Development Of Autoimmune Thyroiditis Research Articles

Transcriptome analysis of the effect of diosgenin on autoimmune thyroiditis in a rat model

In a mouse model of Graves’ disease (GD), diosgenin has been shown to have a therapeutic effect on GD by alleviating goitre. However, research on the effect of diosgenin on autoimmune thyroiditis (AIT) is lacking. In this study, transcriptomics was used to comprehensively analyse the protective effect of diosgenin against AIT in rats and the possible mechanism. The results showed that in the diosgenin-intervention group, compared to the model group, the expression of serum triiodothyronine, thyroxine, free triiodothyronine, and free thyroxine was decreased and that of thyroid-stimulating hormone was increased; these changes were accompanied by the downregulation of thyroglobulin, TSH receptor antibody and thyroid peroxidase expression in serum. Furthermore, transcriptome detection, RT-qPCR and immunohistochemistry verification revealed that in thyroid tissue, the relative mRNA and protein expression of cyclic adenosine 3′,5′-monophosphate (cAMP), protein kinase A (PKA) and cAMP response element-binding protein (Creb) were increased and the mRNA expression of S100 calcium-binding protein A9 (S100A9) was decreased in the diosgenin groups. In summary, diosgenin alleviates the development of AIT, possibly via the activation of the cAMP/PKA/Creb pathway and downregulation of S100A9 gene expression.

Selenium Supplementation May Decrease Thyroid Peroxidase Antibody Titer via Reducing Oxidative Stress in Euthyroid Patients with Autoimmune Thyroiditis.

Objective Selenium, as an antioxidant, has been implicated in the development of autoimmune thyroiditis (AIT). Many studies showed selenium supplementation could decrease thyroid autoantibodies in patients with AIT. However, the underlying mechanisms have not been well determined. Therefore, we performed a clinical study to investigate the possible mechanism of beneficial effects of selenium treatment on AIT patients. Methods Forty euthyroid patients with AIT were randomized into two groups. Group I was treated with 200 μg/day selenium supplementation, and group II received a placebo over a 3-month period. Thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb), malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD) were measured before and 3 months after treatments. Additionally, twenty healthy volunteers also served as a control group for the evaluation of such parameters in basic condition. Results Totally, 32 patients (group I, n = 18; group II, n = 14) completed the clinical study and were incorporated into the statistics. MDA level was higher and SOD activity and TAC were lower in patients compared to healthy individuals. After 3 months, TPOAb titer significantly decreased within group I (P < 0.001) but did not change within group II (P=0.001). There were also no statistically significant changes in TSH and TgAb titers within the two groups (all P > 0.05). Additionally, decreased MDA level (from 6.8 ± 1.3 nmol/ml to 4.9 ± 0.7 nmol/ml; P < 0.001) and increased TAC (from 10.0 ± 1.9 mmol/l to 12.9 ± 3.1 mmol/l; P=0.003) and SOD activity (from 72.3 ± 10.3 U/ml to 84.3 ± 13.2 U/ml; P=0.007) were simultaneously observed after 3 months' selenium treatment. Moreover, there was a negative correlation between TAC and TgAb/TPOAb and a positive correlation between MDA and TgAb/TPOAb in AIT patients. Conclusions Our findings support the hypothesis that selenium treatment could decrease TPOAb titer via enforcing the defense against oxidative stress in euthyroid patients with AIT, which may be a potential underlying mechanism.

HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis.

The aim of this study was to investigate the role of human herpesvirus-6 (HHV-6) in autoimmune thyroiditis (AIT) development. We examined the possible involvement of HHV-6 gene expression encoding immunomodulating proteins U12 and U51 in AIT development and their role in the modulation of chemokine signaling. One hundred patients with autoimmune thyroiditis following thyroidectomy were enrolled in this study. Nested polymerase chain reaction (nPCR) was used to detect the HHV-6 sequence in DNA samples. Reverse transcription PCR (RT-PCR) with three different HHV-6 gene targets (U79/80, U51 and U12) was to detect active infection markers. HHV-6 load was identified using a commercial real-time PCR kit. Immunohistochemistry was performed to investigate the expression of the HHV-6 antigen and RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in thyroid gland tissue. Different commercial immunosorbent assay kits were used for the detection of RANTES, IFNγ, IL-6, and TNFα levels in the AIT patient group and controls. We detected 98% presence of the HHV-6 genomic sequence in AIT patients’ thyroid gland tissues. Markers of active HHV-6 infection (HHV-6 U79/80, U12 and/or U51 mRNA) were predominant in AIT patients’ thyroid tissue samples in comparison with the control group (56% vs. 6%). Evidence from immunofluorescence microscopy showed that HHV-6 can persist in thyrocytes and can interact with RANTES. Visual confirmation of the intense immunofluorescence signal of RANTES detected in thyroid tissues could indicate high expression of this chemokine in the thyroid gland. On the other hand, immunosorbent assays showed very low RANTES levels in AIT patients’ peripheral plasma. These results indicate that RANTES level in AIT patients could be influenced by HHV-6 activation, which in turn may aid AIT development.

A Novel Mouse Model of Autoimmune Thyroiditis Induced by Immunization with Adenovirus Containing Full-Length Thyroglobulin cDNA: Implications to Genetic Studies of Thyroid Autoimmunity.

Background: Thyroglobulin (TG) is a key autoantigen in autoimmune thyroid diseases (AITD). Several single nucleotide polymorphisms (SNPs) in the TG locus were shown to be strongly associated with disease susceptibility in both humans and mice, and autoimmune response to TG is the earliest event in the development of thyroid autoimmunity in mice. The classical model of experimental autoimmune thyroiditis (EAT) is induced by immunizing mice with TG protein together with an adjuvant to break down immune tolerance. The classical EAT model has limited utility in genetic studies of TG since it does not allow testing the effects of TG sequence variants on the development of autoimmune thyroiditis. In this study, we have immunized CBA-J mice, an EAT-susceptible strain, with an adenovirus vector encoding the full-length human TG (hTG) to generate a model of EAT in which the TG sequence can be manipulated to test AITD-associated TG SNPs. Methods: We immunized CBA-J mice with hTG-expressing adenovirus following the well-recognized experimental autoimmune Graves' disease protocol that also uses an adenovirus vector to deliver the immunogen. Results: After hTG adenovirus immunizations, mice developed higher T cell proliferative and cytokine responses to hTG and TG2098 (a major T cell epitope in AITD) and higher titers of TG and thyroperoxidase autoantibodies compared with mice immunized with control LacZ-expressing adenovirus. The mice, however, did not develop thyroidal lymphocytic infiltration and hypothyroidism. Conclusions: Our data describe a novel murine model of autoimmune thyroiditis that does not require the use of adjuvants to break down tolerance and that will allow investigators to test the effects of hTG variants in the pathoetiology of Hashimoto's thyroiditis.

Thyrocyte-derived exosome-targeted dendritic cells stimulate strong CD4+ T lymphocyte responses

Exosomes have been intensively studied in autoimmune diseases, and circulating exosomes and microvesicles have also been explored in autoimmune thyroiditis (AITD). However, the role of thyroid cell-derived exosomes in immune responses is unclear. We showed that IFN-γ-treated Nthy-ori 3-1 cell-derived exosomes (IFN-γ-Exo) harbored TPO, HSP60 and MHC-II and activated dendritic cells (DCs) in vitro. Compared with Exo-targeted DCs (DCExo), IFN-γ-Exo-targeted DCs (DCIFN-γ-Exo) promoted the expression and release of proinflammatory cytokines, such as IFN-γ, IL-17A and IL-22, from CD4+ T lymphocytes and inhibited the expression and release of anti-inflammatory cytokines, such as IL-4, IL-10 and TGF-β1; however, IFN-γ-Exo did not have this effect compared with Nthy-ori 3-1 cell-derived exosomes (Exo). DCIFN-γ-Exo stimulates the expression and release of cytokines from CD4+ T lymphocytes more efficiently than IFN-γ-Exo. Thus, DCIFN-γ-Exo may effectively induce CD4+ T lymphocyte-mediated immune responses and play a role in the occurrence and development of AITD.

Oxidative stress and its role in the development of autoimmune thyroid diseases

A large number of socially significant diseases is accompanied with oxidative stress and carry with tissue damage. Free radicals play a crucial role in the development of these diseases. Similar processes occur under the influence of ionizing radiation and bacterial infections. Recently, was indicated the significant role of oxidative stress in the development of autoimmune thyroiditis. It is assumed that the synthesis of thyroid hormones depends on the concentration of H2O2, which, due to its high toxicity, must be in strict accordance with the activity of antioxidant systems. Many biochemically negative processes occur on the apical membrane of the thyrocyte, which allows limiting the effect of free radicals and avoid cell destruction. However, in pathological conditions, enzymatic systems are disturbed and their components become abnormally activated in the cytoplasm, and it is leads to functional and morphological disorders. A deeper understanding of oxidative stress and its role in the development of autoimmune thyroiditis can contribute to the identification of new methods for its assessment, the expansion of therapeutic ranges for this disease. This review discusses oxidative stress, which is the accumulation of active damaging agents (free radicals, prooxidants, reactive oxygen species) that initiate cell damage and lead to the development of various pathological conditions.

Hashimoto Thyroiditis and Dyslipidemia in Childhood: A Review

Hashimoto autoimmune thyroiditis (AIT) is the most common cause of acquired hypothyroidism in the pediatric population. Development of AIT is mediated mainly by cellular immune response directed toward thyroid autoantigens, leading to inflammation and impaired function of thyroid gland. Both thyroid dysfunction and inflammation affect the metabolism of plasma lipoproteins. The alterations in lipid profile worsen with the advancement of hypothyroidism, ranging from discrete changes in euthyroid AIT patients, to atherogenic dyslipidemia in the overt hypothyroidism. In this review, characteristics of dyslipidemia in pediatric AIT patients, and the consequences in respect to the risk for cardiovascular disease (CVD) development are discussed. Additionally, benefit of L-thyroxine treatment on serum lipid profile in pediatric AIT patients is addressed. Finally, potential usefulness of novel lipid biomarkers, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), non-cholesterol sterols, low-density lipoprotein particle size and number, and high-density lipoprotein structure and functionality in AIT patients is also covered. Further longitudinal studies are needed in order to elucidate the long-term cardiovascular outcomes of dyslipidemia in pediatric patients with Hashimoto AIT.

Vitamin D Receptor Gene Polymorphisms and Autoimmune Thyroiditis: Are They Associated with Disease Occurrence and Its Features?

Purpose Vitamin D, besides its role in calcium-phosphorus metabolism, turned out to play a significant immunomodulating function. Until now four single nucleotide polymorphisms of vitamin D receptor gene (VDR), rs2228570 (FokI), rs1544410 (BsmI), rs7975232 (ApaI), and rs731236 (TaqI), have been studied in autoimmune thyroid disorders, with conflicting results. Another functional polymorphism of the VDR gene, rs11568820 (Cdx2), has been shown to influence the immune system, although it has not been studied for its association with autoimmune thyroiditis to date. Therefore, the study aimed to evaluate the association of these five VDR gene polymorphisms with susceptibility to autoimmune thyroiditis among Caucasian Polish population. A relationship between the studied polymorphisms and selected clinical features of the disease was additionally assessed. Methods 223 patients with autoimmune thyroiditis and 130 control subjects were enrolled in the study. VDR polymorphisms were studied by PCR-RFLP or TaqMan real-time PCR. Results Allele and genotype distributions of any of the studied polymorphisms did not differ significantly between patients and controls. Similarly, frequencies of haplotypes derived from rs1544410-rs7975232-rs731236 (BsmI-ApaI-TaqI) polymorphisms were not significantly different in the two studied groups. However, a weak association between rs1544410 (BsmI) or rs7975232 (ApaI) VDR polymorphisms and thyroid volume was found (p = 0.03 and p = 0.04, resp.). Conclusions Our results suggest that VDR gene is not a major susceptibility factor for autoimmune thyroiditis development, at least in Caucasian Polish population.

Current State of the Autoimmune Thyroiditis Problem

The review provides up-to-date data on pathogenetic mechanisms, opportunities of diagnosis, and organizational and medical measures concerning autoimmune thyroiditis (AIT). AIT is a polyetiological disease which is mainly caused by environmental factors, genetic predisposition and disorder in immune regulation. Primary AIT incidence in the Republic of Belarus in 2017 is 58 cases per 100,000 population in the overall structure of the thyroid gland pathology, the AIT accounts for up to 40 %. The upward trend in the number of autoimmune diseases of the thyroid gland, including that in ecologically unfavorable regions, is explained not only by the true increase in the number of patients with AIT, the consequences of stress, but also by the overdiagnosis. There is contradictory data on the correlation of the level of iodine sufficiency of the population with the AIT development; there is no convincing evidence of the role of radiation factors in increasing the risk of AIT. The review analyzes the correlation of AIT with an imbalance in a number of microelements involved in the synthesis of thyroid hormones and affecting the iodine exchange. The article presents the study results that determined the nature of immune disorders in AIT and hypothyroidism in such forms as disorders of lymphocyte subpopulations, proinflammatory and anti-inflammatory cytokines, changes in the apoptosis mechanisms, which were proposed for use as predictors of the severity of thyroid immune inflammation and hypothyroidism. The criteria for selecting patients with an increased risk of developing AIT complications remain unclear, that necessitates the development and implementation of additional organizational and medical measures for following-up of such patients and assessing their quality of life.

Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2h4 Mice.

Background: There is growing evidence that sphingosine-1-phosphate (S1P), a pleiotropic bioactive sphingolipid metabolite synthesized intracellularly by two closely related sphingosine kinases (SphKs), SphK1 and SphK2, is involved in inflammation. However, the role of SphKs/S1P/S1P receptors (S1PRs) in autoimmune thyroiditis (AIT) has not been studied to date. Methods: This study examined whether SphK1/S1P/S1PR1 signaling is aberrantly altered in thyroid tissues and serum of both AIT patients and a spontaneously autoimmune thyroiditis (SAT) mouse model. Murine CD4+T cells were employed to further investigate the downstream signaling of SphK1/S1P/S1PR1. Furthermore, a total of 102 NOD.H-2h4 mice, randomly divided into different groups, were used to investigate the therapeutic effect of S1PR1 blockade and its potential mechanism. Results: We found that components of the SphK1/S1P/S1PR1 pathway were abnormally expressed in patients with Hashimoto thyroiditis and in a SAT mouse model. In addition, S1P could activate signal transducer and activator of transcription 3 (STAT3) through S1PR1 and its downstream signaling pathways in CD4+T cells of NOD.H-2h4 mice. Furthermore, an in vivo study demonstrated that blocking S1PR1 by FTY720 administration could reduce the incidence and severity of thyroiditis and goiter in SAT mice in a time-dependent manner. The proportions of STAT3-related and inflammation-related cell subtypes, such as T helper 1, T helper 17, and follicular T helper cells, were elevated in the SAT group when compared to the control group, and these cell subtypes decreased after FTY720 administration. Furthermore, the downstream inflammatory cytokines of STAT3 were also downregulated after FTY720 administration. Conclusion: The present study shows that blocking Sphk1/S1P/S1PR1 signaling can ameliorate the severity of AIT, providing evidence of a promising therapeutic target for AIT.

Possible Involvement of Human Herpesvirus-6 U83 Gene Expression in Autoimmune Thyroiditis Development

Abstract Viral infections have been frequently cited as important environmental factors implicated in autoimmune thyroiditis (AIT) development, although no specific virus has yet been conclusively associated with the disease. Some evidence implicates human herpesvirus-6 (HHV-6) in this disease. The aim of this study was to investigate the role of the HHV-6 U83 gene expression in autoimmune thyroiditis development. Fifty-one patients with AIT following thyroidectomy and a control group of 30 autopsied subjects without thyroid pathologies for comparing virology results and 30 healthy blood donors for comparing serology results were enrolled in this study. HHV-6 U83 gene expression was determined using nested PCR with complementary DNA as the template acquired from thyroid gland extracted RNA. Plasma samples of AIT patients and blood donors were tested for IL-2, IL-4, IL-10, sTNF-RII and IL-1beta levels by ELISA. Virology results were compared with pro- and anti-inflammatory cytokine levels to determine possible interaction of HHV-6 with host immune response. HHV-6 U83 gene expression was found only in 24% (12/49) of AIT patient thyroid gland tissue samples and in none of the control group individuals, showing possible involvement of this gene in AIT development. However, no interaction between HHV-6 and changes in cytokine levels was found.

MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1 protein.

MicroRNA-326 (miR-326), as a member of the microRNA (miRNA) family, which includes endogenous single-stranded, conserved, noncoding small RNAs, has been reported to play important roles in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus. However, few studies of the role of miR-326 in autoimmune thyroiditis (AIT) have been published. Here, we explored the roles of miR-326 and the involved pathway in iodine-induced AIT. NOD.H-2h4 mice, which are a model of human AIT, were randomly divided into a normal water control group and a high-iodine group. Mice in the high-iodine group were administered 0.05% NaI (~1000 times the normal daily iodine intake), and mice in the control group received sterile water. Furthermore, we evaluated small interfering RNA (siRNA) interference in spleen mononuclear cell experiments in vitro. In this study, we found that Th17 cells were significantly increased with a high expression of miR-326 in an iodine-induced thyroiditis NOD.H-2h4 mouse model. In addition, the expression of Ets-1 protein, a negative regulator of Th17 differentiation, was significantly decreased. Intriguingly, our analysis showed that Ets-1 protein expression was negatively correlated with miR-326 levels in AIT mice (r = -0.814, p < 0.01). Our study indicated that miR-326 inhibited Ets-1 protein expression and promoted the differentiation of Th17 cells during the onset and development of AIT. The addition of a miR-326 inhibitor reversed Th17 cell production and Ets-1 protein expression, supporting this hypothesis. The results of our study suggest that miR-326 may target the Ets-1 protein to contribute to iodide-induced thyroiditis, providing a new theoretical basis for the use of miRNA targeting therapy for the treatment of autoimmune diseases.

Phagocytosis Deficiency of Macrophages in NOD.H-2h4 Mice Accelerates the Severity of Iodine-Induced Autoimmune Thyroiditis.

Apoptosis occurs in many autoimmune diseases. Excess iodine induces thyrocyte apoptosis and increases the incidence and prevalence of autoimmune thyroiditis (AIT). However, the sequence of events between the appearance of thyrocyte apoptosis and the occurrence of thyroiditis remains uncharacterized. Furthermore, few studies have investigated the role of macrophage phagocytosis in the development of AIT. Therefore, we evaluated the relationship between apoptosis and inflammatory infiltration in NOD.H-2h4 mouse thyroids by comparing the sequence of events in tissue samples. We also investigated the role of macrophages by comparing macrophage phagocytosis function in BALB/c, C57BL/6, and NOD.H-2h4 mice treated with different levels of iodine. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays and thyroid inflammatory scores revealed that apoptosis (2weeks) occurred before inflammatory infiltration (4weeks). Phosphatidylserine (PS) expression on the extracellular surface of the cell membrane and double-stranded DNA fragments associated with apoptosis appeared at 2 and 8weeks, respectively. Additionally, although apoptosis was enhanced in the thyroids of mice supplemented with excess iodine (0.05±0.12 vs 1.63±0.82% for BALB/c, 0.09±0.14 vs 1.51±0.34% for C57BL/6, and 0.07±1.11 vs 4.72±0.62% for NOD.H-2h4 mice), only NOD.H-2h4 mouse thyroids presented with inflammation. Furthermore, macrophages from NOD.H-2h4 mice (44.46±1.79%) exhibited decreased phagocytotic activity relative to that in BALB/c (54.21±4.58%) and C57BL/6 (58.96±4.04%) mice. There were no differences in phagocytosis function between NOD.H-2h4 mice supplemented with excess iodine or left untreated (24.50±2.66 vs 21.71±1.79%, p=0.06). In conclusion, deficiencies in the apoptosis clearance of macrophages in NOD.H-2h4 mice may constitute an early pathogenic mechanism in AIT that is not influenced by iodine intake.

Autoimmune manifestations in aged mice arise from early-life immune dysregulation

Abstract Autoantibodies that arise in autoimmunity can be present years to decades prior to the onset of disease manifestations. This suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which ultimately drives disease pathology in local tissues later in life. Here we show Sjögren’s Syndrome manifestations that develop in aged NOD.H-2h4 mice were driven by and dependent on peripheral dysregulation that arose in early life. Specifically, elimination of spontaneous germinal centers that developed in spleens of young NOD.H-2h4 mice by transient blockade of CD40 ligand (CD40L) or splenectomy abolished Sjögren’s pathology of aged mice. Strikingly, a single injection of anti-CD40L at 4 weeks-of-age prevented tertiary follicle neogenesis and greatly blunted the formation of key autoantibodies implicated in glandular pathology. Microarray profiling of salivary gland characterized the expression pattern of genes that increased with disease progression and showed early anti-CD40L greatly repressed B cell function, while having a broader effect on multiple biological pathways including IL-12 and interferon signaling. Importantly, a single, prophylactic treatment with anti-CD40L also inhibited the development of autoimmune thyroiditis and diabetes in NOD.H-2h4 and NOD mice, respectively, supporting a key role for CD40L in the pathophysiology of several autoimmune models. These results suggest that early peripheral immune dysregulation gives rise to autoimmune manifestations later in life and for diseases pre-dated by autoantibodies, early prophylactic intervention with biologics may prove efficacious.

Association between thyroid autoimmunity and Helicobacter pylori infection.

Background/AimsThere have been controversial reports linking Helicobacter pylori infection to autoimmune thyroid disease (AITD). However, data regarding the relationship are limited for Asian populations, which have an extremely high prevalence of H. pylori infection. We performed this study to investigate the association between H. pylori infection and AITD in Koreans.MethodsThis study involved adults aged 30 to 70 years who had visited a health promotion center. A total of 5,502 subjects were analysed. Thyroid status was assessed by free thyroxine, thyroid stimulating hormone, and anti-thyroid peroxidase antibody (TPO-Ab). Immunoglobulin G (IgG) antibodies to H. pylori were measured as an indication of H. pylori infection. We compared the prevalence of TPO-Ab in subjects with and without H. pylori infection.ResultsH. pylori IgG antibodies were found in 2,875 subjects (52.3%), and TPO-Ab were found in 430 (7.8%). Individuals positive for H. pylori Ab were older than those negative for H. pylori Ab (p < 0.01). The proportion of females was significantly higher in the TPO-Ab positive group (41.0% vs. 64.2%, p < 0.01). Prevalence of TPO-Ab positivity was higher in subjects with H. pylori infection (8.6% vs. 7.00%, p = 0.03), and this association was significant after adjusting for age, sex, and body mass index (odds ratio, 1.02; 95% confidence interval, 1.00 to 1.03; p = 0.04).ConclusionsIn our study, prevalence of TPO-Ab positivity is more frequent in subjects with H. pylori infection. Our findings suggest H. pylori infection may play a role in the development of autoimmune thyroiditis.

AUTOIMMUNE THYROIDITIS AMONG IONIZING RADIATION EXPOSED WORKERS IN CARDIAC CATHETERIZATION UNITS.

Introduction: It is well known that ionizing radiation (IR) exposure increases the risk of thyroid cancer; however less is known about its role in development of autoimmune thyroiditis. Aim of work: to investigate the thyroid gland functions,level of anti TPO among interventional cardiology team members searching for an association between the level of their occupational exposure to ionizing radiation and the thyroid gland integrity. Materials and methods: This work was carried out in Cardiac Catheterization Unit in National Heart Institute Center. The study comprised two groups, an exposed group of 47 cardiac catheterization workers (19 physicians, 15 nurses and 13 technicians) and a control group of 47 workers matched with the exposed group as regards age and sex. The studied groups were subjected to a detailed questionnaire, full clinical examinations. laboratory investigations in the form of serum thyroid stimulating hormone (TSH), Triiodothyronine (T3), Thyroxine (T4) and antithyroxiperoxidase antibodies (anti-TPO). Radiation exposure was monitored by digital dosimeter. Results: Dosimeter readings were higher among physicians followed by nurses and technicians. Statistically significant higher level of serum TSH, anti-TPO along with statistically significant lower levels of T3, were found among the exposed compared to control groups (P<0.05). Significant positive correlation was detectedbetween the level of anti-TPO and TSH (r= 0.876 P<0.001). Moreover, a significant negative correlation was found between anti-TPO and each of T3 (r= -0.814 P<0.001) and T4 (r= -0.324 P<0.05). ANOVA and Post Hoc tests showed significantly higher level of anti-TPO with significantly lower levels of T3 among the physicians compared to control group. Conclusion: Autoimmune thyroiditis may be considered as one of the adverse health hazards of occupational exposure to ionizing radiation in cardiac catheterization units. Recommendations: We recommend the regular measurement of thyroid hormone especially TSH and anti-TPO to detect early affection of thyroid glandamong radiation exposed workers.

Histologic pattern of thyroid disorders in Southern Kerala

Since the implementation of universal salt iodization in 1986, India is said to be in the transition phase from iodine deficiency to iodine sufficiency, and this is expected to change the spectrum of thyroid disorders in the country. Materials and Methods: A retrospective study of 246 biopsy specimens of subtotal/total/hemi thyroidectomy cases done during a period of 6 years from 2007 to 2012 at a tertiary hospital in Trivandrum, Kerala, is analyzed. Results: Thyroidectomy specimens accounted for 3.2% of the total surgical specimens received during the study period. Among the 246 thyroidectomy specimens, nodular colloid goiter (NCG) with or without other associated thyroid lesions outnumbered other disorders accounting for a total of 142 cases (58%) followed by 90 cases of autoimmune thyroiditis (AIT) with or without other thyroid lesions (37%). Dual lesions such as AIT with colloid goiter (7 cases, 3%), AIT with tumors (45 cases, 18%), and NCG with tumors (40 cases 16%) were also noted. The presence of tumors was found in 106 cases (43%). The overall incidence of malignancy was 36%. Forty-one cases of AIT and 36 cases of NCG were associated with papillary thyroid carcinoma (PTC) (46% and 25%, respectively); the difference was statistically significant ( P = 0.01). Conclusions: This study showed that the incidence of AIT and associated PTC is high, and the role of iodine or any other goitrogens in triggering or enhancing the onset and development of AIT in this area deserves further study.

Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases

ObjectivesViral infections frequently have been cited as important environmental factors implicated in the onset of autoimmune thyroiditis (AIT). The aim of this study was to determine the involvement of HHV-6 infection in the development of autoimmune thyroiditis. MethodsThis study included 45 patients (42 female and 3 male; median age 47.00 IQR 38.50–57.00) with histologically, laboratory, and clinically confirmed autoimmune thyroiditis, as well as 30 autopsied subjects (26 female and 4 male; median age 58.50, IQR 51.50–67.00) without thyroid pathologies and 30 healthy blood donors (25 female and 5 male; median age 33.50, IQR 27.75–44.25) as controls. Results were obtained by applying molecular virology and immunohistochemistry techniques. ResultsThe presence of persistent HHV-6 infection in AIT patients was significantly higher (p 0.0058) than in the control group (44/45 (98%) vs. 23/30 (77%), respectively). Also, a significantly higher frequency of HHV-6 activation marker (U79/80 mRNA) was found in patients’ thyroid gland tissue samples with AIT in comparison with the control group (18/44 (41%) vs. 1/17 (6%), respectively; p 0.0118). The median HHV-6 load was found to be higher in patients with active viral infection than in patients without it (2147, IQR 971–4188 vs. 551, IQR 145–1589 copies/1×106 cells; p 0.003). The presence of HHV-6 antigen expression was demonstrated in intrafollicular cellular clusters and immunohistochemistry indicated thyrocytes in the follicle wall. ConclusionsThese findings provide evidence of strong HHV-6 infection association with AIT development.

The effect of radionuclide and pesticide pollution on the development of autoimmune thyroiditis in high school children.

Objective: Hormonal diagnostics of autoimmune thyroiditis in high school children residing in different ecological, biogeochemical, pesticide-polluted and unpolluted areas. Materials and methods: A...

Coumestrol inhibits autoantibody production through modulating Th1 response in experimental autoimmune thyroiditis.

Coumestrol is a common phytoestrogen found in plants and Chinese medicinal herbs. Its influences on experimental autoimmune thyroiditis (EAT) were investigated in this study. Female adult CBA/J mice were fed with drinking water containing 1% Tween80 only (Control group), 0.8 mg/l (L group) and 8 mg/l coumestrol (H group) from 6 to 15 weeks of age, respectively. Their serum coumestrol concentrations were determined by high performance liquid chromatography, which were undetectable, 43.70 ± 21.74 ng/ml and 135.07 ± 70.40 ng/ml, respectively. In addition, the mice (n = 14–16/group) were immunized twice with thyroglobulin (Tg) and Freund's adjuvant to induce EAT during the meantime. Although no overt changes in the extent of intrathyroidal mononuclear cell infiltration were shown in the two coumestrol-treated groups as compared with the controls, serum anti-Tg IgG2a, IgG3 and IgG1 titers, ratio of IgG2a to IgG1 and the percentage of T helper (Th)1 cells in the splenocytes were significantly reduced in the L group. Another consistent change was the significantly decreased expression of splenic IFN-γ mRNA after low dose of coumestrol exposure. Uterine weight was also markedly reduced in the mice of L group. These findings suggest that coumestrol treatment may have some beneficial actions against thyroid-specific autoantibody production in the development of autoimmune thyroiditis through suppression of Th1 response due to its anti-estrogenic activity.