Caractéristiques épidémio-cliniques et évolutives des dysthyroïdies autoimmunes au centre national hospitalier universitaire Hubert Koudougou Maga (CNHU-HKM) de Cotonou / Epidemiological, clinical and evolutionary characteristics of autoimmune dysthyroidism in the National University Center Hubert Koutoukou Maga (CNHU-HKM) Of Cotonou

Objectif : Etudier les caractéristiques épidémio cliniques et évolutives des dysthyroïdies auto immunes dans le service d'endocrinologie diabétologie du CNHU-HKM. Matériel et méthode d'étude : Il s'agit d'une étude transversale descriptive et analytique ayant porté sur les patients reçus en consultation pour une pathologie thyroïdienne dans le service d'endocrinologie diabétologie sur une période de 10 ans. Ont été inclus les patients ayant au moins une TSH anormale et les anticorps anti thyroïdiens positifs. Résultats : Sur la période d'étude, nous avons enregistré 2883 consultants, 347 avaient une pathologie thyroïdienne, dont 69 cas de dysthyroïdie auto-immune répartis en 54 cas de maladie de Basedow et 15 cas de maladie de Hashimoto. Les dysthyroïdies auto immunes représentaient donc 2,39 % des consultations et 19,89% des thyroïdopathies. Les fréquences de la maladie de Basedow et de la maladie de Hashimoto étaient respectivement de 1,87% (54 cas) et 0,52% (15 cas) parmi les consultations. Les dysthyroïdies auto immunes étaient plus fréquentes dans les tranches d'âge de 30 à 40 et 40 à 50 ans. Les manifestations les plus fréquentes de la maladie de Basedow étaient l'asthénie (94,4%), l'amaigrissement (87,0%) et la tachycardie (85,2%) . Quant à la maladie de Hashimoto les principales manifestations étaient représentées par une asthénie (86,66%), un goitre (66,6%) et une prise de poids (60%). Le titre initial élevé des anticorps anti R-TSH, l'hypothyroïdie iatrogène ont été retrouvés comme des facteurs associés au suivi prolongé de la maladie de Basedow au-delà de 18 mois. Conclusion : Les dysthyroïdies auto-immunes sont des affections fréquentes dominées par la maladie de Basedow. Leur évolution sous traitement est influencée par des facteurs cliniques, biologiques et échographiques.

Objective: To study the epidemiological, clinical and evolutionary characteristics of autoimmune dysthyroidism in the endocrinology-diabetes department of the CNHU-HKM. Material and method: This was a descriptive and analytical cross-sectional study of patients seen for thyroid pathology in the endocrinology diabetology department over a 10-year period. Patients with at least one abnormal TSH and positive anti-thyroid antibodies were included. Results: Over the study period, we recorded 2883 consultants, 347 of them having thyroid diseases, including 69 cases of autoimmune dysthyroidism divided into 54 cases of Graves' disease and 15 cases of Hashimoto's disease. Autoimmune dysthyroidism represented 2.39% of consultations and 19.89% of thyroid disorders. Graves' disease and Hashimoto's disease accounted for 1.87% (54 cases) and 0.52% (15 cases) of consultations respectively. Autoimmune dysthyroidism was more frequent in the 30-40 and 40-50 age groups. The most frequent symptoms of Graves' disease were asthenia (94.4%), weight loss (87.0%) and tachycardia (85.2%). In Hashimoto's disease, the main symptoms were asthenia (86.66%), goiter (66.6%) and weight gain (60%). High initial R-TSH antibody levels and iatrogenic hypothyroidism were found to be factors associated with extended follow-up of Graves' disease beyond 18 months. Conclusion: Autoimmune dysthyroidism is a frequent condition, with Graves' disease predominating. Their evolution under therapy is influenced by clinical, biological and ultrasonographic factors.

Structural similarity between thyroid peroxidase [Homo sapiens] and SARS-CoV-2 spike glycoprotein ­ An autoimmune thyroiditis triggering mechanism in COVID-19 carriers? / Similaridade estrutural entre a tireoperoxidase humana [Homo sapiens] e a glicoproteína de superfície do SARS-CoV-2 ­ Um mecanismo de desencadeamento da tiroidite autoimune nos portadores da COVID-19?

Introduction: there are reports of autoimmune disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) such neurological syndromes and hematological syndromes, and more recently autoimmune thyroid dysfunctions have been described. These reports suggest that SARS-CoV-2 acts as a probable trigger for triggering the autoimmunity process. Aim: to evaluate structural similarity between thyroid peroxidase [Homo sapiens] (TPO) and SARS-CoV-2 spike glycoprotein (COVID-19), and to propose this similarity as a likely trigger for autoimmune thyroiditis. Methodology: using bioinformatics tools, we compare the amino acids (AA) sequences between protein structure of TPO and chain A COVID-19, chain B COVID-19, and chain C COVID-19, accessible in the National Center for Biotechnology Information database, by Basic Local Alignment Search Tool in order to locate the homologous regions between the sequences of AA. Results: the homology sequence between the TPO and COVID-19 ranged from 27.0 % (10 identical residues out of 37 AA in the sequence) to 56.0% (5 identical residues out of 9 AA in the sequence). The similar alignments demonstrated relatively high E values in function of short alignment. Conclusion: data suggest a possible pathological link between TPO and COVID-19. The structural similarity of AA sequences between TPO and COVID-19 may present a molecular mimicry suggesting the possibility of antigen crossover between TPO and COVID-19 that might represent an immunological basis for autoimmune thyroiditis associated with COVID-19.

Introdução: há relatos de doenças autoimunes relacionadas à síndrome respiratória aguda grave por coronavírus 2 (SARS-CoV-2), tais como síndromes neurológicas e hematológicas, e mais recentemente disfunções autoimunes da tireoide foram descritas. Esses relatos sugerem que o SARS-CoV-2 atue como um provável gatilho para desencadear o processo de autoimunidade. Objetivo: avaliar a similaridade estrutural entre a peroxidase tireoidiana [Homo sapiens] (TPO) e a glicoproteína de superfície SARS-CoV-2 (COVID-19) e propor essa similaridade como provável gatilho para o desencadeamento da tireoidite autoimune. Metodologia: utilizando ferramentas de bioinformática, comparamos as sequências de aminoácidos (AA) entre a estrutura da TPO e a estrutura da cadeia A do COVID-19, a cadeia B do COVID-19 e a cadeia C do COVID-19, acessível no banco de dados do National Center for Biotechnology Information, através da Ferramenta Básica de Pesquisa de Alinhamento Local para localizar as regiões homólogas entre as sequências de AA. Resultados: a sequência de homologia entre o TPO e COVID-19 variou de 27,0% (10 resíduos idênticos em 37 AA nas sequências) a 56,0% (5 resíduos idênticos em 9 AA nas sequências). Os alinhamentos semelhantes demonstraram valores E relativamente altos em função do alinhamento curto. Conclusão: os dados sugerem uma possível ligação patológica entre TPO e COVID-19. A similaridade estrutural das sequências de AA entre TPO e COVID-19 pode apresentar um mimetismo molecular sugerindo a possibilidade de cruzamento de antígeno entre TPO e COVID-19 que podem representar uma base imunológica para tireoidite autoimune associada a COVID-19.

Potential targets for the hepatitis C virus-mediated autoimmune thyroiditis

2021.174934ABSTRACTIntroduction: The mechanisms by which hepatitis C virus (HCV) infection induces autoimmune thyroiditis (AIT) have been studied, and it was suggested that inflammatory cytokines during HCV infection would change the thy-roperoxidase (TPO) signaling cascade and thyroglobulin (Tg) determining autoimmune thyroid disease.Objective: To show the signaling pathway, of TPO and Tg, and their potential targets mediated HCV in individuals with hepatitis C.Methods: The mapping of the signaling pathway was based on a review study approach and performed using the automatic annotation server of the Kyoto and Genome Encyclopedia (KEGG). PathVisio is free software for analysis and design of open source routes, and was used for the graphic representation of the signaling pathway.Results: The contigs were extracted from the KEGG database and their mapped transcription represents the signa-ling pathway of the main biomolecules that triggers the AIT. The action of HCV, or its treatment can trigger AIT that is characterized by the presence of autoantibodies against TPO and Tg. In AIT, autoreactive CD4 + T lymphocytes recruit B cells and CD8 + T cells in the thyroid. The progression of the disease leads to the death of thyroid cells and hypothyroidism. Conclusion: HCV or its treatment activates several signaling pathways with thyroid cells damage resulting in AIT and secondary hypothyroidism to cellular apoptosis. (AU)

RESUMOIntrodução: Os mecanismos pelos quais a infecção com o vírus da hepatite C (HCV) induz à tireoidite autoimune (TAI) têm sido alvo de estudos. Tem sido sugerido que citocinas inflamatórias, como a elevação das interleucinas na inflamação causadas pelo HCV, alterariam a cascata de sinalização da tireoperoxidase (TPO) e tireoglobulina (Tg) determinando um quadro de doença autoimune da tireóide.Objetivo: Demonstrar a via de sinalização da TPO e da Tg e seus potenciais alvos para a TAI mediados pelo HCV em indivíduos com hepatite C.Método: O mapeamento da via de sinalização foi realizado usando o servidor de anotação automática da Enciclopé-dia Quioto de Genes e Genomas (KEGG). O PathVisio, um software gratuito de análise e desenho de vias de código aberto, foi utilizado para a representação gráfica da via de sinalização.Resultado: As sequências foram retiradas do banco de dados KEGG e sua transcrição mapeada representa a via de . sinalização das principais biomoléculas que desencadeia a TAI. A ação do HCV, ou seu tratamento pode desen-cadear a TAI que é caracterizada pela presença de autoanticorpos contra a TPO e Tg. Na TAI os linfócitos T CD4+ auto-reativos recrutam células B e células T CD8+ na tireóide. A progressão da doença leva à morte de células da tireóide e hipotireoidismo.Conclusão: O HCV ou o seu tratamento ativa várias vias de sinalização com dano na célula tireoidiana, tendo como resultado TAI e hipotireoidismo secundário a apoptose celular. (AU)

Disfunción tiroidea y diabetes mellitus tipo 1 / Thyroid dysfunction and type 1 diabetes mellitus

Introducción: La diabetes mellitus tipo 1 es una enfermedad autoinmunitaria que se relaciona con alteraciones tiroideas. Objetivo: Describir la relación que existe entre diabetes mellitus tipo 1 y enfermedad tiroidea autoinmune. Métodos: Se realizó una revisión de la literatura nacional e internacional de los últimos 15 años en bases de datos, en español y en inglés. Se utilizaron las siguientes palabras clave: diabetes mellitus tipo 1, autoinmunidad, enfermad tiroidea autoinmune, disfunción tiroidea y anticuerpos antitiroideos. Análisis e integración de la información: La alteración más frecuente es el hipotiroidismo subclínico y se presenta con mayor frecuencia en el sexo femenino, por lo que se sugiere realizar periódicamente el perfil tiroideo a estos pacientes. Conclusiones: Se debe tener en cuenta en la práctica clínica estas implicaciones para brindar un tratamiento oportuno, mejorar complicaciones derivadas como las enfermedades cardiovasculares y disminuir las cifras de morbilidad y mortalidad(AU)

Introduction: Type 1 diabetes mellitus is an autoimmune disease that is related to thyroid abnormalities. Objective: Describe the relationship between type 1 diabetes mellitus and autoimmune thyroid disease. Methods: A review of the national and international literature of the last 15 years was carried out in databases, in Spanish and in English. The following keywords were used: type 1 diabetes mellitus, autoimmune, autoimmune thyroid disease, thyroid dysfunction and antithyroid antibodies. Analysis and integration of information: The most common alteration is subclinical hypothyroidism and it occurs most often in the female sex, so it is suggested to periodically perform the thyroid profile to these patients. Conclusions: These implications should be taken into account in clinical practice to provide timely treatment, improve complications such as cardiovascular disease and reduce morbidity and mortality figures(AU)

Frequency of alleles associated with celiac disease in patients with autoimmune thyroid disease / Frequência dos alelos associados com a doença celíaca em portadores de doenças autoimunes da tireoide

ABSTRACT Objective To determine the frequency of Human leukocyte antigen alleles and to verify the association of the presence of these alleles with symptoms and other diseases related to celiac disease in patients with autoimmune thyroid diseases. Methods A questionnaire on the symptoms and diseases associated with celiac disease was applied. Genomic deoxyribonucleic acid was extracted by collecting cells from the oral mucosa. The alleles (DQA1*0501; DQB1*0201; DRB1*04) were identified by means of the polymerase chain reaction. Results A total of 110 patients with autoimmune thyroid diseases participated in this study. It was observed that 66.4% of the individuals carried at least one of the alleles assessed and that 58.2% of the individuals were positive for at least one of the DQ2 alleles (DQA1*0501; DQB1*0201) and out of these 18.2% were positive for both DQ2 alleles (DQA1*0501; DQB1*0201). With regard to DQ8 (DRB1*04), 21.8% of the studied population was positive for this allele and 3.6% was positive for both DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04). A significant association was found between the presence of the DRB1*04 allele and gastrointestinal symptoms (p=0.02). A significant association of the DRB1*04 allele with type 1 diabetes mellitus (p=0.02) was observed. Conclusion The genetic profiles most commonly associated with celiac disease, such as DQ2 (DQA1*0501; DQB1*0201) and DQ8 (DRB1*04) were around 20.0% prevalent in the studied population. These are risk haplotypes for celiac disease especially when symptoms and diseases related to celiac disease are present. Therefore, it is important to screen patients to investigate a potential diagnosis for celiac disease.

RESUMO Objetivo Determinar a frequência dos alelos do Human leukocyte antigen e verificar a associação da presença desses alelos com sintomas e outras doenças relacionados à doença celíaca em portadores de doenças autoimunes da tireoide. Métodos Aplicou-se um questionário relacionado aos sintomas e doenças associados à doença celíaca. O ácido desoxirribonucleico genômico foi extraído por meio da coleta das células da mucosa bucal. Os alelos (DQA1*0501; DQB1*0201; DRB1*04) foram identificados por meio da reação em cadeia da polimerase. Resultados Participaram deste estudo 110 portadores de doenças autoimunes da tireoide. Observou-se que 66,4% dos indivíduos carregavam pelo menos um dos alelos estudados e que 58,2% dos indivíduos eram positivos para pelo menos um dos alelos DQ2 (DQA1*0501; DQB1*0201) e destes 18,2% foram positivos para ambos alelos do DQ2(DQA1*0501; DQB1*0201). Com relação ao DQ8 (DRB1*04), 21,8% da população estudada eram positivos para esse alelo e 3,6% eram positivos tanto para o DQ2 (DQA1*0501; DQB1*0201) quanto para o DQ8 (DRB1*04). Foi encontrada associação significativa da presença do alelo DRB1*04 com os sintomas gastrointestinais (p=0,02). Houve associação significativa do alelo DRB1*04 com diabetes mellitus tipo 1 (p=0,02). Conclusão O perfil genético mais fortemente associado à doença celíaca, tais como DQ2 (DQA1*0501; DQB1*0201) e DQ8 (DRB1*04) estavam presentes em torno de 20,0% da população estudada, estes são haplótipos de risco para doença celíaca e principalmente na presença de sintomas e doenças relacionadas à doença celíaca. Sendo assim, é importante realizar o rastreamento para investigar um possível diagnóstico para doença celíaca.

Relación entre tiroiditis autoinmune y lupus eritematoso sistémico / Relationship between autoinmune thyroiditis and systemic lupus erythematosus

Introducción: El lupus eritematoso sistémico es una enfermedad autoinmune que se caracteriza por la presencia de autoanticuerpos, los cuales, junto con el proceso inflamatorio, son los responsables de las manifestaciones clínicas de la enfermedad. Se puede asociar con otras afecciones como la tiroiditis autoinmune, la que, en ocasiones, precede al diagnóstico de lupus. Objetivo: Describir la relación entre tiroiditis autoinmune y lupus eritematoso sistémico. Métodos: Estudio descriptivo, correlacional y retrospectivo, realizado en la Consulta Externa del Hospital Andino de Chimborazo en el periodo comprendido entre enero de 2017 y julio de 2018. El universo estuvo constituido por la totalidad de los pacientes (137) que acudieron a consulta y que presentaron diagnóstico de lupus eritematoso sistémico. La muestra quedó conformada por los 97 pacientes que cumplieron los criterios de inclusión y exclusión definidos para la investigación. Se empleó la correlación de Pearson para establecer la relación existente entre tiroiditis autoinmune y lupus eritematoso sistémico. Resultados: El promedio de edad de los pacientes fue de 36,32 años, con predominio de edad entre 26 y 35 años. Predominó el sexo femenino (91,75 por ciento) y el tiempo de evolución fue menor de 3 años (46,40 por ciento). El 32,99 por ciento de los casos con lupus eritematoso sistémico presentaron también diagnóstico de tiroiditis autoinmune, que precedió al diagnóstico de lupus en un 90,63 por ciento de los casos. Conclusiones: Existe una relación entre tiroiditis autoinmune y lupus eritematoso sistémico. Ambas afecciones comparten mecanismos autoinmunes comunes, pero no queda totalmente esclarecido el mecanismo que las interrelaciona(AU)

Introduction: Systemic lupus erythematous is an autoimmune disease characterized by the presence of autoantibodies, in adition to the inflammatory process are responsible for the disease's clinical manifestations. It can be associated with other conditions such as autoimmune thyroiditis, this affection, sometimes, precedes the diagnosis of lupus. Objective: To describe the relationship between autoimmune thyroiditis and systemic lupus erythematous. Method: It is a descriptive, correlational and retrospective study, carried out in the outpatient clinic of the Andean hospital of Chimborazo in the period between January 2017 and July 2018. The universe was constituted by the totality of patients (137) who attended the consultation and who presented a diagnosis of systemic lupus erythematous. The sample was constituted by 97 patients who met the inclusion and exclusion criteria defined for the investigation. Pearson correlation was used to establish the relationship between autoimmune thyroiditis and systemic lupus erythematous. Results: The average age of 36.32 years with predominance of patients between 26 and 35 years of age. The female sex is predominated (91.75 percent) and the evolution time is less than three years (46.40 percent. 32.99 percent. of the cases with SLE also present a diagnosis of autoimmune thyroiditis that preceded the diagnosis of lupus in 90.63 percent. Conclusions: The relationship between autoimmune thyroiditis and systemic lupus erythematous is described; both conditions share common autoimmune mechanisms, but the mechanism which interrelate both conditions is not completely clarified(AU)

The Association between Low Vitamin D Status and Autoimmune Thyroid Disease in Korean Premenopausal Women: The 6th Korea National Health and Nutrition Examination Survey, 2013–2014 / 가정의학회지

BACKGROUND: This study aimed to analyze the association of low vitamin D status with thyroid autoimmunity and dysfunction in the Korean population according to sex and menopausal status in women. METHODS: This study was based on the data acquired from the 6th Korea National Health and Nutrition Examination Survey. We enrolled 4,356 subjects who had data of thyroid function, antithyroid peroxidase antibody (TPOAb), and serum 25-hydroxyvitamin D (25[OH]D) levels. We excluded subjects who were pregnant and who had a history of thyroid disease or thyroid cancer, and those with transient thyroid dysfunction who tested negative for TPOAb (TPOAb[−]). RESULTS: TPOAb positivity (TPOAb[+]) with thyroid dysfunction (subclinical and overt hypothyroidism) was more prevalent in the vitamin D deficient group than in the vitamin D insufficient and sufficient groups including premenopausal (P=0.046) and postmenopausal women (P=0.032), although no significant differences were observed in men. The mean serum 25(OH)D level was significantly lower in the TPOAb(+) with thyroid dysfunction group than in the TPOAb(+) with euthyroidism and TPOAb(−) groups of premenopausal women (P=0.001), although no significant differences were observed in men and postmenopausal women. Multivariate binary logistic regression analysis, adjusted for age, body mass index, and current smoking status, showed that vitamin D insufficiency and deficiency were significantly associated with TPOAb(+) with thyroid dysfunction in premenopausal women (P<0.001), although no significant associations were observed in men and postmenopausal women. CONCLUSION: Low vitamin D status was significantly associated with thyroid autoimmunity and dysfunction in the Korean population, especially in premenopausal women.

Encefalopatía asociada a enfermedad tiroídea, un diagnóstico a tener en mente / Encephalopathy associated with thyroid disease, a diagnosis to take into account

Mujer de 54 años con antecedentes de Hipertensión arterial e Hipotiroidismo. Historia de aproximadamente 3 meses de evolución caracterizado al inicio por ánimo bajo, cambios en el comportamiento con aparición progresiva de conductas extraña, ideas delirantes y alucinaciones visuales y auditivas, junto con disminución en requerimientos de hormonas tiroídeas hasta la suspensión. Consulta en varios centros donde se cataloga como Trastorno depresivo severo con síntomas psicóticos, Síndrome confusional, Síndrome Psicótico. En este contexto se pesquisa Hipertiroidismo con títulos elevados de Anticuerpos Antitiroídeos e inicia tratamiento con Metimazol y Betabloqueo. Tras extenso estudio que descartan causas infecciosas, neoplásicas y autoinmunes; se inicia tratamiento con pulsos de Metilprednisolona con excelente y rápida respuesta clínica, la cual mantiene durante el curso del seguimiento con dosis decrecientes de corticoides.

A 54-year-old woman with a history of arterial hypertension and hypothyroidism. History of approximately 3 months of evolution characterized at the beginning by low mood, changes in behavior with progressive appearance of bizarre behaviors, delusional ideas and visual and auditory hallucinations. Consultation in several centers where it is classified as severe Depressive disorder with psychotic symptoms, Confusional syndrome, Psychotic syndrome. Hyperthyroidism is investigated with high titers of Antithyroid Antibodies and initiates treatment with Methimazole and Betablock. After extensive study that ruled out infectious, neoplastic and autoimmune causes; Treatment with Methylprednisolone pulses is initiated with excellent and rapid clinical response, which is maintained during the course of follow-up with decreasing doses of corticosteroid.

La función tiroidea en pacientes con enfermedades autoinmunes / Thyroid function in patients with autoimmune diseases

Introducción: la aparición de enfermedad tiroidea autoinmune presenta una gran prevalencia en pacientes con diagnósticos de enfermedades autoinmunes. Objetivo: describir las enfermedades tiroideas autoinmunes en pacientes con enfermedades autoinmunes, atendidos en el Hospital Pediátrico William Soler Ledea, del 1ro. de octubre de 2014 al 31 de enero de 2017. Métodos: estudio descriptivo, transversal y prospectivo en 42 pacientes con diagnóstico de enfermedad autoinmune. Se midieron variables demográficas, enfermedad autoinmune (lupus eritematoso sistémico, hepatitis autoinmune, artritis idiopática juvenil y esclerodermia), función tiroidea (eutiroidismo, hipotiroidismo e hipertiroidismo) y anticuerpos antitiroideos (antiperoxidasa y antitiroglobulina). Resultados: las enfermedades autoinmunes, con enfermedad tiroidea, se presentaron en 26,2 por ciento (n= 11): con hipotiroidismo 81,8 por ciento (n= 9) y con hipertiroidismo 18,2 por ciento (n= 2). El hipotiroidismo estuvo presente en adolescentes del sexo femenino (n= 7), el lupus eritematoso sistémico en el 88,9 por ciento (n= 8), seguido de esclerodermia en el 11,1 por ciento (n= 1). El hipertiroidismo solo se diagnosticó en el lupus eritematoso sistémico 100 por ciento (n= 2), ambas en adolescentes del sexo femenino. Solo 3 pacientes tuvieron anticuerpos antitiroideos positivos, solo 2 se correspondieron con enfermedad tiroidea autoinmune: hipotiroidismo con anticuerpos antitiroideos positivos 22,2 por ciento (n= 2, en este caso correspondiente al lupus eritematoso sistémico). Los pacientes sin enfermedad tiroidea (73,8 por ciento; n= 31), a su vez, predominaron en edades de 10-14 años (n= 15; 48,4 por ciento) y en el sexo femenino (n= 22; 71,0 por ciento). Conclusión: el hipotiroidismo es más frecuente en adolescentes femeninas, con diagnóstico de lupus eritematoso sistémico, y con evidencia de anticuerpos antitiroideos positivos(AU)

Introduction: the appearance of autoimmune thyroid disease has high prevalence in patients diagnosed with autoimmune diseases. Objective: to describe the autoimmune thyroid diseases in patients with autoimmune diseases attended at William Soler Ledea Pediatric Hospital from October 1, 2014 to January 31, 2017. Methods: descriptive, cross-sectional and prospective study in 42 patients diagnosed with autoimmune disease. Demographic variables, autoimmune disease (systemic lupus erythematosus, autoimmune hepatitis, juvenile idiopathic arthritis and scleroderma), thyroid function (euthyroidism, hypothyroidism and hyperthyroidism) and antithyroid antibodies (antiperoxidase and antithyroglobulin) were measured. Results: autoimmune diseases with thyroid disease occurred in 26.2 percent (n= 11), with hypothyroidism 81.8 percent (n= 9), and with hyperthyroidism 18.2 percent (n= 2). Hypothyroidism was present in female adolescents (n= 7), systemic erythematosus lupus in 88.9 percent (n= 8) followed by scleroderma in 11.1 percent (n= 1). Hyperthyroidism was only diagnosed 100 percent in systemic erythematosus lupus (n= 2), both in female adolescents. Only 3 patients had positive antithyroid antibodies, only 2 corresponded to autoimmune thyroid disease: hypothyroidism with positive antithyroid antibodies with 22.2 percent (n= 2, in this case corresponding to systemic lupus erythematosus). Patients without thyroid disease (73.8 percent; n= 31) predominated at ages from 10 to 14 years old (n= 15; 48.4 percent) and in females (n= 22; 71.0 percent). Conclusion: hypothyroidism is more frequent in female adolescents, with a diagnosis of systemic erythematosus lupus, and with evidence of positive antithyroid antibodies(AU)

Efecto combinado de la interacción genética sobre el desarrollo del bocio nodular con tiroiditis autoinmune y adenoma tiroideo en los habitantes de Bucovina del Norte / Combined effect of gene-gene interaction on the development of nodular goiter with autoimmune thyroiditis and thyroid adenoma in the inhabitants of Northern Bukovyna

ABSTRAC This article presents the results of a comprehensive analysis of the combined influence of genetic polymorphisms associated with various links of apoptosis regulation (BCL-2, CTLA-4 and APO-1/Fas) on the development of nodular goiter with autoimmune thyroiditis and thyroid adenoma in the studied population. The analysis was performed using the Multifactor Dimensionality Reduction (MDR) method by calculating the prediction potential. Graphic models of gene-gene interaction with the highest cross-validation consistency created by the MDR method showed complex "synergistic or independent" impact of polymorphic loci of the CTLA-4 (+49G/A), Fas (-1377G/A) and BCL-2 (63291411 A>G) genes on the onset of thyroid pathology in general, or its individual types (nodular goiter with autoimmune thyroiditis and thyroid adenoma) in the population of Northern Bukovyna.

RESUMEN Este artículo presenta los resultados de un análisis exhaustivo de la influencia combinada de polimorfismos genéticos asociados a diversos enlaces en la regulación de la apoptosis (BCL-2, CTLA-4 y APO-1/FAS) sobre el desarrollo de bocio nodular con tiroiditis autoinmune y adenoma tiroideo en la población estudiada. Para ello, se utilizó el método de reducción de dimensionalidad multifactorial (MDR) mediante el cálculo de los potenciales de predicción. Los modelos gráficos de interacción gen-gen con la mayor consistencia de validación cruzada creada por el método MDR mostraron un complejo impacto «sinérgico o independiente¼ de los loci polimórficos de los genes CTLA-4 (+49G/A), FAS (-1377G/A) y BCL-2 (63291411A>G) en el inicio de la patología tiroidea en general, o sus tipos individuales (bocio nodular con tiroiditis autoinmune y adenoma tiroideo) en la población de Bucovina septentrional.

Enfermedad de Hashimoto en una cohorte de 29 niños y adolescentes: Epidemiología, evolución y comorbilidad a corto y largo plazo / Hashimoto's disease in a cohort of 29 children and adolescents: Epidemiology, clinical course, and comorbidities in the short and long term

La tiroiditis de Hashimoto es la causa más común de bocio e hipotiroidismo en niños y adolescentes. Las manifestaciones clínicas y la evolución son variables. El objetivo de este trabajo es revisar las particularidades clínicas y evolutivas de la enfermedad de Hashimoto en población pediátrica. Se analizaron datos clínicos, analíticos, ecográficos, epidemiológicos y evolutivos de los pacientes con tiroiditis autoinmune del Hospital Universitario San Juan de Alicante desde enero de 2010 hasta enero de 2016. En el estudio, se incluyeron un total de 29 pacientes. Se observó una mayor prevalencia en niñas con una relación 2:1. El principal motivo de consulta fue la detección casual de una hormona estimulante de la tiroides elevada o de positividad de anticuerpos antitiroideos en una analítica por otro motivo. En la analítica inicial, el 53,3% de los pacientes presentaba hipotiroidismo subclínico y tan solo el 10% de ellos, hipotiroidismo franco. Dos de los pacientes desarrollaron cáncer de tiroides.

Hashimoto's thyroiditis is the most common cause of goiter and hypothyroidism among children and adolescents. Its clinical manifestations and course vary. The objective of this study was to review the clinical and evolutionary characteristics of Hashimoto's disease in the pediatric population. Clinical, analytical, ultrasound, epidemiological, and evolutionary data of patients with autoimmune thyroiditis seen at Hospital Universitario San Juan de Alicante between January 2010 and January 2016 were analyzed. A total of 29 patients were included in the study. A higher prevalence of girls was observed, at a 2:1 ratio. The main reason for consultation was the accidental detection of high thyroid stimulating hormone levels or positive anti-thyroid antibodies in a lab test done for other reason. In the initial analysis, 53.3% of patients had subclinical hypothyroidism and only 10% of them had frank hypothyroidism. Two patients developed thyroid cancer.

Expression of Sodium-Iodide Symporter Depending on Mutational Status and Lymphocytic Thyroiditis in Papillary Thyroid Carcinoma

BACKGROUND AND OBJECTIVES: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). MATERIALS AND METHODS: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. RESULTS: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p < 0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p < 0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p < 0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p < 0.001) and GLUT-1 gene (r=−0.204, p < 0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. CONCLUSION: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.

Pretibial Myxedema Presenting as Severe Elephantiasis

Elephantiasis is a symptom characterized by the thickening of the skin and underlying tissues in the legs. Pretibial myxedema (PTM) is a non-frequent manifestation of autoimmune thyroiditis, particularly Graves' disease. Lesions of myxedema occur most commonly on the pretibial surfaces, also develop at sites of previous injury or scars and other areas. A 49-year-old male presented with severe elephantiasis on the both pretibial areas, dorsum of the feet, ankles and toes. Twenty years previously, he had received radioactive iodine treatment for thyrotoxicosis. Laboratory tests showed that the patient's thyroid function was normal, but the level of thyroid stimulating hormone (TSH) receptor antibodies was very high (>40 IU/L). The biopsy confirmed PTM. Interestingly, the connective tissue was stained with the TSH receptor antibodies in the deep dermis. Elephantiasic PTM is a severe form of the myxedema and there is few reported case. We report a rare case of PTM with appearance of severe elephantiasis.

BRAF(V600E) Mutation is a Strong Preoperative Indicator for Predicting Malignancy in Thyroid Nodule Patients with Atypia of Undetermined Significance Identified by Fine Needle Aspiration / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). SUBJECTS AND METHOD: This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. RESULTS: The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: BRAFV600E gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p < 0.05). Multivariate analysis revealed that only BRAFV600E mutation was a statistically significant risk factor for malignancy (p < 0.05). When BRAFV600E mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. CONCLUSION: Patients with AUS thyroid nodules should undergo BRAFV600E gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.

Prevalence of autoimmune thyroiditis in patients with type 1 diabetes: a long-term follow-up study

PURPOSE: Type 1 diabetes mellitus (DM) is associated with autoimmune diseases such as thyroiditis. Therefore, we aimed to investigate the prevalence of autoimmune thyroiditis in patients with type 1 DM. METHODS: A total of 102 patients who were diagnosed and followed up (mean age, 8.1±4.0 years) in Ajou University Hospital were enrolled in this study. All the patients were evaluated for beta cell autoimmunity, including insulin autoantibody, glutamic acid decarboxylase antibodies (GADA), and islet cell antibody. Moreover, autoantibodies to thyroid peroxidase and thyroglobulin were assessed at initial diagnosis and annually thereafter. RESULTS: The mean patient age (49 men and 53 women) was 19.2±4.8 years. The prevalence of at least one thyroid antibody was 30.4%. Patients with thyroid anti­bodies had a significantly higher frequency of GADA at the time of the diagnosis. Autoimmune thyroiditis was more prevalent in the older age group. GADA was a significant risk factor for development of thyroid autoantibodies after diagnosis of type 1 DM (odds ratio, 4.45; 95% confidence interval, 1.399–14.153). CONCLUSIONS: In patients with type 1 DM, the prevalence of autoimmune thyroiditis was higher than in the general population. Moreover, GADA positivity at diagnosis was associated with thyroid autoimmunity.

Research progress on systemic lupus erythematosus overlapping organ-specific autoimmune diseases / 浙江大学学报·医学版

Systemic lupus erythematosus (SLE) is a multiorgan-involved autoimmune disease, and it can overlap organ-specific autoimmune diseases such as autoimmune thyroid diseases, autoimmune hepatitis and inflammatory bowel disease. There may be some association between SLE and these autoimmune diseases, such as common immunological and genetic basis, but the pathogenic mechanism is still unclear. This review focuses on current knowledge regarding the prevalence and possible pathogenesis of SLE overlapping the above three autoimmune diseases.

Preoperative Cytologic Diagnosis of Warthin-like Variant of Papillary Thyroid Carcinoma

BACKGROUND: Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. METHODS: Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. RESULTS: WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. CONCLUSIONS: The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.

Síndrome poliglandular autoinmune tipo iii c: reporte de caso / Autoimmune polyglandular syndrome type iiic: case report

El síndrome poliglandular autoinmune comprende un grupo de enfermedades autoinmunes de las glándulas endócrinas, y que afecta órganos no endócrinos, puede ser de tipo I, II y III. Paciente masculino de 26 años presenta palpitaciones, debilidad, y disnea de esfuerzos de 2 meses de evolución. Al examen físico, índice de masa corporal 29,6 kg/m², obesidad central, con acromía en cara, axilas y cuello. Los estudios muestran TSH 0,01 uUl/ml,T4 libre 3,67 ng/dl, antitiroperoxidasa 505,70 Ul/ml, insulina en ayunas 32,77 U/l, y a las 2 horas 77 U/l, glicemia en ayunas 101 mg/dl, curva tolerancia oral a la glucosa a las 2 horas de 140 mg/dl. La ecografía tiroidea revela bocio multinodular. Diagnósticos: tiroiditis autoinmune, vitíligo, prediabetes, sobrepeso. Manejo con metimazol 5 mg c/12 h, y metformina 850 mg en la noche. El paciente baja de peso y la glicemia mejora. El diagnóstico definitivo fue Tiroiditis autoinmune y vitíligo compatible con síndrome poliglandular tipo IIIC.

Autoimmune Polyglandular Syndrome comprises a group of autoimmune diseases of the endocrine glands, and affecting non-endocrine organs, there are type I, II and III. Male patient, aged 26 years old has palpitations, weakness, and exertional dyspnea for 2 months. The physical examination found body mass index 29,6 kg/m², central obesity, with acromia on face, armpits and neck. Studies show TSH 0,01 uUl/ml, freeT4 3,67 ng/dl, antithyroperoxidase 505,70 U/ml, fasting insulin 32,77 U/l, after 2 hours 77 U/l, fasting glycemia 101 mg/dl, glucose tolerance at 2 hours 140 mg/dl. Thyroid ultrasound reveals multinodular goiter. Diagnoses: autoimmune thyroiditis, vitiligo, prediabetes, overweight. It prescribed metimazole 5 mg every 12 hours, and metformin 850 mg at night. Patient with weight reduction and glucose improvement. Definitive diagnoses patient with autoimmune thyroiditis and vitiligo, compatible with polyglandular syndrome type IIIC.

Niveles de tirotrofina y anticuerpos antitiroperoxidasa en el primer trimestre de gestación asociados a complicaciones del embarazo en la mujer eutiroidea / Thyrotropin levels and anti-thyroid peroxidase antibodies during first trimester of pregnancy associated with maternal and foetal complications in euthyroid women

Introducción: El embarazo es una situación fisiológica que presenta cambios endócrinos e inmunológicos. La tiroides modifica su economía para proveer suficientes hormonas a la madre y al feto. La autoinmunidad y las disfunciones tiroideas tienen alta prevalencia en mujeres en edad fértil y pueden afectar el curso de la gestación, con repercusiones clínicas adversas maternas y fetales. El objetivo de este estudio fue relacionar la proporción de gestantes eutiroideas con tirotrofina (TSH) en 2 niveles del rango de referencia ( ± DS; 1,57 ± 0,82 vs. 1,16 ± 0,54 mUI/l, p = 0,001). Los niveles séricos de T4L y T4 fueron similares en ambos grupos. De la subpoblación EP, el 63% fue incluida en EP1 y el 37% en EP2, y en EN el 80% en EN1 y el 20% en EN2. Se observó un incremento significativo (p = 0,001) en las complicaciones en EP (22%) vs. EN (10%). En mujeres EP con y sin aborto espontáneo, la TSH ( ± DS) fue 1,65 ± 0,67 vs. 0,99± 0,77 mUI/l (p = 0, 014). Las mujeres EP con y sin parto prematuro presentaron niveles de TSH (X ± DS) 1,63 ± 0,70 vs. 1,15 ± 0,53 mUI/l (p = 0,012). En el grupo EN, el nivel de TSH ( ± DS) para las mujeres con y sin aborto fue 1,45 ± 0,61 vs. 0,85± 0,66 mUI/l (p = 0,001), mientras que en mujeres con y sin parto prematuro la TSH ( ± DS) fue 1,59 ± 0,71 vs. 0,83 ± 0,64 mUI/l (p = 0,001), respectivamente. Sin embargo, no hubo diferencias entre los niveles promedio de TSH encontrados en aborto vs. parto pretérmino en ambos grupos. En EP, 32 mujeres y 19 en EN desarrollaron hipotiroidismo en el curso del embarazo (ns) y 29 en EP y 10 en EN tiroiditis posparto (p = 0,005). La autoinmunidad tiroidea y los mayores niveles de TSH dentro del rango de referencia en mujeres en primer trimestre de embarazo estarían asociados a complicaciones en el transcurso de la gestación y desarrollo de disfunción tiroidea posparto.

Introduction: Pregnancy is a physiological state presenting with endocrine and immunological changes. The thyroid gland modifies its output in order to provide enough hormonesto the mother and foetus. Thyroid autoimmunity and thyroid dysfunction are prevalent in women of childbearing age and may affect the course of gestation and having maternal and foetal clinical consequences. The purpose of the present study was to establish the relationship between euthyroid pregnant women with thyrotropin (TSH) at two levels of the reference range ( ± SD; 1.57 ± 0.82 vs 1.16 ± 0.54 mIU/L, P=.01). FT4 and T4 values were similar in both groups. Out of the pregnant women in the EP group, 63% were included in EP1, and 37% in EP2. In the EN group, 80% of women were included in EN1 and 20% in EN2. A significant (P=.001) increase in pregnancy complications in EP group (22%) vs EN (10%) was observed. In the EP group, TSH levels were: 1.65 ± 0.67 vs 0.99± 0.77 ( ± SD) mIU/L (P=.014) respectively, in women with and without miscarriage. TSH levels were 1.63 ± 0.70 vs 1.15 ± 0.53 ( ± SD) mIU/L (P=.012), respectively, in women with and without preterm delivery. In the EN group TSH levels were: 1.45 ± 0.61 vs 0.85± 0.66 ( ± SD) mIU/L (P=.001), respectively, in women with and without miscarriage. TSH levels were 1.59 ± 0.71 vs 0.83 ± 0.64 ( ± SD) mIU/L (P=.001), respectively, in women with and without preterm delivery. However, TSH levels in miscarriage and preterm delivery were similar. Thirty-two EP, and 19 EN women developed hypothyroidism in pregnancy (ns), and 29 EP and 10 EN women developed post-partum thyroiditis (P=.005). Conclusion: Thyroid autoimmunity and higher TSH levels within the reference range during the first trimester of pregnancy were associated with pregnancy complications and with the development of thyroid postpartum dysfunction.

An evaluation of thyroid autoimmunity in patients with beta thalassemia minor: a case-control study

Objective: The tendency to autoimmune diseases has been reported to be increased in beta thalassemia minor [BTM]. The aim of this study was to evaluate whether thyroid autoimmunity is higher in BTM

Methods: Patients with BTM [n=86] and a healthy control group [n=93] were included in this cross-sectional case-control study. The two groups were compared in terms of anti-thyroglobulin [anti-TG] and anti-thyroid peroxidase [anti-TPO] and thyroid hormones

Results: In the BTM group, thyroid hormones and serum anti-TG and anti-TPO antibody levels were not statistically different from those of the control group. The BTM and control groups were similar in terms of anti-thyroid antibody [ATA] positivity prevalence. In the BTM group, anti-TG was 11.6% and anti-TPO was 14% positive, while these values were 14% and 12.9% positive, respectively in the control group [p=0.806 and p=0.989, respectively]. The proportion of anti-TG and/or anti-TPO antibody positive subjects was found to be 20.9% in the BTM group, and 20.4% in the control group [p=0.919]. The ratios of subjects with euthyroidism, hyperthyroidism and hypothyroidism were similar in both groups

Conclusions: As the thyroid autoimmunity prevalence in the BTM group was not increased compared to the control group, it can be considered that there is no necessity for routine ATA and thyroid hormone testing in subjects with BTM