Encefalopatía de Hashimoto. Un diagnóstico por exclusión y revisión de la literatura a partir de un reporte de caso

La encefalopatía de Hashimoto es una entidad poco frecuente, con una amplia gama de manifestaciones neurológicas que incluyen déficits focales, alteraciones cognitivas, crisis convulsivas, trastorno del movimiento e incluso el coma. Con un curso de la enfermedad de subagudo a fluctuante. Afecta más a mujeres que a hombres, con edad de presentación alrededor de los 44 años, aunque se han reportado casos en la edad pediátrica. De etiología poco clara, se desarrolla en el contexto de la presencia de anticuerpos antitiroideos, independientemente de la función tiroidea. La presencia de estos anticuerpos, sumado a la exclusión de otras etiologías y la respuesta al manejo esteroide son claves para su diagnóstico. Presentamos un caso clínico de una mujer de 57 años de edad que evoluciona con psicosis, alteración del lenguaje, deterioro cognitivo, mioclonías y crisis convulsivas de 5 meses de evolución, quien se excluyó otras causas de demencia rápidamente progresiva con presencia de anticuerpos anti tiroglobulina de 83,6 UI/mL (V.R. < 100 UI/mL) normal y anti tiroperoxidasa en 217 UI/mL (V.R. < 100 UI/mL) elevado. Recibió valoración por el Servicio de Endocrinología, donde se detectó hipotiroidismo y se indicó manejo con levotiroxina sin mejoría del cuadro neurológico. Se indicó manejo esteroide con pulsos de metilprednisona a 500 mg/día por 5 días, con mejoría clínica y se concluyó por criterios de exclusión como una encefalopatía de Hashimoto.

Hashimoto encephalopathy is a rare entity, with wide range of neurological manifestations including focal deficits, cognitive alterations, seizures, movement disorders, and even coma, with a subacute to fluctuating disease course. It affects more women than men, it has age of presentation around 44 years, although cases have been reported in the pediatric age. Its etiology is unclear, it develops in the presence of antithyroid antibodies, regardless of thyroid function. The presence of these antibodies, added to the exclusion of other etiologies and the response to steroid management are key to the diagnosis. We report a clinical case of a 57-year-old woman who evolved with psychosis, language impairment, cognitive impairment, myoclonus, and seizures of 5 month-duration. Other causes of rapidly progressive dementia with the presence of normal antithyroglobulin antibodies of 83.6 IU/mL (RV < 100 IU/mL) and elevated antithyroperoxidase 217 IU/mL (RV < 100 IU/mL) were excluded. She was evaluated in the Endocrinology Department that detected hypothyroidism and indicated management with levothyroxine with no improvement in the neurological condition. Steroid management with methylprednisone pulses at 500 mg/day for 5 days was indicated. Clinical improvement was observed and was concluded to be a Hashimoto encephalopathy by exclusion criteria.

Factores clínicos y ambientales asociados a la tiroiditis de Hashimoto / Clinical and environmental factors associated with Hashimoto's thyroiditis

Introducción: La tiroiditis de Hashimoto es una enfermedad tiroidea autoinmune poligénica y multifactorial resultante de una interacción compleja de factores genéticos y ambientales. Objetivo: Determinar la posible asociación de los factores clínicos y ambientales con los niveles de anticuerpos antitiroideos y las pruebas de función tiroidea en la tiroiditis de Hashimoto. Métodos: Estudio observacional, descriptivo y transversal con 120 personas con diagnóstico de tiroiditis de Hashimoto. Variables estudiadas: edad, sexo, color de la piel, estado nutricional, paridad, hábito de fumar, consumo de alcohol, preparados estrogénicos, antecedentes familiares de enfermedad autoinmune tiroidea y personales de otras enfermedades autoinmunes. Se realizaron determinaciones de anticuerpos AbTPO, TSH, T3 y T4. Resultados: Predominio del sexo femenino (92,5 por ciento), de pacientes de piel blanca (50,8 por ciento) y con sobrepeso corporal (40 por ciento). El 73 por ciento no consumían preparados estrogénicos. El 20 por ciento tenían antecedentes familiares de enfermedad tiroidea y personales de diabetes mellitus tipo 1 (7,5 por ciento). La media del anticuerpo en pacientes con antecedentes de infecciones virales fue superior a los que no tuvieron este antecedente (732,6 vs. 624,6). El resto de las variables no mostraron diferencias entre las medias del anticuerpo. Ninguno de los factores estudiados mostró asociación con el estado de la función tiroidea. (p>0,05). Conclusiones: No existió asociación entre los factores clínicos y ambientales en relación a los niveles de Ac TPO y el estado de la función tiroidea, con predominio del hipotiroidismo manifiesto al diagnóstico de la TH(AU)

Introduction: Hashimoto's thyroiditis is a polygenic and multifactorial autoimmune thyroid disease, resulting from a complex interaction of genetic and environmental factors. Objective: To determine the possible association of clinical and environmental factors with antithyroid antibody levels and thyroid function tests in HT. Methods: An observational, descriptive, cross-sectional study was carried out with 120 subjects diagnosed with Hashimoto's thyroiditis. We studied variables such as age, sex, skin color, nutritional status, parity, smoking, alcohol consumption, estrogen preparations, family history of autoimmune thyroid disease and personal history of other autoimmune diseases. Additionally, AbTPO, TSH, T3 and T4 antibody determinations were made. Results: Predominance of the female sex (92.5 percent), white skin (50.8 percent) and body overweight (40 percent). 73 percent did not consume estrogenic preparations. Twenty percent had family history of thyroid disease and personal history of type 1 diabetes mellitus (7.5 percent). The mean antibody in patients with history of viral infections was higher than those without this history (732.6 vs. 624.6). The rest of the variables did not show differences between the means of the antibody. None of the factors studied showed association with the state of thyroid function. (p > 0.05). Conclusions: There was no association between clinical and environmental factors in relation to Ac TPO levels and the state of thyroid function, with a predominance of overt hypothyroidism at diagnosis of HT(AU)

Disminución de los anticuerpos antitiroideos durante el embarazo en la tiroiditis de Hashimoto / Decreased antithyroid antibodies during pregnancy in the Hashimoto´s thyroiditis

RESUMEN Se comunica la disminución del título de anticuerpos antitiroideos en dos casos de tiroiditis de Hashimoto durante el embarazo. A las dos mujeres, de 37 y 32 años de edad, respectivamente, con diagnóstico de tiroiditis de Hashimoto e hipotiroidismo, se les evaluó secuencialmente la función tiroidea y los títulos en sangre de anticuerpos antitiroglobulina (Ac-TG) y antiperoxidasa (Ac-TPO), antes, durante y después del embarazo. Se observó caída progresiva y significativa de ambos anticuerpos durante el embarazo, que no guardó relación con las modificaciones de la función tiroidea. Después del parto hubo un rebrote del título de los anticuerpos antitiroideos. Se concluye que durante el embarazo se produce una disminución de la respuesta inmunitaria en la tiroiditis de Hashimoto.

ABSTRACT The decrease in antithyroid antibody titer in two cases of Hashimoto's thyroiditis during pregnancy is reported. The two women, aged 37 and 32 years, respectively, diagnosed with Hashimoto's thyroiditis and hypothyroidism, were sequentially evaluated for thyroid function and blood titers of antithyroglobulin (TGAb) and antiperoxidase (TPOAb) antibodies before, during and after pregnancy. A progressive and significant drop in both antibodies was observed during pregnancy, which was not related to changes in thyroid function. After delivery there was a regrowth of antithyroid antibody titer. It is concluded that during pregnancy there is a decrease in the immune response in Hashimoto's thyroiditis.

Autoinmunidad tiroidea en mujeres con Síndrome de Ovario Poliquístico / Thyroid autoimmunity in women with polycystic ovary syndrome

Introducción: Las bases fisiopatológicas del Síndrome de ovario poliquístico pueden predisponer a mayor riesgo de autoinmunidad a las mujeres que tienen esta condición y existen evidencias, aunque escasas, de mayor prevalencia de autoinmunidad tiroidea en ellas. Objetivos: Determinar la frecuencia de marcadores serológicos de autoinmunidad tiroidea en mujeres con Síndrome de ovario poliquístico e identificar si existe asociación entre la presencia de ellos y las concentraciones de progesterona y testosterona. Métodos: Se realizó un estudio en 50 mujeres con Síndrome de ovario poliquístico y 50 sin el síndrome. Se realizaron determinaciones de autoanticuerpos tiroideos (anti tiroglobulina (Anti-Tg) y anti peroxidasa (anti-TPO) a las mujeres de ambos grupos de estudio. Se realizaron determinaciones de hormonas (testosterona y progesterona) solo al grupo de estudio de mujeres con SOP. Se crearon categorías por anticuerpos: Positivo si los títulos fueron superior al rango de referencia y negativo dentro del rango. Se consideró respuesta autoinmune positiva, cuando al menos uno de los anticuerpos se encontró elevado. Para la asociación entre la presencia de autoinmunidad y las variables independientes se hicieron análisis bivariados mediante comparación de medias y test no paramétricos. Se consideró un nivel de significancia de α = 0,05. Resultados: En las mujeres con Síndrome de ovario poliquístico, 62 por ciento mostraron anticuerpos positivos y 14 por ciento en las sin el síndrome. En las mujeres sin síndrome, de las 7 mujeres con marcadores de autoinmunidad positivos, en 6 (85,7 por ciento) el anti-Tg fue el que dio positivo. No hubo diferencias significativas en cuanto a la asociación con los niveles de testosterona y progesterona. Conclusiones: Las mujeres con Síndrome de ovario poliquístico tienen mayor frecuencia de desarrollar respuesta autoinmune tiroidea, independiente de los niveles de progesterona y testosterona(AU)

Introduction: The physio-pathological bases of polycystic ovary syndrome may predispose women with this condition to a higher risk of autoimmunity and there is evidence, albeit scarce, of higher prevalence of thyroid autoimmunity in them. Objectives: Determine the frequency of serological markers of thyroid autoimmunity in women with polycystic ovary syndrome and identify whether there is an association between the presence of them and progesterone and testosterone concentrations. Methods: A study was conducted in 50 women with polycystic ovary syndrome and 50 without the syndrome. Determinations of thyroid autoantiantibodies (anti-thyroglobulin (Anti-Tg) and anti-peroxidase (anti-TPO) were made to women in both study groups. Hormone determinations (testosterone and progesterone) were made only to the study group of women with PCOS. Categories were created by antibodies: Positive if the titles were greater than the reference range, and negative if within the range. It was considered a positive autoimmune response when at least one of the antibodies was found increased. For the association between the presence of autoimmunity and independent variables, bivariate analyses were performed by means comparison and non-parametric tests. It was considered a significance level of α =0.05. Results: In women with polycystic ovary syndrome, 62 percent showed positive antibodies and 14 percent in those without the syndrome. In women without the syndrome, of the 7 women with positive autoimmune markers, in 6 (85.7 percent) the anti-Tg was the one that tested positive. There were no significant differences in the association with testosterone and progesterone levels. Conclusions: Women with polycystic ovary syndrome are more often able to develop thyroid autoimmune response, independently from the progesterone and testosterone levels(AU)

Clinical characteristics and follow-up of Hashimoto encephalopathy in children / 临床儿科杂志

Objective To explore the clinical characteristics of Hashimoto encephalopathy (HE) in children. Methods The clinical data of 4 children with HE were analyzed retrospectively. Results All the 4 cases were school-age children and 3 of them were girls. They were physically healthy before onset. The main clinical manifestations were epileptic seizures in 3 cases, mental symptoms in 2 cases, disturbance of consciousness in 2 cases, stroke like symptoms in 1 case, decreased memory and decreased sleep in 1 case. Electroencephalogram showed that the background activity was decreased in 4 cases, and MRI showed abnormal in 3 cases. Serum thyroid antibodies were significantly increased in 4 cases, and were returned to normal in 2 cases when clinical symptoms disappeared, while they were significantly reduced, but not completely back to normal in another 2 cases. Only one out of 4 cases had abnormal thyroid function. All the 4 cases responded well to corticosteroid therapy. One of them relapsed after discontinuation of the therapy, but it was still effective when the therapy was reassumed. Conclusions HE is rare in children. When there are manifestations of unknown cause, such as epileptic seizures, mental disorders, cognitive impairment, movement disorders and disturbance of consciousness, HE should be considered. In addition, the increase of serum thyroid antibody should be considered as a necessary condition for diagnosis.

Clinical Significance of Autoantibodies and Thyroid Function in Patients with Recurrent Spontaneous Abortion / 现代检验医学杂志

Objective To study the clinical significance of antinuclear antibody (ANA),anti-thyroid peroxidase antibody (TPO-Ab) and antithyroglobulin antibody (Tg-Ab),thyroid stimulating hormone (TSH),free triiodothyronine (FT3),free thyroxine (FT4) in patients with recurrent spontaneous abortion (RSA).Methods 46 women with RSA diagnosis in out patient department in Peking University Shenzhen Hospital from March 2015 to December 2016 were recruited as the study group,20 women with normal childbirth history were enrolled as the control group,ANA was detected by indirect immunofluorescence (IIF) assay and ELISA,TSH,FT3 and FT4 were detected by chemiluminescence immunoassay technology.Results The positive rates of ANA(IIF),TPO-Ab and Tg-Ab in patients with RSA were 24％,24％ and 15％ respectively which were significantly higher than those in healthy control (P＜0.05).Serum levels of TSH,TPO-Ab and Tg-Ab in patients with RSA were 2.70 ± 1.38 mIU/L,38.99 ± 10.18 IU/ml and 3.07 ± 1.69 IU/ml respectively,which were significantly higher than those in healthy cases (P＜0.05).Conclusion ANA and antithyroid antibodies were closely related with RSA.It is very important to screen ANA and antithyroid antibodies for etiological diagnosis and appropriate intervention in patients with RSA to reduce the incidence of abortion.

Utilidad clínica de las pruebas hormonales e inmunológicas en la evaluación de las enfermedades del tiroides / Clinical usefulness of hormonal and immunological tests for the evaluation of thyroid diseases

Las enfermedades tiroideas son un importante problema de salud que afecta a un gran porcentaje de la población. Las pruebas bioquímicas constituyen el pilar fundamental para su diagnóstico y seguimiento. El desarrollo de ensayos de segunda y tercera generación ha supuesto un gran avance en el diagnóstico de estas enfermedades. El texto incluye los ensayos utilizados para diagnosticar y tratar las diferentes enfermedades tiroideas, provee información bioquímica y clínica actualizada contenida en secciones referidas a la utilidad clínica de las determinaciones de hormonas tiroideas totales y libres, anticuerpos antitiroideos, tirotropina humana y tiroglobulina, de manera que pueda ofrecer, tanto al laboratorio como al médico, un panorama general de la utilidad y la capacidad actual de estas pruebas(AU)

Thyroid diseases are a significant health problem affecting a high percentage of the population. The biochemical tests are the fundamental pillar for diagnosis and follow-up. The development of second and third-generation assays has represented a great advance in diagnosing these diseases. The text covers the tests to diagnose and treat a number of thyroid diseases, and provides the reader with updated biochemical and clinical information in sections about the clinical usefulness of total and free thyroid hormone determinations, antithyroid antibodies, human thyrotropin and thyroglobulin. In this way, it can offer both the lab and the physician a general overview of the usefulness and the current capability of these tests(AU)

Prevalencia de anticuerpos antiperoxidasa y antitiroglobulina en jóvenes con hipotiroidismo subclínico y clínico / Prevalence of antiperoxidase and antithyroglobulin antibodies in young people with clinical and subclinical hypothyroidism

Introducción: El diagnóstico temprano de hipotiroidismosubclínico y el hallazgo de anticuerpos antitiroideos son de granvalor para el estudio de las enfermedades tiroideas. Objetivos: determinarla prevalencia de anticuerpos antitiroideos en hombres ymujeres jóvenes con hipotiroidismo subclínico y clínico, y compararsu frecuencia entre ambos sexos. Materiales y métodos: se estudiaron280 estudiantes de la Universidad Antonio Nariño, en laciudad de Bogotá, entre los 18 y 30 años. A los participantes en elestudio se les realizó TSH y T4 libre por quimioluminiscencia parala identificación de casos de hipotiroidismo subclínico y clínico. Atodos los individuos con alteraciones en las pruebas de función tiroidease les realizaron anticuerpos antitiroideos antiperoxidasa yantitiroglobulina por microelisa. Resultados: se encontró una altaprevalencia de anticuerpos antitiroideos antiperoxidasa y antitiroglobulinaen los jóvenes que presentaron hipotiroidismo, y unaprevalencia de hipotiroidismo en jóvenes de 4,64%, sin encontrarsediferencias estadísticamente significativas entre hombres y mujeres.Conclusión: existe en la población de jóvenes estudiados conhipotiroidismo subclínico una alta prevalencia de anticuerpos quesugerirían causa autoinmune en nuestra población universitaria. Sedeben realizar ensayos clínicos adicionales que permitan investigarotras posibles causas de hipotiroidismo como postinfecciosas, tóxicasy medioambientales, así mismo una posible asociación de estapatología con otras condiciones autoinmunes.

Abstract: Introduction: An early diagnosis of subclinical hypothy-roidism and the discovery of antithyroid antibodies are really valu-able in preventing severe thyroid diseases. Objectives: To determine the prevalence of antithyroid antibodies in young men and women with subclinical and clinical hypothyroidism, and to compare their frequency among both genders. Materials and methods: The case study enrolled 280 students between 18 and 30 years of age from the Antonio Nariño University in Bogotá. TSH and free T4 was deter-mined by chemoluminescence in all participants of the study for the identification of possible clinical and subclinical hypothyroidism. All individuals with alterations in their thyroid function tests had also their antiperoxidase and antithyroglobulin antibodies as-sessed by microelisa. Results: A high prevalence of antiperoxi-dase and antithyroglobulin antithyroid antibodies was detected in young people who had hypothyroidism, and the prevalence of hypothyroidism in young people was 4,64%. No statistically sig-nificant difference was found between the prevalence in men and women. Conclusion: There was a high prevalence of antibodies in the study population of young people with subclinical hypo-thyroidism, which could suggest an autoimmune cause in our university population. It is also necessary to carry out other clini-cal trials which could allow the investigation of possible causes of hypothyroidism like post-infectious, toxic and environmental and also a possible association between this disease and other autoimmune conditions.

Disfunção tireoidiana autoimune em diabetes mellitus tipo 1 / Autoimmune thyroid dysfunction in type 1 diabetes mellitus

Objetivo: Determinar a frequência de disfunção tireoidiana autoimune (DAT) em pacientes com diabetes mellitus tipo 1 (DM1) acompanhados pelo Serviço de Endocrinologia Pediátrica do Hospital da Santa Casa de Misericórdia de Vitória-ES (HSC). Materiais e métodos: Foi realizado um estudo de coorte transversal nos quais 38 prontuários médicos de pacientes de ambos os sexos, com diagnóstico de DM1, foram revisados e deles coletados dados referentes à função tireoidiana, como se deu a descoberta do diabetes, história familiar de tireoidopatias, dosagens TSH, T4L, anticorpos antireoidianos e dose diária de insulina. Resultados: Dos pacientes analisados, 18,4% tiveram o diagnóstico de hipofunção tireoidiana corroborando com estudos brasileiros realizados. Conclusão: Devido à elevada prevalência de doença autoimune da tireoide em diabéticos, é justificável uma investigação rotineira da função tireoidiana nesses pacientes.

Prevalência de disfunção tireoidiana e anticorpos antitireoidianos em pacientes portadores de diabetes melito tipo 1 e em seus familiares de primeiro grau / Prevalence of thyroid dysfunction and antithyroid antibodies in type 1 diabetic mellitus patients and their first degree relatives

O diabetes melito tipo 1 (DM1) freqüentemente encontra-se associado à doença auto-imune da tireóide (DAT). A prevalência de DAT varia de 3 por cento a 50 por cento entre diabéticos, e é maior também entre seus familiares, comparada à população geral. OBJETIVOS: Investigar a prevalência da DAT em pacientes com DM1, avaliar possíveis diferenças de comportamento clínico-evolutivo do DM1 entre diabéticos com e sem DAT e estudar a prevalência de DAT nos familiares dos pacientes diabéticos. MATERIAIS E MÉTODOS: Os prontuários de 124 diabéticos tipo 1 foram revisados e coletados os dados referentes à função e aos anticorpos tireoidianos; pacientes com e sem DAT foram comparados em relação à média de Hb glicosilada, complicações agudas e crônicas, idade ao diagnóstico e tempo de evolução do DM, dose de insulina e outros. Um estudo caso-controle foi realizado com 54 familiares em primeiro grau destes pacientes; foram avaliadas a função tireoidiana e a presença de anticorpos antitireoidianos em 32 familiares de diabéticos sem DAT e 22 familiares de diabéticos com DAT. RESULTADOS: As prevalências de DAT e de disfunção hormonal entre os diabéticos foram de 35,5 por cento e 19,3 por cento, respectivamente. Quanto à avaliação dos parâmetros de evolução do DM1, comportamento clínico e controle metabólico não houve diferenças significantes entre os diabéticos com e sem DAT. Houve maior prevalência de DAT nos familiares de diabéticos com DAT do que no grupo dos familiares dos diabéticos sem DAT, sem diferença significativa quanto à prevalência de disfunção hormonal. CONCLUSÕES: A prevalência de doença auto-imune de tireóide em diabéticos e em seus familiares é elevada, justificando-se, nesses casos, a investigação rotineira da função tireoidiana, particularmente dos familiares de primeiro grau de diabéticos com DAT.

Diabetes Mellius Type 1 (DM1) is frequently associated to Autoimmune Thyroid Disease (AITD). The prevalence of AITD among diabetic patients varies between 3 to 50 percent and the incidence is also big among their family members, when compared to the population in general. OBJECTIVES: To investigate the prevalence of AITD in patients with DM1; to evaluate possible differences concerning the clinical-evolutive behavior of DM1 among diabetic patients with or without AITD and to study the prevalence of AITD among the diabetes patients' relatives. MATERIALS AND METHODS: 124 prontuaries of diabetic patients (type 1) were revised and data was gathered concerning the thyroid function and the anti-thyroid antibodies. Patients with and without AITD were compared in relation to the level of glycosylated hemoglobin, the presence of acute and chronic complications, the age of the patient at the time of the diagnosis, time of evolution of the disease, daily dose of insulin and other factors. A control case study was conducted with 54 first degree relatives of the diabetic patients who took part in the study; the thyroid function as well as the presence of anti-thyroid antibodies were evaluated in 32 of those first degree relatives with AITD, and in 22 of those without AITD. RESULTS: The prevalence of AITD and of hormonal dysfunction among diabetic patients was 35.5 percent and 19.3 percent, respectively. No significant differences were found between groups in respect to clinical outcome or to diabetic chronic complications. However, prevalence of AITD and hormonal dysfunction were found to be higher among first degree relatives of diabetic patients with AITD than among relatives of diabetic patients without AITD. CONCLUSIONS: The prevalence of autoimmune thyroid disease in diabetic patients and in their first degree relatives is high. Thyroid function screening is therefore justified in these cases, especially in first degree relatives of diabetics ...

Hashimoto's encephalopathy——case report and literature review / 中华内分泌代谢杂志

Hashimoto's encephalopathy(steroid-responsive encephalopathy associated with autoimmune thyroiditis,SREAT)is a rare disorder,accompanied by seizures,tremor,myoclonus,ataxia,psychosis,and stroke-like episodes,breaking out with an acute or subacute onset and having a relapsing/remitting or progressive course which is not correlated to thyroid hormone levels.Patients with Hashimoto's encephalopathy are usually euthyroid or dysthyroid with positive antithyroid antibodies,have a moderately raised cerebrospinal fluid protein content,and have a global slowing of the electroencephalogram and a normal or near normal imaging except in rare cases.The pathogenesis of Hashimoto's encephalopathy is still obscure.This paper reports a case diagnosed as"Hashimoto's encephalopathy".It is suggested that the diagnosis of Hashimoto's encephalopathy should be considered in cases with unexplained encephalopathy associated with high levels of antithyroid antibodies despite normal thyroid function.