Treg cells as a protective factor for Hashimoto`s thyroiditis: a Mendelian randomization study.

Background and objectives: Hashimoto's thyroiditis (HT), a chronic autoimmune disorder impacting thyroid function, is a growing public health concern. The relationship between Treg cells and HT has been extensively studied, with Treg cells considered crucial in suppressing HT progression. However, these studies have mainly been observational, limiting our understanding of Treg cells' impact on HT risk. Leveraging large datasets, we utilized Mendelian randomization (MR) analysis to examine the causal association between Treg cell biomarkers and HT, providing additional validation for these relationships. Methods: Comprehensive two-sample Mendelian randomization analysis was performed to determine the causal association between Treg cells signatures and HT in this study. Based on publicly available genetic data, we explored causal associations between 165 Treg cells signatures and HT risk. Results: The European cohort study has identified five Treg cell phenotypes that causally protect against HT risk. Resting Treg %CD4 (OR = 0.975, 95% CI = 0.954~0.998, P = 0.030); CD4 on resting Treg (OR = 0.938, 95% CI = 0.882~0.997, P = 0.041; CD28- CD8dim %CD8dim (OR = 0.983, 95% CI = 0.969~0.998, P = 0.030); CD25 on CD39+ resting Treg (OR = 0.926, 95% CI = 0.864~0.991, P = 0.026); 5) CD28 on activated & secreting Treg (OR = 0.969, 95% CI = 0.942~0.996, P = 0.025). The Asian cohort study has identified four Treg cell phenotypes negatively correlated with the risk of HT. CD25hi %T cell (OR = 0.635, 95% CI = 0.473~852, P = 0.002); CD4 Treg %CD4 (OR = 0.829, 95% CI = 0.687~1.000, P = 0.050); CD127-CD8br %T cell (OR = 0.463, 95% CI =0.311~0.687, P< 0.001); CD3 on resting Treg (OR = 0.786, 95% CI = 0.621~0.994, P = 0.044). Conclusion: Our study has demonstrated the close connection between Treg cells and HT by genetic means, thus providing foundational basis for future research.

Characterization of Hashimoto´s thyroiditis in Sudanese children: a cross-sectional study at Gaafar Ibnauf Hospital, Khartoum.

Introduction: literature on Hashimoto´s thyroiditis, the common thyroid illness in the young populations, in Sudan and Africa is scarce. We aimed to study its clinical profile and outcome among Sudanese children and adolescents. Methods: records of 73 patients were reviewed. Data related to demographics, presenting features, family history and coexistence of autoimmune diseases, physical examination findings, and biochemical progression over time were obtained. Results: patients´ mean age at the diagnosis was 10.6 ± 2.9 years, 80.8% (n = 59) of them were female and 83.6% (n = 61) were residing in iodine-sufficient areas. The commonest presenting features were thyromegaly and fatigability (79.5%, n = 58 and 43.8%, n = 32, respectively) after an illness duration of 0.5-48 months. Autoimmune comorbidities were documented in 8.2% (n = 6) of our series and more than half (53.4%, n = 39) of them were pre-pubertal at the diagnosis. Sixty point three percent (60.3%) (n = 44), 20.5% (n = 15), 13.7% (n = 10) and 5.5% (n = 4) of patients presented with overt hypothyroidism, sub-clinical hypothyroidism, euthyroidism and hyperthyroidism respectively, and there were no significant differences in the clinical profile between them. In patients' continued follow-up, 94.1% (n = 32/34) of those presented with overt hypothyroidism required levothyroxine therapy to maintain euthyroidism for 0.5-13 years, while 85.7% (n = 6/7) of those with euthyroidism remained so for 0.5-6 years. Remission was reported in all hyperthyroid patients and in only 5.9% (n = 2/34) of those with overt hypothyroidism at diagnosis. The majority of our patients with subclinical hypothyroidism were treated with levothyroxine and continued to be euthyroid for 10 months to 13 years. Conclusion: goiter was the commonest presenting feature of Hashimoto´s thyroiditis. The majority of patients had overt or subclinical hypothyroidism and almost all of them required long-term levothyroxine therapy.

Single-cell transcriptome analysis of T cells in thyroid and peripheral blood of patients with Hashimoto′s thyroiditis / 中华内分泌代谢杂志

Objective:To construct single-cell transcription landscape of T cell in peripheral blood mononuclear cells(PBMCs) and thyroid tissue of patients with Hashimoto ′s thyroiditis(HT), and to analyze the changes in the proportion and functionality of T cell clusters in HT disease state.Methods:Single cell RNA sequencing was performed on PBMCs and thyroid tissue from 5 HT patients. Single cell RNA sequencing data of PBMCs from 5 healthy individuals were retrieved from public databases. After preliminary clustering, the clusters expressing CD3E were extracted and clustering again, and the names of each cluster were determined according to the known cell markers. The proportion of each cell subtype was compared, and the differentially expressed genes in different samples were analyzed.Results:After quality control, the 71 533 T cells were classified into 19 cell clusters. Among them, the proportion and function of C1_CD4 + Naive T cell clusters, C3_CD4 + Treg cell clusters, C7_CD8 + Naive T cell clusters, C8_GNLY -CD8 + T cell clusters, C10_RORC + CD8 + T cell clusters, C11_ GZMK + CD8 + T cell clusters, C12_CCL4 + CD8 + T cell clusters, and C18_PTGDS + NK cell clusters in thyroid tissue of HT patients were significantly different from those in PBMCs of healthy controls and HT patients. Conclusion:The proportion of multiple T cells in thyroid tissue of HT patients were significantly different from those in PBMCs. Among them, the proportion of three of CD8 + T cell subsets with high expression of cell killing-related genes in thyroid tissue T cells of HT patients is higher than that in PBMCs T cells, and it is statistically significant. In addition, the functionality of various T cells in the thyroid tissue of HT patients are also significantly different from those in PBMCs. A cluster of GZMK + CD8 + T cells showes significantly lower expression of genes related to PD1 pathway in thyroid tissues of HT patients compared with cells in PBMCs of HT patients, also a cluster of CCL4 + CD8 + T cells showes significantly lower expression of genes related to IL-12 pathway.

Graves' disease following hypothyroidism due to Hashimoto's thyroiditis in a black South African lady: a case report.

Graves' disease and Hashimoto's thyroiditis are autoimmune thyroid disorders with distinct pathological and histopathological features. The conversion from Hashimoto's thyroiditis to Graves' disease has been rarely reported throughout the world with no reports in the African race to our knowledge. We here report an African lady who was initially diagnosed with primary hypothyroidism following Hashimoto's disease but later became thyrotoxic due to Graves' disease.

Serum polyamine metabolic profile in autoimmune thyroid disease patients.

OBJECTIVE: Polyamines are indispensable polycations and play important physiological roles in living cells. Some polyamine metabolites have been associated with autoimmune disorders. The aims of this study were to profile polyamine metabolites in autoimmune thyroid disease (AITD) and predict whether polyamine metabolites are associated with thyroid hormone, thyroid autoantibodies or disease progression. DESIGN, PATIENTS AND MEASUREMENTS: A total of 136 participants were recruited, including Graves' disease (GD) (n = 36), Hashimoto's thyroiditis (HT) (n = 33) and thyroid autoantibody-positive (pTAb) (n = 29) patients and 38 age- and sex-matched healthy controls (HCs). Fourteen polyamine metabolites, including polyamine precursors, polyamines and polyamine catabolite, were measured by UFLC-MS/MS RESULTS: Both GD and HT patients had higher L-arginine, L-ornithine, lysine and agmatine levels and lower putrescine, 1,3-diaminopropane, spermine, N-acetylputrescine levels than HCs. Some polyamine metabolite levels were different only in GD or HT patients compared to HCs: GD patients had significantly higher spermidine, N-acetylspermidine and γ-aminobutyric acid and lower cadaverine, whereas HT patients had significantly decreased N-acetylspermine. Only spermine and N-acetylspermine were significantly lower in pTAb than HCs. The spermine:spermidine ratio was significantly reduced in all AITD patients. In addition, spermine was negatively correlated with thyroid-specific antibodies grade. N-acetylspermidine might be a risk factor for pTAb progression to overt hypothyroidism. CONCLUSIONS: Compared with the HCs, most metabolites of GD and HT showed similar patterns, suggesting the possibility of a common pathophysiological basis or metabolic pathway. Moreover, pTAb progression to overt hypothyroidism may be related to high N-acetylspermidine. Thyroid autoimmunity was associated with low spermine.

Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer.

BACKGROUND: The purpose of this study was to evaluate the potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid carcinoma (PTC). METHODS: A total of 619 patients with PTC who underwent total thyroidectomy with lymph node dissection were enrolled in this study. Univariable and multivariate analyses were used. RESULTS: Hashimoto's thyroiditis was present in 35.9% (222 of 619) of PTCs. Multivariate logistic regressions showed that BRAF(V600E) mutation, sex, extrathyroidal extension, and lymph node metastasis were independent factors for Hashimoto's thyroiditis. Female sex, more frequent extrathyroidal extension, and a higher incidence of lymph node metastasis were significantly associated with PTCs accompanied by BRAF(V600E) mutation without Hashimoto's thyroiditis compared with PTCs accompanied by BRAF(V600E) mutation with Hashimoto's thyroiditis. CONCLUSION: Hashimoto's thyroiditis was negatively associated with BRAF(V600E) mutation, extrathyroidal extension, and lymph node metastasis. In addition, Hashimoto's thyroiditis was related to less lymph node metastasis and extrathyroidal extension in PTCs with BRAF(V600E) mutation. Therefore, Hashimoto's thyroiditis is a potentially protective factor in PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1019-E1025, 2016.

Lack of association between polymorphisms in the UBASH3A gene and autoimmune thyroid disease: a case control study / Falta de associação entre polimorfismos do gene UBASH3A e doença tiroidiana autoimune: estudo caso controle

Objective: The aim of this study was to investigate UBASH3A gene variation association with autoimmune thyroid disease and clinical features in a Chinese Han population. Subjects and methods: A total of 667 AITD patients (417 GD and 250 HT) and 301 healthy controls were genotyped for two single nucleotide polymorphisms (SNPs) rs11203203, rs3788013 of UBASH3A gene, utilizing the Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometer (MALDI-TOF-MS) Platform. Results: Between the control group and AITD, GD and HT group, no statistically significant difference was observed in the genotypic and allelic frequencies of the two SNPs. There was no significant difference in allelic frequencies of the two SNPs between GD with and without ophthalmopathy. There was no significant difference in haplotype distributions between the control group and AITD, GD or HT group. Conclusion: Rs11203203 and rs3788013 in UBASH3A gene may not be associated with AITD patients in Chinese Han population. .

Objetivo: O objetivo deste estudo foi investigar a variação no gene UBASH3A com a doença tiroidiana autoimune e características clínicas na população chinesa Han. Sujeitos e métodos: Um total de 667 pacientes com DTAI (417 com DG e 250 com TH) e 301 controles saudáveis foi genotipado para dois polimorfismos de nucleotídeo simples (SNPs) rs11203203, rs3788013 do gene UBASH3A, usando-se a plataforma MALDI-TOF-MS (Ionização/Dessorção de Matriz Assistida por Laser – Tempo de Voo/Espectrômetro de Massa). Resultados: Não foram observadas diferenças significativas entre as frequências genotípicas e alélicas dos dois SNPs nos grupos controle e DTAI, DG e TH. Não houve diferenças significativas entre as frequências alélicas dos dois SNPs em pacientes com DG com ou sem olftalmopatia. Não houve diferenças significativas nas distribuições de haplótipos no grupo controle e nos grupos DTAI, DG e TH. Conclusão: Os SNPs rs11203203 e rs3788013 do gene UBASH3A podem não estar associados a pacientes com DTAI na população chinesa Han. .

Coexistent primary lymphoma of the thyroid and cerebral aneurysm / Linfoma primário de tiróide coexistente com aneurisma cerebral

Relata-se um raro caso de linfoma primário de tiroide em uma mulher de 52 anos com hipotiroidismo associado à tiroidite crônica de Hashimoto. Houve rápido crescimento de um tumor cervical antero-medial, com sintomas de compressão nas vias aéreas superiores e no esôfago. Imagens de tomografia computadorizada com contraste e de endoscopia digestiva alta confirmaram os efeitos compressivos. O linfoma de células B CD20+ primário de tiróide foi diagnosticado por punção aspirativa com agulha grossa e exame histológico e imunoistoquímico. Imagens incidentais do pescoço e da cabeça revelaram um aneurisma cerebral. Com base no diagnóstico, a paciente se submeteu com sucesso a quimioterapia e radioterapia e houve controle do linfoma. A paciente continua em acompanhamento nos ambulatórios de Oncologia e de Neurocirugia. Olinfoma primário de tiroide pode apresentar-se como uma massa indolor na região cervical anterior e média, causando dificuldades de diagnóstico. A relação, causal ou casual, entre linfomas e aneurismas cerebrais nãoestá bem definida.

A rare case of primary lymphoma of the thyroid is reported in a 52-year-old woman with a previous history of hypothyroidism due to Hashimoto?sthyroiditis, and rapid development of an anteromedial cervical tumor with symptoms of extrinsic compression over the upper airways and the esophagus. Contrasted computed tomography images and upper digestive endoscopy confirmed the compressive mass effects. The primary B-cellCD20+ lymphoma of the thyroid was diagnosed by thick-needle biopsy with histological and immunohistochemical evaluation. Incidental images of the head and neck revealed a cerebral aneurysm. Based on the diagnosis, the patient successfully underwent chemotherapy and radiation therapy with control of the lymphoma and is under surveillance in the Oncology andNeurosurgery outpatient care center. Primary lymphoma of the thyroid can present as a painless anterior and medial mass on the neck, leading to diagnosis challenges. The casual or causal relationship between lymphomas and cerebral aneurysms remains unclear.

La otra cara de Janus y la enfermedad tiroidea autoinmune

La enfermedad tiroidea autoinmune es una de las patologías más comunes dentro de la endocrinología. Este grupo de enfermedades que afectan la función tiroidea se consideran actualmente como parte de un espectro, donde por un lado se evidencia una hipofunción y donde predomina una respuesta inmune Th1 (Tiroiditis de Hashimoto) y en el lado opuesto, el de la hiperfunción, predomina una respuesta Th2 (Enfermedad de Graves). Si bien ambas enfermedades tienen ciertos locus de predisposición genética en común, las manifestaciones clínicas y el pronóstico de estas enfermedades son totalmente opuestas. Aunque se han planteado diversas teorías para explicar las diferencias en el patrón autoinmune de ambos extremos de este espectro, éstas no han logrado ilustrar la amplia variedad de fenotipos de esta patología. Evidencia actual sugiere que un grupo celular encargado de controlar la actividad de los elementos efectores de la respuesta inmune, limitando el daño hacia los tejidos del hospedador mediando la autotolerancia, y conocido como células T reguladoras, juegan un papel protagónico en el desarrollo de las enfermedades autoinmunes. El propósito de ésta revisión es exponer como la disregulación de la cara reguladora del sistema inmune, expresada tanto en la alteración de la función como en la expansión de las células T reguladoras, constituyen una piedra angular en las diversas formas de manifestación de la enfermedad tiroidea autoinmune.

Autoimmune thyroid disease is one of the most common diseases inside the field of endocrinology. This group of diseases affect the thyroid function in a manner that is now considered like a spectrum, where on one side there is evidence of hypofunction and a predominating Th1 response (Hashimoto´s thyroiditis), and on the opposite side, hyperfunction and a predominating Th2 response (Graves´ disease). Even though both diseases share loci for genetic predisposition, the outcome of each of them is totally opposite. Several theories have been proposed to explain the differences in the autoimmune patterns, but haven’t been able to explain the ample phenotypical manifestations of the disease. Current evidence suggests that a recently describe cellular group is in charge of controlling the effector elements of the immune response, limiting tissue damage and enhancing self-tolerance, these are the T regulator cells (Treg), which play a principal role in the development of autoimmune diseases. The purpose of this review is to expose the dysregulation of the regulatory side of the immune system expressed as the alteration of the functioning of Treg, which are now believed to be fundamental in the many phenotypes of autoimmune thyroid diseases.

Forma atípica de tireoidite supurativa aguda em paciente pediátrico: relato de caso / Atypical form of acute suppurative thyroiditis in pediatric patient: case report

A tireoidite aguda é uma doença rara. Na infância associa-se principalmente a anormalidades congênitas com acometimento do lobo esquerdo. Na ausência de tireoidopatia preexistente, a função tireoidiana geralmente está normal. Relatamos um caso de uma menina, 6 anos de idade, com tumoração associada a sinais flogísticos na região cervical anterior há 15 dias acompanhada de leucocitose com desvio à esquerda, VSH e TSH elevados. Não havia história prévia de tireoidopatia. A ultra-sonografia da região cervical foi sugestiva de abscesso tireoidiano. Realizou-se antibioticoterapia e drenagem cirúrgica com boa resposta, porém posteriormente a paciente evoluiu com hipotireoidismo clínico. O esofagograma não detectou fístula do seio piriforme e a ultra-sonografia controle revelou heterogeneidade do parênquima, levantando-se a possibilidade de tireoidite de Hashimoto. A importância do caso deve-se à sua apresentação incomum: ausência de anormalidades congênitas, acometimento difuso da tireóide, alteração da função tireoidiana e provável tireoidite de Hashimoto como fator predisponente da tireoidite aguda.

Acute thyroiditis is an unusual disease. In pediatric patients it is usually associated with congenital abnormalities towards the unilateral envelopment of the left thyroid lobe. In general, in the absence of preexisting thyroid disease, the thyroid function is most often normal. It is here described a case of a six-year-old girl who had presented a mass with flogistic signs in the anterior neck region for fifteen days, together with leukocytosis and increased levels of VSH and TSH. There was no evidence of previous thyroid disease and the cervical ultrasonography suggested thyroid abscess. Intravenous antibiotic and surgical dranaige were done with a good response, however, the patient developed clinical hypothyroidism aftherwards . Barium swallow did not demonstrate pyriform sinus fistula and the follow-up ultrasonography revealed heterogeneous internal texture suggesting Hashimoto's Thyroiditis. The relevance of this case is due to its unusual findings: the absence of congenital abnormalities, bilateral envelopment of thyroid lobes, hypothyroidism and a probable Hashimoto's Thyroiditis as a predisposing factor for acute thyroiditis.