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Objective: Type 1 diabetes and Hashimoto’s thyroiditis frequently cluster in individuals and in families, indicating shared origins. The objective of this study was to investigate familial co-aggregation of these diseases and to quantify shared genetic and environmental factors. Design: This study is a twin cohort study. Methods: National health registers were used to identify cases among 110 814 Swedish twins. Co-aggregation was calculated as risk ratios for type 1 diabetes among co-twins of individuals with Hashimoto’s thyroiditis, and viceversa. Variance explained by genetics (i.e. heritability), and the proportions thereof shared between the diseases, was estimated by contrasting associations in monozygotic and dizygotic twins using structural equation models. Results: Individuals with one disease were at a high risk for the other disease (adjusted risk ratio: 11.4 (95% CI: 8.5– 15.3)). Co-aggregation was more common in monozygotic than in dizygotic pairs, with adjusted risk ratios of 7.0 (95% CI: 3.2–15.1) and 1.7 (95% CI: 0.7–4.1), respectively. Genetic effects shared across diseases accounted for 11% of the variance for type 1 diabetes and 9% of the variance for Hashimoto’s thyroiditis, while environmental factors unique to individual twins, but shared across diseases, accounted for 10% of the variance for type 1 diabetes and 18% of the variance for Hashimoto’s thyroiditis. Conclusions: Both genes and environment unique to individual twins contribute to considerable etiologic overlap between type 1 diabetes and Hashimoto’s thyroiditis. These findings add to the current knowledge on the mechanisms behind autoimmune disease clustering and could guide future research aimed at identifying pathophysiological mechanisms and intervention targets. [ABSTRACT FROM AUTHOR]

Aim: The risk of differentiated thyroid cancer (DTC) recurrence is w idely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to eva luate the relationship between DTC topography and response to initial therapy. Patients and methods: We enrolled 401 low- to intermediate-risk patients with DTC wh o had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compar ed with the response to therapy as assessed 12 months after the end of therapy. Results: Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural responses, resp ectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthm ic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (P = 0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto's thyroiditis, vascular invasion, and extrathyroidal extension (P = 0.78, P = 0.77, P = 0.52, P = 0.19, P = 0.73, and P = 0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio = 6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (P = 0.02). Conclusion: Our data show that isthmus topography of malignant thyroid nod ules is a risk factor for having both persistent disease 12 months after primary treatment and reduce d DFS. [ABSTRACT FROM AUTHOR]

Objective: Indeterminate cytological result at fine-needle aspiration cytology (FNAC) remains a clinical challenge for endocrinologists. Aim of the present study was to evaluate whet her a coexistent chronic autoimmune thyroiditis (CAT) might affect the diagnostic accuracy of fine-needle aspiration cy tology for thyroid nodules. Design and methods: A retrospective cohort study was designed including all nodules receiving an indeterminate cytology result (TIR3A or TIR3B) undergoing thyroid surgery and subsequent histological confirmation. Patients were stratified into two groups according to the presence or absence of CAT. The hypothesis to be tested was whether follicular cell alterations induced by CAT might increase the r ate of indeterminate cytological results in histologically benign thyroid nodules. Additional control groups were represen ted by nodules with determinate cytology, either benign (TIR 2) or malignant (TIR5). Results: One hundred and eighty-nine indeterminate thyroid nodules were included (67 TIR3A and 122 TIR3B). At post-surgical histology, 46 nodules (24.3%) were malignant. No significant differences were observed in the rate of histologically proven malignancy between patients without CAT a nd patients with CAT in the TIR3B (29.4% vs 32.4%; P = 0.843) nor TIR3A (13.0% vs 11.4%; P = 1.000) nodules. The rate of coexistent CAT was similar between TIR3B and TIR5 nodules harboring PTC at histology (30.4% vs 39.4%, P = 0.491) and between indeterminate nodules and a control group of TIR2 nodules (39.2% vs 37.0%; P = 0.720). Conclusions: The similar rates of histologically proven malignancy found in cytologically indeterminate nodules in the presence or absence of concomitant CAT would not support that C AT itself affects the diagnostic accuracy of fineneedle aspiration cytology. [ABSTRACT FROM AUTHOR]

Objective: The association between chronic autoimmune thyroiditis (CAT) a nd differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when scre ening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ult rasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT. Design and methods: A retrospective longitudinal cohort study was designed. For th e study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enro lled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD-; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and dev elopment of DTC during follow-up. Results: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD - group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-n eedle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases. Conclusions: In our series of CAT patients, the appearance of new thyroid-n odules was frequent, but none of them were found to be malignant. The presence of CAT appears to be a ssociated with a negligible risk of developing clinically overt DTC. [ABSTRACT FROM AUTHOR]

Objective: Co-aggregation of autoimmune diseases is common, suggesting pa rtly shared etiologies. Genetic factors are believed to be important, but objective measures of environ mental vs heritable influences on co-aggregation are absent. With a novel approach to twin studies, we aimed at esti mating heritability and genetic overlap in seven organspecific autoimmune diseases. Design: Prospective twin cohort study. Methods: We used a cohort of 110 814 twins to examine co-aggregation an d heritability of Hashimoto's thyroiditis, atrophic gastritis, celiac disease, Graves' disease, type 1 dia betes, vitiligo and Addison's disease. Hazard ratios (HR) were calculated for twins developing the same or different disea se as compared to their co-twin. The differences between monozygotic and dizygotic twin pairs were used to estim ate the genetic influence on co-aggregation. Heritability for individual disorders was calculated using stru ctural equational modeling adjusting for censoring and truncation of data. Results: Co-aggregation was more pronounced in monozygotic twins (media n HR: 3.2, range: 2.2-9.2) than in dizygotic twins (median HR: 2.4, range: 1.1-10.0). Heritability was moder ate for atrophic gastritis (0.38, 95% CI: 0.23-0.53) but high for all other diseases, ranging from 0.60 (95% CI: 0.49-0. 71) for Graves' disease to 0.97 (95% CI: 0.91-1.00) for Addison's disease. Conclusions: Overall, co-aggregation was more pronounced in monozygotic tha n in dizygotic twins, suggesting that disease overlap is largely attributable to genetic factors. Co- aggregation was common, and twins faced up to a ten-fold risk of developing diseases not present in their co-twin. Our r esults validate and refine previous heritability estimates based on smaller twin cohorts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the concordance of serologic and sonographic evidence of Hashimoto's thyroiditis with its gold standard histopathologic identification. Design: We performed a retrospective analysis on a cohort of 825 consecutive patients in whom TPOAb and thyroid ultrasound were performed, and in whom thyroid nodule evaluation led to surgical and histopathologic analysis. The presence or absence of Hashimoto's thyroiditis on histopathology was correlated with serologic and sonographic markers. We further assessed the impact of low versus high titers of TPOAb upon this concordance. Results: Of 825 patients, 277 (33.5%) had histologic confirmation of Hashimoto's thyroiditis, 235 patients (28.4%) had elevated serum levels of TPOAb, and 197 (23.8%) had sonographic evidence of diffuse heterogeneity. Of those with histopathologic evidence, only 64% had elevated TPOAb (sensitivity: 63.9%; specificity: 89.4%), while only 49% were sonographically diffusely heterogeneous (sensitivity: 49.1%; specificity: 88.9%). A subset of only 102 of 277 (37%) with histologically proven Hashimoto's thyroiditis was positive for both TPOAb and diffusely heterogeneous. Concordance analysis demonstrated that TPOAb and histopathology had higher agreement (k = 0.55) than did ultrasound and histopathology (k = 0.40) for the diagnosis of Hashimoto's thyroiditis. Higher titers of TPOAb correlated with a higher likelihood of Hashimoto's thyroiditis, with a best cutoff of 2.11-fold the upper normal level of TPOAb. Conclusion: Only moderate concordance exists between serological evidence of Hashimoto's thyroiditis and histopathologic findings, though it increases with higher TPOAb concentration. Diffuse heterogeneity on ultrasound is a less-sensitive diagnostic tool than elevated TPOAb. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) is fibro-inflammatory, immune-mediated, systemic disease recognized as a defined clinical condition only in 2001. The prevalence of IgG4-RD is 6/100 000, but it is likely to be underestimated due to insufficient awareness of the disease. The diagnostic approach is complex because of the heterogeneity of clinical presentation and because of rather variable diagnostic criteria. Indeed, high concentrations of IgG4 in tissue and serum are not a reliable diagnostic marker. The spectrum of IgG4-RD also includes well-known thyroid diseases including Riedel's thyroiditis, Hashimoto's thyroiditis and its fibrotic variant, Graves' disease and Graves' orbitopathy. Results from clinical studies indicate that a small subset of patients with the above-mentioned thyroid conditions present some features suggestive for IgG4-RD. However, according to more recent views, the use of the term thyroid disease with an elevation of IgG4 rather than IgG4-related thyroid diseases would appear more appropriate. Nevertheless, the occurrence of high IgG4 levels in patients with thyroid disease is relevant due to peculiarities of their clinical course. [ABSTRACT FROM AUTHOR]

Objective: Autoimmune thyroid disease (AITD) and psoriatic disease share auto-immunological components. Few studies have investigated the link between both, yielding inconclusive results. Design: We assessed the association of AITD with psoriatic disease in a prospective cohort study and performed a systematic review and meta-analysis. Methods: 8214 participants of the Rotterdam Study (RS) with thyroid peroxidase antibodies (TPO-Abs), thyroidstimulating hormone (TSH) and/or free thyroxine (FT4) measurements and information on psoriatic disease were included. We performed logistic and Cox regression analyses and a systematic literature search in several electronic databases on AITD and psoriatic disease. We pooled odds ratios (ORs) of included studies using the Mantel-Haenszel method, while adding RS data on prevalent psoriatic disease. Results: Within the RS, we found no association between TPO-Ab positivity and psoriatic disease. There was a positive trend between TSH and prevalent psoriatic disease, and between FT4 and incident psoriatic disease, although not significant. Out of 1850 articles identified, seven were included in the systematic review and four in the metaanalysis. The risk of psoriatic disease (pooled OR) was 1.71 (confidence interval (CI): 1.27-2.31) for TPO-Ab positivity, 1.25 (CI: 1.14-1.37) for AITD and 1.34 (CI: 1.16-1.54) respectively, and 1.17 (CI: 1.03-1.32) for hypothyroidism and hyperthyroidism. Conclusions: Our meta-analysis suggests that TPO-Ab positivity, hypothyroidism and hyperthyroidism might be associated with prevalent psoriatic disease. However, there are only few studies with large heterogeneity regarding psoriatic disease definition and indication of publication bias. Additional prospective data are needed to assess the association of AITD with incident psoriatic disease. [ABSTRACT FROM AUTHOR]

Objective: The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis. Methods: We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis. Results: TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L; P = 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) (P = 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower (P < 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group. Conclusion: Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia. [ABSTRACT FROM AUTHOR]

Objective: Hashimoto's thyroiditis (HT), the most common autoimmune thyroid disease at any age, is often associated with other autoimmune diseases. The present study was aimed to describe the type and frequency of non-thyroidal autoimmune diseases (NTADs) in HT patients and to delineate the clinical pattern of diseases clustering in pediatric/adolescent and adult age. Design: Cross-sectional study. Methods: 1053 newly diagnosed HT patients (500 adults (467 F, mean age 40.2 ± 13.7 years) and 553 children/ adolescents (449 F, mean age 11.1 ± 3.0 years)) were evaluated for common NTADs by means of careful recording of medical history, physical examination and assessment of selected autoantibody profiles. Results: The prevalence of associated NTADs was significantly higher in adults than that in pediatric/adolescent HT patients (P < .0001). In addition, the number of adult patients suffering from two or more associated NTADs was significantly higher than that of children/adolescent (P < 0.0001). A female prevalence was evident in both cohorts, but was significant in the adults (P < 0.0001). The epidemiological distribution of NTADs was strongly different in the two cohorts, the most frequent associated diseases being arthropathies and connective tissue diseases in adults and type 1 diabetes and coeliac disease in children/adolescents. Skin diseases were represented with similar prevalence in both cohorts, vitiligo being the most common. Conclusions: Age at HT presentation may influence autoimmune diseases clustering, favoring the association of specific NTADs in different ages of life. Moreover, the association between HT and NTADs increases with age and occurs most frequently in adults. [ABSTRACT FROM AUTHOR]

Background: The association between chronic lymphocytic thyroiditis (CLT) and thyroid cancer is an interesting topic. The aim of the present study was to evaluate if demographic and histological characteristics as well as the long-term outcome of thyroid cancer was different in children and adolescents with and without CLT. Methods: The medical records of children and adolescents (%21 years old) were reviewed. The following data were recorded: gender, year and age at diagnosis, family history of thyroid cancer, history of external radiation therapy, histological type (papillary and variants, follicular and variants), tumour size, multifocality, infiltration of thyroid parenchyma or surrounding soft tissues, vascular invasion, presence of lymph node and distant metastases. Information about the presence of TgAb and TPOAb was also collected. Results: One hundred eight children and adolescents (median age 19.0, interquartile range 4.0 years) were diagnosed with differentiated thyroid carcinoma (DTC); 31 patients (28.7%) presented histological characteristics compatible with CLT. Infiltration of thyroid parenchyma was more frequent in patients with CLT compared to patients without (74.2% vs 48.1% respectively, PZ0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, PZ0.009). There was no better outcome with respect to the presence of CLT or not. Conclusions: Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. [ABSTRACT FROM AUTHOR]

Objective: We have aimed to study the relation between Hashimoto's thyroiditis (HT) and thyroid autoantibodies and oxidative stress parameters in euthyroid, subclinical and overt hypothyroid stages. Design and methods: A total of 124 patients were included in the study; 93 of whom were newly diagnosed with HT (31 patients in each of the euthyroid, subclinical hypothyroid and overt hypothyroid subgroups), aged over 18 and had not received any prior treatment and 31 of whom were healthy volunteers. Results: Total oxidant status (TOS) and oxidative stress index (OSI) levels were higher, and total antioxidant status (TAS) and total thiol and arylesterase levels were lower in the overt hypothyroid group compared to other groups. TOS and OSI levels increased, and TAS levels decreased significantly in each phase from euthyroid, subclinical hypothyroid, to overt hypothyroid subgroups among HT patients. There was a negative correlation between TAS, log (paraoxonase1) and paraoxonase1/HDL and anti-thyroid peroxidase and a negative correlation between anti-thyroglobulin and total thiol. It was also determined that overt hypothroidism was an individual predictor that effects all of the oxidative stress parameters, but not total thiol, levels. Conclusion: Our results suggest that oxidative stress increases continuously during the development of subclinical hypothyroidism and overt hypothyroidism in patients with HT. To determine whether this is a cause or result, randomized, controlled trials that study the effect of antioxidant treatment on the development of overt hypothyroidism and its consequences, e.g., increase in total cholesterol levels, may be performed in euthyroid and/or subclinical hypothyroid patients with HT. [ABSTRACT FROM AUTHOR]

Introduction: In genetically predisposed individuals, exogenous factors (including pollution) influence the development of Hashimoto's thyroiditis/chronic lymphocytic thyroiditis (CLT). CLT may also be a risk factor for associated thyroid cancer. Few data are available on the role of pollution from petrochemical complexes, one of which is located in the Siracusa province (South-Eastern Sicily), in the pathogenesis of CLT. Aims: i) To study the frequency of CLT in fine-needle aspiration cytology (FNAC)-interrogated thyroid nodules from patients who were stably resident in their zones, comparing it in patients living in the petrochemical complex area (zone A) with that of patients from a control area (zone B). ii) To study the frequency of CLT in the FNAC categories of malignancy risk, comparing the two zones. Patients and methods: We retrospectively evaluated cytologically adequate slides of 1323 nodules in 1013 outpatients who underwent ultrasound-guided FNAC from 2006 to 2012. We stratified by area of residence, gender, and FNAC categories of malignancy risk. Results: CLT was detected with significantly greater frequency in either patients or nodules from zone A compared with zone B (32.0% vs 23.1%, P=0.002 or 28.2% vs 18.8%, P=0.0001), with a female preponderance (F=35.2% vs M=21.1% or 30.4% vs 20.4%, zone A and F=26.5% vs 12.3% or 21.6% vs 9.5%, zone B). Regardless of zone, CLT was approximately twofold more frequent in the suspiciously malignant+malignant classes (TH4+THY5=47.6%, zone A and 32.4%, zone B) compared with the benign+intermediate classes (THY2+THY3=27.3%, zone A and 18.2%, zone B), but with a clear stepwise THY2 through THY5 increase only in zone A (THY2=25.3%, THY5=66.7%; THY2=18.6%, THY5=28.6% in zone B). Conclusions: The petrochemical complex-related pollution is an environmental factor involved in the development of CLT and, likely, in the CLT association with thyroid neoplasms. [ABSTRACT FROM AUTHOR]

Background: Despite high sensitivity of current assays for autoantibodies to thyroperoxidase (TPO) and to thyroglobulin (Tg), some hypothyroid patients still present with negative tests for circulating anti-thyroid Abs. These patients usually referred to as having seronegative autoimmune thyroiditis (seronegative CAT) have not been characterized, and definite proof that their clinical phenotype is similar to that of patients with classic chronic autoimmune thyroiditis (CAT) is lacking. Objective: To compare the clinical phenotype of seronegative CAT (SN-CAT) and CAT as diagnosed according to a raised serum level of TSH with negative and positive tests for anti-thyroid Abs respectively. Methods: A case-control retrospective study enrolling 55 patients with SN-CAT and 110 patients with CAT was performed. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, Tg Abs, and TPO Abs were measured in all patients. Results: Patients with SN-CAT displayed significantly lower mean levels of TSH (6.6G3.4 vs 10.2G9.8 mU/ml; PZ0.009), higher mean FT4 levels (1.1G0.2 vs 0.9G0.2 ng/dl; PZ0.0002), and similar FT3 levels when compared with CAT patients. Mean thyroid volume was significantly greater in patients with CAT when compared with SN-CAT patients (11.2G6.5 vs 8.1 G3.7 ml; PZ0.001). Logistic regression demonstrated that FT4 (0.123 (0.019-0.775); (PZ0.026)) and thyroid volume (1.243 (1.108-1.394); (PZ0.0002)) were significantly and independently related to the diagnosis (CAT/SN-CAT). Patients with SN-CAT had a similar prevalence of thyroid nodules and female gender but a lower prevalence of overt hypothyroidism (5.4 vs 20.9%; PZ0.012) as opposed to patients with CAT. Conclusions: These results suggest an autoimmune etiology of SN-CAT, which, however, seems to have a milder clinical course when compared with CAT. [ABSTRACT FROM AUTHOR]

The last 10 years have seen some progress in understanding the etiology of autoimmune thyroid disease (AITD). The female preponderance can now be explained - at least in part - by fetal microchimerism and X-chromosome inactivation. The number of identified susceptibility genes for AITD is increasing (among others now including TSHR, TG, HLA, CTLA4, PTPN22, CD40, FCRL3, IL2RA, and FOXP3), but these genes together probably do not explain more than about 10% of the heritability of AITD. As twin studies indicate that genes contribute for 70% of AITD, it follows that there must be many more loci, each of them contributing a little. While the genetic studies have clarified why various autoimmune diseases so often cluster in the same patient, the molecular mechanism of action of these genetic polymorphisms (frequently located in introns) has hardly been explained. Polymorphisms in AITD susceptibility genes may become helpful in clinical practice, e.g. in assessing risk of recurrent Graves' hyperthyroidism (GH) after a course of antithyroid drugs. Moderate alcohol intake decreases the risk on overt GH and overt Hashimoto's hypothyroidism. Current smokers - as well known - are at increased risk for Graves' disease, but - surprisingly - at diminished risk for Hashimoto's thyroiditis. Low selenium and low vitamin D levels might increase the risk of developing AITD, but data are still inconclusive. Current options for preventive interventions in subjects at risk to develop AITD are very limited. [ABSTRACT FROM AUTHOR]

Objective: Thyroglobulin antibody (TgAb) is an important autoantibody in thyroid diseases, which is a glycoprotein, predominantly of IgG class. Glycosylation of the IgG-Fc contributes to many effector functions exhibited by antibodies. The aim of our study was to investigate the glycosylation of sera TgAb in patients with different thyroid diseases. Design and methods: Sera from 146 patients were collected and divided into four groups: Hashimoto's thyroiditis (HT, n=90), Graves' disease (GD, n=20), papillary thyroid carcinoma (PTC, n=17), and PTC with histological lymphocytic thyroiditis (PTC-T, n=19). HT patients were further divided into euthyroidism and subclinical and overt hypothyroidism groups. Lectin-ELISAs were performed to detect the relative amount of core fucose, terminal galactose, and sialic acid on each TgAb respectively. Results: Among HT, GD, and PTC groups, HT patients had significantly lower core fucose content on TgAb than the other two groups; an increasing trend of sialylation was found in PTC sera (P=0.076) compared with HT groups. PTC-T patients had significantly higher sialylated TgAb than HT and GD patients, and no significant difference was found between PTC and PTC-T. There was no significant difference in the three carbohydrate residue contents on sera TgAb among HT subgroups. In all the patients, negative correlation was found between sialic acid content and TgAb IgG levels (r=-0.736, P<0.001). Conclusions: Our study showed that glycosylation of sera TgAb varied in different thyroid diseases and it might be involved in pathogenesis of thyroid disorders. [ABSTRACT FROM AUTHOR]

Objective: No consensus exists on the association between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT). To resolve this controversy, this study aimed to evaluate the relationship between the two conditions using a meta-analysis. Methods: We searched relevant published studies using citation databases including PubMed, Embase, and ISI Web of Science. The effect sizes of clinicopathologic parameters were calculated by odds ratio (OR), weighted mean difference, or hazard ratio (HR). The effect sizes were combined using a randomeffects model. Results: Thirty-eight eligible studies including 10 648 PTC cases were selected. Histologically proven HT was identified in 2471 (23.2%) PTCs. HT was more frequently observed in PTCs than in benign thyroid diseases and other carcinomas (OR=2.8 and 2.4; P<0.001). PTCs with coexisting HT were significantly related to female patients (OR=2.7; P<0.001), multifocal involvement (OR=1.5; P=0.010), no extrathyroidal extension (OR=1.3; PZ0.002), and no lymph node metastasis (OR=1.3; P=0.041). Moreover, PTCs with HT were significantly associated with long recurrence-free survival (HR=0.6; P=0.001). Conclusions: Our meta-analysis showed that PTC is significantly associated with pathologically confirmed HT. PTC patients with HT have favorable clinicopathologic characteristics compared with PTCs without HT. However, patients with HT need to be carefully monitored for the development of PTC [ABSTRACT FROM AUTHOR]

Objectives: To determine the status of iodine nutrition in children and adolescents in Almeri'a, Spain. To calculate prevalence of thyroid autoimmunity (TA) and autoimmune thyroiditis (AT) in pediatric ages and to research into associated factors. Methods: Cross-sectional epidemiological study. By a multistage probability sampling 1387 children and adolescents aged between 1 and 16 were selected. Physical examination was carried out including neck palpation. Parents were asked about eating habits as well as about social and demographic aspects. Urinary iodine, free thyroxine, TSH, antiperoxidase and antithyroglobulin antibodies were measured. TA was diagnosed when any antibody was positive and AT when autoimmunity was associated with impaired thyroid function or goitre. Results are shown using percentages (and its 95% confidence interval). To study associated factors we used multiple logistic regression, quantifying the relation with odds ratio (OR), and multiple lineal regression. Results: Median urinary iodine concentration was 199.5 &mgr;g/l. The prevalences of TA and AT were 3.7% (2.4-5.0) and 1.4% (0.4-2.4). TA is associated with female sex (OR 2.78; P<0.001) and age (OR 1.30; P<0.001). Iodine status is associated with the intake of milk and dairy product (P<0.001) and vegetable (P=0.021) but not with use of iodized salt at home (P=0.1). Conclusions: The iodine supply in children and adolescents in our city is optimal. Milk and dairy products are the most important iodine sources. TA and AT are prevalent in pediatric ages in our city mainly in females and older subjects. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Reports on sonoelastography, which provide an objective estimation of tissue elasticity, are scarce in terms of thyroiditis. The aim of this study was to prospectively assess the applicability of sonoelastography in different types of thyroiditis. DESIGN: The study assessed and compared the thyroid tissue stiffness in patients with acute thyroiditis (AT), subacute thyroiditis (SAT), and chronic autoimmune thyroiditis (CAT) with healthy control subjects (CS), followed up for 10 weeks. METHODS: The study group consisted of two patients with AT, 18 patients with SAT, 18 patients with CAT, and 40 CS matched for age and gender. Sonoelastography was performed at baseline, at a 4-week follow-up during treatment, and at 10 weeks following diagnosis and treatment initiation. RESULTS: Thyroid tissue stiffness was higher in SAT at baseline (214.26±32.5 kPa) in comparison with values recorded at a 4-week follow-up (45.92±17.4 kPa) and at 10 weeks following diagnosis and treatment initiation (21.65±5.3 kPa, P<0.0001). Baseline thyroid stiffness in SAT was higher than that found in CAT (36.15±18.7 kPa, P<0.0001) and CS (16.18±5.4 kPa, P<0.0001). In the remission of SAT, thyroid stiffness was lower than that found in CAT (P=0.006), while it was higher than that in CS (P=0.0008). No difference was observed between thyroid stiffness in SAT at 4-week follow-up and in CAT. Patients with CAT presented higher thyroid stiffness than CS (P<0.0001), which was not influenced by L-thyroxine treatment. Thyroid stiffness in patients with AT was 216.6 and 241.9 kPa at baseline; after treatment, it decreased to 17.93 and 85.348 kPa respectively. CONCLUSIONS: Sonoelastography may assist in the diagnosis and treatment monitoring of AT, SAT and CAT, as well as in the differentiation of the various types of thyroiditis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Autoimmune thyroid disease (AITD) is characterized by different defects in immunoregulatory mechanisms. The immunoglobulin-like transcript receptor 2 (ILT2) or leukocyte Ig-like receptor 1 (LIRB1/CD85j) exerts an important immunoregulatory role. We hypothesized that the lymphocytes from AITD patients have a diminished expression and function of ILT2. The aim of this study was to investigate the expression and function of ILT2 in lymphocytes from patients with AITD. DESIGN AND METHODS: In this study, 18 patients with Hashimoto's thyroiditis (HT), 20 with Graves' disease, and 26 healthy controls were studied. ILT2 expression was analyzed by flow cytometry and immunohistochemistry in peripheral blood mononuclear cells (PBMC) and thyroid tissue. The regulatory function of ILT2 was assessed by an assay of inhibition of lymphocyte proliferation and by an analysis of cell cycle progression. The effect of ILT2 on cytokine synthesis was also evaluated. RESULTS: We found a significant increased expression of ILT2 by lymphocytes in AITD patients. ILT2 was also detected in the leukocyte infiltrate of thyroid tissue from HT patients. On the contrary, a significant diminished inhibitory activity of ILT2 on cell proliferation was observed in AITD patients. In addition, PBMC from AITD patients showed a diminished synthesis of interleukin 10 on ILT2 engagement. CONCLUSIONS: The abnormal expression and function of ILT2 detected in AITD suggests that this receptor may participate in the pathogenesis of this condition. [ABSTRACT FROM AUTHOR]

OBJECTIVE: With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200–300 µg/l) or excessive iodine intake levels (MUI >300 µg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations. DESIGN: A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 µg/l; Chengshan, MUI 145 µg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant. RESULTS: The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P<0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, P=0.02; TgAb: 10.27 vs 7.93%, P=0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: ≥500 IU/ml) and low concentrations of TgAb (TgAb: 40–99 IU/ml) in Rongxing. CONCLUSIONS: More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations. [ABSTRACT FROM AUTHOR]

OBJECTIVE: It is unclear whether Hashimoto's thyroiditis and Graves' disease (often referred to as autoimmune thyroid disease, AITD) cluster to the same extent with other autoimmune disorders. METHODS: We assessed adrenal, β-cell, celiac and gastric antibodies in a cohort of 523 adult patients with Graves' disease and 359 patients with Hashimoto's disease and compared their clustering. RESULTS: Adrenal autoimmunity associated more often with Hashimoto's disease (9.0%) than with Graves' disease (3.3%, P=0.001). β-cell autoimmunity was seen more frequently in Hashimoto's disease (25.4%) than in Graves' disease (15.6%, P=0.001) patients. We found low prevalences of celiac autoimmunity (1.2% for Graves' and 1.2% for Hashimoto's disease). Celiac and gastric autoimmunity were not statistically different in Hashimoto's and Graves' disease patients. Although gastric autoimmunity itself was equally prevalent (around 20%), Hashimoto's disease often showed significantly more clustering of adrenal autoimmunity with gastric autoimmunity (5.3%) than Graves' disease (1.2%, P=0.001). Similarly, clustering of adrenal autoimmunity was seen with β-cell autoimmunity in Hashimoto's patients (3.2%), while such clustering was much less encountered in 359 Graves' patients (0.9%, P=0.029). CONCLUSION: In conclusion, Hashimoto's disease shows a markedly higher clustering of additional autoimmunity, especially with adrenal and β-cell autoimmunity. Combined clustering of gastric and adrenal autoimmunity and combined clustering of adrenal and β-cell autoimmunity were both seen more often in Hashimoto's patients. Clustering with celiac disease appears to be low. These findings indicate that Hashimoto's and Graves' disease differ in their clinical expression regarding additional autoimmunity, which argues against the indiscriminate use of AITD as an entity. [ABSTRACT FROM AUTHOR]

OBJECTIVE: An increase in the expression of autoantigens and their presenting molecules human leukocyte antigen (HLA) class I has been demonstrated to be responsible for autoimmune diseases. Thyroid transcription factor-1 (TTF-1 or NKX2-1) synchronously upregulates both HLA class I and thyroid-specific autoantigen, which may be involved in the pathological process of autoimmune thyroiditis. In this study, the expressions and potential role of TTF-1 and HLA class I in Hashimoto's disease (HT) were examined. PATIENTS: In this study, 22 resection specimens clinically and histopathologically confirmed to have Hashimoto's disease and 30 normal thyroid specimens from adjacent tissues of thyroid adenoma were used. MEASUREMENT: Western blot, real-time PCR, and immunohistochemistry were performed to assay TTF-1 and HLA class I in the thyrocytes of Hashimoto's disease as well as in the normal thyroid from adjacent tissues of thyroid adenoma. RESULTS: The TTF-1 and HLA class I in Hashimoto's disease were significantly higher than those in the controls. CONCLUSION: Upregulation of TTF-1 and HLA class I in Hashimoto's disease provide a clinical evidence for possible triggering of autoimmune reaction. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ipilimumab is a fully human MAB against cytotoxic T-lymphocyte antigen 4 (CTLA4). CTLA4 negatively regulates immune cell activation. In patients with metastatic melanoma, ipilimumab increases survival time and induces complete remission in some patients. However, immune-related adverse events including endocrinopathies have been reported. Bevacizumab, an angiogenesis inhibitor, has been used in combination with ipilimumab in patients with advanced melanoma. PATIENTS AND METHODS: In this study, we report three patients who received ipilimumab alone or combined with bevacizumab therapy and developed thyroiditis, and the first report of euthyroid Graves' ophthalmopathy. RESULTS: Case 1 is a 51-year-old female who presented with severe eye pain, proptosis, and periorbital edema. Laboratory results revealed normal TSH, elevated thyroid antibodies but low titer of anti-TSH receptor antibody. Imaging was consistent with Graves' ophthalmopathy. Cases 2 and 3 were referred for hyperthyroidism, and workup revealed thyroiditis. These three cases suggest that patients with advanced melanoma treated with ipilimumab +/– bevacizumab may be susceptible to a variety of thyroid disorders. CONCLUSIONS: Anti-CTLA4 therapy has shown promising results in treating advanced malignancy such as melanoma and renal carcinoma. A number of endocrinopathies, including thyroid disorders, may develop during ipilimumab therapy. The association of bevacizumab with endocrinopathies is not clear, although a few reports suggest a link to hypothyroidism. All patients on ipilimumab and/or bevacizumab therapy should be monitored for signs or symptoms of thyroiditis. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Screening of thyroid disorders in pregnancy has been controversial. Recent recommendations favour targeted high-risk case finding, though this approach may miss a significant number of those affected. We aimed to assess the prevalence of accepted high-risk criteria in women with autoimmune thyroiditis and/or hypothyroidism detected from universal screening in an iodine-sufficient population. DESIGN: In 400 non-selected women in the 9–11th gestational week, thyroid-related tests were performed, and those with abnormalities were offered consultation. METHODS: TSH was determined by IRMA, and the upper cut-off value for screening was set at 3.5 mIU/l. For free thyroxine (FT4) and thyroperoxidase antibodies (TPO-Ab), RIAs were used, with cut-offs of <10 pmol/l and >50 IU/ml respectively. Endocrinological consultation included Doppler ultrasonography and was aimed to confirm autoimmune thyroiditis and/or hypothyroidism. The prevalence of consensus high-risk criteria was assessed. RESULTS: Among the 400 women, 65 (16.3%) had ≥1 abnormality: higher TSH was found in 10.3%, lower FT4in 2% and positive TPO-Ab in 8.3%. Fifty-one women were examined and followed up. Levo-T4treatment was initiated in 49 women for autoimmune thyroiditis (in 42), hypothyroidism (in 34) or both (in 27). Only 22 (45%) of 49 treated women fulfilled ≥1 high-risk criterion: most commonly family history (31%), history of miscarriage or preterm delivery (14%) and personal history (8%). CONCLUSIONS: Over half (55%) of pregnant women with abnormalities suggestive of autoimmune thyroiditis and/or hypothyroidism would be missed if only those with high-risk criteria were examined. A more extensive screening of thyroid autoimmunity and dysfunction seems warranted. [ABSTRACT FROM AUTHOR]

Objective: Thyroid ultrasound (US) scan is a valuable tool for diagnosing thyroid diseases. In autoimmune thyroid disease (AITD), an hypoechoic pattern of the thyroid at US is related to circulating thyroid antibodies (Abs). The aim of this study was to evaluate the diagnostic accuracy of thyroid US for the detection of AITD in patients with morbid obesity. Design: Thyroid US scans showing an hypoechoic pattern of the thyroid were collected from 105 morbid obese patients (body mass index (BMI) O40 kg/m2) and 105 non-obese patients (BMI%30 kg/m2). Results: A thyroid hypoechoic pattern at US was consistent with clinical/biochemical features of AITD in 90/105 (85.7%) non-obese patients and in 22/105 (20.9%) morbid-obese patients (P<0.0001). By performing a complete thyroid work-up, including clinical examination, thyroid morphology, serum hormones, and auto-Ab measurements, the discrepancy between the US pattern and the results of the thyroid Ab tests was justified in 6/15 non-obese patients, and only in 1/83 morbid obese patients. Thus, an unexplained hypoechoic pattern of the thyroid at US, defined as negative tests for thyroid Ab and absence of justifying thyroid disturbances, was found in 2/105 (1.9%) non-obese patients and in 68/105 (64.8%) morbid obese patients (P<0.0001). Conclusions: Our results suggest that i) morbid obesity may affect thyroid morphology, and ii) an hypoechoic pattern of the thyroid at US, a well-established parameter for diagnosing AITD, has a poor diagnostic accuracy when patients with morbid obesity are taken into account. [ABSTRACT FROM AUTHOR]

The article reports on a study to investigate the association of thyroid autoimmunity (TAI) with increased risk for spontaneous miscarriage in subfertile, euthyroid women undergoing in vitro fertilization (IVF). The study included 1,098 subfertile women and was conducted in the electronic database MEDLINE using combinations of the auto antibodies (MeSH) and thyroid gland (MeSH) and reproductive techniques (MeSH). It found TAI responsible for an increased risk for spontaneous miscarriage.

The article reports on a study to compare the presentation and clinical course of Graves’ disease (GD) in children and adolescents with Down’s syndrome (DS). The study reviewed case records of 28 DS patients before the diagnosis of GD followed by the diagnosis of autoimmune thyroiditis (HT). The study reveals that GD in DS children and adolescents can be identified by several peculiarities including earlier presentation, no gender predominance and less severe clinical course.

CONTEXT: Although coronary flow reserve (CFR) is reduced in patients with subclinical hypothyroidism (SHypo), the endothelial response of coronary vasomotion has never been explored in this clinical setting. OBJECTIVE: To investigate the endothelial response of coronary flow in young and middle-aged patients with SHypo, without associated cardiovascular risk factors compared with healthy control subjects. PATIENTS AND METHODS: The study population consisted of 20 women (mean age 38.4+12.1 years) with newly diagnosed, untreated and persistent SHypo due to Hashimoto's thyroiditis. A total of 15 volunteers served as controls. Age, gender, body surface area, glucose, insulin levels, heart rate, systolic, diastolic, and mean blood pressure were similar in patients and controls. Body mass index was significantly higher in SHypo patients. Total cholesterol and low-density lipoprotein cholesterol, despite not significant, tended to be higher, and high-density lipoprotein cholesterol to be lower in SHypo. Coronary blood flow velocities were recorded in patients at rest and after the cold pressor test (CPT), a stimulus that can be considered totally endothelium-dependent. CFR was calculated as the ratio of hyperemic-to-resting diastolic peak velocities. RESULTS: Coronary diastolic peak velocities at rest did not differ between the two groups but were significantly lower after CPT in patients with SHypo, thereby resulting in a lower CFR. The difference remained significant after adjusting resting and CPT velocities for the respective mean blood pressures. TSH was inversely correlated with CFR in the pooled population. CONCLUSION: Patients with SHypo without associated cardiovascular risk factors have a coronary endothelial dysfunction that appears in response to a physiological stimulus (the CPT). [ABSTRACT FROM AUTHOR]

Objective: Both genetic and environmental factors contribute to susceptibility of Graves' disease. In this study, we evaluated whether the duration of symptoms or a positive family history of autoimmune thyroid disease (AITD) are related to specific phenotypes in patients with a first episode of Graves' hyperthyroidism (GH). Design: Cross-sectional multicentre observational study. Patients: Two hundred and sixty-three consecutive untreated patients (mean age (± S.D.) 42.6 ± 12.4 years; range 16-79 years) with a first episode of GH were included. Biochemical and clinical severity of GH was evaluated. Participants were asked to complete questionnaires about environmental factors (smoking behavior, use of estrogens, stress etc.), the duration of symptoms (interval between start of symptoms and date of referral) and family history for AITD.We ascertained the autoimmune nature of thyroid disease in affected relatives. Family history scores (FHS; high score indicating a close genetic relationship and/or a large number of affected relatives) were calculated for patients with a positive family history for AITD. Results: The peak incidence for the diagnosis of GH was 2-3 months after onset of symptoms (32% of patients). Duration of symptoms was negatively associated with age (P for trend=0.04). A positive family history for AITD was present in 42.6% of patients. Patients with the highest FHS were more often male (P=0.01) while age at onset was lower (P=0.02) compared to patients with a lower FHS. Among patient groups with different FHS, no differences were found in exposure to environmental factors, nor in clinical or biochemical severity of hyperthyroidism. Conclusion: Our study does not support the hypothesis that a short duration of thyrotoxic symptoms until diagnosis is related to more severe hyperthyroidism in Graves' disease.We have found supporting evidence for the existence of genetic anticipation in Graves' disease by means of a lower age of onset in the group with the highest FHS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced hypothyroidism, hyperthyroidism (overt and subclinical), and goiter in a population exposed to excessive iodine intake for 5 years (table salt iodine concentrations: 40–100 mg/kg salt). DESIGN: This was a population-based, cross-sectional study with 1085 participants randomly selected from a metropolitan area in São Paulo, Brazil, and conducted during the first semester of 2004. METHODS: Thyroid ultrasound examination was performed in all participants and samples of urine and blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration, thyroid volume, and thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations. RESULTS: At the time the study was conducted, table salt iodine concentrations were within the new official limits (20–60 mg/kg salt). Nevertheless, in 45.6% of the participants, urinary iodine excretion was excessive (above 300 µg/l) and, in 14.1%, it was higher than 400 µg/l. The prevalence of CAT (including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs 9.1% respectively, P=0.02). Hypothyroidism was detected in 8.0% (87/1085) of the population with CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in 3.1% (34/1085). CONCLUSIONS: Five years of excessive iodine intake by the Brazilian population may have increased the prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Activating mutations of the BRAF oncogene are frequently detected in papillary thyroid carcinoma (PTC) and have been associated with a worse prognosis. The amino acid substitution V600E accounts for 90% of all oncogenic BRAF mutations and is typically detected in classic PTCs, whereas other less frequent BRAF mutations seem to be associated with other PTC histotypes. CASE: Screening for activating BRAF mutations in a series of 83 PTCs identified the most common V600E mutation in 39 cases (histologically, 38 classic PTCs and 1 sclerosing variant PTC) and a complex in-frame mutation involving amino acids V600–S605 in a stage III multicentric follicular variant PTC, occurring in a 50-year-old female patient, who was affected by hypothyroidism in autoimmune thyroiditis and had a family history of PTC and autoimmune thyroiditis. Since the identified BRAF mutation was novel in the literature, bioinformatic modeling was performed to predict its impact on BRAF activity. Although the mutation resulted in loss of a phosphorylation site in the activation loop of BRAF, it was predicted to increase BRAF kinase activity by mimicking an activating phosphorylation. CONCLUSIONS: This study, which reports a new BRAF mutation, highlights the usefulness of bioinformatic modeling in the prediction of functional effects of new mutations and indicates that mutation-specific screening tests might miss some rare BRAF mutations. These facts should be taken into consideration in the molecular diagnosis of thyroid cancer and in the design of therapeutic protocols based on inhibitors of the BRAF pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Autoimmune thyroid diseases are common and the prevalence of circulating thyroid antibodies (thyroid peroxidase antibody, TPO-Ab and thyroglobulin antibody, Tg-Ab) is high in the population. The knowledge of a possible association between lifestyle factors and circulating thyroid antibodies is limited. AIM: To evaluate the correlation between smoking habits and the presence of circulating TPO-Ab and Tg-Ab. MATERIAL AND METHODS: In a cross-sectional comparative population study performed in two areas of Denmark with moderate and mild iodine deficiency, 4649 randomly selected subjects from the population in some predefined age groups between 18 and 65 years were examined. Blood tests were analysed for TPO-Ab and Tg-Ab using assays based on the RIA technique. The participants answered questionnaires, were clinically examined and blood and urine samples collected. RESULTS: Data were analysed in multivariate logistic regression models. There was a negative association between smoking and the presence of thyroid autoantibodies in serum. This association was observed for the presence of TPO-Ab and/or Tg-Ab, TPO-Ab (without respect to Tg-Ab status), Tg-Ab (without respect to TPO-Ab status) and both antibodies together. The association between smoking and thyroid autoantibodies was stronger for Tg-Ab than for TPO-Ab. There was no association between smoking and TPO-Ab measured alone or between smoking and TPO-Ab when Tg-Ab was included in the model as an explanatory variable. CONCLUSION: Smoking was negatively associated with the presence of thyroid autoantibodies with the strongest association between smoking and Tg-Ab. The study design precludes any conclusions as to the cause of the negative association between smoking thyroid autoantibodies. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We aimed to test the viral hypothesis in the pathogenesis of autoimmune thyroid disease (AITD). DESIGN: We determined the pattern of month of birth (MOB) distribution in patients with AITD and in the general population and searched for differences between them. METHODS: A total of 1023 patients were included in this study; 359 patients had Graves’ hyperthyroidism (GrH) and 664 had Hashimoto’s hypothyroidism (HH). We divided the patients with HH into three subgroups according to their thyroid peroxidase (TPO) antibody titers at diagnosis: low levels (<500 IU/ml), high levels (500–1000 IU/ml), and extremely high levels (>1000 IU/ml). We used cosinor analysis to analyze the data. RESULTS: Overall, patients with GrH and HH had a different pattern of MOB distribution when compared with the general population and between groups. Furthermore, among both patients with GrH and HH, both genders had a different pattern of MOB distribution when compared with the general population and this pattern was also different between genders. Finally, only women with extremely high titers of TPO antibodies at diagnosis and men with low or extremely high TPO antibody levels showed rhythmicity in MOB, with a pattern of MOB distribution different from that in controls. CONCLUSIONS: The different MOB seasonality in both GrH and HH points towards a similar maybe even common etiology with type 1 diabetes mellitus and multiple sclerosis, namely a seasonal viral infection as the initial trigger in the perinatal period, the clinical disease resulting from further specific damage over time. [ABSTRACT FROM AUTHOR]