Genetic and Environmental Factors in the Pathophysiology of Hashimoto's Thyroiditis.

Hashimoto's thyroiditis (HT) is a chronic autoimmune thyroid disease caused by an interaction between genetic factors and environmental conditions, both of which are yet to be fully understood. The management of HT depends on its clinical manifestations, commonly including diffuse or nodular goiter with euthyroidism, subclinical hypothyroidism and permanent hypothyroidism. However, in most cases of patients with HT, lifelong levothyroxine substitution is required. The additional role of diet for the management of HT is usually overlooked. A literature search regarding the importance and the influence of iodine, selenium, vitamin D and gluten on HT was conducted. In HT careful supplementation of possible deficiencies is recommended for the dietary management of these patients. The use of a diet low in gluten among HT patients with or without celiac disease (CD) is discussed.

Fine needle aspiration (FNA) biopsy is an established procedure by which to sample thyroid nodules to ascertain etiology and produce a diagnosis conveying risk of malignancy with recommended patient follow-up. This procedure is well-tolerated and endorsed given the accessibility and vascularity of the thyroid gland. FNA cytopathology has proven efficacious for the primary assessment of thyroid nodules. Well-differentiated papillary thyroid carcinoma (PTC) and benign lymphocytic (Hashimoto) thyroiditis (HT) are distinct thyroid lesions that may be reported with diagnostic confidence based on their characteristic cytomorphologic features. However depending on the adequacy of FNA sampling and the morphology of aspirated cellular material, thyroid nodules with coexisting PTC and HT may pose diagnostic pitfalls. This may be dependent upon: (a) the architectural nature of the coexisting lesions in-vivo; (b) whether both lesions are adequately sampled through FNA; and (c) which of the cell types and cytomorpholo...

BackgroundBoth genetic and environmental factors contribute to human diseases. Most common diseases are influenced by a large number of genetic and environmental factors, most of which individually have only a modest effect on the disease. Though genetic contributions are relatively well characterized for some monogenetic diseases, there has been no effort at curating the extensive list of environmental etiological factors.ResultsFrom a comprehensive search of the MeSH annotation of MEDLINE articles, we identified 3,342 environmental etiological factors associated with 3,159 diseases. We also identified 1,100 genes associated with 1,034 complex diseases from the NIH Genetic Association Database (GAD), a database of genetic association studies. 863 diseases have both genetic and environmental etiological factors available. Integrating genetic and environmental factors results in the "etiome", which we define as the comprehensive compendium of disease etiology. Clustering of environmental factors may alert clinicians of the risks of added exposures, or synergy in interventions to alter these factors. Clustering of both genetic and environmental etiological factors puts genes in the context of environment in a quantitative manner.ConclusionIn this paper, we obtained a comprehensive list of associations between disease and environmental factors using MeSH annotation of MEDLINE articles. It serves as a summary of current knowledge between etiological factors and diseases. By combining the environmental etiological factors and genetic factors from GAD, we computed the "etiome" profile for 863 diseases. Comparing diseases across these profiles may have utility for clinical medicine, basic science research, and population-based science.

Osteoporosis is a disease characterized by an inadequate amount and/or faulty structure of bone, resulting in fractures from relatively minor trauma. Although, osteoporotic fractures are most commonly observed among the elderly, the pathogenesis of osteoporosis starts early in life and involves the interaction of multiple environmental and genetic factors (1,2). Considerable past research has centered on the influence of reproductive, nutritional and/or lifestyle factors on the development of osteoporosis. With the advent of new molecular genetic approaches, the focus of research has recently shifted towards genetic factors. Genetic epidemiological studies provide convincing descriptive data demonstrating population and ethnic differences. In addition, studies of familial aggregation, familial transmission patterns, and comparisons of twin concordance rates consistently identify a significant portion of the vulnerability to develop osteoporosis as being inherited. Almost certainly, the development of osteoporosis will be found to involve a complex interplay between both genetic and environmental factors.

Tracing the Origins of Autism: A Spectrum of New Studies

Objective To investigate the differential diagnosis value of ultrasound elastography in Hashimoto's thyroiditis with benign and malignant nodules. Methods From January 2013 to December 2015, 21 patients(25 nodules) with Hashimoto's thyroiditis and malignant nodules and 52 patients(76 nodules) with benign nodules in Jiangshan Hospital of Traditional Chinese Medicine were studied.All nodules were detected by color Doppler ultrasound and ultrasound elastography. Results The proportion of boundaries clear, morphological rules, non-low-echo, no calcification or coarse calcifications, RI value <0.70, blood flow grade 0-Ⅰin patients with malignant nodules(32.0%, 24.0%, 12.0%, 40.0%, 32.0%, 24.0%) were lower than those of the benign group(80.3%, 51.3%, 47.4%, 97.4%, 60.5%, 51.3%)(χ2=20.245, 5.682, 9.928, 44.228, 6.153, 5.682, P=0.000, 0.017, 0.002, 0.000, 0.013, 0.017). The sensitivity, specificity and diagnostic accuracy of two-dimensional color Doppler ultrasound in diagnosing Hashimoto's thyroiditis with malignant and benign nodules were 68.0%, 75.0% and 73.2%, respectively.The ultrasound elastography ≥Ⅲ grade level was as the predictor of malignant nodules, the sensitivity, specificity and diagnostic accuracy of ultrasound elastography in diagnosing Hashimoto's thyroiditis with benign and malignant nodules were 88.0%, 69.7% and 74.3%, respectively.The ultrasound elastography strain rate ratio=5.13 was the cut-off point, the ultrasound elastography strain rate ratio in diagnosing Hashimoto's thyroiditis with benign and malignant nodules, the sensitivity was 76.0%, the specificity was 92.1%, the diagnostic accuracy was 88.1%. Conclusion Ultrasound elastography grading and ultrasound elastography strain rate have certain value in the differential diagnosis of Hashimoto's thyroiditis with malignant and benign nodule. Key words: Hashimoto disease; Thyroid neoplasms; Thyroid nodule; Ultrasounography; Sensitivity and Specificity

Immunohistochemistry was carried out for assessment of the expression of IgG4 and IgG in 29 patients with Hashimoto's thyroiditis(HT) and 26 other patients with subacute thyroiditis, thyroid adenoma, and thyroid carcinoma. HT group were divided into IgG4 HT(10/29) and non-IgG4 HT(19/29)groups. Statistical analyses of clinical and histological characteristics were also conducted in both groups. 2 cases of subacute thyroiditis were IgG4 positive(2/26). The IgG4 positive plasma cells, IgG positive plasma cells, and ratio of IgG4+ /IgG+ plasma cells in IgG4 HT cases were significantly higher than non-IgG4 HT ones(P<0.05). The serum FT4 in IgG4 HT cases were lower than non-IgG4 HT ones(P<0.05). After operation, IgG4 HT had a greater proportion for accepting thyroxin treatment(P<0.05). IgG4 HT is a new-found disease which has particular histological and immunological features and would have good response for cortical hormone therapy. Serum and tissue examination of IgG4 seems to be helpful to the diagnosis of IgG4 HT. (Chin J Endocrinol Metab, 2015, 31: 883-886) Key words: Hashimoto's thyroiditis; Immunoglobulin G

Although both genetic and environmental factors affect risk of individual personality disorders (PDs), we know little of how they contribute to the pattern of comorbidity between the PDs in the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV). To clarify the structure of the genetic and environmental risk factors for the 10 DSM-IV PDs. Assessment of PDs at personal interview and multivariate twin modeling with the Mx program. General community. A total of 2794 young adult members of the Norwegian Institute of Public Health Twin Panel. Main Outcome Measure Number of endorsed criteria for the 10 DSM-IV PDs. The best-fit multivariate twin model required 3 genetic and 3 individual-specific environmental factors and genetic and individual-specific factors unique to each PD. The first genetic factor had high loadings on PDs from all 3 clusters including paranoid, histrionic, borderline, narcissistic, dependent, and obsessive-compulsive. The second genetic factor had substantial loadings only on borderline and antisocial PD. The third genetic factor had high loadings only on schizoid and avoidant PD. Several PDs had substantial disorder-specific genetic risk factors. The first, second, and third individual-specific environmental factors had high loadings on the cluster B, A, and C PDs, respectively, with 1 exception: obsessive-compulsive PD loaded with cluster B and not cluster C PDs. Genetic risk factors for DSM-IV PDs do not reflect the cluster A, B, and C typology. Rather, 1 genetic factor reflects a broad vulnerability to PD pathology and/or negative emotionality. The 2 other genetic factors are more specific and reflect high impulsivity/low agreeableness and introversion. Unexpectedly, the cluster A, B, and C typology is well reflected in the structure of environmental risk factors, suggesting that environmental experiences may be responsible for the tendency of cluster A, B, and C PDs to co-occur.

BackgroundLow birth weight (LBW) is a leading cause of neonatal morbidity and mortality, and increases various disease risks across life stages. Prediction models of LBW have been developed before, but have limitations including small sample sizes, absence of genetic factors and no stratification of neonate into preterm and term birth groups. In this study, we challenged the development of early prediction models of LBW based on environmental and genetic factors in preterm and term birth groups, and clarified influential variables for LBW prediction.MethodsWe selected 22,711 neonates, their 21,581 mothers and 8,593 fathers from the Tohoku Medical Megabank Project Birth and Three-Generation cohort study. To establish early prediction models of LBW for preterm birth and term birth groups, we trained AI-based models using genetic and environmental factors of lifestyles. We then clarified influential environmental and genetic factors for predicting LBW in the term and preterm groups.ResultsWe identified 2,327 (10.22%) LBW neonates consisting of 1,077 preterm births and 1,248 term births. Our early prediction models archived the area under curve 0.96 and 0.95 for term LBW and preterm LBW models, respectively. We revealed that environmental factors regarding eating habits and genetic features related to fetal growth were influential for predicting LBW in the term LBW model. On the other hand, we identified that genomic features related to toll-like receptor regulations and infection reactions are influential genetic factors for prediction in the preterm LBW model.ConclusionsWe developed precise early prediction models of LBW based on lifestyle factors in the term birth group and genetic factors in the preterm birth group. Because of its accuracy and generalisability, our prediction model could contribute to risk assessment of LBW in the early stage of pregnancy and control LBW risk in the term birth group. Our prediction model could also contribute to precise prediction of LBW based on genetic factors in the preterm birth group. We then identified parental genetic and maternal environmental factors during pregnancy influencing LBW prediction, which are major targets for understanding the LBW to address serious burdens on newborns' health throughout life.

Th17 cells are considered as a novel Th-cell subset which has been recently proposed.Th17 cells are involved in a number of diseases,including inflammation,autoimmune disorders and cancer by secreting interleukine(IL)-17,IL-21,IL-22 and IL-6.Recent studies have identified that the proportions of Thl7-related cytokines in the peripheral blood of patients with Graves' disease and Hashimoto thyroiditis are significantly elevated.It is suggested that Thl7-related cytokines may play a pathophysiological role in thyroid diseases.The study of Thl7-related cytokines is helpful in elucidating the pathogenesis of thyroid diseases and in developing new therapeutic approaches. Key words: Th17 cells; Graves' disease; Hashimoto's thyroiditis

Objective To explore the expression of BRAFV600E in papillary thyroid carcinoma and Hashimoto's thyroiditis,and investigate the correlation between papillary thyroid carcinoma and Hashimoto's thyroiditis.Methods The paraffin embedded tissue specimens of pathologically confirmed thyroid disease during 2012.1-2014.6 in the Air Force General Hospital were collected,including 40 cases of papillary thyroid carcinoma,20 cases of Hashimoto' s thyroiditis,20 cases of papillary thyroid carcinoma with Hashimoto's thyroiditis and 20 cases of thyroid adenoma.Immunohistochemistry (Envision method) was used to detect the expression of BRAFV600E and semi quantitative analysis was used to compare the difference of different thyroid diseases.Results The positive rate of BRAFV600E was 77.5％ (31/40) in papillary thyroid carcinoma and 45％ (9/20) in Hashimoto' s thyroiditis (P =0.012).In papillary thyroid carcinoma with Hashimoto's thyroiditis,the positive rate of BRAFV600E in thyroid papillary carcinoma tissue was 70.0％ (14/20),which was not different from thyroid papillary carcinoma (P =0.156) ; and the positive rate of BRAFV600E in Hashimoto's thyroiditis tissue was 55.0％ (11/20),which was not different from Hashimoto's thyroiditis(P =0.527).The positive rate of BRAFVE600 in metastatic papillary thyroid carcinoma was 88.2％ (15/17),which was higher than that in papillary thyroid carcinoma without metastasis (69.5％,16/23,P =0.030).There was no expression of BRAFV600E in thyroid adenoma.Conclusion Papillary thyroid carcinoma and Hashimoto's thyroiditis have a higher BRAFV600E mutation rate. Key words: Thyroid papillary carcinoma; Hashimoto's thyroiditis; BRAFV600E

Objective To study the relationship between cellular immunity in vivo,humoral immunity and different iodine intakes in patients with hashimoto thyroiditis(HT).Methods Seventy-six HT patients were divided into two groups acconding to the median of urine iodine (MUI =491.20 μ g/L):HT I group (urine iodine≥MUI) with 37 cases and HT Ⅱ group (urine iodine ＜ MUI) with 39 cases.And 49healthy persons were selected as control group.The level of free three triiodothyronine (FT3),free thyroxine (FT4),thyroid stimulating hormone (TSH),thyroglobulin antibody (TGAb),thyroid peroxidase antibody (TPOAb),thyroid hormone receptor antibody ( TRAb ),tumor necrosis factor-alpha ( TNF- α )of all groups were detected.Results The levels of FT3 and FT4 in HT I group [ (2.67 ± 1.93 ),( 4.22 ± 3.77) pmol/L ]and HT Ⅱ group [ ( 3.19 ± 1.63 ),( 5.99 ± 3.97 ) pmol/L ] were significantly lower than those in control group [(5.30± 1.10),(16.50 ±2.70) pmol/L] (P ＜ 0.01).The levels of TNF-α in HT I group [(6.14 ± 1.83)ng/L] and HT Ⅱ group [ (6.09 ± 1.50) ng/L] were both obviously higher than that in control group [ ( 1.90 ±0.60) ng/L] (P ＜ 0.01 ).The levels of FT3 and FT4 were lower and TNF α was higher in HT I group than those in HT Ⅱ group,but there was no statistically significance (P ＞ 0.05 ).The positive rate of TPOAb,TGAb in HT I group [97.3％(36/37),81.1％(30/37)] and HT Ⅱ group [89.7％(35/39),74.4％(29/39)]were significantly higher than those in contnol group [ 18.4％(9/49),12.2％(6/49 ) ] (P ＜ 0.01 ).There was no statistically difference of the positive rate of TPOAb,TGAb and TRAb between HT I group and HT Ⅱ group (P ＞ 0.05).While the percentage of patients with high titer of TPOAb and TGAb in HT I group was higher than that in HT [Ⅱ group,and there was statistical difference(P ＜ 0.05 ).The level of TRAb in HT I group was higher than that in HT Ⅱ group [ ( 1.25 ± 0.14) mU/L vs.( 1.16 ± 0.21 ) mU/L ],but there was no significant difference (P ＞ 0.05).Correlated anlysis showed that FT3 was negatively correlated with TGAb and TPOAb (r =0.342,-0.397,P ＜0.05),and TNF-αwas positively correhted with TGAb and TPOAb (r =0.405,0.561,P ＜ 0.05).Conclusions High iodine intake influences the autoimmune mechanism of HT patients.The iodine intake should be limited in HT patients. Key words: Thyroiditis,autoimmune; Tumor necrosis factor-alpha; Thyroid hormones; Autoantibodies

Objective To analyze the clinical and biological characteristics of papillary thyroid carcinoma(PTC) associated with Hashimoto's thyroiditis(HT).Methods From January 2011 to October 2011,clinical data of 445 PTC patients (97 coexisting with HT) treated at Department of Thyroid and Neck Tumor,Tianjin Medical University Cancer Hospital were retrospectively analyzed.Results In PTC patients coexisting with HT,as compared with those PTC without HT,there were more women patients and more cases with intrathyroid multifocal lesions (all P ＜ 0.05).There were no differences in age,tumor size,extrathyroid extension,lymph node metastasis and TNM stage between the 2 groups.There were lower levels of preoperative serum FT3 and FT4,higher levels of TSH,Anti-TG and Anti-TPO in the HT group (P ＜0.05).Tumor samples of 134 patients was examined for the BRAFV600E mutation.The frequency of BRAFV600E mutation in HT group was lower than that in the papillary thyroid carcinoma group without HT (35.3％ vs.64.0％,P ＜0.01).Conclusions There were more women in papillary thyroid carcinoma coexisting HT group,and multifocal lesions were more common.The high serum TSH levels may be associated with the occurrence of papillary thyroid carcinoma in some HT patients.The frequency of BRAFV600E mutation in the HT group was lower than that in the papillary thyroid carcinoma group without HT. Key words: Thyroid neoplasms ; Carcinoma, papillary; Hashimoto disease; Thyrotropin; Proto-oncogene proteins B-raf

Objective To investigate the diagnostic value of ultrasound on patients with papillary thyroid carcinoma (PTC) coexisted with Hashimoto thyroiditis (HT).Methods The preoperative ultrasonography data of 2144 cases with PTC from January 2006 to December 2011 who treated with operation and diagnosed by pathology were analyzed retrospectively.Among them,265 cases coexisted with HT (PTC coexisted with HT group),1879 cases were not coexisted with HT (non-PTC coexisted with HT group).Results Most of the cancerous nodes in two groups exhibited in the ultrasonographic performance just like irregular shape,unclear boundary and so on (P ＞ 0.05).Most of the cancerous nodes in non-PTC coexisted with HT group exhibited hypoechoic nodules with microcalcifications,those in PTC coexisted with HT group exhibited various internal echoes with mainly microcalcifications,and the coarse calcification occupied a certain proportion(P＜ 0.01 ).The cancerous nodes in PTC coexisted with HT group were not rich in blood flow compared with non-PTC coexisted with HT group,but mostly exhibited blood disorders.When compared with non-PTC coexisted with HT group,the rate of ultrasound diagnosis in PTC coexisted with HT group was lower [ 52.8 ％( 140/265 ) vs.75.0 ％ (1409/1879),P ＜ 0.01 ],and the false positive rate in lymph node was higher [84.0％(487/580) vs.74.8％ (77/103)] (P ＜0.05).Conclusions The nodules are malignant when they appear as hypoechoic solid nodules,have unclear boundary and have microcalcifications should be highly suspected.The hyperechoic solid nodules or coarse calcification nodules should also be awared and taken further observation of the characteristics around the echoes and the internal blood flow,making comprehensive analysis to determine whether it could be malignant transformation and try best to reduce the misdiagnosis and missed diagnosis rates of this disease. Key words: Thyroiditis; Thyroid neoplasms; Ultrasonography

Corneal fluorescence is believed to be caused by advanced glycation end products formed by non-enzymatic glycation on corneal proteins. The purpose of the present twin study was to examine whether the process is related to genetic or environmental factors. Corneal fluorescence was measured in 59 monozygotic and 54 dizygotic twin pairs. The influences of genetic and environmental factors were estimated using structural equation modelling. Interindividual variation in corneal fluorescence was attributable to environmental factors, whereas the effect of genetic factors was of little or no significance. Corneal fluorescence correlated significantly with smoking habits (r = 0.38) and the 2-hour oral glucose tolerance test response (r = 0.27), and increased with age (p < 0.0001). Fluorophore accumulation in the cornea was attributable to age and environmental effects, of which smoking was the most conspicuous identifiable factor, although glucose was also of relevance. However, the greater part of interindividual variation in corneal fluorescence remains unexplained.