Prevalence of latent and overt polyautoimmunity in type 1 diabetes: A systematic review and meta-analysis.

BACKGROUND: Patients afflicted by type 1 diabetes (T1D) exhibit polyautoimmunity (PolyA). However, the frequency and distribution of PolyA in T1D is still unknown. OBJECTIVE: We conducted a systematic review and meta-analysis to define the prevalence of latent and overt PolyA in individuals with T1D. METHODS: Following PRISMA guidelines, a comprehensive search across medical databases identified studies on latent and overt PolyA in T1D. Two researchers independently screened, extracted data, and assessed study quality. A random effects model was utilized to calculate the pooled prevalence, along with its corresponding 95 % confidence interval (CI), for latent PolyA and overt PolyA. Meta-regression analysis was conducted to study the effect of study designs, age, sex, and duration of disease on pooled prevalence. RESULTS: A total of 158 articles, encompassing a diverse composition of study designs were scrutinized. The analysis included 270,890 individuals with a confirmed diagnosis of T1D. The gender was evenly distributed (50.30 % male). Notably, our analysis unveiled an overt PolyA prevalence rate of 8.50 % (95 % CI, 6.77 to 10.62), with North America having the highest rates (14.50 %, 95 % CI, 7.58 to 24.89). This PolyA profile was further characterized by a substantial incidence of concurrent autoimmune thyroid disease (7.44 %, 95 % CI, 5.65 to 9.74). Moreover, we identified a notable prevalence of latent PolyA in the T1D population, quantified at 14.45 % (95 % CI, 11.17 to 18.49) being most frequent in Asia (23.29 %, 95 % CI, 16.29 to 32.15) and Oceania (21.53 %, 95 % CI, 16.48 to 27.62). Remarkably, this latent PolyA phenomenon primarily featured an array of autoantibodies, including rheumatoid factor, followed by Ro52, thyroid peroxidase antibodies, and thyroglobulin antibodies. Duration of the disease was associated with a highest frequency of latent (ß: 0.0456, P-value: 0.0140) and overt PolyA (ß: 0.0373, P-value: 0.0152). No difference in the pooled prevalence by study design was observed. CONCLUSION: This meta-analysis constitutes a substantial advancement in the realm of early detection of PolyA in the context of T1D. Individuals with T1D should regularly undergo assessments to identify potential concurrent autoimmune diseases, especially as they age.

[Molecular mimicry between human thyroid peroxidase, thyroglobulin, cosinophil peroxidase, IL-24 and microorganisms antigens]. / Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos.

OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.

OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.

Response to sorafenib in a locally advanced oncocytic cell carcinoma of the thyroid.

We present the case of a female patient in her late 70s, diagnosed with widely invasive oncocytic cell carcinoma, with extrathyroidal extension, infiltration into the extrathyroidal muscle, involvement of the sternohyoid muscle and infiltration into the external muscle fibres of the oesophagus. Over the following year, metastases were documented in the lungs, bones and brain. Additionally, there was progression of the locally advanced lesion involving the airway and upper gastrointestinal tract. After considering iodine refractoriness, treatment with sorafenib was initiated. Notably, regression of the locoregional lesion at the cervical level was observed following treatment with the multikinase inhibitor.

Clinical and molecular impact of concurrent thyroid autoimmune disease and thyroid cancer: From the bench to bedside.

The recent incorporation of immune checkpoint inhibitors targeting the PD-1 (programmed cell death receptor 1) and CTLA-4 (cytotoxic T lymphocyte antigen 4) pathways into the therapeutic armamentarium of cancer has increased the need to understand the correlation between the immune system, autoimmunity, and malignant neoplasms. Both autoimmune thyroid diseases and thyroid cancer are common clinical conditions. The molecular pathology of autoimmune thyroid diseases is characterized by the important impact of the PD-1/PD-L1 axis, an important inhibitory pathway involved in the regulation of T-cell responses. Insufficient inhibitory pathways may prone the thyroid tissue to a self-destructive immune response that leads to hypothyroidism. On the other hand, the PD-1/PD-L1 axis and other co-inhibitory pathways are the cornerstones of the immune escape mechanisms in thyroid cancer, which is a mechanism through which the immune response fails to recognize and eradicate thyroid tumor cells. This common mechanism raises the idea that thyroid autoimmunity and thyroid cancer may be opposite sides of the same coin, meaning that both conditions share similar molecular signatures. When associated with thyroid autoimmunity, thyroid cancer may have a less aggressive presentation, even though the molecular explanation of this clinical consequence is unclear. More studies are warranted to elucidate the molecular link between thyroid autoimmune disease and thyroid cancer. The prognostic impact that thyroid autoimmune disease, especially chronic lymphocytic thyroiditis, may exert on thyroid cancer raises important insights that can help physicians to better individualize the management of patients with thyroid cancer.

Heterotopic bone formation with extramedullary haematopoiesis in a thyroid nodule.

The presence of mature bone and bone marrow in the thyroid gland is an exceedingly rare occurrence. Extramedullary haematopoiesis (EMH) and heterotopic bone formation (HBF) should be suspected when cytology of thyroid nodules reveals evidence of megakaryocytes or bone marrow fat, respectively. The cause of these abnormalities has not been fully elucidated, but the role of bone morphogenic factors (BMPs) in their pathogenesis has been suggested. Both EMH and HBF can be seen in both benign and malignant primary thyroid conditions, and although they have not been definitively associated with significant pathology, it is recommended that extension studies be considered in the event of these findings to rule out concomitant haematological conditions.

Construção e validação de um Bundle para avaliação da função tireoidiana em pacientes com cirrose hepatica / Construction and validation of a bundle for evaluation of thyroid function in patients with cirrhosis

ABSTRACT Background: Thyroid dysfunction has been reported in association with several chronic diseases, including advanced liver disease. This disease and its management are often neglected in clinical practice. The bundle discussed here is aimed at proposing systematic assistance according to the best evidence-based practices available. Objective: To construct and validate a bundle to evaluate thyroid function in patients with liver cirrhosis. Methods: The process of constructing and validating the bundle was carried out in the following stages: a) bibliographic survey; b) bundle elaboration; and c) content validation. The bibliographic survey was carried out in an integrative review about evidence related with the thyroid function of patients with liver cirrhosis. The findings from the integrative review were considered as supporting evidence for the elaboration of the bundle. The tool then created used accessible language and was evidence-based, ensuring that information was based on current literature. Results: The bundle was restructured to provide guidance on the management of patients with liver dysfunctions, including: cirrhosis due to general causes, cirrhosis due to hepatitis C, non-alcoholic fatty liver disease, primary biliary cholangitis, and hepatocellular carcinoma. The orientations in the bundle included: exams to be requested to screen for thyroid disorders, and guidance about the treatment of these dysfunctions and their associated complications. We analyzed specialist evaluation of the bundle using the Content Validity Index (CVI). We carried out a binomial test to evaluate consistency and specialist agreement regarding the items in the bundle, considering values >0.61 as a good level. The items in the bundle were considered to be valid (CVI >0.80). The general CVI of the instrument was 0.95 (CI95%: 0.91-0.98). Conclusion: The bundle was considered valid to facilitate medical decision making, aiding physicians to manage, in a practical and effective approach, the thyroid function of patients with liver cirrhosis. This tool should not be used as a replacement for individual, evaluation of the physician providing assistance. We recommend the structured bundle to be added to medical practice, considering its simple application, low cost, and potential to contribute for the management of these patients.

RESUMO Contexto: A disfunção tireoidiana tem sido relatada em associação com várias doenças crônicas, incluindo a doença hepática avançada. O seu reconhecimento e manejo são, muitas vezes, negligenciados na prática clínica. O bundle consiste em um pacote de cuidados, com a finalidade de promover a assistência de forma sistematizada, a partir da melhor prática baseada em evidências. Objetivo: Construir e validar um bundle para avaliação da função tireoidiana em pacientes com cirrose hepática. Métodos: O processo de construção e validação do bundle foi realizado a partir das seguintes etapas: a) levantamento bibliográfico; b) elaboração do bundle; e c) validação do conteúdo. O levantamento bibliográfico foi realizado a partir de revisão integrativa sobre as evidências relacionadas à função tireoidiana em pacientes com cirrose hepática. Os achados encontrados na revisão integrativa foram considerados como subsídios para construção do bundle. A ferramenta construída se baseou em evidências científicas, de forma a garantir informação pautada em literatura atual e com linguagem acessível. Resultados: O bundle foi estruturado com base nas seguintes finalidades: fornecer orientações sobre o manejo de pacientes com disfunção hepática, categorizado por: cirrose por causas gerais, cirrose por vírus da hepatite C, doença hepática gordurosa não alcoólica, colangite biliar primária e carcinoma hepatocelular. As orientações do bundle incluíram: exames a serem solicitados no rastreio dos distúrbios tireoidianos; orientações sobre indicação de tratamento destas disfunções e possíveis complicações associadas. A análise da avaliação do bundle pelos especialistas foi realizada a partir do cálculo do Índice de Validade do Conteúdo (IVC). Foi feito o cálculo do teste binomial para avaliar a concordância e consistência dos especialistas em relação aos itens do bundle, aceitando-se como bom nível o valor >0,61. Os itens do bundle foram considerados validados (IVC >0,80). O instrumento apresentou IVC geral de 0,95 (IC95%: 0,91-0,98). Conclusão: O bundle foi considerado válido para facilitar a tomada de decisão para o médico conduzir, de maneira prática e efetiva, o manejo da função tireoidiana em pacientes com cirrose hepática. Defende-se que a ferramenta não deve ser utilizada em substituição à avaliação individualizada e autonomia do médico assistente. Recomenda-se que a forma estruturada seja incorporada ao atendimento médico tendo em vista a fácil aplicabilidade, o baixo custo e o potencial para contribuir com o manejo desses pacientes.

Vitamin B12 levels in thyroid disorders: A systematic review and meta-analysis.

Background and aims: Numerous studies have found an association between vitamin deficiency and thyroid disorders (TD). The presence of anti-parietal cell antibodies is indicative of reduced ability to absorb vitamin B12. Thus, this study reviewed the existing studies with the objective of assessing differences in the serum levels of vitamin B12 among patients with and without TD, the frequency of vitamin B12 deficiency in patients with TD, and the presence of anti-parietal cell antibodies in patients with TD. Methods: A meta-analysis of random-effects model was conducted to calculate pooled frequencies, mean differences (MD), and their respective 95% confidence intervals (CI). We identified 64 studies that met our inclusion criteria (n = 28597). Results: We found that patients with hypothyroidism had lower vitamin B12 levels than healthy participants (MD: -60.67 pg/mL; 95% CI: -107.31 to -14.03 pg/mL; p = 0.01). No significant differences in vitamin B12 levels were observed between healthy participants and patients with hyperthyroidism (p = 0.78), autoimmune thyroid disease (AITD) (p = 0.22), or subclinical hypothyroidism (SH) (p = 0.79). The frequencies of vitamin B12 deficiency among patients with hypothyroidism, hyperthyroidism, SH, and AITD were 27%, 6%, 27%, and 18%, respectively. Conclusions: Patients with hypothyroidism had lower levels of vitamin B12 than healthy participants. No significant differences were observed between vitamin B12 levels and hyperthyroidism, AITD, or SH. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=324422, identifier (CRD42022324422).

Caracterización de los pacientes operados de afecciones nodulares de tiroides / Characterization of Patients Operated on for Nodular Thyroid Conditions

Introducción: Los nódulos tiroideos son un problema frecuente, deben ser estudiados, sobre todo por la posibilidad de que puedan ser malignos. Objetivo: Caracterizar el comportamiento de los pacientes con afecciones quirúrgicas del tiroides en la provincia de Cienfuegos desde el 1 de enero del 2015 al 31 de diciembre del 2017. Métodos: Se realizó un estudio descriptivo, retrospectivo de 225 pacientes con afecciones quirúrgicas del tiroides en el Servicio de Cirugía del Hospital General Universitario "Dr. Gustavo Aldereguía Lima" en la provincia Cienfuegos durante un trienio. Las variables analizadas fueron: edad, sexo, lóbulo afectado, características físicas y ecográficas de los nódulos, modalidades de biopsias utilizadas y su correlación, técnica quirúrgica, variedad histológica y complicaciones posoperatorias. Se empleó modelo recolector de datos con las variables de interés, presentándose en tablas de frecuencia, números y porciento. Resultados: Predominaron las féminas (87,1 por ciento), el grupo etareo 41 - 50 años (34,7 por ciento) y el lóbulo izquierdo (45,3 por ciento). Prevalecieron los nódulos únicos, móviles, renitentes y ecogénicos. Predominó el carcinoma papilar (59,6 por ciento) y el bocio multinodular (25,3 por ciento). La hemitiroidectomía, el procedimiento quirúrgico más empleado (44,9 por ciento) y la disfonía transitoria (4,9 por ciento) complicación más frecuente. Conclusiones: En la práctica clínica cotidiana de las afecciones del tiroides se evidencia la necesaria interrelación entre endocrinólogos, cirujanos, oncólogos, imaginólogos y patólogos, entre otros, para el abordaje multi e interdisciplinario en el diagnóstico y el tratamiento de estos pacientes(AU)

Introduction: Thyroid nodules are a frequent problem; they should be studied, especially because of the possibility that they may be malignant. Objective: To characterize patients with thyroid surgical conditions in Cienfuegos Province, from January 1, 2015 to December 31, 2017. Methods: A descriptive and retrospective study of 225 patients with thyroid surgical affections was carried out in the surgery service of Dr. Gustavo Aldereguía Lima General University Hospital, in Cienfuegos Province, during a three-year period. The variables analyzed were age, sex, affected lobe, physical and ultrasound nodular characteristics of nodules, used biopsy modalities and their correlation, surgical technique, histological variety and postoperative complications. A data collection model was used with the variables of interest, presented in tables of frequency, numbers and percentages. Results: Females predominated (87.1 percent), together with the age group 41-50 years (34.7 percent) and the left lobe (45.3 percent). Single, mobile, refractory and echogenic nodules prevailed. Papillary carcinoma (59.6 percent) and multinodular goiter (25.3 percent) predominated. Hemithyroidectomy was the most employed surgical procedure (44.9 percent) and transient dysphonia (4.9 percent) was the most frequent complication. Conclusions: The daily clinical practice of thyroid conditions evidences the necessary interrelation between endocrinologists, surgical doctors, oncologists, imaginologists and pathologists, among others, for the multi- and interdisciplinary approach in the diagnosis and managment of these patients(AU)

[Autoimmunity in chronic urticaria. A historical and current perspective]. / Autoinmunidad en urticaria crónica. Perspectiva histórica y actual.

Chronic spontaneous urticaria is a condition that persists for more than six weeks, it occurs in the absence of an identifiable triggering factor and from the pathogenic activation of mast cells and basophils. The possibility of autoimmune etiology in up to 40 % of patients is presented, followed by subclinical infections and psychological factors. Two main mechanisms of the pathogenesis of chronic urticaria have been proposed: the former is the dysregulation of intracellular signaling pathways within mast cells and basophils, which leads to defects in the traffic or function of these cells. The latter is the development of autoantibodies against FcεRIα or IgE, in both mast cells and basophils. Numerous autoimmune diseases such as systemic lupus erythematosus, polymyositis, dermatomyositis, and rheumatoid arthritis have been associated with chronic urticaria; however, autoimmune thyroid disease deserves a special mention. A higher prevalence of antithyroid antibodies has been found, regardless of thyroid function (euthyroidism, hypo and hyperthyroidism) in patients with chronic spontaneous urticaria. Several infections have been linked to chronic urticaria. The best evidence is for Helicobacter pylori infection. Finally, stress is associated with the onset of the disease through the activation of the sympathetic and adrenomedullary system and the hypothalamic-pituitary- adrenal axis. Diagnosis may vary in different regions of the world, but the common feature is the completion of a thorough medical history.

La urticaria crónica espontánea es una afección que persiste durante más de seis semanas y ocurre en ausencia de un factor desencadenante identificable y resulta de la activación patógena de células cebadas y basófilos. Se plantea la posible etiología autoinmune hasta en 40 % de los pacientes, seguida de infecciones subclínicas y factores psicológicos. Se han propuesto dos mecanismos principales de la patogénesis de la urticaria crónica: la desregulación de las vías de señalización intracelular dentro de las células cebadas y basófilos que conduce a defectos en el tráfico o la función de estas células, así como el desarrollo de autoanticuerpos contra FcεRIα o IgE, tanto en células cebadas como en basófilos. Numerosas enfermedades autoinmunes como lupus eritematoso sistémico, polimiositis, dermatomiositis y artritis reumatoide se han asociado a urticaria crónica; sin embargo, la enfermedad tiroidea autoinmune merece una mención especial. Se ha encontrado una mayor prevalencia de anticuerpos antitiroideos, independientemente de la función tiroidea (eutiroidismo, hipo e hipertiroidismo), en pacientes con urticaria crónica espontánea. Varias infecciones se han relacionado a urticaria crónica. Existe la mejor evidencia de infección por Helicobacter pylori. Por último, el estrés está asociado al inicio de la enfermedad mediante la activación del sistema simpático y adrenomedular y el eje hipotálamo hipófisis suprarrenal. El diagnóstico puede variar en las diferentes regiones del mundo, pero el rasgo común es la realización de una historia clínica completa.

Autoimmune Thyroid Disease in Primary Sjögren's Syndrome: Real-life Screening Practice and Clinical Outcomes.

BACKGROUND: Notwithstanding the frequent coexistence of autoimmune thyroid disease (ATD) and primary Sjögren's Syndrome (SS), it is still unknown how often this association is studied along with its clinical impact. OBJECTIVE: This study aimed to describe real-world screening practices for ATD in patients with SS and evaluate clinical outcomes of patients with both diagnoses using validated activity and chronicity indexes. METHODS: It is a retrospective study of 223 patients with SS attending a tertiary referral center. Patients were under rheumatology surveillance and might have attended other clinics, including internal medicine and/or endocrinology. We registered glandular and extraglandular features, serology and scored the activity (ESSDAI) and the accrual damage (SSDDI) indexes. We also identified any thyroid function tests (TFT) performed, anti-thyroid antibodies, images, and histological thyroid examinations. A single endocrinologist reviewed all data. RESULTS: One hundred forty-nine patients had at least one set of TFT. Younger age was associated with a lack of screening (OR 0.98, 95 % CI 0.95-0.99, p=0.01). Sixty-nine patients had thyroid disease, with the most common diagnosis being ATD (n=24). Patients with ATD had a lower prevalence of Ro/SSA and anti-La/SSB antibodies but similar cumulative SS activity and damage scores. CONCLUSION: At least one-third of our patients were not screened for thyroid disease, with these patients being the youngest. Thyroid disorders were found in about 40 % of patients with SS, with ATD being the most common. Having SS/ATD did not confer more disease activity or damage accrual. These results highlight the importance of making treating physicians aware of screening for thyroid disease in this population.

New insights into the taxonomy of autoimmune diseases based on polyautoimmunity.

OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ABSTRACT Objective: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. Materials and methods: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. Results: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. Conclusion: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

Incidence of TPOAb over a 4-year follow-up period: results from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

OBJECTIVE: Although some previous data have suggested a high iodine intake in Brazil, the prevalence of antithyroperoxidase antibodies (TPOAb) in the country is compatible with rates from countries with adequate iodine intake. This observation emphasizes the importance of knowing the incidence of TPOAb in Brazil. METHODS: This prospective analysis included euthyroid participants with negative TPOAb at baseline and a thyroid function assessment at a 4-year follow-up. TPOAb was measured by electrochemiluminescence and considered positive when titers were ≥34 IU/mL. TSH and free T4 (FT4) levels were determined by a third-generation immunoenzymatic assay. The incidence of TPOAb is expressed in percentage per year or as a cumulative incidence within the 4-year follow-up period. RESULTS: Of 8,922 euthyroid participants (mean age 51.1 years; 50.9% women) with a negative TPOAb test at baseline, 130 presented incident TPOAb at the 4-year follow-up, yielding an annual incidence of TPOAb of 0.38%/year (95% confidence interval [95% CI], 0.37-0.39%/year) and a cumulative incidence over 4 years of 1.46% (95% CI, 1.21-1.71%). In men, the annual incidence was 0.32% (95% CI, 0.31-0.33%), and the cumulative incidence over 4 years was 1.23% (95% CI, 0.90-1.56%). In women, the annual incidence was 0.43%/year (95% CI, 0.42-0.44%/year) and the cumulative incidence over 4 years was 1.67% (95% CI, 1.30-2.04%). The only factor associated with incident TPOAb was the occurrence of thyroid diseases at follow-up. No differences in TPOAb incidence were detected across ELSA-Brasil research centers. CONCLUSION: Based on the results of this study, the incidence of TPOAb per year and at a 4-year follow-up period are compatible with those of a country with adequate iodine intake.

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)

Enfermedad nodular tiroidea en personas con diagnóstico de acromegalia / Nodular thyroid disease in people diagnosed with acromegaly

La aparición de nódulos tiroideos en las personas con acromegalia es una consecuencia de la elevación crónica de la hormona de crecimiento y el factor de crecimiento similar a la insulina tipo 1. Su naturaleza varía según la zona geográfica, suficiencia de yodo y antecedentes patológicos familiares, entre otros factores. No se han publicado estudios cubanos sobre la enfermedad nodular tiroidea en estas personas. Objetivos: Describir las características clínicas, bioquímicas y ultrasonográficas de la glándula tiroidea, según la presencia o no de la enfermedad nodular tiroidea. Métodos: Estudio observacional descriptivo, transversal, que incluyó 73 pacientes con acromegalia entre enero de 2003 y diciembre de 2017. Se estudiaron las variables: edad, sexo, color de la piel, antecedentes familiares de la enfermedad nodular tiroidea, niveles de la hormona de crecimiento, hormona estimulante del tiroides, T4 libre, anticuerpos contra la peroxidasa tiroidea y contra la tiroglobulina, volumen tiroideo, patrón ecográfico nodular y estudio citológico. Resultados: La enfermedad nodular tiroidea se presentó en el 75,3 por ciento de los casos, con predominio del bocio multinodular. La edad al diagnóstico fue menor en los pacientes con la enfermedad (43,53 ± 9,67), que en los que no la tenían (49,33 ± 6,96 años) (p = 0,02). La hormona de crecimiento al diagnóstico de acromegalia, resultó menor en los pacientes con este padecimiento (18,73 ± 11,33 µg/L vs. 35,91 ± 21,68 µg/L; (p = 0,00). El volumen tiroideo mostró diferencias significativas entre ambos grupos (14,2 ± 4,5 mL en los casos positivos de la enfermedad nodular tiroidea y 10,5 ± 2,8 mL en los casos negativos; p = 0,002), siendo el nódulo de baja sospecha de malignidad el más frecuente. El resto de las variables resultaron similares entre los pacientes con y sin la enfermedad. La citología se informó como benigna en el 75 por ciento en los nódulos únicos, el 80 por ciento de los bocios nodulares y el 90 por ciento de los bocios multinodulares (p = 0,51). Conclusiones: La enfermedad nodular tiroidea fue frecuente en los casos de acromegalia, y se asoció a la menor edad y los niveles inferiores de la hormona de crecimiento al diagnóstico. El bocio multinodular constituyó la forma clínica más frecuente y los parámetros hormonales y de autoinmunidad no se asociaron al tipo de la enfermedad nodular tiroidea(AU)

The appearance of thyroid nodules in people with acromegaly is a consequence of chronic elevation of growth hormone (GH) and insulin-like growth factor type 1 (IGF-1). Its nature varies according to the geographical area, the iodine sufficiency and family pathological history, among other factors. No Cuban studies on thyroid nodular disease (TND) in these people have been published. Objectives: Describe some clinical characteristics, as well as biochemical and ultrasonographic ones related to the thyroid gland, according to the presence or not of TND, and to identify the possible association of clinical, biochemical, ultrasonographic and cytological factors with the different types of TND in patients with acromegaly. Methods: A descriptive, cross-sectional observational study that included 73 patients with acromegaly between January 2003 and December 2017. The following variables were studied: age, sex, skin color, family history of TND, GH levels, thyroid stimulating hormone, free T4, antibodies against thyroid peroxidase and thyroglobulin, thyroid volume, nodular ultrasound pattern and cytological study. Results: TND occurred in 75.3 percent of cases, with a predominance of multinodular goiter. The age at diagnosis time was lower in patients with TND (43.53 ± 9.67) than in those who did not have it (49.33 ± 6.96 years) (p=0.02). GH at diagnosis time of acromegaly was lower in patients with TND (18.73±11.33µg/L vs 35.91±21.68µg/L; (p=0.00). The thyroid volume showed significant differences between both groups (14.2±4.5mL in positive cases of TND and 10.5±2.8mL in negative cases; p=0.002), being the most frequent the nodule with low suspicion of malignancy. The rest of the variables were similar between patients with and without TNDs. Cytology was reported as benign in 75 percent in single nodules, 80 percent of nodular goiters and 90 percent of multinodular goiters (p=0.51). Conclusions: TND was frequent in cases of acromegaly, and was associated with lower age and lower GH levels at diagnosis time. Multinodular goiter was the most frequent clinical form and hormonal and autoimmunity parameters were not associated with the type of TND(AU)

Family history of thyroid disease and risk of congenital hypothyroidism in neonates with Down síndrome.

INTRODUCTION: Family history of thyroid disease (FHTD) constitutes a possible risk factor for congenital hypothyroidism (CH) in the general population; however, FHTD possible relationship with CH in subjects with Down syndrome (DS) has not yet been explored. OBJECTIVE: To determine whether FHTD is associated with an increased incidence of CH in neonates with DS. METHOD: Hospital-based case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and positive FHTD (cases) were compared with those of 183 newborns with DS without FHTD (control group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. RESULTS: Nine newborns with DS in our sample had CH (4.1 %). In the multivariate analysis, FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). CONCLUSIONS: Newborns with DS and FHTD have an eight-fold higher risk for CH, particularly when the index case is male. FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

INTRODUCCIÓN: La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada. OBJETIVO: Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD. MÉTODO: Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %). RESULTADOS: Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8). CONCLUSIONES: La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Historia familiar de enfermedad tiroidea y riesgo de hipotiroidismo congénito en neonatos con síndrome de Down / Family history of thyroid disease and risk of congenital hypothyroidism in neonates with Down syndrome

Resumen Introducción: La historia familiar de enfermedad tiroidea (HFET) como factor de riesgo para hipotiroidismo congénito (HC), en síndrome de Down (SD) aún no ha sido explorada. Objetivo: Determinar si la HFET está asociada a mayor riesgo de HC en neonatos con SD. Método: Estudio de casos y controles en 220 neonatos con SD. Se compararon las pruebas de función tiroidea (PFT) de 37 con SD e HFET (casos), frente a las PFT de 183 recién nacidos con SD sin HFET (grupo de referencia). Se realizó análisis de regresión logística multivariante y se calculó la razón de momios (RM) y sus respectivos intervalos de confianza del 95 % (IC 95 %). Resultados: Nueve casos HC (4.1 %). El HC mostró asociación con la HFET (RMa = 8.3, IC 95 %: 2.0-34.3), particularmente en los varones (RMa = 9.0, IC 95 %: 1.6-49.6). La ausencia de HFET tuvo una RM de protección para HC (RMa = 0.4, IC 95 %: 0.1-0.8). Conclusiones: La HFET puede es una estrategia fácil y accesible para identificar pacientes con SD con mayor riesgo de HC.

Abstract Introduction: Family history of thyroid disease (FHTD) as risk factor for congenital hypothyroidism (CH) in patients with Down syndrome (DS) has not yet been explored. Objective: To determine whether FHTD is associated with an increased risk for CH in DS. Method: Case-control study in 220 neonates with DS. Thyroid function tests of 37 infants with DS and FHTD (cases) were compared with those of 183 DS newborns without FHTD (reference group). Data were analyzed using multivariate logistic regression analysis and adjusted odds ratios (aORs) with their respective 95 % confidence intervals (CI) were calculated. Results: Nine newborns with DS in our sample had CH (4.1 %). FHTD showed an association with CH in neonates with DS (aOR = 8.3, 95 % CI: 2.0-34.3), particularly in males (aOR = 9.0, 95 % CI: 1.6-49.6). In contrast, newborns with DS without FHTD were less likely to suffer from CH (aOR = 0.4, 95 % CI: 0.1-0.8). Conclusions: FHTD detailed evaluation can be an easy and accessible strategy to identify those newborns with DS at higher risk for CH.

Graves' disease inducing a massive cardiac tamponade.

A 23-year-old woman was diagnosed with Graves' disease 5 months ago with decompensated thyroid function, for which she is taking thiamazole and propranolol. She developed progressive respiratory dyspnoea [New York Heart Association (NYHA) class III] and frequent palpitations. On emergency admission, the patient was tachypnoeic, hypotensive (77/54 mm Hg) and tachycardic (120 beats per minute), with an oxygen saturation of 94%. She also presented with cold, swollen and shaky extremities, with extended capillary filling time, and a significant reduction in heart sounds. Echocardiogram showed massive pericardial effusion compatible with cardiac tamponade. Pericardiocentesis was performed, with a drainage of 1420 mL serosanguinolent fluid, with prompt haemodynamic recovery. Analysis of the pericardial fluid showed exudates. A diagnosis of pericardial effusion secondary to Graves' disease was determined and corticotherapy, lithium carbonate, cholestyramine and phenobarbital were prescribed. An oral iodine-131 was performed and the patient showed reasonable control of the clinical manifestations of hyperthyroidism. After 3 months, the patient showed no symptoms of hyperthyroidism and a new echocardiogram revealed a significant reduction in pericardial effusion.