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      An autoimmune cause of confusion in a patient with a background of hypothyroidism

      research-article
      1 , 2
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd

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          Summary

          A 68-year-old previously independent woman presented multiple times to hospital over the course of 3 months with a history of intermittent weakness, vacant episodes, word finding difficulty and reduced cognition. She was initially diagnosed with a TIA, and later with a traumatic subarachnoid haemorrhage following a fall; however, despite resolution of the haemorrhage, symptoms were ongoing and continued to worsen. Confusion screen blood tests showed no cause for the ongoing symptoms. More specialised investigations, such as brain imaging, cerebrospinal fluid analysis, electroencephalogram and serology also gave no clear diagnosis. The patient had a background of hypothyroidism, with plasma thyroid function tests throughout showing normal free thyroxine and a mildly raised thyroid-stimulating hormone (TSH). However plasma anti-thyroid peroxidise (TPO) antibody titres were very high. After discussion with specialists, it was felt she may have a rare and poorly understood condition known as Hashimoto’s encephalopathy (HE). After a trial with steroids, her symptoms dramatically improved and she was able to live independently again, something which would have been impossible at presentation.

          Learning points:
          • In cases of subacute onset confusion where most other diagnoses have already been excluded, testing for anti-thyroid antibodies can identify patients potentially suffering from HE.

          • In these patients, and under the guidance of specialists, a trial of steroids can dramatically improve patient’s symptoms.

          • The majority of patients are euthyroid at the time of presentation, and so normal thyroid function tests should not prevent anti-thyroid antibodies being tested for.

          • Due to high titres of anti-thyroid antibodies being found in a small percentage of the healthy population, HE should be treated as a diagnosis of exclusion, particularly as treatment with steroids may potentially worsen the outcome in other causes of confusion, such as infection.

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          Most cited references8

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          Hashimoto encephalopathy: syndrome or myth?

          Hashimoto encephalopathy has been described as a syndrome of encephalopathy and high serum antithyroid antibody concentrations that is responsive to glucocorticoid therapy, but these could be chance associations. To study a patient with Hashimoto encephalopathy and to review the literature to determine whether Hashimoto encephalopathy is an identifiable syndrome. We searched the MEDLINE database to June 2002 for "Hashimoto" or "autoimmune thyroiditis" and "encephalopathy" and examined all identified articles and articles referenced therein, including all languages. We included all patients with noninfectious encephalopathy (clouding of consciousness and impaired cognitive function) and high serum antithyroid antibody concentrations. We excluded patients if they did not meet these inclusion criteria or if their symptoms could be explained by another neurologic disorder. We recorded clinical features and the results of imaging, electroencephalographic, thyroid function, and cerebrospinal fluid studies. We identified 85 patients (69 women and 16 men; mean age, 44 years) with encephalopathy and high serum antithyroid antibody concentrations. Among these patients, 23 (27%) had strokelike signs, 56 (66%) had seizures, 32 (38%) had psychosis, 66 (78%) had a high cerebrospinal fluid protein concentration, and 80 (98%) of 82 had abnormal electroencephalographic findings. Thyroid function varied from overt hypothyroidism to overt hyperthyroidism; the most common abnormality was subclinical hypothyroidism (30 patients [35%]). Among patients treated with glucocorticoids, 66 (96%) improved. The combination of encephalopathy, high serum antithyroid antibody concentrations, and responsiveness to glucocorticoid therapy seems unlikely to be due to chance. However, there is no evidence of a pathogenic role for the antibodies, which are probably markers of some other autoimmune disorder affecting the brain.
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            Hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations.

            Hashimoto's encephalopathy (HE) is a condition believed to complicate Hashimoto's thyroiditis (HT). The diagnosis is suspected in the presence of high levels of serum anti-thyroid antibodies. We have recently demonstrated that in patients with HE there is an intrathecal synthesis of anti-thyroid antibodies, and concluded that the diagnosis of HE should be based on this cerebrospinal fluid (CSF) finding. getting an estimate of the prevalence of the disease, verifying the association with HT and investigating the pathogenetic role of anti-thyroid antibodies. 34-months prospective study in a hospital setting serving a community of 150,000 people. Patients with unexplained symptoms of acute or subacute encephalopathy or myelopathy or with a history of thyroid disorders were selected for the measurement of anti-thyroid antibodies. In the presence of high serum levels of autoantibodies, the same tests were performed in the CSF. Twelve patients had increased concentrations of serum autoantibodies but HE was diagnosed only in nine patients. The estimated prevalence of HE is 2.1/100,000. Only six HE patients had also HT. Four patients received corticosteroids, five patients were not treated. Five patients improved, four patients spontaneously, one patient after corticosteroids. Repeated CSF examinations showed that the titer of CSF autoantibodies did not correlate with the clinical stage of the disease nor was influenced by corticosteroids. In addition, the course of symptoms was independent of therapy. The association of encephalopathy and high titers of anti-thyroid antibodies is not sufficient to make a diagnosis of HE. Independent of the clinical status of the thyroid gland, the intrathecal synthesis of autoantibodies is a distinctive marker of this elusive condition.
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              High prevalence of serum autoantibodies against the amino terminal of alpha-enolase in Hashimoto's encephalopathy.

              Recently, we discovered autoantibodies against the amino (NH(2))-terminal of alpha-enolase (NAE) in patients with Hashimoto's encephalopathy (HE) (83.3%; 5/6) [Fujii, A., Yoneda, M., Ito, T., Yamamura, O., Satomi, S., Higa, H., Kimura, M., Suzuki, M., Yamashita, M., Yuasa, T., Suzuki, H., Kuriyama, M., 2005. Autoantibodies against the amino terminal of alpha-enolase are a useful diagnostic marker of Hashimoto's encephalopathy. J. Neuroimmunol. 162, 130-136]. We further investigated the anti-NAE autoantibodies in 25 patients who fit the diagnostic criteria for HE, based on the presence of anti-thyroid antibodies and responsiveness to immunotherapy. In this study, we demonstrated a high prevalence (68%, 17 of 25) and high specificity of anti-NAE autoantibodies in patients with HE, and clarified the clinical features of HE. This result demonstrated that anti-NAE autoantibodies, in addition to anti-thyroid autoantibodies, are emphasized as useful serological diagnostic markers of HE.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                23 May 2019
                2019
                : 2019
                : 19-0014
                Affiliations
                [1 ]Brighton and Sussex University Hospitals NHS Trust , Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
                [2 ]Elderly Care , Brighton and Sussex University Hospitals NHS Trust, Brighton, UK
                Author notes
                Correspondence should be addressed to J Brown; Email: jonathan.brown10@ 123456nhs.net
                Article
                EDM190014
                10.1530/EDM-19-0014
                6548216
                31125974
                4bafe89f-fdb4-4cc1-9e10-010bc6d85fcb
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 26 March 2019
                : 08 April 2019
                Categories
                New Disease or Syndrome: Presentations/Diagnosis/Management

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