Non-autoimmune Thyroid Disease Research Articles

Prevalences of Other Non-Thyroid Autoimmune Diseases and Factor Associated with Their Presence in Ocular Myasthenia Gravis.

To report the prevalences of other non-thyroid autoimmune diseases and identify factors associated with their presence in ocular myasthenia gravis (OMG) subjects. A total of 208 subjects with OMG diagnosis were included. Demographic data, clinical characteristics, the ice-pack test, the acetylcholine receptor (AChR) antibody test, electrophysiology tests (single-fiber electromyography and repetitive nerve stimulation), the presence of thymoma, generalized myasthenia gravis conversion, and the presence of other non-thyroid autoimmune diseases (defined as the presence of at least one other non-thyroid autoimmune disease) were retrospectively reviewed. Factors associated with the presence of other non-thyroid autoimmune diseases were analyzed by univariate and multivariate logistic regression. Of the total 208 subjects, 21 (10.10%) exhibited the presence of other non-thyroid autoimmune diseases (19 subjects (9.14%) and 2 subjects (0.96%) had one and two other non-thyroid autoimmune diseases, respectively), and systemic lupus erythematosus (SLE) was diagnosed in 9 subjects, followed by Sjogren's syndrome (7 subjects), rheumatoid arthritis (6 subjects), and ankylosing spondylitis (1 subject). Therefore, the prevalences of SLE, Sjogren's syndrome, rheumatoid arthritis, and ankylosing spondylitis in OMG subjects were estimated to be 4.33% (95% confidence interval (CI): 2.29-8.02%), 3.37% (95% CI: 1.64-6.79%), 2.88% (95% CI: 1.33-6.14%), and 0.48% (95% CI: 0.08-2.67%), respectively. Positivity of the AChR antibody was the only significant factor associated with the presence of other non-thyroid autoimmune diseases (odds ratio 4.10, 95% CI: 1.11-15.21, p = 0.035). The presence of other non-thyroid autoimmune diseases was found in approximately 10% of OMG patients, with SLE displaying the highest prevalence. We recommend screening and monitoring for other non-thyroid autoimmune diseases in OMG patients, particularly those with positivity of the AChR antibody.

Risk of non-thyroidal autoimmune diseases in patients with Graves' disease: a nationwide retrospective cohort study.

Graves' disease (GD) is a major autoimmune thyroid disorder and associated with non-thyroidal autoimmune disease (NTAD). We aimed to investigate the risk of NTAD in patients with GD compared with age- and sex-matched controls and to evaluate whether the risk differs between individuals with or without Graves' ophthalmopathy (GO). This was a retrospective cohort study using data from the Korean National Health Claims database. We included 77 401 patients with GD (2,310 with GO) and 77 401 age- and sex-matched controls. Risk of NTAD were compared between the entire cohort and within the GD cohort. During a mean follow-up period of 9 years, NTAD developed in 12 341 (16.1%) patients in the GD cohort. Risk for systemic lupus erythematosus (SLE) [adjusted hazard ratio (aHR):1.15, 95% confidence interval (CI): 1.02-1.29], vitiligo (aHR: 1.24, 95% CI: 1.10-1.40), and alopecia areata (aHR: 1.11, 95% CI: 1.10-1.40) were higher in the GD cohort than in the control cohort. In the GD cohort, risk for SLE (aHR: 1.60, 95% CI: 1.11-2.33), Sjogren's syndrome (aHR: 1.89, 95% CI: 1.30-2.74), and ankylosing spondylitis (aHR: 1.53, 95% CI: 1.08-2.17) were higher in the GO group than in the non-GO group. This study demonstrated an increased risk of SLE, vitiligo and alopecia areata in patient with GD. In the GD cohort, patients with GO had an increased risk of SLE, Sjogren's syndrome and ankylosing spondylitis. These findings suggest that importance of implementing a strategy for early detection of NTAD based on the presence of GO.

Сhronic autoimmune thyroiditis is a «signal disease» in the multiorgan autoimmune syndrome

The current century has been declared by the WHO as the «century of autoimmune diseases», of which there are more than a hundred today. The natural course of any autoimmune disease is characterized by progression from a latent and subclinical to a clinical stage and is associated with the presence of specific circulating autoantibodies. During the life of a person with one verified autoimmune disease, there is a high probability of consecutive manifestation of other autoimmune pathologies. Every fourth patient with chronic autoimmune thyroiditis develops autoimmune non-thyroid pathologies during his life, and vice versa, chronic autoimmune thyroiditis is present among people with non-thyroid autoimmune diseases. Modern ideas about the pathogenetic mechanisms of the development and progression of autoimmune diseases make it possible to consider chronic autoimmune thyroiditis as a «signal pathology» in the multiorgan autoimmune syndrome.

Association of Helicobacter pylori Infection with Autoimmune Thyroid Disease in the Female Sex.

Helicobacter pylori infection has been associated with an increased risk of thyroid diseases (TDs), although scientific evidence is conflicting. In the present study the relationship between TDs, including both autoimmune (AI) and non-autoimmune TD, and H. pylori infection was investigated. Data from records of patients undergoing upper endoscopy and histologically evaluated for H. pylori infection were retrieved. In addition to demographic information, the features of gastritis based on non-targeted biopsies collected from the antrum, angulus, and corpus were analyzed. The presence of H. pylori infection and atrophy and/or metaplasia and/or dysplasia in at least one gastric specimen was defined as a long-lasting H. pylori infection and the presence of a chronic-active gastritis as a current infection. Hashimoto's and Graves' diseases were included in the AITD group, and thyroid nodules, goiter, iatrogenic thyroid hypo/hyper function, and thyroidectomy in the non-autoimmune TD group. A total of 8322 records from adult patients from Northern Sardinia, characterized by a similar genetic background, was analyzed. Participants were aged 18-93 years (females 5339, 64.1%), and more specifically, 562 (6.7%) had a diagnosis of AITD and 448 (5.4%) of non-autoimmune TD. A significant association between long-lasting H. pylori and AITD (OR 1.34; 95%CI 1.13-1.60) was found, irrespective of age, sex, body mass index, and smoking status, while it was not associated with non-autoimmune TD. Current H. pylori infection did not show significant ORs for AITD (OR 0.99; 95%CI 0.64-1.57) and non-autoimmune TD (OR 0.86; 95%CI 0.66-1.15). The association with long-lasting H. pylori infection was confirmed to be significant for both Hashimoto's thyroiditis and Graves' disease by multivariable regression analysis. Stratification according to sex revealed a significant association only for females (OR 1.39; 95%CI 1.12-1.72). Our results indicate that long-lasting H. pylori infection is associated with AITD in the female adult population of Northern Sardinia.

Effect of gluten-free diet on autoimmune thyroiditis progression in patients with no symptoms or histology of celiac disease: a meta-analysis.

Hashimoto's thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own. The aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD. The study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges' g was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17. The online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: -0.39 for TgAb (95% CI: -0.81 to +0.02; p = 0.06; I² = 46.98%) and -0.40 for TPOAb (95% CI: -0.82 to +0.03; p = 0.07; I² = 47.58%). TSH showed a reduction with ES: -0.35 (95% CI: -0.64 to -0.05; p = 0.02; I² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; p = 0.02; I² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: -0.38 to +0.48; p = 0.82; I² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb p = 0.02; TPOAb p = 0.02; FT3 p = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 (p = 0.03). This is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.

Correlation Analysis of HHV-6A Viral Load and Anti-TPO Antibody Levels in Patients with Hashimoto’s Thyroiditis

Aim: This study investigated the correlation between anti-thyroid peroxidase (anti-TPO) antibody levels and human herpesvirus 6 (HHV-6) viral load as triggers for Hashimoto's thyroiditis (HT). Materials & methods: The study included 60 HT patients, 60 patients with non-autoimmune thyroid disease, and 60 subjects with normal thyroid function. HHV-6 viral loads in serum samples were detected using real-time PCR. Results: A significant correlation was found between the increase in viral load and increased levels of anti-TPO antibodies in serum samples from HT patients (p = 0.001). Conclusion: The aim of this study was to explore the potential involvement of HHV-6A in the onset of HT, with the goal of identifying improved treatment options for affected individuals.

Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy.

The number of recognised distinct autoimmune diseases (AIDs) has progressively increased over the years with more than 100 being reported today. The natural history of AIDs is characterized by progression from latent and subclinical to clinical stages and is associated with the presence of the specific circulating autoantibodies. Once presented, AIDs are generally chronic conditions. AIDs have the tendency to cluster and co-occur in a single patient. Autoimmune thyroid diseases (AITD) are the most prevalent of AIDs in the world population, and about one-third of the AITD patients also present with a non-thyroid AID during their life-span. Furthermore, patient with non-thyroid AIDs often presents with a form of AITD as a concurrent condition. Many of the clusters of AIDs are well characterized as distinctive syndromes, while some are infrequent and only described in case reports. In this review, we describe the wide spectrum of the combinations and the intricate relationships between AITD and the other AIDs, excluding Addison's disease. These combinations are collectively termed type 3 Autoimmune Polyglandular Syndrome (APS-3), also called type 3 Multiple Autoimmune Syndrome (MAS-3), and represent the most frequent APS in the world populations. Numerous associations of AITD with various AIDs could be viewed as if the other AIDs were gravitating like satellites around AITD located in the center of a progressively expanding galaxy of autoimmunity.

Clinical evaluation of an automated TSI bridge immunoassay in the diagnosis of Graves’ disease and its relationship to the degree of hyperthyroidism

BackgroundThe rapid and accurate detection of thyroid-stimulating hormone (TSH) receptor antibodies has always been an urgent need for the clinical diagnosis and management of Graves’ disease (GD). We aimed to evaluate the use of an automated thyroid-stimulating immunoglobulin (TSI) bridge immunoassay in the diagnosis of GD and to analyze the relationship between TSI and the degree of hyperthyroidism.MethodsA total of 227 new-onset GD patients, 29 Hashimoto thyroiditis, 43 non-autoimmune thyroid diseases and 37 euthyroid controls were consecutively recruited. All participants accepted the measurement of their serum thyroid function and thyroid-associated antibodies, including TSI being measured by an Immulite 2000 bridge immunoassay and TSH receptor autoantibodies (TRAb) being measured by a third-generation Roche electrochemiluminescence immunoassay. The quantitative consistency between the TSI and TRAb detection methods was analyzed by using Passing-Bablok regression and Bland–Altman plots. The diagnostic performance for GD was assessed by receiver operating characteristic (ROC) curve analysis.ResultsAmong 227 GD patients (174 females and 53 males, with a mean age of 39 years), the quantitative TSI was positively correlated with TRAb (r = 0.8099). According to the cut-off values proposed by the manufacturers (TSI: 0.55 IU/L, TRAb: 1.75 IU/L), the positive rates of TSI and TRAb in new-onset GD patients were 96.92% and 95.15%, respectively. Both TSI and TRAb levels positively correlated with FT4 levels (TSI: r = 0.243, TRAb: r = 0.317; all P < 0.001) and FT3 levels (TSI: r = 0.288, TRAb: r = 0.360; all P < 0.001) in new-onset GD patients. The ROC analysis showed that the optimal TSI cut-off value was 0.577 IU/L for GD diagnosis in this Chinese population, with a sensitivity of 96.92% and a specificity of 97.25%, respectively. The optimal TRAb cut-off value of was 1.38 IU/L, with a sensitivity of 96.92% and a specificity of 99.08%. There were no significant differences between the cut-off values obtained through the ROC analysis and those provided by the manufacturer for both TSI and TRAb when calculating their sensitivity and specificity in diagnosing GD. Among the 8 newly diagnosed GD cases with discordant qualitative antibody results, TSI was more likely than TRAb to match the clinical diagnosis of GD (6 TSI-positive vs. 2 TRAb-positive patients).ConclusionThe automated TSI bridge immunoassay was positively correlated with thyroxine levels in new-onset GD patients and was more likely to be consistent with the clinical diagnosis of GD than with that of TRAb. The positive Immulite 2000 TSI cut-off value of 0.577 IU/L for GD diagnosis in the Chinese population were close to the value recommended by the manufacturer.

The Frequency of Intrathyroidal Follicular Helper T Cells Varies with the Progression of Graves' Disease and Hashimoto's Thyroiditis.

Objective Autoimmune thyroid diseases (AITD), mainly Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common organ-specific autoimmune diseases characterized by circulating antibodies and lymphocyte infiltration. Follicular helper T (Tfh) cell dysregulation is involved in the development of autoimmune pathologies. We aimed to explore the role of intrathyroidal and circulating Tfh cells in patients with GD and HT. Methods Ultrasound-guided thyroid fine-needle aspiration (FNA) was conducted in 35 patients with GD, 40 patients with HT, and 22 patients with nonautoimmune thyroid disease (nAITD). Peripheral blood samples were also obtained from 40 patients with GD, 40 patients with HT, and 40 healthy controls. The frequencies of intrathyroidal and circulating Tfh cells from FNA and peripheral blood samples were assessed by flow cytometry. Additionally, the correlations between the frequencies of the Tfh cells and the levels of autoantibodies and hormones or disease duration were analyzed. Results The frequency of intrathyroidal CD4+CXCR5+ICOShigh Tfh cells was higher in HT patients than in GD patients. Significant correlations were identified between the percentages of circulating and intrathyroidal Tfh cells and the serum concentrations of thyroid autoantibodies, especially thyroglobulin antibodies (TgAb), in AITD. Intrathyroidal CD4+CXCR5+ICOShigh Tfh cells were positively correlated with free triiodothyronine (FT3) in HT patients but negatively correlated with FT3 in GD patients. In addition, HT patients with a longer disease duration had an increased frequency of intrathyroidal CD4+CXCR5+ICOShigh and CD4+CXCR5+PD-1+ Tfh cells. In contrast, in the GD patients, a longer disease duration did not affect the frequency of intrathyroidal CD4+CXCR5+ICOShigh but was associated with a lower frequency of CD4+CXCR5+PD-1+ Tfh cells. Conclusions Our data suggest that intrathyroidal Tfh cells might play a role in the pathogenesis of AITD and they are potential immunobiomarkers for AITD.

Correlation between Maternal Vitamin D and Thyroid Function in Pregnancy with Maternal and Neonatal Outcomes: A Cross-Sectional Study.

Background The aim of this study was to evaluate the prevalence of vitamin D deficiency in pregnant women to investigate the relationship between vitamin D level and thyroid function. Methods In this cross-sectional descriptive study, a total number of 66 patients during the three trimesters of pregnancy were investigated; 22 pregnant women were studied in each trimester of pregnancy. We evaluated thyroid function tests and thyroid autoantibodies (TPOAb and TGAb), as well as the serum level of 25OHD, to determine the relationship between vitamin D level and autoimmune or non-autoimmune thyroid disease in pregnancy. Results Pearson's correlation in all subjects showed that vitamin D levels did not have a significant relationship with maternal age. Only in the third trimester, there was a significant difference in maternal age based on their vitamin D status. There was no significant difference between the trimesters of pregnancy and vitamin D status (P > 0.05). Also, there were no significant differences between serum levels of vitamin D within three trimesters. Examination of thyroid function tests during pregnancy in relation to vitamin D showed that there was no significant Spearman's correlation between thyroid function status and serum vitamin D level (P > 0.05). There was no significant difference in the mean level of serum 25OH vitamin D in each subgroup of thyroid status (P > 0.05). Regarding the pregnancy outcomes, two newborns were admitted to NICU, meconium aspiration was in one case, and IUFD in another case led to pregnancy termination. These four cases were related to the maternal history of hypothyroidism. Conclusion There was no significant relationship between vitamin D and pregnancy trimester. The serum level of vitamin D had no particular effect on the outcome of pregnancy and the thyroid gland function.

High prevalence of thyroid hormone autoantibody and low rate of thyroid hormone detection interference.

ObjectiveThyroid hormone autoantibody (THAb) is a common antibody in autoimmune disease and can interfere with the detection of thyroid hormone (TH). There was no research reporting the prevalence of THAb in Chinese and the rate of THAb interfering with TH detection.MethodsWe collected 114 patients with autoimmune thyroid disease (AITD) (Hashimoto's thyroiditis, 57 cases; Graves’ disease, 57 cases), 106 patients with nonthyroid autoimmune diseases (NTAID), and 120 healthy subjects. According to the presence or absence of thyroid antibodies, patients with NTAID were divided into two groups: NTAID‐AITD and NTAID groups. Radioimmunoprecipitation technique was used to detect THAb in all subjects. TH was detected on Abbot and Roche platforms in patients with positive THAb.ResultsThe prevalence of THAb was 22.8% in Hashimoto's thyroiditis and 45.6% in Graves’ disease. The prevalence of THAb in AITD group was lower than that in NTAID or NTAID‐AITD groups (34.2% vs. 61.5%, p = 0.014; 34.2% vs. 71.3%, p < 0.01). Among total 98 patients with positive THAb, TH levels of 9 patients were falsely elevated (9.18%).ConclusionThe prevalence of THAb in AITD patients was lower than that in NTAID patients. Although THAb had a high frequency in various autoimmune diseases, the prevalence of THAb interfering with TH detection was only 9.18%.

Third generation radioimmunoassay (RIA) for TSH receptor autoantibodies (TRAb) - one step less, similar results?

Aim TSH-receptor (TSHR)-autoantibody (TRAb) is the serological hallmark of Graves’ disease (GD). Recently, 3 rd -generation radioimmunoassays (RIA) employing monoclonal TRAb such as M22 or T7 instead of TSH for the inhibition of human TRAb binding with solid-phase TSHR (coated tubes) have been introduced into laboratory routine. Methods As current assays typically employ a consecutive incubation of patient serum and labelled monoclonal TRAb, automation of TRAb RIA is a challenge. Thus, the assay procedure using human TSHR-coated tubes and the mouse monoclonal TRAb T7 was modified by combining both steps. The novel one-step method was compared with its corresponding consecutive 3 rd -generation RIA by investigating 304 individuals encompassing 102 patients with active GD (GD a ), 43 patients with GD after successful therapy (GD t ), 31 with Hashimoto’s disease (HD), 28 with non-autoimmune thyroid diseases (NAITD) and 100 healthy subjects (HS). Results With the new method, the incubation time was shortened by approximately one hour. Both 3 rd -generation RIAs did not reveal a significantly different assay performance by comparing areas under the curve (AUC) with receiver operating characteristics curve analysis (AUC one-step: 0.94, AUC two-step: 0.96, p > 0.05, respectively). The two-step TRAb RIA demonstrated sensitivity and specificity values of 87.5 % and 96.2 %, respectively, whereas the one-step revealed 84.6 % and 96.2 %, respectively. Conclusion One-step 3 rd -generation RIA may be used for the reliable detection of TRAb. The shorter and easier assay design may improve its use and enable automation in routine nuclear medicine laboratories.

Safety of Alemtuzumab and Autologous Hematopoietic Stem Cell Transplantation Compared to Noninduction Therapies for Multiple Sclerosis.

ObjectiveTo assess safety outcomes for the induction therapies alemtuzumab and autologous hematopoietic stem cell transplantation (AHSCT) compared to noninduction disease-modifying therapies.MethodsWe performed a population-based cohort study linking the Swedish Multiple Sclerosis Register to national health care registers. Alemtuzumab, AHSCT, and a matched reference group of noninduction therapies (natalizumab, dimethyl fumarate, rituximab, fingolimod) were included if started between 2008 and 2017. Main outcomes were death, thyroid disease, nonthyroid autoimmune disease, and infection.ResultsWe identified 132 alemtuzumab-treated and 139 AHSCT-treated (68% high-dose cyclophosphamide and anti-thymocyte globulin [ATG], 32% BCNU, etoposide, cytosine-arabinoside, and melphalan/ATG) patients, together with 2,486 matched patients treated with noninduction therapies. Four patients in the alemtuzumab group died (incidence rate [IR] per 1,000 person-years 8.6, 95% confidence interval [CI] 2.3–22.0) compared to 1 patient in the AHSCT group (IR 1.7, 95% CI 0.0–9.6), and the mortality rate in the reference group was 0.7 (95% CI 0.3–1.3). Thyroid disease was most frequent in the alemtuzumab group (IR 109, 95% CI 75–154) but also occurred more often for AHSCT (IR 34, 95% CI 18–56) compared to the reference (IR 5.3 95% CI 3.9–7.1). The incidence of nonthyroid autoimmune disease was similar in all groups. IR for infection diagnosed ≥6 months from therapy initiation was 53 (95% CI 30–87) for alemtuzumab, 108 (95% CI 75–150) for AHSCT, and 51 (95% CI 46–57) for the reference.ConclusionWe confirmed a high incidence of thyroid disease in alemtuzumab- and, to a smaller extent, AHSCT-treated patients and found a higher incidence of infection for AHSCT compared to both alemtuzumab and noninduction therapies. The incidence of nonthyroid autoimmune disease was low for both therapies.Classification of EvidenceThis study provides Class III evidence of an increased risk of thyroid disease with alemtuzumab and an increased risk of infection with AHSCT treatment.

The Prevalence of Autoimmune Diseases in Longstanding Diabetes: Results from the Canadian Study of Longevity in Adults with Type 1 Diabetes

ObjectiveWe aimed to determine the prevalence of autoimmune diseases (e.g. thyroid disease, celiac disease, etc) in Canadians with longstanding type 1 diabetes (T1D) and to explore sex-specific differences and the association with complications. MethodsCross-sectional data were analyzed in an exploratory secondary analysis from the Canadian Study of Longevity in Type 1 Diabetes, a nationwide registry of people with T1D of at least 50 years’ duration. In total, 374 participants provided self-reported questionnaire data and physician-reported laboratory results. Student’s t-test, the Wilcoxon rank-sum test, the χ2 test and logistic regression were used to identify associations with autoimmune diseases. ResultsThe 374 participants had a median T1D duration of 53 years (interquartile range, 51 to 58) and a median age of onset of 11 years (6 to 16), and 57.1% were females. Females had a greater prevalence of autoimmune diseases (60.6% vs 34.4%, p<0.001). Thyroid disease was most prevalent (41%, 153/374), especially in females (51.6% vs 26.9%), and the prevalence of 1 or more autoimmune disease was 49.3% (184/374). Autoimmune disease was associated with lower odds of cardiovascular disease (CVD)—odds ratio [OR] 0.61, 95% confidence interval [CI] 0.37 to 1.00 for thyroid autoimmune disease and OR 0.34 (95% CI 0.12 to 0.93) for nonthyroid autoimmune disease, both compared to those without autoimmune disease (p=0.033). Autoimmune diseases were not associated with the presence of nephropathy, neuropathy or retinopathy. ConclusionsLifetime risk of autoimmune disease in longstanding T1D approaches 50%, is greater in females and is driven by thyroid disease. The probability of diabetes complications, such as CVD, was lower in those with autoimmune disease, which was driven mostly by nonthyroid autoimmune diseases.

Clinical diagnostic performance of a fully automated TSI immunoassay vs. that of an automated anti‑TSHR immunoassay for Graves' disease: a Chinese multicenter study.

Both thyroid-stimulating immunoglobulins immunoassay (TSI IA) and thyrotrophin receptor antibody immunoassay (TRAb IA) are commonly used for the diagnosis of Graves' disease (GD). The aim of the present study was to compare the clinical diagnostic performance of these two methods. Sera were obtained from 1103 subjects presenting a variety of clinical conditions from three centers: 100 subjects with untreated GD, 200 with treated GD, 62 with autoimmune thyroid disease(AIT), 216 with other thyroid diseases (OTHER-T), 214 with non-thyroid autoimmune diseases (NTAD), 191 with other diseases (OD), and 120 healthy subjects (HS). Both TSI and TRAb IAs were performed for all 1013 serum samples. Bioassay was performed for 86 samples whose TSI results were inconsistent the TRAb assay results. Comparing untreated GD patients with the control groups (AIT, NTAD, OTHER-T, OD, and HS) resulted in an area under the curve (AUC) of 0.992 for the TSI IA and 0.989 for the TRAb IA with no statistically significant difference observed between these AUC values (P = 0.2733). The best TSI CDP (clinical decision point) value was 0.42 IU/L. The differences in sensitivity (100% vs. 95%, P = 0.7991) and specificity (97.1% vs. 97.6%, P = 0.9426) between the TSI and TRAb IA were not statistically significant. TSI IA had a higher agreement with the TSI bioassay than TRAb IA. The clinical diagnostic performance of the TSI IA for diagnosing Graves' disease was very similar to that of the TRAb IA. TSI IA can be used to diagnose GD in the Chinese.

Thyroid autoimmunity is associated with hypothyroid-like symptoms compared with nonautoimmune benign thyroid diseases using a thyroid-specific questionnaire

BackgroundAutoimmune hypothyroidism, also commonly known as Hashimoto thyroiditis (HT), is the most common cause of hypothyroidism in iodine-replete areas. Thyroid autoimmunity was shown to be associated with lower quality of life, higher symptom load, and poor physical and psychological well-being. The aim of this study is to evaluate the disease burden of HT using a thyroid-specific questionnaire, the thyroid patient reported outcomes (ThyPRO).Patients and methodsThe study included 194 patients, divided into two groups: group 1 included 124 patients with HT stable in euthyroidism 6 months before inclusion in the study, and group 2 included 70 patients with euthyroid benign thyroid disease other than HT. All patients completed a professionally translated, carefully revised version of the ThyPRO questionnaire into Arabic language. All patients had their thyroid stimulating hormone (TSH) measured at inclusion. Anti-thyroperoxidase and/or anti-thyroglobulin antibodies were recorded for each patient where available.ResultsThere were no significant differences between the two studied groups regarding age, sex, and TSH. Both anti-thyroperoxidase and anti-thyroglobulin antibodies were significantly higher in HT group versus group 2. Group 1, HT group, showed significantly higher score in the hypothyroid symptom scale compared with group 2. No significant differences were found regarding the remaining symptom scales. Within hypothyroid symptom score scale, group 1 showed significantly higher scores in dry skin and swollen hands and feet items but not in cold sensitivity and itchy skin questions.ConclusionThis study showed that thyroid autoimmunity, independent of thyroid function status, is associated with hypothyroid-like symptoms compared with benign thyroid disease other than HT. This may be caused by a direct or an indirect role of thyroid autoantibodies.

Postoperative complications after total thyroidectomy for benign thyroid diseases

Background: The thyroid gland is normally impalpable, once enlarged it is called goiter which may be simple, toxic, inflammatory or neoplastic. Autoimmune thyroid disease (ATD) includes goiters associated with antigen antibody reaction that initiates a series of inflammatory reactions. Due to these inflammatory reactions surgeries become more difficult with a tendency to develop postoperative complications.Methods: This is a prospective study on 207 patients with thyroid disorders who were treated with total thyroidectomy in general surgery department, Menoufia university hospital between October 2015 and December 2018. Patients were divided into two groups based on postoperative histopathological findings group A included 73 patients with autoimmune thyroid disease while group B included 134 patients with non-autoimmune thyroid disease. All patients were followed up for 6 months postoperatively to evaluate vocal cord palsy and hypoparathyroidism.Results: In our study, the rate of temporary and permanent vocal cord palsies were 4.1% and 1.4% in ATD group respectively while in non-ATD group were 1.5% and 0.7% respectively with no statistically significant difference between both groups, whereas the rate of temporary and permanent hypoparathyroidism were 9.5% and 4.1% in ATD group respectively while in non-ATD group were 2.9% and 0.7% respectively with significantly higher rate in ATD group.Conclusions: Surgery for ATD is a challenging procedure but safe with a low incidence of general complications and vocal cord palsy when compared with surgery for non-ATD. However, postoperative hypoparathyroidism is significantly higher due to dense adhesions which obscure the surgical field so a special attention should be paid to the parathyroid glands during total thyroidectomy.

Phenotypic Expression of Autoimmunity in Children With Autoimmune Thyroid Disorders.

Autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), tend to aggregate with other non-thyroidal autoimmune diseases (NTADs). Aim of this Mini-review is to report the most recent insights concerning the clustering of NTADs in pediatric patients with either HT or GD, the pathophysiology of AITDs and the metamorphic thyroid autoimmunity. A systematic literature research of the last 15 years, according to EQUATOR statement, was carried out through MEDLINE via PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) Embase, CINAHL, Cochrane Library, based on the following keywords: (autoimmune thyroid disease OR Hashimoto thyroiditis OR Grave's disease) AND (autoimmune comorbidities OR extra-thyroidal autoimmune disorders) AND (children OR adolescents OR pediatrics) AND (celiac disease OR type 1 diabetes mellitus OR arthropathies OR cutaneous diseases) AND (Turner syndrome OR Down syndrome). One-hundred and twenty-eight manuscripts were extrapolated but only seventeen were eligible. On the basis of the available reports it may be inferred that clustering of NTADs can be significantly modified by both patients' age at AITDs presentation and association with Down's syndrome (DS). Particularly, the association of AITDs with celiac disease and type 1 diabetes was most commonly reported in children than in adults. A sequential shifting from HT to GD has been described in children with AITDs, and it seems to be more frequent in children with DS than in those without DS. Coexistence of autoimmune diseases might be the result of a complex interaction among genetics, environment and epigenetic modifications that are able to affect gene expression, immune system response and, finally, the pathogenesis of autoimmune diseases.

MON-596 Male Individuals with Autoimmune Thyroid Disease Present Higher Risk for Clustering Other Non-Thyroidal Autoimmune Diseases

Background: Autoimmune thyroid disease (ATD) share common pathophysiology pathways with several other autoimmune diseases. It can be a first manifestation of an immunoregulatory diathesis, leading to a cluster of associated autoimmunities. Aim: The present study aimed to evaluate and compare the frequency of Type 1 diabetes (T1DM) and celiac disease (CD) related antibodies among pediatric and adult patients with Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). Methods: A total of 145 individuals, aged 2 to 50 years (114 females; 89 pediatric patients) were included in a cross-sectional descriptive study (74 HT). Determination of antibodies related to T1DM (GADA65 and IA2), CD (tTG-IgA and EMA-IgA) and Anti-Saccharomyces Cerevisiae (ASCA) were performed. Results: Non-thyroidal autoimmune diseases (NTAID) was found in 8.3% of individuals. Males presented a 3.2-time higher risk for a second NTAID (p=0.004) and a 4-time higher risk for a third NTAID (p=0.017). The pediatric group had 53% higher risk for developing a second NTAID (p=0.042). GADA65, IA2 and ASCA-IgG positivity were found in 11%, 2.7% and 14.4% of the individuals, respectively. CD-related antibodies were found in a ratio of 1:48 patients. Conclusion: Individuals with ATD present high rates of T1DM and CD-related antibodies. The male group, regardless of age, has a higher rate of CD-related antibodies and also higher risk for developing two or more NTAIDs. The pediatric population with ATD presents a higher rate of AID clustering than adults. A closer surveillance for associated NTAID throughout follow-up should be performed, mainly in young male group.

MON-616 Potential Relationship between Hypothyroidism and Periodontal Disease Severity

Introduction: Hypothyroidism is an endocrine disorder having autoimmune and inflammatory etiologies. There is evidence that periodontal disease might be influenced by a variety of systemic inflammatory conditions in a bidirectional manner, including diabetes, cardiovascular disease, adverse pregnancy outcomes, and osteoporosis.1 Consequently, we hypothesized that the severity of periodontitis also might be influenced by hypothyroidism. Methods: IRB approval was obtained prior to initiation of this study. To test our hypothesis, records of patients referred to a faculty periodontal practice during the 20-year period from 1996-2015 were reviewed (N=1093). Inclusion criteria included the presence of chronic, generalized moderate-to-severe periodontitis (stage III to IV; grade B to C).2 Exclusion criteria were diabetes, smoking, systemic steroids, hormonal supplementation unrelated to thyroid disease, and non-thyroid autoimmune disease. After applying those criteria, 538 patients were considered for further analysis. Periodontal disease severity was measured by calculating the percent of teeth with probing depths ≥5 mm or ≥6 mm. The presence of hypothyroidism was determined by review of patient medical history for use of prescription medication(s) for thyroid hormone supplementation. Significance was measured via analysis of variance and independent sample t-tests calculated using IBM SPSS Statistics v25. Results: Patients with hypothyroidism had more teeth with greater probing depths, implying more severe periodontal disease. Specifically, 61.4% of teeth from periodontitis patients with hypothyroidism had periodontal probing depths ≥5 mm, vs. 48.1% of teeth in periodontitis patients without hypothyroidism (27.7% increase, mean difference= 13.3%, 95% confidence interval= 7.9%-18.8%, P=5E-06). Similarly, the prevalence of probing depths ≥6 mm was 36.2% in periodontitis patients with hypothyroidism, vs. 28.2% for periodontitis patients without hypothyroidism (28.4% increase, mean difference= 8.0%, 95% confidence interval= 3.1%-12.9%, P=0.002). Conclusions: Our data indicate that the prevalence of moderate to advanced periodontitis might be influenced by hypothyroidism. Prospective and retrospective studies are currently underway to determine whether hypothyroidism might be associated with systemic or inflammatory changes that might affect periodontal disease progression. Studies measuring the relationship of hypothyroidism on less severe forms of periodontitis also are in progress. Collectively, our data suggest that periodontists should consider thyroid disease, and endocrinologists should consider clinical history or signs of periodontal disease, as a component of patient evaluation.