Hashimoto's Disease Research Articles

Hashimoto's Disease and Thyroid Cancer in Children: Are They Associated?

Hashimoto's thyroiditis (HT) is the most common cause of thyroid disease in children and adolescents. Along with significant modifications of thyroid function, HT in pediatric age can be accompanied by relevant thyroid structural alterations. Over time, benign thyroid nodules, carcinoma and, rarely, primary non-Hodgkin lymphoma can develop. However, the relationships between HT and neoplasms are poorly defined. The main aim of this paper is to discuss what is presently known regarding the coexistence of HT and thyroid tumors. Moreover, we attempt to define the pathogenesis of cancer development in children with HT. Literature analysis showed that despite its rarity and relatively promising prognosis, thyroid cancer is associated with HT. Although not all reasons for the coexistence of these diseases are clearly defined, children with HT should be considered at higher risk for thyroid cancer development. Strict correlations between high levels of serum TSH and anti-thyroid antibodies with cancer must be remembered. The same is true for the presence of nodules, especially if multiple nodules are present and ultrasonography and thyroid fine needle aspiration cytology should be promptly used in uncertain cases.

Clinicopathological features and treatment outcome of 37 cases of primary thyroid lymphoma

Objective:The aim of this study is to explore the clinicopathological features and treatment outcome of primary thyroid lymphoma(PTL). Method:Clinicopathological data of 37 cases of PTL were retrospectively reviewed, and analyzed in combined with followup data. Result:Of the 37 patients, Hashimoto's disease was diagnosed in 28(75.7%) patients. The diagnostic rate of preoperative fine needle biopsy (75%) was higher than the fine needle aspiration (53%). The pathological types of these patients included diffuse large B cell lymphoma(n=23), extranodal marginal zone lymphoma of mucosaassociated lymphoid tissue type (MALT) (n=10), follicular lymphoma(FL) grade 3 (n=3) and burkitt lymphoma(BL) (n=1). According to Ann Arbor staging system, 12 patients with stage ⅠE, and 25 patients with stage ⅡE. With a median followup period of 37 months (2－93 months), the 3year overall survival (OS) rate and progression free survival(PFS) was 87.0% and 81.6%, and 5year overall survival(OS) rate and PFS was 79.8% and 74.8%. Univariate survival analysis found that comprehensive treatment was an important factor affecting prognosis, but there was no statistical difference in the effects of age, gender, lactate dehydrogenase, level, β2 microglobulin, Ann Arbor staging, international prognostic index, and tissue subtype on survival (P>0.05). Conclusion:PTL mostly affects middle aged and old female and has a favorable prognosis. Core needle biopsy can improve the diagnostic rate when compared with fine needle aspiration. The optimal treatment is combined modality strategy based on chemotherapy and radiotherapy, and supplemented by surgery.

Association between CTLA-4 + 49A > G and - 318C > T single-nucleotide polymorphisms and susceptibility to thyroid neoplasm.

Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4 or CD152) is among the immune checkpoint molecules and its abnormal expression in cancer predisposed individuals might make the person more susceptible to tumor initiation and progression. Considering the implication of single-nucleotide polymorphisms (SNPs) in CTLA-4 gene expression and probably protein function, one can assume the involvement of these SNPs in neoplastic diseases. rs5742909 ( - 318C > T) and rs231775 ( + 49 A > G) are among the most commonly studied SNPs and have been considered as genetic factors related to thyroid diseases. In this cross-sectional study, we aimed to elucidate the association between these SNPs and susceptibility to various types of thyroid cancers. We investigated the genetic polymorphisms of - 318C > T and + 49 A > G in the CTLA-4 gene by means of ARMS-PCR and RFLP-PCR, respectively, in 167 patients with thyroid carcinomas (papillary, follicular, and anaplastic). The results were then compared with a group of 100 age-sex matched healthy individuals. A statistically significant association was observed between the presence of G allele in + 49 A > G locus and thyroid carcinoma, when comparing cases and controls (OR = 2.10; 95% CI = 1.35-3.28; P = 0.001) and the frequency of heterozygotes (AG) was higher than homozygotes for allele A (AA), in patients with and papillary thyroid carcinoma (PTC). Regarding Hashimoto's thyroiditis, the frequencies of A allele and AA genotype in PTC patients were higher than Hashimoto patients with no history of cancer (OR = 4.67, 95% CI = 2.70-8.08, P < 0.0001; and, OR = 4.68, 95% CI = 1.84-11.91, P = 0.0012; respectively). However; we observed no difference among allele/genotype frequencies in regards to locus - 318C > T. In this study, we observed that G allele in + 49 A > G and possibly lower expression of mutated CTLA-4 molecule, is associated with higher susceptibility to thyroid carcinoma. Although the G allele frequency was higher in thyroid cancer patients, when justified for the presence of lymphocytic thyroiditis, the presence of A allele seemed to increase the odds for PTC in patients with Hashimoto's disease.

The assessment of vitamin D3 deficiency in patients with Hashimoto's disease and the relationship between the disease duration and 25OHD3 levels

The assessment of vitamin D3 deficiency in patients with Hashimoto's disease and the relationship between the disease duration and 25OHD3 levels

Hashimoto's disease in a cohort of 29 children and adolescents. Epidemiology, clinical course, and comorbidities in the short and long term.

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

Identification of a novel HRAS variant and its association with papillary thyroid carcinoma.

HRas proto-oncogene (HRAS) is one of the most commonly mutated genes in thyroid cancer, with mutations frequently occurring in the follicular and Hurthle cell subtypes. However, the contribution of mutations in HRAS to papillary thyroid carcinoma (PTC) progression and the tall-cell variant (TCV) is poorly understood. The aim of the present study was to investigate the somatic genetic variants present in HRAS in patients with PTC, and to investigate the association of these mutations with PTC. The present study is a retrospective case-control study using tumor samples collected from 139 patients with PTC and blood samples from 195 healthy individuals. All patient samples were screened for mutations in 'hotspot' regions of HRAS and B-raf proto-oncogene (BRAF) by single-stranded conformational polymorphism analysis, followed by direct sequencing. A novel variant (IVS1-82del gctgggcctggg) in the HRAS 5'-untranslated region was identified. There was no difference in age or sex of patients with PTC and the healthy controls; however, the HRAS variant was more frequently detected in PTC tissue than in the healthy control samples (37 vs. 26%, P=0.04). There was no association between the HRAS variant and age, sex, tumor size, encapsulation, multifocality/intra-thyroidal spread, Tumor-Node-Metastasis stage, history of Hashimoto's disease, BRAF V600E mutation or PTC subtype (all P>0.05). There were differences of BRAF V600E distribution among different subtypes (χ2=6.390, P=0.041). HRAS variant co-occurring with the BRAF V600E mutation accounted for 31.6% of the total number (P=0.196). Therefore, this novel variant of HRAS (IVS1-82del gctgggcctggg) may be associated with PTC; however, larger scale studies are required to assess the contribution of this novel HRAS variant to PTC progression.

Levothyroxine supplementation improves serum anti-Müllerian hormone levels in infertile patients with Hashimoto's thyroiditis.

Thyroid dysfunction and autoimmunity are associated with an adverse effect on fertility. An aberrant high thyroid stimulating hormone level is associated with diminished ovarian reserve in women of reproductive age; however, the utility of levothyroxine (LT4) replacement for infertile patients with subclinical hypothyroidism is still under discussion. The aim of this study was to investigate whether LT4 supplementation for infertile patients with subclinical hypothyroidism improves impaired ovarian function. We measured levels of serum thyroid-related hormones and a biomarker of ovarian function, anti-Müllerian hormone (AMH) in infertile women from 2014 to 2015. Out of a consecutive 1431 infertile patients, 311 patients with an elevated thyroid stimulating hormone level (≥ 2.5 μIU/mL) underwent detailed thyroid examinations, including blood tests of thyroid antibodies. We recruited 174 infertile patients, excluding patients with factors impacting ovarian and thyroid function. We evaluated alterations in AMH and thyroid related hormone levels during LT4 supplementation and infertility treatment with assisted reproductive technology. After LT4 supplementation, no significant change in the average AMH level was detected overall. However, the AMH level in 35 patients with Hashimoto's disease increased significantly after treatment (1 month 1.3 ± 0.5 fold, P = 0.007; 3 months 1.3 ± 0.4 fold, P = 0.040). The AMH level in patients with thyroglobulin antibody-positive and thyroid peroxidase antibody-negative also significantly increased after LT4 treatment (1 and 3 months 1.5 fold; P = 0.023). In the patients with Hashimoto's disease, preconception LT4 treatment may relieve adverse effects, including autoimmune antibodies, and support follicular development.

Warthin-like papillary thyroid carcinoma with immunoglobulin G4-positive plasma cells possibly related to Hashimoto's thyroiditis.

Hashimoto's thyroiditis with heavy lymphoplasmacytic infiltration is a common comorbidity of immunoglobulin G4 (IgG4)-related thyroiditis and Warthin-like papillary thyroid carcinoma (WL-PTC). We hypothesized that WL-PTC may have a strong association with IgG4-related thyroiditis. To validate this hypothesis, we clinically and immunohistochemically studied 17 WL-PTC cases. Fourteen patients (82.4%) had anti-thyroglobulin antibody and were confirmed to have Hashimoto's thyroiditis through microscopic analysis. Among them, five (29.4%) had disease consistent with IgG4-related thyroiditis but did not exhibit a "storiform" pattern or obliterative phlebitis. IgG4-related diseases were not found in other organs. No cases with serum IgG4 level of >135 mg/dL were noted. A total of 94.1% of WL-PTC cases had IgG4-positive plasma cells (+PCs) in the stroma, and cases with rich IgG4+PCs were more frequently associated with Hashimoto's thyroiditis than those with poor IgG4+PCs. In this study, all three cases without Hashimoto's thyroiditis had poor IgG4+PCs, and one of them did not exhibit IgG4+PCs in the stroma of WL-PTC and Hashimoto's thyroiditis. Nodal metastatic lesions were seen in eight cases, all of which were not WL-PTC. As such, we should consider that the Hashimoto's disease with rich IgG4+PCs seen in our cases is representative of non-IgG4-related disease and not IgG4-related disease involving multiple organs. This study is the first to demonstrate the presence of IgG4+PCs in the stroma of WL-PTC. We concluded that the appearance of IgG4+PCs in the stroma of WL-PTC may be related to Hashimoto's thyroiditis with rich IgG4+PC.

The Place of Interventional Blocks in the Treatment of Pain Due to Fibromyalgia in Hashimoto's Disease

The Place of Interventional Blocks in the Treatment of Pain Due to Fibromyalgia in Hashimoto's Disease

Cytodiagnosis of mucosa-associated lymphoid tissue lymphoma of thyroid gland: An extremely rare presentation in a young female

Thyroid lymphoma, a rare tumor, constitutes about 1%–5% of all thyroid malignancies and 1%–2% of all extranodal lymphomas. The thyroid gland contains no native lymphoid tissue and is seen only in various pathological conditions such as primary thyroid lymphoma (PTL). PTL is more common in women than men (3:1 predominance) with a peak incidence in the sixth and seventh decades. Mucosa-associated lymphoid tissue (MALT) lymphoma of thyroid is one of the rare variants. Chronic autoimmune thyroiditis (Hashimoto's disease) has been associated with an increased risk of lymphoma, including MALT lymphoma. Here, we report a case of a 38-year-old female who presented with rapidly progressive swelling on the right side of the neck for previous 3 months. No history suggestive of hypothyroidism or hyperthyroidism was present. Ultrasonography showed enlarged thyroid gland with hypoechoic echotexture and multiple echogenic septations. Fine-needle aspiration cytology revealed features suggestive of MALT lymphoma. The swelling was operated, and subsequent histopathology and immunohistochemistry confirmed the diagnosis. Thereafter, the patient was treated by radiotherapy. However, after 6 months' follow-up, there was a recurrence of the tumor. Then, combination of cyclophosphamide, doxorubicin, vincristine, prednisone regime and rituximab was started, and the patient was free of recurrence at the next 12-month follow-up. Here, we report a very rare case of MALT lymphoma of Thyroid occurring in a young female with no known history of Hashimoto's thyroiditis. The tumor recurred after radiotherapy treatment and was successfully treated with subsequent chemotherapy.

Derivation of thyroid lymphoepithelial cysts from follicular cells.

The pathogenesis of thyroid lymphoepithelial cysts is controversial, and two hypotheses have been proposed, namely derivation from branchial-derived remnants or from squamous metaplasia of the follicular cells. The aim of this study was to clarify the pathogenesis of thyroid lymphoepithelial cysts. We performed pathological and immunohistochemical examination of 21 thyroid lymphoepithelial cysts, 13 non-neoplastic squamous metaplasia samples without thyroid carcinoma, 13 solid cell nests, and 14 lateral cervical cysts. On ultrasound, half of thyroid lymphoepithelial cysts were interpreted as calcified nodules regardless of no calcification. Thyroid lymphoepithelial cysts and squamous metaplasia tended to be located in the central and lower portions of the thyroid, while solid cell nests were located in the upper and central portions (p < 0.05). In 95.2% of patients with thyroid lymphoepithelial cysts and all patients with squamous metaplasia, lesions were histologically associated with chronic thyroiditis forming lymph follicles. Hashimoto's disease was serologically confirmed in 18 patients with lymphoepithelial cysts (85.7%) and 10 patients with squamous metaplasia (76.9%). Immunohistochemically, lymphoepithelial cysts showed nuclear positivity for PAX8, thyroid transcription factor 1, and p63. One lateral cervical cyst (7.1%) showed positive staining for PAX8, while solid cell nests were PAX8-negative. In three (14.3%) cases of thyroid lymphoepithelial cysts, squamous cells located on the superficial layer were focally and weakly positive for CEA. We concluded that thyroid lymphoepithelial cysts originate from follicular cells and are unrelated to solid cell nests and lateral cervical cysts arising from branchial-derived remnants.

Relationship between Chronic urticaria and autoimmune thyroid disease.

Hives is an erythematous and itchy disease that commonly affects the trunk and the organs. Acute urticaria is a common disease and affects about 10%–20% of the population during its lifetime. In patients with chronic urticaria, about 25%–30% of cases, antithyroid peroxidase (TPO) was detected and Hashimoto's disease was diagnosed. This study aimed to evaluate the anti-TPO antibody in patients with chronic urticaria and the effect of treatment of levothyroxine on its recovery. In this study, 72 people with chronic urticaria and positive anti-TPO antibody were randomly divided into two groups. Low-dose antihistamine was administered to both groups, and the first group received levothyroxine at a dose of 50 μg/day. The severity of itching was evaluated according to the visual analog scale before and after therapy. There was no significant difference in the age, sex, thyroid-stimulating hormone (TSH), and anti-TPO between the two groups. Ninety-two patients were female. In this study, all patients took a small dose of loratadine. Relative healing was observed in both the groups. However, in a group of patients taking levothyroxine and loratadine, recovery was faster and patients with no itching were significantly more likely than the other groups. The prevalence of chronic urticaria and anti-TPO antibody in this study was very high and was due to sex hormones. Therefore, in young women with chronic urticaria, especially in refractory cases, they should be monitored for anti-TPO. Anti-TPO and TSH should be evaluated for the diagnosis and treatment of patients with urticaria or chronic angioedema. Levothyroxine therapy in hives and chronic urticaria is beneficial in the treatment of thyroid dysfunction.

Acute Myelopathy Associated with Hashimoto's Disease

Acute Myelopathy Associated with Hashimoto's Disease

Caveolin-1 regulates autophagy activity in thyroid follicular cells and is involved in Hashimoto's thyroiditis disease.

Hashimoto's thyroiditis (HT) is considered a T helper-type 1 (Th1) cytokine-dominant autoimmune thyroid disease. Caveolin-1 (Cav-1), a part of the thyroxisome multiprotein complex, is localized at the apical pole of thyrocytes and is indispensable for synthesis of thyroid hormones and modulation of oxidative stress in order to avoid cell damage and apoptosis. Reduced autophagy induces thyroid follicular cells (TFC) apoptosis by activating reactive oxygen species (ROS) in HT patients. Nevertheless, whether Cav-1 has roles in the regulation of autophagy remains largely unclear. In this study, we examined Th1 cytokines and Cav-1 expression in HT thyroid tissues, determined the effects of interleukin-1beta (IL-1β) and interferon-gamma (IFN-γ) on Cav-1 and autophagy activity in TFC, and investigated the association between Cav-1 and autophagy activity in vitro. Our results indicate that higher levels of IL-1β and IFN-γ and lower levels of Cav-1 were expressed in thyroid tissues of HT patients than in those of normal controls. Cav-1 mRNA and protein levels were significantly decreased in TFC exposed to IL-1β and IFN-γ, accompanied by decreased expression of autophagy-related protein LC3B-II. Interestingly, small interfering RNA (siRNA)-mediated Cav-1 knockdown in TFC reduced LC3B-II protein expression. Taken together, these results suggest that lack of Cav-1 expression inhibited autophagy activity in TFC exposed to Th1 cytokines (IL-1β and IFN-γ), which might be a novel pathogenetic mechanism of HT.

Perfil clínico y epidemiológico de pacientes atendidos por hipertiroidismo e hipotiroidismo en el servicio de endocrinología de una institución hospitalaria de Medellín (Colombia) entre 2013 y 2015

Objetivo: determinar el perfil epidemiológico en pacientes hipertiroideos e hipotiroideos que acudieron al servicio de endocrinología de una institución hospitalaria de Medellín (Colombia) entre 2013 y 2015. Materiales y métodos: se realizó un estudio descriptivo retrospectivo y se incluyeron todas las historias clínicas de pacientes con diagnóstico de hipertiroidismo o hipotiroidismo. Se realizó un análisis univariado con estadística descriptiva por medio de frecuencias absolutas y proporciones en el programa IBM SPSS versión 19.0. Resultados: Se estudiaron 149 pacientes: 131 con hipotiroidismo y 18 con hipertiroidismo, la media de edad fue 57,8±17,8 años y 48,2±15,1 años respectivamente. La frecuencia de sexo femenino fue mayor en hipotiroideos que en hipertiroideos (86,3% versus 66,7%). Las principales etiologías en los hipotiroideos fueron el hipotiroidismo postquirúrgico 11,5% y la enfermedad de Hashimoto 5,3%, mientras que en el hipertiroidismo estuvieron la enfermedad de Graves 33,3% y tirotoxicosis 22,2%. El síntoma más frecuente en los pacientes estudiados fue el bocio con un 14,5% en los hipotiroideos versus un 38,9% en los hipertiroideos. Los antecedentes personales más frecuentes en ambos grupos de pacientes fueron hipertensión arterial y Diabetes Mellitus. Conclusión: Los resultados del presente estudio son acordes a la información existente en la literatura, la presentación de patologías tiroideas es más común en el sexo femenino; y la principal etiología es cirugía y enfermedad de Graves para hipo e hipertiroidismo respectivamente.

Towards a further understanding of prenatal thyroid theory of homosexuality: Autoimmune thyroiditis, polycystic ovary syndrome, autism and low birth weight

Research into the neurobiological origins of same-sex attraction is inconclusive. A recent theory of homosexuality posited that maternal thyroid dysfunction during pregnancy is associated with an increased rate of homosexual orientation in offspring. Relevant studies from the prenatal thyroid model perspective were reviewed, the major findings of which are as follows: i) An increased prevalence of Hashimoto's disease in lesbian women suggests a maternal and even familial presence of the same autoimmune thyroid disease. Female-to-male transsexuals and lesbian women were also reported to have higher rates of polycystic ovary syndrome (PCOS). Over the last several years, reports suggesting a strong link between PCOS and thyroid autoimmunity have accumulated. ii) The increased risk of autism spectrum disorders (ASD) in the offspring of mothers with thyroid autoimmunity in pregnancy and the association between ASD and gender dysphoria indicate a link between maternal thyroid dysfunction and gender dysphoria/same-sex attraction in the off-spring. iii) The high risk of miscarriage and retarded fetal growth in pregnancies of mothers who give birth to homosexual off-spring can be explained by the impact of maternal thyroid dysfunction during pregnancy. This perspective review highlights relevant research findings and integrates them into the prenatal thyroid model of homosexuality. A better understanding of the mechanisms involved in the generation of same-sex orientation will contribute to the betterment of individual lives, as well as of society.

Differential expression levels of plasma microRNA in Hashimoto's disease

BackgroundThe altered expression of circulating miRNAs has been discovered in many autoimmune diseases (ADs). With rare existing research, it is still unclear in Hashimoto's thyroiditis (HT). We detected plasma miRNA expression of HT patients in this three-stage designed study. MethodsDifferently expressed miRNAs (4 HT pools vs. 1 normal control pool) were identified using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel (miRCURY-Ready-to-Use- PCR-Human- panel-I+II-V1.M) in the initial discovery stage. These miRNAs were then confirmed in the training stage and further validated in the testing stage using qRT-PCR with 64 (32 HT vs. 32 NCs) and 136 samples (68 HT vs. 68 NCs), respectively. ResultsA total of 10 miRNAs showed differential expression through the training stage. For further validation in the testing stage, expression of 6 miRNAs (miR-205, miR-20a-3p, miR-375, miR-296, miR-451, miR-500a) were consistent with those in the training stage. Combination results showed that these 6 miRNAs were significantly up-regulated in peripheral plasma of HT patients compared with normal controls (P<0.05). In addition, the six-miRNA signature was evaluated to be a potential diagnostic marker of HT. The areas under the receiver operating characteristic curve of the signature were 0.80, 0.75 and 0.69 for the training, testing and the combined stages, respectively. Three miRNAs were associated with TSH levels in HT patients (miR-451, P=0.043; miR-375, P=0.043; miR-500a, P=0.043). Additionally, miR-20a-3p was related with TgAb level (P=0.046). ConclusionsWe identified a miRNA signature including six dysregulated plasma miRNAs which could act as a diagnostic marker in plasma of HT, providing more evidence and better understanding for the association between circulating miRNAs and autoimmune diseases.

Selenium status parameters in patients with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. To date, no systematic study of interactions between selenium status parameters (SSPs: serum selenium concentration, plasma glutathione peroxidase, GPX3, plasma selenoprotein P, SELENOP), sex hormones, thyroid function parameters, and other laboratory parameters in patients with PCOS has been undertaken. Therefore we aimed to compare such parameters in women with PCOS and in the control groups, and to investigate the multidimensional interactions between various parameters in PCOS patients and in controls. The subjects were diagnosed either with PCOS (n=28, 25.4±5.2 y) or with PCOS+Hashimoto disease (n=13, 27.3±5.6 y). Female patients having normal menses were recruited into the first control group (n=70, 26.8±7.3 y) or to the second control group comprising women only with Hashimoto disease (n=10, 26.2±6.9 y).No apparent differences in SSPs between control subjects and patients with PCOS, also complicated with Hashimoto disease, were identified, though such differences were noticeable for total testosterone (tT), sex hormone binding globulin, free androgen index, dehydroepiandrosterone sulfate (DHEAS), and insulin profile. The correlation between tT and DHEAS was found the strongest. The other group of mutually highly and positively correlated parameters consisted of GPX3, follicle stimulating hormone, free triiodothyronine and free thyroxine. All the latter parameters correlated negatively with vitamin D3. SSPs took part in interactions with thyroid hormones, sex hormones and some other parameters, but only for GPX3 such interactions were statistically significant. The significance of these findings remains open for further investigation, particularly in patients with PCOS and/or Hashimoto disease.

Single nucleotide polymorphism 1623 A/G (rs180195) in the promoter of the Thyroglobulin gene is associated with autoimmune thyroid disease but not with thyroid ophthalmopathy.

BackgroundOur studies over recent years have focused on some new ideas concerning the pathogenesis for the orbital reaction that characterizes Graves’ ophthalmopathy namely, that there are antigens expressed by thyroid tissue and orbital tissue where they are targeted by autoantibodies and/or sensitized T cells, leading to orbital inflammation. While this has been well studied for the thyroid stimulating hormone-receptor, the possible role of another major thyroid antigen, Thyroglobulin (TG), has been largely ignored.MethodsWe identified novel variant 1623 A/G single nucleotide polymorphism (SNP) (rs180195) in the promoter of TG gene associated with autoimmune thyroid disorders. We genotyped the TG SNPs rs2069566, rs2076739, rs121912646, rs121912647, rs121912648, rs121912649, rs121912650, rs137854433, rs137854434, and rs180195 by MassARRAY SNP analysis using iPLEX technology in a cohort of 529 patients with thyroid autoimmunity with and without ophthalmopathy, and controls.ResultsWe showed that variant 1623 A/G SNP (rs180195) in the promoter of TG gene is a marker for thyroid autoimmunity, but not for ophthalmopathy. We showed that there was a significant difference in the distribution of the major allele (G) vs minor allele (A) in patients with Hashimoto’s thyroiditis (HT). In HT the wild-type (GG) genotype was less common. We showed that the genotypes homozygous AA and heterozygous GA rs180195 SNP in the promoter of TG gene were more closely associated with thyroid autoimmunity than the wild-type (GG) polymorphism, and are thus, markers of autoimmunity.Conclusionrs180195 SNP was previously identified by Stefan et al independently of us, who showed that this TG SNP predisposed to autoimmune thyroid diseases. However, this is the first study to explore the association between TG SNPs and HT. Our findings support the notion that the thyroid and orbital disorders are not part of the same disease, ie, “Graves’ disease” or “Hashimoto’s disease”, but separate autoimmune disorders.

Coffee and autoimmunity: More than a mere hot beverage!

Coffee is one of the world's most consumed beverage. In the last decades, coffee consumption has attracted a huge body of research due to its impact on health. Recent scientific evidences showed that coffee intake could be associated with decreased mortality from cardiovascular and neurological diseases, diabetes type II, as well as from endometrial and liver cancer, among others. In this review, on the basis of available data in the literature, we aimed to investigate the association between coffee intake and its influence on the immune system and the insurgence of the most relevant autoimmune diseases. While some studies reported conflicting results, general trends have been identified. Coffee consumption seems to increase the risk of developing rheumatoid arthritis (RA) and type 1 diabetes mellitus (T1DM). By contrast, coffee consumption may exert a protective role against multiple sclerosis, primary sclerosing cholangitis, and ulcerative colitis. Concerning other autoimmune diseases such as systemic lupus erythematosus, psoriasis, primary biliary cholangitis and Crohn's disease, no significant association was found. In other studies, coffee consumption was shown to influence disease course and management options. Coffee intake led to a decrease in insulin sensitivity in T1DM, in methotrexate efficacy in RA, and in levothyroxine absorption in Hashimoto's disease. Further, coffee consumption was associated with cross reactivity with gliadin antibodies in celiac patients. Data on certain autoimmune diseases like systemic sclerosis, Sjögren's syndrome, and Behçet's disease, among others, are lacking in the existent literature. As such, further research is warranted.