Hashimoto encephalopathy is a chronic relapsing steroid responsive encephalopathy characterized by antibodies against thyroid components. Etiology is still unknown. Confusion, seizures and coma are frequent reported symptoms. We present a 65-year old patient with acute onset of partial seizures and cognitive impairment. Hashimoto encephalopathy was assumed with diagnosis of Hashimoto thyroiditis and clinical syndrome. Symptoms resolved with thyroid treatment alone. Hashimoto encephalopathy should be considered in patients with unexplained encephalopathy, even when thyroid function seems to be normal.

Hashimoto thyroiditis is an autoimmune disease that destroys thyroid cells by cell and antibody-mediated immune processes. It is the most common cause of hypothyroidism in developed countries. In contrast, worldwide, the most common cause of hypothyroidism is an inadequate dietary intake of iodine. This disease is also known as chronic autoimmune thyroiditis and chronic lymphocytic thyroiditis. The pathology of the disease involves the formation of antithyroid antibodies that attack the thyroid tissue, causing progressive fibrosis. The diagnosis is often challenging and may take time until later in the disease process. The most common laboratory findings demonstrate an elevated thyroid-stimulating hormone (TSH) and low levels of free thyroxine (fT4), coupled with increased antithyroid peroxidase (TPO) antibodies. However, earlier on in the course of the disease, patients may exhibit signs, symptoms, and laboratory findings of hyperthyroidism or normal values. This is because the destruction of the thyroid gland cells may be intermittent.

Women are more often affected. The female-to-male ratio is at least 10:1. Although some sources cite diagnosis happening more so in the fifth decade of life, most women are diagnosed between the ages of 30 to 50 years. Conventional treatment is comprised of levothyroxine at the recommended dose of 1.6 to 1.8 mcg/kg/day. The T4 converts to T3, which is the active form of thyroid hormone in the human body. Excessive supplementation can lead to deleterious and morbid effects, such as arrhythmias (the most common being atrial fibrillation) and osteoporosis. In this chapter, we review the pathogenesis, diagnosis, and management of Hashimoto thyroiditis.

The authors present a case report and review the literature on Hashimoto encephalopathy. The onset of the disease may be marked by focal and then progressively generalized seizures or other neurological symptoms, but a cognitive decline or various psychiatric symptoms may also emerge. High levels of anti-thyroid peroxidase antibodies and/or anti-thyroglobulin antibodies are present in the serum. Corticosteroid treatment usually results in an improvement of symptoms. The syndrome is frequently overlooked and, therefore, the authors strongly recommend testing serum thyroid autoantibodies in cases with encephalopathy of unknown origin independently on the presence of thyroid disease in the patient or family history. The importance of long-term immunosuppressive treatment should also be stressed.

Hashimoto disease is a representative organ-specific autoimmune disease. It occurs very frequently in middle-aged women. Generally, the symptom is only diffuse and elastic hard goiters detected by careful plpation. Immunological tests frequently reveal anti-thyroglobulin antibody and anti-TPO antibody. Hypothyroidism develops in some patient along with progression of the disease. In some patient, on the other hand, a condition called destructive thyroiditis may develop during the course of the disease, in which the thyroid gland is transiently destroyed, accompanied by thyrotoxic state. In this state, namely painless thyroiditis, 123I-uptake ratio is extremely low and TSH-receptor antibody is generally not observed. The thyroid hormone is administered to patient with large goiter or hypothyroidism, and antiphlogistic analgesics or adrenocortical hormone with beta-blockers in case of destructive thyroiditis.

Hashimoto encephalopathy (HE) has been recognized as a new clinical disease based on an autoimmune mechanism associated with Hashimoto's thyroiditis. HE is successfully treated with steroids. In 2005, we discovered serum autoantibodies against the NH₂-terminal of α-enolase (NAE) as a highly specific diagnostic biomarker for HE. We analyzed the serum anti-NAE autoantibodies and clinical features in many cases of HE from institutions in Japan and other countries. Approximately half of the patients with HE had anti-NAE antibodies. In our study, HE was widely distributed in patients aged 50-60 years. Most patients with HE were in euthyroid states, and all patients had anti-thyroid antibodies. The common neuropsychiatric features of these patients were consciousness disturbance and psychosis, followed by cognitive dysfunction, involuntary movements, seizures, and ataxia. Abnormalities in EEG and decreased cerebral blood flow on the brain SPECT were common findings. In contrast, abnormalities on the brain MRI were rare except for diffuse subcortical lesions and limbic lesions. Patients with HE had varied clinical phenotypes, including acute encephalopathy, chronic psychiatric form, and other particular clinical presentations, such as limbic encephalitis, progressive cerebellar ataxia, and Creutzfeldt-Jakob disease (CJD)-mimic form. The cerebellar ataxic form of HE clinically mimics spinocerebellar degeneration (SCD) and is characterized by the absence of nystagmus, absent or mild cerebellar atrophy, and lazy background activities on electroencephalography (EEG). Taken together, these features should indicate the possibility of encephalopathy associated with thyroid disorders.

Hashimoto encephalopathy (HE) is a steroid-responsive, acute or subacute encephalopathy, characterised by autoimmune thyroiditis associated with elevated antithyroid antibody titres. An 11-year-old girl was admitted to the Department of Paediatrics with generalised tonic-clonic seizures, left facial paralysis and right hemiparesis. Ceftriaxone and acyclovir were applied, and methyl prednisolone 2 mg kg-1 day-1 was administered orally. The hemiparesis improved on the 3rd day of treatment, but the facial paralysis persisted into the 15th day. When she developed somnolence, she was transferred to the paediatric intensive care unit and provided with respiratory support after intubation. Antithyroid peroxidase (Anti-TPO) and Antithyroglobulin antibody (Anti-Tg) levels were measured at 112.3 IU mL-1 and 74.6 IU mL-1, respectively. HE was considered as the provisional diagnosis, for which intravenous methyl prednisolone 30 mg kg-1 for 5 days followed by prednisolone 1.5 mg kg-1 day-1 were administered. The patient's clinical status did not improve; therefore, she underwent therapeutic plasma exchange (1/1 ratio) for 8 days, followed by intravenous immunoglobulin 1 gr kg-1 for 2 days. As her clinical condition did not improve, rituximab and endoxane treatments were planned. Unfortunately, these treatments were postponed as she developed ventilator-associated pneumonia at the follow-up. She developed septic shock on the 14th day of follow-up, and noradrenaline and dopamine infusions were commenced. Despite all the efforts, she remained unresponsive and died from cardiac arrest. By reporting this case, we aimed to stress that HE should be considered as an aetiology of encephalopathy when infectious, neoplastic, autoimmune, toxic and metabolic causes are excluded.

Hashimoto's encephalopathy is a steroid-responsive, relapsing or progressive encephalopathy associated with Hashimoto's thyroiditis. Characteristic clinical features are confusion, seizures, alteration in conscious level, stroke-like episodes, myoclonus, and tremulousness. High CSF protein levels without pleocytosis and a diffusely abnormal EEG are typical findings. Brain CT and MRI and cerebral angiogram are usually normal. We present two case reports of Hashimoto's encephalopathy in 55- and 77-year-old patients who both responded well to steroid therapy, and review the literature.

Hashimotova tyreoiditida je chronické orgánově specifické autoimunitní onemocnění. Je charakterizována tvorbou autoprotilátek proti antigenům štítné žlázy s její lymfocytární infiltrací, vede k postupné destrukci funkčního parenchymu žlázy. Onemocnění je nejčastější příčinou vzniku hypotyreózy v oblastech, kde není dostatek jódu. Jeho etiologie není dosud přesně objasněna, často se u pacientů vyskytuje současně s dalšími autoimunitními poruchami, byl pozorován i jeho familiární výskyt. Bývá spojeno se zvýšeným rizikem rozvoje nádorového onemocnění štítné žlázy. Léčba je většinou konzervativní, chirurgický výkon bývá indikován při podezření na malignitu, nebo pokud se u pacientů vytvoří objemná struma působící mechanický útlak.

Keywords: chronic lymphocytic thyroiditis − Hashimoto‘s thyroiditis − surgical treatment.

A 15-year-old girl is described with encephalopathy associated with Hashimoto thyroiditis which subsequently developed into autoimmune thyrotoxicosis (hashitoxicosis) and distal renal tubular acidosis at age 5 years, pernicious anemia at age 9, and encephalopathy at age 12. Thyroid hormone levels were within the normal ranges at the time of neurologic presentation. Serum IgG concentration and oligoclonal IgG bands in cerebrospinal fluid closely correlated with the severity of neurologic symptoms. Treatment with glucocorticoids improved the level of consciousness but her mental state continued to deteriorate. Repeated cranial computed tomographic scans revealed progressive symmetric atrophy in the gray matter without infarction. These findings suggest that encephalopathy associated with Hashimoto thyroiditis is caused by an antineuronal antibody-mediated reaction.

Hashimoto encephalitis (he) is an auto-immune disease, with 40-50% of patients developing psychopathology. This could require targeted treatment. HE and prednison could both cloud the identification of a concurrent depressive disorder. We saw a 78-year-old woman with he and a severe depression, and treated her succesfully with ect.

Patients with Hashimoto thyroiditis may have neurologic manifestations that have been described in the literature for some decades now; these include psychiatric disorders, abnormal movements, and simulation of cerebrovascular events. Nuclear magnetic resonance (MRI) studies have revealed diffuse leukoencephalopathy in most cases. We describe a case having clinical manifestations simulating cerebrovascular events, together with cognitive alterations (a presentation already described in other patients). Among the 2 main forms of neurologic manifestations, the cognitive type, which is probably associated with endocrinologic alteration, may improve with hormone supplement. Those alterations simulating cerebrovascular events are most probably related to autoimmune vasculitis. The latter may improve with the administration of corticosteroids, which are proposed as treatment of this disorder.

Hashimoto encephalopathy (HE) presents as an encephalopathy without central nervous system infection or tumor. HE is associated with autoimmune thyroiditis and is thus considered to be an autoimmune disorder. The prevalence of HE is low, but death and status epilepticus have been reported. HE manifests with a wide range of symptoms that include behavioral changes and confusion. Elevated thyroid antibodies are present in the majority of cases and are required for the diagnosis of HE. Normal brain MRI findings are found in the majority of patients diagnosed with HE. The most consistent CSF abnormality noted in HE patients is the presence of elevated protein. Most HE patients respond well to steroid therapy. Clinical improvements are also observed with IV immunoglobulin and plasmapheresis. In conclusion, it is now generally accepted that the diagnosis of HE must include encephalopathy characterized by cognitive impairment associated with psychiatric features, such as hallucinations, delusions, and paranoia. Autoimmune encephalitis and prion disease should be considered in the differential diagnosis due to the similarity of the clinical features of these conditions to those of HE.

OBJECTIVE

The purpose of this article is to analyze the sonographic appearance of nodular Hashimoto thyroiditis.

METHODS

As part of an ongoing multiinstitutional study, patients who underwent ultrasound examination and fine-needle aspiration of one or more thyroid nodules were analyzed for multiple predetermined sonographic features. Patients completed a questionnaire, including information about thyroid function and thyroid medication. Patients (n = 61) with fine-needle aspiration cytologic results consistent with nodular Hashimoto thyroiditis (n = 64) were included in the study.

RESULTS

The mean (+/- SD) diameter of nodular Hashimoto thyroiditis was 15 +/- 7.33 mm. Nodular Hashimoto thyroiditis occurred as a solitary nodule in 36% (23/64) of cases and in the setting of five or more nodules in 23% (15/64) of cases. Fifty-five percent (35/64) of the cases of nodular Hashimoto thyroiditis occurred within a sonographic background of diffuse Hashimoto thyroiditis, and 45% (29/64) of cases occurred within normal thyroid parenchyma. The sonographic appearance was extremely variable. It was most commonly solid (69% [42/61] of cases) and hypoechoic (47% [27/58] of cases). Twenty percent (13/64) of nodules had calcifications (seven with nonspecific bright reflectors, four with macrocalcifications, and three eggshell), and 5% (3/64) of nodules had colloid. Twenty-seven percent (17/64) of nodules had a hypoechoic halo. The margins were well defined in 60% (36/60) and ill defined in 40% (24/60) of nodules. On Doppler analysis, 35% (22/62) of nodules were hypervascular, 42% (26/62) were isovascular or hypovascular, and 23% (14/62) were avascular.

CONCLUSIONS

The sonographic features and vascularity of nodular Hashimoto thyroiditis were extremely variable.