades, multiple cases were reported with various clinical findings (Shaw et al., 1991; Chong et al., 2003).  An alternative moniker was proposed to encapsulate the concept of a triad of encephalopathy, thyroid autoimmunity (clinical, serological or both) and steroid-response [steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT)] (Castillo et al., 2006).

 

Criteria for the diagnosis of HE was proposed in 2016, and was classified within the ‘probable’ autoimmune encephalitis (AE) category because the underlying pathogenic mechanism is unknown (Graus et al., 2016). Author’s  (26 of the world’s most promenent researchers in the field of autoimmune encephalitis), recommended that HE/SREAT be referred to as ‘possible’ or ‘probable’ Autoimmune Encephalitis.

 

In 2019 the paper Hashimoto encephalopathy in the 21st century  Concluded: Current pretreatment criteria of HE do not predict steroid responsiveness. The detection of TPOAb across all control groups reveals their poor disease-specificity. NH2-α-enolaseAb did not help in the diagnosis of HE. These findings imply a redefinition of HE that requires a systematic exclusion of antibody-mediated encephalitis.

 

In June 2021- The paper Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis where Mayo Clinic retrospectively reviewed 144 cases referred with suspected Hashimoto encephalopathy over a 13-year period, and to determine the clinical utility of thyroid antibodies in the course of evaluation of those patients.

After clinical and testing evaluations had been completed for 144 patients, 39/144 patients (27%) were assigned a diagnosis of an autoimmune CNS disorder (Table 2), and 105/144 (73%) were given an alternative clinical diagnosis.

Of 39 patients with an autoimmune CNS disorder, all but three fulfilled diagnostic criteria for one or other diagnosis as previously suggested by others (A Clinical Approach to Diagnosis of Autoimmune Encephalitis by Graus et al., 2016) [probable HE, 27 (13 of whom also fulfilled criteria for possible AE); probable AE,4;  definite AE, 2; definite limbic encephalitis, 2; and possible AE, 1], sensitivity 92%.

Almost three-quarters of patients referred to Mayo’s specialty practice as HE/SREAT in the context of thyroid autoimmunity left Mayo Clinic with an alternative non-autoimmune CNS diagnosis. These findings validate the AE criteria proposed previously (Graus et al., 2016). TPO antibody values in the patients diagnosed with autoimmune CNS disorders were not significantly different to those in patients with an alternative clinical diagnosis, and the proportion of patients with very high TPO titres was similar in both groups.

The papers conclusion: AE experts conclude that thyroid antibodies have served their time as diagnostic biomarkers in autoimmune encephalopathy well, but their role in the evaluation of autoimmune encephalopathy is likely redundant at this point, and certainly less specific than a clinical history of autoimmune disease and neural-specific antibodies. Experience indicates that a diagnosis of HE/SREAT is often given to patients presenting with cognitive symptoms and a variety of neurological and non-neurological complaints, in the setting of elevated thyroid antibodies in serum without objective cognitive abnormalities. The utility of testing for thyroid antibodies seems questionable in the modern era which has brought availability of validated clinical criteria and advanced neuroimmunologic diagnostics. Over diagnosis of autoimmune encephalopathy brings undesired consequences such as iatrogenic harm, cost of unnecessary immunosuppressive therapies and delayed diagnosis of the correct neurological disorder. As always, test results need to be interpreted in the context of detailed clinical history and examination.

 

This scientific commentary,Thyroid antibodies: the end of an era? refers to ‘Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis’, by Valencia-Sanchezet al.  and carries a heartfelt concern for patients. “In the interest of our patients, we must recognize the new evidence that demonstrates that the diagnostic utility of thyroid antibody testing is limited in the evaluation of autoimmune neurologic conditions. Its role is, at best, limited to demonstrating a potential propensity to systemic autoimmunity. Cessation of thyroid antibody testing in the evaluation of suspected autoimmune encephalitis and encephalopathy will hopefully reduce harm from misdiagnosis and unwarranted treatment, and minimize financial toxicity related to unnecessary interventions”

Our website is not a substitute for independent professional medical advice. Nothing contained on our website is intended to be used as medical advice. No content is intended to be used to diagnose, treat, cure or prevent any disease, nor should it be used for therapeutic purposes or as a substitute for your own health professional's advice. Although THE INTERNATIONAL AUTOIMMUNE ENCEPHALITIS SOCIETY  provides a great deal of information about AUTOIMMUNE ENCEPHALITIS, all content is provided for informational purposes only. The International Autoimmune Encephalitis Society  cannot provide medical advice.


International Autoimmune Encephalitis Society is a charitable non-profit 501(c)(3) organization founded in 2016 by Tabitha Andrews Orth, Gene Desotell and Anji Hogan-Fesler. Tax ID# 81-3752344. Donations raised directly supports research, patients, families and caregivers impacted by autoimmune encephalitis and to educating healthcare communities around the world. Financial statement will be made available upon request.

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