Sonographic characteristics and clinical characteristics combined with nomogram for predicting the aggressiveness of papillary thyroid carcinoma coexisted with Hashimoto's thyroiditis.

OBJECTIVE: The association between Papillary Thyroid Carcinoma (PTC) and coexistent Hashimoto's Thyroiditis (HT) was controversial. The purpose of this study was to evaluate the presence of HT exerts any influence on the aggressiveness of PTC, and to establish a nomogram for predicting the possibility of aggressiveness in PTC. METHODS: 373 consecutive PTC patients with/without coexistent HT from January 2017 to December 2020 were retrospective reviewed. Patients' clinicopathologic and sonographic characteristics were collected for univariate and multivariate analyses. A nomogram was established based on the risk factors for aggressiveness in PTC. RESULTS: Male (p = 0.001), tumor size >1.0 cm (p = 0.046) and lymph node metastasis (p = 0.018) were negatively associated with PTC coexisted with HT, while it was significantly positively associated with the frequence of multifocality (p = 0.010). Univariate and multivariate analyses suggested that age ≥55 years (p = 0.000), male (p = 0.027), HT (p = 0.017), tumor size >1.0 cm (p = 0.015), multifocality (p = 0.041), distance to capsular ≤0 cm (p = 0.050) and blood flow (Grade I: p = 0.044) were independent risk factors for predicting the aggressiveness in PTC. A nomogram according to these predictors was further developed and validated. The receiver operating characteristic curve (AUC = 0.734 and 0.809 for training and validation cohorts, respectively) and decision curve analyses indicated that the nomogram model was clinically useful. The calibration curve revealed that the nomogram exhibited an excellent consistency. CONCLUSIONS: In this study, the coexistent HT might play a protective role in preventing the proliferation of PTC. Dispensable aggressive treatment may be reduced in PTC by pre-operative identification of sonographic and clinical characteristics and incorporating with the predicted nomogram model.

Association between Benign Paroxysmal Positional Vertigo and Thyroid Diseases: Systematic Review and Meta-Analysis.

Introduction Benign paroxysmal positional vertigo (BPPV) is the peripheral vestibular dysfunction that most affects people worldwide, but its etiopathogenesis is still not fully understood. Considering the etiological diversity, some studies highlight the association between BPPV and thyroid diseases. Objective To investigate the association between thyroid diseases and BPPV. Data Synthesis Systematic review and meta-analysis of epidemiological studies searched in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases. Studies that were fully available and investigated the association between BPPV and thyroid diseases were selected. The articles that composed the meta-analysis were analyzed using the dichotomous model, the Mantel-Haenszel statistical test, odds ratio (OR), and a 95% confidence interval (CI). Of the 67 articles retrieved from the databases, 7 met the eligibility criteria of the systematic review, and 4 had data necessary to perform the meta-analysis. Qualitative analysis revealed that the studies were conducted in the European and Asian continents. The predominant methodological design was the case-control type, and thyroid dysfunctions, hypothyroidism, and Hashimoto thyroiditis occurred more frequently. The meta-analysis showed no association between hypothyroidism and BPPV; however, there was a statistically significant relationship between Hashimoto thyroiditis and BPPV. Conclusion The meta-analysis results suggest a possible association between BPPV and Hashimoto thyroiditis. Nevertheless, we emphasize the need for further studies to elucidate the evidence obtained.

Characterization of serum vitamin D levels in pediatric patients with chronic lymphocytic thyroiditis.

BACKGROUND: Chronic lymphocytic thyroiditis or Hashimoto's thyroiditis is the most frequent cause of acquired hypothyroidism in children. An association between low levels of 25-hydroxyvitamin D (25OH vitamin D) and the development of the disease have been detected. The aim of this study was to describe 25OH vitamin D levels in patients aged 5 to 18 years with a diagnosis of Hashimoto's thyroiditis in three pediatric endocrinology outpatient centers in Medellín, Colombia. METHODS: We conducted a cross-sectional observational study with retrospective data collection. We evaluated the sociodemographic characteristics, diagnoses, presence of comorbidities, and frequency of vitamin D deficiency. RESULTS: Sixty patients were included. The 25OH vitamin D levels were sufficient in 65% of the cases according to the Institute of Medicine (IOM) criteria and in 10% of the cases according to the Endocrine Society criteria. Serum calcium and phosphorus values were normal in 53% and 45% of the patients, respectively. All patients had normal magnesium and parathyroid hormone levels. No differences were found in the exploratory analysis when comparing 25OH vitamin D levels, thyroid antibody levels, and thyroid volume. CONCLUSIONS: In this chronic lymphocytic thyroiditis population, we did not find an increased prevalence of vitamin D deficiency according to IOM or the Endocrine Society criteria compared with previous data from the general population. No statistically significant differences were found in the exploratory analysis.

INTRODUCCIÓN: La tiroiditis linfocítica crónica o tiroiditis de Hashimoto es la causa más frecuente de hipotiroidismo adquirido en la edad pediátrica. Se ha detectado una asociación entre concentraciones bajas de 25-hidroxivitamina D (25OH vitamina D) y el desarrollo de la enfermedad. El objetivo de este trabajo fue describir las concentraciones de 25OH vitamina D en pacientes de 5 a 18 años con diagnóstico de tiroiditis linfocítica crónica en tres centros de consulta externa de endocrinología pediátrica enMedellín,Colombia. MÉTODOS: Se llevó a cabo un estudio observacional de corte transversal con recolección retrospectiva de la información. Se evaluaron características sociodemográficas, particularidades del diagnóstico, presencia de comorbilidad y frecuencia de deficiencia de vitamina D. RESULTADOS: Se incluyeron 60 pacientes. La concentración de 25OH vitamina D fue suficiente en el 65% de los casos según los criterios de Institute of Medicine (IOM) y en el 10% de los casos según los criterios de la Endocrine Society. Los valores de calcio y fósforo sérico fueron normales en el 53% y el 45% de los pacientes, respectivamente. Todos los pacientes presentaron concentraciones normales de magnesio y paratohormona. No se encontraron diferencias en el análisis exploratorio al comparar la concentración de 25OH vitamina D, de anticuerpos tiroideos y el volumen tiroideo. CONCLUSIONES: En esta población con tiroiditis linfocítica crónica no se encontró una mayor prevalencia de deficiencia de 25OH vitamina D según los criterios del IOM y de la Endocrine Society en comparación con datos previos de la población general. En el análisis exploratorio no se encontraron diferencias estadísticamente significativas.

Role of papillary thyroid carcinoma patients with Hashimoto thyroiditis: evaluation of oxidative stress and inflammatory markers.

PURPOSE: Papillary thyroid carcinoma (PTC) is the most frequent subtype of thyroid cancer; Hashimoto's thyroiditis (HT), autoimmune disease, commonly affects the thyroid gland; there is possibly a correlation between both, but the exact mechanisms that involve this relationship are still under debate. Since oxidative stress (OS) and the inflammatory environment participate in the development of several types of cancer, the objective of the present study was to establish the microenvironment and systemic participation of OS and inflammatory markers in patients with PTC and HT. METHODS: Blood and tissue samples were collected from 115 patients: BENIGN (n = 63); PTC (n = 27); HT (n = 15) and PTC + HT (n = 10), and sixty-three were samples from healthy individuals (control group). RESULTS: Superoxide dismutase, Catalase, reduced Glutathione, markers of lipid peroxidation and inflammation were evaluated in blood. Immunohistochemistry was performed on 3-nitrotyrosine, 4-hydroxynonenal, Ki-67 and VEGF. The results indicate that antioxidant enzymes were more active in groups with thyroid disorders compared to control, while the concentration of Reduced glutathione was reduced in BENIGN and PTC groups. When PTC and PTC + HT groups were analyzed, no significant differences were found in relation to the antioxidant defense and inflammatory markers. The ability to contain the induced lipid peroxidation was lower and a high level of malondialdehyde was observed in the PTC group. All immunohistochemical markers had higher scores in the PTC group compared to PTC + HT. CONCLUSION: There was a more pronounced presence of OS and a greater activity of cell proliferation and angiogenesis markers in PTC than in PTC + HT group.

Caracterización de la concentración sérica de vitamina D en pacientes pediátricos con tiroiditis linfocítica crónica / Characterization of serum vitamin D levels in pediatric patients with chronic lymphocytic thyroiditis

Resumen Introducción: La tiroiditis linfocítica crónica o tiroiditis de Hashimoto es la causa más frecuente de hipotiroidismo adquirido en la edad pediátrica. Se ha detectado una asociación entre concentraciones bajas de 25-hidroxivitamina D (25OH vitamina D) y el desarrollo de la enfermedad. El objetivo de este trabajo fue describir las concentraciones de 25OH vitamina D en pacientes de 5 a 18 años con diagnóstico de tiroiditis linfocítica crónica en tres centros de consulta externa de endocrinología pediátrica enMedellín,Colombia. Métodos: Se llevó a cabo un estudio observacional de corte transversal con recolección retrospectiva de la información. Se evaluaron características sociodemográficas, particularidades del diagnóstico, presencia de comorbilidad y frecuencia de deficiencia de vitamina D. Resultados: Se incluyeron 60 pacientes. La concentración de 25OH vitamina D fue suficiente en el 65% de los casos según los criterios de Institute of Medicine (IOM) y en el 10% de los casos según los criterios de la Endocrine Society. Los valores de calcio y fósforo sérico fueron normales en el 53% y el 45% de los pacientes, respectivamente. Todos los pacientes presentaron concentraciones normales de magnesio y paratohormona. No se encontraron diferencias en el análisis exploratorio al comparar la concentración de 25OH vitamina D, de anticuerpos tiroideos y el volumen tiroideo. Conclusiones: En esta población con tiroiditis linfocítica crónica no se encontró una mayor prevalencia de deficiencia de 25OH vitamina D según los criterios del IOM y de la Endocrine Society en comparación con datos previos de la población general. En el análisis exploratorio no se encontraron diferencias estadísticamente significativas.

Abstract Background: Chronic lymphocytic thyroiditis or Hashimoto's thyroiditis is the most frequent cause of acquired hypothyroidism in children. An association between low levels of 25-hydroxyvitamin D (25OH vitamin D) and the development of the disease have been detected. The aim of this study was to describe 25OH vitamin D levels in patients aged 5 to 18 years with a diagnosis of Hashimoto's thyroiditis in three pediatric endocrinology outpatient centers in Medellín, Colombia. Methods: We conducted a cross-sectional observational study with retrospective data collection. We evaluated the sociodemographic characteristics, diagnoses, presence of comorbidities, and frequency of vitamin D deficiency. Results: Sixty patients were included. The 25OH vitamin D levels were sufficient in 65% of the cases according to the Institute of Medicine (IOM) criteria and in 10% of the cases according to the Endocrine Society criteria. Serum calcium and phosphorus values were normal in 53% and 45% of the patients, respectively. All patients had normal magnesium and parathyroid hormone levels. No differences were found in the exploratory analysis when comparing 25OH vitamin D levels, thyroid antibody levels, and thyroid volume. Conclusions: In this chronic lymphocytic thyroiditis population, we did not find an increased prevalence of vitamin D deficiency according to IOM or the Endocrine Society criteria compared with previous data from the general population. No statistically significant differences were found in the exploratory analysis.

Detection of Alterations in the Gut Microbiota and Intestinal Permeability in Patients With Hashimoto Thyroiditis.

Hashimoto thyroiditis (HT) is the most common autoimmune disease worldwide, characterized by chronic inflammation and circulating autoantibodies against thyroid peroxidase and thyroglobulin. Patients require hormone replacement with oral levothyroxine, and if untreated, they can develop serious adverse health effects and ultimately death. There is a lot of evidence that the intestinal dysbiosis, bacterial overgrowth, and increased intestinal permeability favor the HT development, and a thyroid-gut axis has been proposed, which seems to impact our entire metabolism. Here, we evaluated alterations in the gut microbiota in Brazilian patients with HT and correlated this data with dietary habits, clinical data, and systemic cytokines and zonulin concentrations. Stool samples from 40 patients with HT and 53 controls were analyzed using real-time PCR, the serum cytokine levels were evaluated by flow cytometry, zonulin concentrations by ELISA, and the dietary habits were recorded by a food frequency questionnaire. We observed a significant increase (p < 0.05) in the Bacteroides species and a decrease in Bifidobacterium in samples of patients with HT. In addition, Lactobacillus species were higher in patients without thyroid hormone replacement, compared with those who use oral levothyroxine. Regarding dietary habits, we demonstrated that there are significant differences in the consumption of vegetables, fruits, animal-derived proteins, dairy products, saturated fats, and carbohydrates between patients and control group, and an inverse correlation between animal-derived protein and Bacteroides genus was detected. The microbiota modulation by diet directly influences the inflammatory profile due to the generated microbiota metabolites and their direct or indirect action on immune cells in the gut mucosa. Although there are no differences in systemic cytokines in our patients with HT, we detected increased zonulin concentrations, suggesting a leaky gut in patients with HT. These findings could help understand the development and progression of HT, while further investigations to clarify the underlying mechanisms of the diet-microbiota-immune system axis are still needed.

Thyroid cancer and thyroid autoimmune disease: A review of molecular aspects and clinical outcomes.

Thyroid cancer (TC) is the most prevalent malignant neoplasm that affects the endocrine system. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is the most common autoimmune thyroid disease (AITD) that, together with Graves' disease (GD), represent the main autoimmune diseases that affect the thyroid gland. Some studies suggest a greater risk of AITD and the development of TC, while others, investigate its relationship with TC progression and patient prognosis. In this review, we have analyzed published data on the molecular aspects related to the association between AITD and TC, addressing their influence on TC progression, diagnosis, and prognosis of the patients. MEDLINE database (PubMed) platform was used as a search engine and the original articles related to the topic were selected using the keywords combination "thyroid cancer and Hashimoto thyroiditis" or "thyroid carcinoma and thyroid autoimmune disease". After the selection, we categorized the main findings of the papers into four topics: antitumor immunity, tumor progression, diagnosis, and prognosis. Although most of the studies have pointed out the presence of AITD as a factor that increases the risk of TC, few molecular mechanisms to support this conclusion have been described. Additionally, little information is available to explain, pathophysiologically, the effects of autoimmunity in TC diagnosis, progression, and prognosis.

Prevalence of latent and overt polyautoimmunity in autoimmune thyroid disease: A systematic review and meta-analysis.

BACKGROUND: Thyroid autoimmunity is the most frequent condition involved in polyautoimmunity (PolyA). However, the frequency of latent and overt PolyA in patients with autoimmune thyroid disease (AITD) as the index condition is unknown. Therefore, the purpose of this study was to determine the prevalence of these types of PolyA in patients with AITD as the index condition. METHODS: This study adhered to the relevant sections of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline. Searches through MEDLINE, Embase and LILACS were done to find articles in Spanish and English. Relevant vocabulary terms and key terms related to AITD and other autoimmune diseases were used. Two investigators independently screened the eligible studies, extracted data and assessed the quality and risk of bias. Fixed and random effect models were used accordingly. Cluster analysis was used to determine similarities among diseases in the articles included (based on Jaccard index). RESULTS: A total of 56 articles fulfilled the inclusion criteria. Of these, 25 were case-controls, 17 were cohorts, and 14 were cross-sectional studies. These studies included a total of 47 509 patients. Female was the predominant gender and included 38 950 patients (81.23%, 95% CI: 80.85-81.60). Graves' disease (GD) was the most common type of thyroid autoimmunity (69.16%, 95% CI: 68.23-70.07). Globally, overt PolyA was found in 13.46% of the patients with AITD. This type of PolyA was represented mainly by type 1 diabetes and autoimmune gastritis. Latent PolyA was presented in 17.45% of the patients, and anti-proinsulin, anti-parietal cells and dsDNA antibodies were the most common. HT had the highest frequency of overt PolyA in Europe (15.60%, 95% CI: 14.72-16.53), whereas latent PolyA was most common in patients with GD in Asia (21.03%, 95% CI: 17.76-24.71). Overt and latent PolyA were associated with gastrointestinal and endocrinological ADs in most of cases and clustered with rheumatological, dermatological and neurological ADs. CONCLUSIONS: Latent and overt PolyA are common in patients with AITD. These results provide insightful information for early diagnosis and management of concurrent ADs in patients with AITD. Aggregation of ADs in different clusters may help to define different phenotypes associated with thyroid autoimmunity that are critically relevant in clinical settings.

Enfermedad celiaca silente en pacientes adultos con enfermedades tiroideas / Silent celiac disease in adult patients with autoimmune thyroid diseases

Introducción: la enfermedad celiaca puede estar asociada en forma silente a las tiroiditis autoinmunes. Objetivo: determinar la presencia de enfermedad celiaca silente en pacientes con tiroiditis autoinmunes. Metodología: estudio observacional, prospectivo, multicéntrico realizado en pacientes adultos con tiroiditis de Hashimoto y enfermedad de Graves de tres centros hospitalarios de Paraguay en años 2018-2019. Se determinó la presencia anticuerpos IgA antitransglutaminasa e IgA sérica en aquellos que aceptaron participar del estudio. Se midieron además variables demográficas y clínicas. El estudio fue aprobado por el Comité de Ética de la Universidad Nacional de Itapúa.Resultados: se contactaron 87 pacientes, pero la muestra final estuvo constituida por 22 sujetos. La edad media fue 50 años, con predominio del sexo femenino (77%). Se detectaron anticuerpos para enfermedad celiaca en 3 casos (13%) y todos fueron confirmados con biopsia duodenal. Conclusiones: la frecuencia de enfermedad celiaca silente en pacientes con tiroiditis de Hashimoto y enfermedad de Graves fue 13%.

Introduction: celiac disease may be asymptomatically associated with autoimmune thyroiditis.Objective: to determine the presence of silent celiac disease in patients with autoimmune thyroiditis.Methodology: we carried out a observational, prospective, multicenter study in adult patients with Hashimoto's thyroiditis and Graves' disease from three hospitals in Paraguay in the years 2018-2019. The presence of IgA antitransglutaminase and serum IgA antibodies was determined in those who agreed to participate in the study. Demographic and clinical variables were also measured. The study was approved by the Ethics Committee of the National University of Itapúa. Results: 87 patients were contacted, but the final sample was established with 22 subjects. The mean age was 50 years, with a predominance of the female (77%). Antibodies to celiac disease were detected in 3 cases (13%) and all were confirmed with a duodenal biopsy. Conclusions: the frequency of silent celiac disease in patients with Hashimoto's thyroiditis and Graves' disease was 13%.

Chronic urticaria and thyroid pathology.

Urticaria is defined as the sudden appearance of erythematous, itchy wheals of variable size, with or without angioedema (AE) (swelling of the deeper layers of the skin). Its classification depends on time course of symptoms and the presence of eliciting factors. When it lasts less than 6 weeks it is classified as acute urticaria (AU), and if the symptoms persist for more than 6 weeks, it is classified as chronic urticaria (CU). Current International Guidelines also classify CU as chronic spontaneous urticaria (CSU) and inducible urticarial, according to the absence or presence of environmental triggering factors. CSU is defined as urticaria and/or angioedema in which there is no evidence of a specific eliciting factor. CSU is associated with autoimmunity in 30-45% of the cases, sharing some immunological mechanisms with other autoimmune diseases, and is associated with autoimmune thyroid disease (ATD) in about 4.3%-57.4% patients. Several studies suggest that adequate therapy with anti-thyroid drugs or levothyroxine in early stages of ATD and CSU, may help to remit the latter; but there is still a lack of double-blind, placebo-controlled studies that support this hypothesis in patients without abnormal thyroid hormone levels. The objective of this review is to describe the pathophysiology of chronic spontaneous urticaria and its association with autoimmune thyroid disease.

Variables predictivas de talla baja adulta en pacientes con hipotiroidismo adquirido grave de origen autoinmune / Predictive outcome measures of adult short stature in patients with severe acquired autoimmune hypothyroidism

El hipotiroidismo por tiroiditis de Hashimoto es la causa más frecuente de disfunción tiroidea en niños.Nuestro objetivo fue analizar el impacto en la talla final según la talla y el estadio puberal al momento del diagnóstico en menores de 18 años con hipotiroidismo grave de origen autoinmune. De los 79 pacientes, el 78,5 % fueron mujeres. Los que presentaron bocio (el 56 %) mostraron mejor talla en el diagnóstico que los que no lo tenían (puntaje de desvío estándar de media de talla: 0,2 vs. -2,42; p < 0,0001). Cinco niñas (el 6,3 %) presentaron pubertad precoz. De los pacientes con talla final (n: 33), dentro de los que presentaron talla baja al momento del diagnóstico, los púberes tuvieron una talla final significativamente menor que los prepúberes (puntaje de desvío estándar media: -2,82 vs. -1,52; p = 0,0311).El diagnóstico tardío de hipotiroidismo grave en pediatría tiene un impacto negativo en la talla final, especialmente, en los pacientes puberales al momento del diagnóstico.

Hypothyroidism caused by Hashimoto's thyroiditis is the most common reason for thyroid dysfunction in children. Our objective was to analyze its impact on final stature in relation to height and pubertal stage at the time of diagnosis in children younger than 18 years with severe autoimmune hypothyroidism. Out of 79 patients, 78.5 % were girls. Those with goiter (56 %) had a better height at diagnosis than those without goiter (mean standard deviation score for height: 0.2 versus −2.42; p < 0.0001). Five girls (6.3 %) had precocious puberty. When considering the final stature of patients (n: 33), among those with short stature at the time of diagnosis, pubertal children had a significantly shorter final stature than prepubertal children (mean standard deviation score for height: −2.82 versus −1.52; p = 0.0311). The late diagnosis of severe hypothyroidism in pediatrics has a negative impact on final stature, especially in those who were pubertal patients at the time of diagnosis

Predictive outcome measures of adult short stature in patients with severe acquired autoimmune hypothyroidism. / Variables predictivas de talla baja adulta en pacientes con hipotiroidismo adquirido grave de origen autoinmune.

Hypothyroidism caused by Hashimoto's thyroiditis is the most common reason for thyroid dysfunction in children. Our objective was to analyze its impact on final stature in relation to height and pubertal stage at the time of diagnosis in children younger than 18 years with severe autoimmune hypothyroidism. Out of 79 patients, 78.5 % were girls. Those with goiter (56 %) had a better height at diagnosis than those without goiter (mean standard deviation score for height: 0.2 versus -2.42; p < 0.0001). Five girls (6.3 %) had precocious puberty. When considering the final stature of patients (n: 33), among those with short stature at the time of diagnosis, pubertal children had a significantly shorter final stature than prepubertal children (mean standard deviation score for height: -2.82 versus -1.52; p = 0.0311). The late diagnosis of severe hypothyroidism in pediatrics has a negative impact on final stature, especially in those who were pubertal patients at the time of diagnosis.

El hipotiroidismo por tiroiditis de Hashimoto es la causa más frecuente de disfunción tiroidea en niños. Nuestro objetivo fue analizar el impacto en la talla final según la talla y el estadio puberal al momento del diagnóstico en menores de 18 años con hipotiroidismo grave de origen autoinmune. De los 79 pacientes, el 78,5 % fueron mujeres. Los que presentaron bocio (el 56 %) mostraron mejor talla en el diagnóstico que los que no lo tenían (puntaje de desvío estándar de media de talla: 0,2 vs. -2,42; p < 0,0001). Cinco niñas (el 6,3 %) presentaron pubertad precoz. De los pacientes con talla final (n: 33), dentro de los que presentaron talla baja al momento del diagnóstico, los púberes tuvieron una talla final significativamente menor que los prepúberes (puntaje de desvío estándar media: -2,82 vs. -1,52; p = 0,0311). El diagnóstico tardío de hipotiroidismo grave en pediatría tiene un impacto negativo en la talla final, especialmente, en los pacientes puberales al momento del diagnóstico.

Artritis reumatoide y enfermedad tiroidea autoinmunitaria / Rheumatoid arthritis and autoimmune thyroid disease

Resumen: ANTECEDENTES: Las enfermedades autoinmunitarias sistémicas, como la artritis reumatoide, pueden coexistir con enfermedades autoinmunitarias órgano-específicas. OBJETIVO: Describir una serie de casos de artritis reumatoide y enfermedad tiroidea autoinmunitaria (tiroiditis de Hashimoto, enfermedad de Graves). MATERIAL Y MÉTODO: Estudio retrospectivo en el que de enero a diciembre de 2017 se incluyeron pacientes con artritis reumatoide y enfermedad tiroidea autoinmunitaria. La artritis reumatoide se evaluó de acuerdo con los criterios diagnósticos de 2010 (ACR/EULAR). RESULTADOS: Se identificaron 26 pacientes con artritis reumatoide y enfermedad tiroidea autoinmunitaria. En 14 casos la manifestación inicial fue artritis reumatoide y en 12 la manifestación inicial fue enfermedad de Graves. Todos los pacientes (mujeres, mediana de edad: 46 años) acudieron con un cuadro clínico de poliartritis simétrica de las manos, los carpos y las rodillas. En total, la serología fue positiva para factor reumatoide (21), anticuerpo contra péptidos cíclicos citrulinados (11), anti-peroxidasa (21) y TSH elevada (15). En 5 casos, la enfermedad de Graves precedió a la artritis reumatoide. En cuatro casos se encontró anormalidad palpable de la glándula tiroidea. El tratamiento consistió en hormonas tiroideas sintéticas, yodo radioactivo, cirugía de tiroides y fármacos modificadores de artritis reumatoide. CONCLUSIÓN: En esta serie de casos, la causa más común de hipotiroidismo fue tiroiditis de Hashimoto que precedió o siguió el diagnóstico de artritis reumatoide.

Abstract: BACKGROUND: Systemic autoimmune diseases including rheumatoid arthritis can coexist with organ-specific autoimmune diseases. OBJECTIVE: To report a case series of rheumatoid arthritis patients who developed autoimmune thyroid disease (Hashimoto's thyroiditis, Graves' disease). MATERIAL AND METHOD: A retrospective study was done from January to December 2017 including patients with rheumatoid arthritis and autoimmune thyroid disease. Rheumatoid arthritis was assessed according to the diagnostic criteria of 2010 (ACR/ EULAR). RESULTS: There were identified 26 cases with rheumatoid arthritis and an autoimmune thyroid disease. In 14 cases rheumatoid arthritis was the initial manifestation and in 12 the initial manifestation was hypothyroidism or Graves' disease (GD). All the patients (females, median age: 46) had symmetrical polyarthritis of hands, wrists and knees. In total, serology was positive for rheumatoid factor (21), anti-cyclic citrullinated peptide antibody (11), anti-thyroid peroxidase antibody (21) and elevated levels of TSH in 15 cases. In 5 cases, hyperthyroidism was the initial feature. Palpable abnormality of the thyroid gland was present in 5 cases. The treatment consisted on synthetic thyroid hormones, radioactive iodine therapy, thyroid surgery and disease modifying drugs. CONCLUSION: In this case series, the most common cause of hypothyroidism was Hashimoto's thyroiditis preceding or following rheumatoid arthritis.

Association between BRAF (V600E) mutation and clinicopathological features of papillary thyroid carcinoma: a Brazilian single-centre case series

ABSTRACT Objectives: We aimed to investigate the prevalence of the BRAF (V600E) mutation in consecutive cases of papillary thyroid carcinoma (PTC) in patients diagnosed and treated at the Hospital Sao Rafael (Salvador, BA, Brazil) and evaluate its association with clinical and pathological characteristics of PTC. Subjects and methods: We retrospectively enrolled in the study a total of 43 consecutive PTC patients who underwent total thyroidectomy. We performed DNA extraction from formalin-fixed paraffin-embedded (FFPE) tumour tissue samples. Polymerase chain reaction (PCR) and direct sequencing were used to determine BRAF (V600E) mutation status. Univariate and multivariate logistic regression analyses were employed to identify independent associations. Results: The prevalence of BRAF (V600E) mutation was 65.1% (28/43). A high frequency of older patients (p value: 0.004) was observed among the BRAF-mutated PTC group and, in contrast, a low frequency of concurrent Hashimoto's thyroiditis (HT) (p value: 0.011) was noted. Multivariate analysis confirmed that older age (OR: 1.15; 95% CI: 1.00 - 1.33; p value: 0.047) and HT (OR: 0.05; 95% CI: 0.006-0.40; p value: 0.005) were independent factors associated with BRAF (V600E) mutation. Conclusion: We found a high prevalence of BRAF (V600E) mutation in PTC cases. Older age and no concurrent HT were independently associated with BRAF (V600E) mutation.

Sjögren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.

The coexistence of Sjögren's syndrome (SS) and autoimmune thyroid disease (AITD) has been documented. However, there is no consensus whether this coexistence should be considered as the same nosological condition or as polyautoimmunity. Thus, in this monocentric retrospective study, patients with SS alone (i.e., primary) were compared with patients with SS and AITD. In addition, a discussion of previous studies including those about genetic and environmental factors influencing the development of both conditions is presented. In our series, all patients with AITD had Hashimoto's thyroiditis (HT). No significant differences in age, gender, age of disease onset, and disease duration were found between the two groups. Lymphadenopathy and urticaria were more frequently registered in patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients were more likely to report a positive history of smoking (p = 0.03). The clinical expression of SS varies slightly when HT coexists. Although both entities share common physiopathological mechanisms as part of the autoimmune tautology, they are nosologically different and their coexistence should be interpreted as polyautoimmunity. Further studies based on polyautoimmunity would allow establishing a new taxonomy of autoimmune diseases.

Conversion to Graves disease from Hashimoto thyroiditis: a study of 24 patients

ABSTRACT Objective: The conversion of Hashimoto's thyroiditis (HT) to hyperthyroidism due to thyrotropin receptor antibodies is intriguing and considered rare. The contribution of TSH receptor blocking antibodies (TRAb), which may be stimulators (TSAb) or blockers (TBAb), is suspected. We describe clinical and biological variables in a series of patients switching from Hashimoto's thyroiditis to Grave's disease. Subjects and methods: Retrospective case study of 24 patients with Hashimoto's thyroiditis followed during 48 ± 36 months that developed later Graves' disease (GD). These variables were analysed in the hypo and hyperthyroid phase: age, sex, initial TSH, free triiodothyronine (fT3), free thyroxine (fT4), anti-TPO, TBII antibodies, parietal cell autoantibodies, time between hypo and hyperthyroidism, thyroid volume and levothyroxine doses (LT). Results: In HT, mean TSH was 9.4 ± 26.1 UI/L and levothyroxine treatment was 66.2 ± 30.8 µg/day. The switch to GD was observed 38 ± 45 months after HT diagnosis. As expected, we found significant differences on TSH, FT3, FT4 and TBAb levels. Three out of 14 patients had parietal cell autoantibodies. In two of these three cases there was an Helicobacter pylori infection. There were no significant differences between HT and GD groups with respect to thyroid volume. Conclusions: To our knowledge, large series documenting the conversion of HT to GD are scarce. Although rare, this phenomenon should not be misdiagnosed. Suspicion should be raised whenever thyroxine posology must be tapered down during the follow-up of HT patients. Further immunological and genetic studies are needed to explain this unusual autoimmune change.

Hashimoto's thyroiditis - an independent risk factor for papillary carcinoma / Hashimoto's thyroiditis - an independent risk factor for papillary carcinoma

Abstract Introduction: The link between Hashimoto's thyroiditis and thyroid carcinoma has long been a topic of controversy. Objective: The aim of our study was to determine the prevalence of thyroid carcinoma and Hashimoto's thyroiditis coexistence in histopathologic material of thyroidectomized patients. Methods: In a retrospective study, the clinicohistopathologic data of 2117 patients (1738 females/379 males), who underwent total or partial thyroidectomy for thyroid gland disorder at a single institution from the 1st of January 2005 to the 31st of December 2014 were analyzed. Results: Thyroid carcinoma was detected in 318 cases (15%) and microcarcinoma (thyroid cancer ≤10 mm in diameter) was found in permanent sections in 169 cases (8%). Hashimoto's thyroiditis was detected in 318 (15%) patients. Hashimoto's thyroiditis was significantly more often associated with thyroid carcinoma and microcarcinoma compare to benign condition (p = 0.048, p = 0.00014, respectively). Coexistence of Hashimoto's thyroiditis and thyroid carcinoma/thyroid microcarcinoma did not affect tumor size (p = 0.251, p = 0.098, respectively), or tumor multifocality (p = 0.831, p = 0.957, respectively). Bilateral thyroid microcarcinoma was significantly more often detected when Hashimoto's thyroiditis was also diagnosed (p = 0.041), but presence of Hashimoto's thyroiditis did not affect bilateral occurrence of thyroid carcinoma (p = 0.731). Conclusion: Hashimoto's thyroiditis is associated with significantly increased risk of developing thyroid carcinoma, especially thyroid microcarcinoma.

Resumo: Introdução: A relação entre a tireoidite de Hashimoto e o carcinoma de tireoide tem sido um tema de controvérsia por um longo tempo. Objetivo: Determinar a prevalência da coexistência de carcinoma de tireoide e tireoidite de Hashimoto no exame histopatológico de amostras de pacientes tireoidectomizados. Método: Em um estudo retrospectivo, foram analisados os dados clinico-histopatológicos de 2.117 pacientes (1.738 mulheres/379 homens), submetidos à tireoidectomia total ou parcial por distúrbio da glândula tireoide em uma única instituição, de 1º de janeiro de 2005 a 31 de dezembro de 2014. Resultados: O carcinoma de tireoide foi detectado em 318 casos (15%) e o microcarcinoma (câncer de tireoide ≤ 10 mm de diâmetro) foi encontrado em secções permanentes em 169 casos (8%). A tireoidite de Hashimoto foi detectada em 318 (15%) pacientes e foi associada ao carcinoma da tireoide e ao microcarcinoma com maior frequência em comparação com condições benignas (p = 0,048, p = 0,00014, respectivamente). A coexistência de tireoidite de Hashimoto e carcinoma/microcarcinoma não influenciou o tamanho do tumor (p = 0,251, p = 0,098, respectivamente) ou a multifocalidade tumoral (p = 0,831, p = 0,957, respectivamente). O microcarcinoma de tireoide bilateral foi detectado com maior frequência quando a tireoidite de Hashimoto também foi diagnosticada (p = 0,041), mas a presença de tireoidite não influenciou na ocorrência bilateral de carcinoma (p = 0,731). Conclusão: A tireoidite de Hashimoto está associada a um aumento significativo do risco do desenvolvimento de carcinoma de tireoide, especialmente microcarcinoma da tireoide.

Vitamin D in Hashimoto's thyroiditis and its relationship with thyroid function and inflammatory status.

Several studies have shown the correlation between vitamin D [25(OH)D] deficiency and thyroid autoimmunity and reducing of thyroid autoantibodies in patients with normal levels of vitamin D combining with thyroid hormone replacement. However, other authors not agree with this association. It is still unclear whether the low 25(OH)D levels are the result of HT disease or a part of its cause. We studied 88 patients with HT regarding vitamin D status and thyroid autoimmunity markers as well as the relationship with cytokines produced by Th1, Th2, and Th17 cells compared with a control group of 71 euthyroid healthy subjects. The present study demonstrated that vitamin D concentrations were similar in patients HT and the control group. The reduction of free T4 levels was a predictor of vitamin D insufficiency for Hashimoto's thyroiditis, but not for the control group. Lower concentrations of TNF-α was a predictor of lower levels of vitamin D. Differences in the association between HT and vitamin D insufficiency remain unresolved in the literature. The thyroid hormone status would play a role in the maintenance of vitamin D sufficiency, and its immunomodulatory role would influence the presence of autoimmune thyroid disease. The positive correlation between free T4 and vitamin D concentrations suggests that adequate levothyroxine replacement in HT would be an essential factor in maintaining vitamin D at sufficient levels.

Hashimoto's thyroiditis - an independent risk factor for papillary carcinoma.

INTRODUCTION: The link between Hashimoto's thyroiditis and thyroid carcinoma has long been a topic of controversy. OBJECTIVE: The aim of our study was to determine the prevalence of thyroid carcinoma and Hashimoto's thyroiditis coexistence in histopathologic material of thyroidectomized patients. METHODS: In a retrospective study, the clinicohistopathologic data of 2117 patients (1738 females/379 males), who underwent total or partial thyroidectomy for thyroid gland disorder at a single institution from the 1st of January 2005 to the 31st of December 2014 were analyzed. RESULTS: Thyroid carcinoma was detected in 318 cases (15%) and microcarcinoma (thyroid cancer ≤10mm in diameter) was found in permanent sections in 169 cases (8%). Hashimoto's thyroiditis was detected in 318 (15%) patients. Hashimoto's thyroiditis was significantly more often associated with thyroid carcinoma and microcarcinoma compare to benign condition (p=0.048, p=0.00014, respectively). Coexistence of Hashimoto's thyroiditis and thyroid carcinoma/thyroid microcarcinoma did not affect tumor size (p=0.251, p=0.098, respectively), or tumor multifocality (p=0.831, p=0.957, respectively). Bilateral thyroid microcarcinoma was significantly more often detected when Hashimoto's thyroiditis was also diagnosed (p=0.041), but presence of Hashimoto's thyroiditis did not affect bilateral occurrence of thyroid carcinoma (p=0.731). CONCLUSION: Hashimoto's thyroiditis is associated with significantly increased risk of developing thyroid carcinoma, especially thyroid microcarcinoma.