Showing papers on "Thyroglobulin published in 2014"
TL;DR: Hashimoto thyroiditis (HT), now considered the most common autoimmune disease, was described over a century ago as a pronounced lymphoid goiter affecting predominantly women, and several other clinico-pathologic entities are now included under the term HT.
571 citations
TL;DR: The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen-specific, not blanket, therapeutic approach.
Abstract: Thyroid autoimmunity involves loss of tolerance to thyroid proteins in genetically susceptible individuals in association with environmental factors. In central tolerance, intrathymic autoantigen presentation deletes immature T cells with high affinity for autoantigen-derived peptides. Regulatory T cells provide an alternative mechanism to silence autoimmune T cells in the periphery. The TSH receptor (TSHR), thyroid peroxidase (TPO), and thyroglobulin (Tg) have unusual properties ("immunogenicity") that contribute to breaking tolerance, including size, abundance, membrane association, glycosylation, and polymorphisms. Insight into loss of tolerance to thyroid proteins comes from spontaneous and induced animal models: 1) intrathymic expression controls self-tolerance to the TSHR, not TPO or Tg; 2) regulatory T cells are not involved in TSHR self-tolerance and instead control the balance between Graves' disease and thyroiditis; 3) breaking TSHR tolerance involves contributions from major histocompatibility complex molecules (humans and induced mouse models), TSHR polymorphism(s) (humans), and alternative splicing (mice); 4) loss of tolerance to Tg before TPO indicates that greater Tg immunogenicity vs TPO dominates central tolerance expectations; 5) tolerance is induced by thyroid autoantigen administration before autoimmunity is established; 6) interferon-α therapy for hepatitis C infection enhances thyroid autoimmunity in patients with intact immunity; Graves' disease developing after T-cell depletion reflects reconstitution autoimmunity; and 7) most environmental factors (including excess iodine) "reveal," but do not induce, thyroid autoimmunity. Micro-organisms likely exert their effects via bystander stimulation. Finally, no single mechanism explains the loss of tolerance to thyroid proteins. The goal of inducing self-tolerance to prevent autoimmune thyroid disease will require accurate prediction of at-risk individuals together with an antigen-specific, not blanket, therapeutic approach.
160 citations
TL;DR: Data suggest that thyroglobulin does hold promise as a biomarker of iodine deficiency, however, it is associated with limitations.
Abstract: Background: Thyroglobulin, produced exclusively by the thyroid gland, has been proposed to be a more sensitive biomarker of iodine status than thyrotropin or the thyroid hormones triiodothyronine and thyroxine. However, evidence on the usefulness of thyroglobulin (Tg) to assess iodine status has not been extensively reviewed, particularly in pregnant women and adults. Summary: An electronic literature search was conducted using the Cochrane CENTRAL, Web of Science, PubMed, and Medline to locate relevant studies on Tg as a biomarker of iodine status. Since urinary iodine concentration (UIC) is the recommended method to assess iodine status in populations, only studies that clearly reported both Tg and UIC were included. For the purpose of this review, a median Tg <13 μg/L and a median UIC ≥100 μg/L (UIC ≥150 μg/L for pregnant women) were used to indicate adequate iodine status. We excluded studies conducted in subjects with either known thyroid disease or those with thyroglobulin antibodies. The search str...
127 citations
Journal Article•
TL;DR: Many aspects of AITD are addressed including disease mechanisms, involved thyroid antigens, environmental factors and genetic factors, including the thyroid-specific genes, thyroglobulin and thyroid-stimulating hormone receptor and also many immune-regulatory genes.
Abstract: Recent epidemiological studies recognized a steady increase in the incidence of different autoimmune endocrine disorders, including autoimmune thyroid disease (AITD). The etiology of AITD is multifactorial and involves genetic and environmental factors and apparently with a strong preponderance in females. There are mainly two types of AITD, Graves' disease and Hashimoto's disease and both of these show strong association in age groups above 45-50 years. Among environmental factors smoking and alcohol have significant effects, both protective as well as for aggravating the disease, even though the precise nature of these effects are not clearly known. There are elevated levels of circulating antibodies against the thyroid proteins, mainly thyroid oxidase, thyroglobulin and thyroid stimulating hormone receptor, in patients with Graves' disease or Hashimoto's disease. Linkage and association studies in AITD identified several major genes that are relevant for the onset of AITD, including the thyroid-specific genes, thyroglobulin and thyroid-stimulating hormone receptor and also many immune-regulatory genes. In this review we addressed many aspects of AITD including disease mechanisms, involved thyroid antigens, environmental factors and genetic factors.
124 citations
TL;DR: Preoperative serum TSH level is associated with higher DTC stage, gross extrathyroidal extension, and neck node metastases, and perioperative TgAb is not an independent predictor of DTC prognosis.
Abstract: Background: Serum thyrotropin (TSH) concentration and thyroid autoimmunity may be of prognostic importance in differentiated thyroid cancer (DTC). Preoperative serum TSH level has been associated with higher DTC stage in cross-sectional studies; data are contradictory on the significance of thyroid autoimmunity at the time of diagnosis. Objective: We sought to assess whether preoperative serum TSH and perioperative antithyroglobulin antibodies (TgAb) were associated with thyroid cancer stage and outcome in DTC patients followed by the National Thyroid Cancer Treatment Cooperative Study, a large multicenter thyroid cancer registry. Methods: Patients registered after 1996 with available preoperative serum TSH (n=617; the TSH cohort) or perioperative TgAb status (n=1770; the TgAb cohort) were analyzed for tumor stage, persistent disease, recurrence, and overall survival (OS; median follow-up, 5.5 years). Parametric tests assessed log-transformed TSH, and categorical variables were tested with chi square. Dis...
117 citations
TL;DR: This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease.
Abstract: The global effort to prevent iodine deficiency disorders through iodine supplementation, such as universal salt iodization, has achieved impressive progress during the last few decades. However, iodine excess, due to extensive environmental iodine exposure in addition to poor monitoring, is currently a more frequent occurrence than iodine deficiency. Iodine excess is a precipitating environmental factor in the development of autoimmune thyroid disease. Excessive amounts of iodide have been linked to the development of autoimmune thyroiditis in humans and animals, while intrathyroidal depletion of iodine prevents disease in animal strains susceptible to severe thyroiditis. Although the mechanisms by which iodide induces thyroiditis are still unclear, several mechanisms have been proposed: (1) excess iodine induces the production of cytokines and chemokines that can recruit immunocompetent cells to the thyroid; (2) processing excess iodine in thyroid epithelial cells may result in elevated levels of oxidative stress, leading to harmful lipid oxidation and thyroid tissue injuries; and (3) iodine incorporation in the protein chain of thyroglobulin may augment the antigenicity of this molecule. This review will summarize the current knowledge regarding excess iodide as an environmental toxicant and relate it to the development of autoimmune thyroid disease.
117 citations
TL;DR: Thyroglobulin measurement in washout from LN FNA has high accuracy in early detection of nodal metastases from differentiated thyroid cancer (DTC), but a better standardization of criteria for patient selection, analytical methods, and cutoff levels is required.
Abstract: Context: The thyroglobulin measurement in the needle washout after fine-needle aspiration (FNA) has been reported to increase the sensitivity of FNA in identifying lymph node (LN) metastases from differentiated thyroid cancer (DTC). Objective: The aim of the study was to estimate the diagnostic accuracy of this technique. Data Sources: To identify eligible studies, we searched electronic databases for original articles in English from 1975 through 2013. Study Selection: Studies that enrolled participants with suspicious neck LNs during thyroid nodule workup or thyroid cancer follow-up were included. Data Extraction: Working independently, authors used a standard form to extract data. For quality assessment, QUADAS2 guidelines were applied. Data Synthesis: Including all the selected studies (24 studies, 2865 LNs) in the pooled analysis, overall sensitivity was 95.0% (95% confidence interval [CI], 93.7–96.0%), specificity was 94.5% (95% CI, 93.2–95.7%), and diagnostic odds ratio (DOR) was 338.91 (95% CI, 16...
113 citations
TL;DR: Immunological mechanisms involved in the pathogenesis of AITD are strongly related to each other, but differences in the image of cAIT and GD phenotype are possibly due to a different type of immune response observed in these two counteracting clinical thyroid diseases.
Abstract: Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disorder. AITD development occurs due to loss of immune tolerance and reactivity to thyroid autoantigens: thyroid peroxidase (TPO), thyroglobulin (TG) and thyroid stimulating hormone receptor (TSHR). This leads to infiltration of the gland by T cells and B cells that produce antibodies specific for clinical manifestations of hyperthyroidism in Graves' disease (GD) and chronic autoimmune thyroiditis (cAIT). In addition, T cells in Hashimoto's thyroiditis induce apoptosis in thyroid follicular cells, leading ultimately to the destruction of the gland. Cytokines are involved in the pathogenesis of thyroid diseases working in both the immune system and directly targeting the thyroid follicular cells. They are involved in the induction and effector phase of the immune response and inflammation, playing a key role in the pathogenesis of autoimmune thyroid disease. The presence of multiple cytokines has been demonstrated: IL-1alpha, IL-1b, IL-2, IL-4 , IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-alpha and IFN-gamma within the inflammatory cells and thyroid follicular cells. Finally, cytokines derived from T cells can directly damage thyroid cells, leading to functional disorders and may also stimulate the production of nitric oxide (NO) and prostaglandin (PG), thus increasing the inflammatory response in AITD. Immunological mechanisms involved in the pathogenesis of AITD are strongly related to each other, but differences in the image of cAIT and GD phenotype are possibly due to a different type of immune response observed in these two counteracting clinical thyroid diseases. This article describes the potential role of cytokines and immune mechanisms in the pathogenesis of AITD.
97 citations
TL;DR: A meta-analysis of published data about the diagnostic performance of highly sensitive serum Tg during levothyroxine therapy in DTC follow-up found that basal hsTg measurement has a very high negative predictive value but an insufficient positive predictive value for monitoring DTC patients.
Abstract: Context: Serum thyroglobulin (Tg) is an indicator of differentiated thyroid cancer (DTC) relapse. Objective: Our objective was to conduct a meta-analysis of published data about the diagnostic performance of highly sensitive serum Tg (hsTg) during levothyroxine therapy in DTC follow-up. Data Sources: We performed a comprehensive literature search of PubMed/MEDLINE and Scopus for studies published until July 2013. Study Selection: Studies investigating the diagnostic performance of basal hsTg in monitoring DTC were eligible. Exclusion criteria were 1) articles not within the field of interest; 2) reviews, letters, or conference proceedings; 3) articles evaluating serum Tg measurement with a functional sensitivity >0.1 ng/mL; 4) overlap in patient data; and 5) insufficient data to reassess diagnostic performance of basal serum hsTg. Data Extraction: Information was collected concerning basic study data, patient characteristics, and technical aspects. For each study, the number of true-positive, false-positi...
92 citations
International Agency for Research on Cancer1, University of Cambridge2, University of Oxford3, Aalborg University4, Université Paris-Saclay5, Institut Gustave Roussy6, German Cancer Research Center7, National and Kapodistrian University of Athens8, Harvard University9, Academy of Athens10, Imperial College London11, University of Naples Federico II12, Oklahoma State University Center for Health Sciences13, Utrecht University14, Andalusian School of Public Health15, Umeå University16, University of Ioannina17
TL;DR: High Tg levels precede by up to 8 years the detection of TC, pointing to a long sojourn time of the disease, and low TSH levels may predispose to TC onset.
Abstract: Background Increased levels of thyroglobulin (Tg) and thyroid-stimulating hormone (TSH) are associated with differentiated thyroid carcinoma (TC) risk, but strong epidemiological evidence is lacking. Methods Three hundred fifty-seven incident TC case patients (n = 300 women and 57 men; mean age at blood collection = 51.5 years) were identified in the EPIC cohort study and matched with 2 (women) or 3 (men) control subjects using incidence density sampling. Matching included study center, sex, age, date, time, and fasting status at blood collection. Levels of total and free (f) thyroxine (T4) and triiodo-thyronine (T3), TSH, Tg, and anti-Tg antibodies (TgAb) were measured by commercially available immunoassays. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using conditional logistic regression. All statistical tests were two-sided. Results TC risk was positively associated with Tg (OR for the highest vs lowest quartile = 9.15; 95% CI = 5.28 to 15.90; P < .001) and negatively associated with TSH level (OR = 0.56; 95% CI = 0.38 to 0.81; P = .001). Odds ratios were not modified by adjustment for weight and height and were consistent across sexes, age groups, and countries. The association with Tg was stronger in follicular than papillary TC. The odds ratio for TgAb-positivity was 1.50 (95% CI = 1.05 to 2.15; P = .03). Among case patients, TSH level was stable over time, whereas Tg level was higher in proximity to TC diagnosis. Areas under the receiver operating characteristic curve were 57% and 74% for TSH and Tg level, respectively. Conclusions High Tg levels precede by up to 8 years the detection of TC, pointing to a long sojourn time of the disease. Low TSH levels may predispose to TC onset. Neither marker has sufficient accuracy to be a screening test.
90 citations
TL;DR: The growing use of Tg2GIMA measurement is changing paradigms for postoperative DTC monitoring, and the trend and doubling time of low basal thyroglobulin values arising from postsurgical thyroid remnants have recognized prognostic significance.
Abstract: Purpose of review
To discuss new insights regarding how sensitive (second-generation) thyroglobulin immunometric assays (Tg2GIMAs), (functional sensitivities ≤0.10 μg/L) necessitate different approaches for postoperative thyroglobulin monitoring of patients with differentiated thyroid cancer (DTC), depending on the presence of thyroglobulin autoantibodies (TgAbs).
TL;DR: In this article, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation.
Abstract: Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous TSH is recommended by current clinical guidelines to detect occult disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations reflecting minimal amounts of thyroid tissue without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.
TL;DR: Clinical, biochemical and radiological phenotypes and molecular aspects of the known genetic forms of TD and thyroid dyshormonogenesis relevant for genetic counseling and molecular studies are summarized.
Abstract: Congenital hypothyroidism (CH) is a state of insufficient thyroid hormone supply to the organism, starting in utero. Two forms of permanent primary or thyroidal CH are known. Thyroid dysgenesis (TD) describes a spectrum of defects of thyroid organogenesis. Five monogenetic forms due to mutations in TSHR, PAX8, NKX2-1, FOXE1 and NKX2-5 have been identified so far. Thyroid dyshormonogenesis comprises defects at every step of thyroid hormone synthesis. Mutations in 7 genes are well described causing iodine transport defect (SLC5A5), iodine organification defect (TPO, DUOX2, DUOXA2, SLC26A4), thyroglobulin (TG) synthesis or transport defect or iodotyrosine deiodinase (IYD/DEHAL1) deficiency. The new consensus guidelines for CH recommend genetic counseling for each family with an affected child. Mode of inheritance, recurrence rate and possible associated malformations in the context of syndromic forms should be outlined. Molecular genetic studies should be preceded by a detailed phenotypic description of the patient's thyroid disease and a detailed family history. This review summarizes clinical, biochemical and radiological phenotypes and molecular aspects of the known genetic forms of TD and thyroid dyshormonogenesis relevant for genetic counseling and molecular studies.
TL;DR: Assessing how different Kronus (K) vs Roche (R) TgAb method cutoffs for "positivity" influence false-negative vs false-positive serum Tg Ab misclassifications may reduce the clinical utility of reflex Tg testing foundFunctional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision that could cause T gAb status to fluctuate for patients with low TGAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring.
Abstract: Context: Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay (2GIMA) measurements as free from TgAb interference and when reflexing “TgAb-positive” sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]). Objective: The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for “positivity” influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing. Methods: Serum Tg2GIMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ≥1.0 μg/L had false-negative and false-positive TgAb frequencies determined using low Tg...
TL;DR: The development of powerful molecular biology techniques has enabled targeted next-generation sequencing for detection of mutations in thyroid cancer, and this technique can make a specific diagnosis of thyroid cancer in cytologically indeterminate cases.
Abstract: Thyroid cancer is increasing all over the world. The exact cause of this increase is still debated and there are conflicting reports. Sophisticated molecular studies suggest that environmental chemicals may have effects of thyroid carcinogenesis. The development of powerful molecular biology techniques has enabled targeted next-generation sequencing for detection of mutations in thyroid cancer, and this technique can make a specific diagnosis of thyroid cancer in cytologically indeterminate cases. The initial treatment of well-differentiated thyroid cancer (DTC) is surgery followed by radioiodine remnant ablation. However, further studies are needed to determine the optimal dosage of radioactive iodine for DTC patients with lateral neck metastasis. DTC is an indolent tumor and may cause death even decades later. Thus, long-term follow-up is mandatory. Recently, dynamic risk stratification (DRS) has begun to use stimulated thyroglobulin level at 1 year after the initial treatment and restratified the risk in accordance with the response to the initial treatment. This DRS strategy accurately predicts disease free survival and can be widely used in daily clinical settings. For the iodine refractory metastatic disease, redifferentiation therapy and targeted therapy are two promising alternative treatments. Sorafenib is the first approved agent for the treatment of progressive iodine refractory advanced thyroid cancer in Korea and may be very helpful for radioactive-refractory locally advanced or metastatic DTC. Selumetinib may be an effective redifferentiating agent and could be used within several years.
TL;DR: Cadmium has the affinity to accumulate not only in the liver, kidneys, and pancreas but also in the thyroid gland, and it has been established that cadmium blood concentration correlates positively with its accumulation in the gland.
Abstract: Cadmium has been listed as one of the 126 priority pollutants and a category I carcinogen. Carcinogenic effects of cadmium on the lungs, testicles, and prostate are widely recognized, but there has been insufficient research on the effect of cadmium on the thyroid gland. Cadmium has the affinity to accumulate not only in the liver, kidneys, and pancreas but also in the thyroid gland. It has been established that cadmium blood concentration correlates positively with its accumulation in the thyroid gland. Women of fertile age have higher cadmium blood and urine concentrations than men. In spite of its redox inertia, cadmium brings about oxidative stress and damage to the tissue by indirect mechanisms. Mitochondria are considered to be the main intracellular targets for cadmium. Colloid cystic goiter, adenomatoid follicular hyperplasia with low-grade dysplasia and thyroglobulin hypo- and asecretion, and parafollicular cell diffuse and nodular hyperplasia and hypertrophy are often found in chronic cadmium toxicity.
TL;DR: In patients with TN, elevated serum concentration of TgAb and TSH ≥1 μIU/ml are independent predictors for TC, and the association between HT and TC is antibody specific.
Abstract: This prospective study investigates the relationship between Hashimoto's thyroiditis (HT) and thyroid cancer (TC) in patients with thyroid nodules (TNs). We prospectively examined 2100 patients with 2753 TNs between January 5, 2010 and August 15, 2013. A total of 2023 patients with 2669 TNs met the inclusion criteria of TN ≥5 mm and age ≥18 years. Each patient had blood drawn before fine-needle aspiration biopsy (FNAB) for the following measurements: TSH, free thyroxine, free tri-iodothyronine, thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb). Diagnosis of TC was based on pathology analysis of thyroidectomy tissue. The associations of TC with the independent variables were determined by univariate and multivariate logistic regression analysis and reported as adjusted odds ratio (OR) with 95% CI. A total of 248 malignant nodules were found in 233 patients. There was an association of TC with both increased serum TgAb concentration and age<45 years. An elevated serum TgAb concentration was found in 10.2% of patients (182 of 1790) with benign nodules as compared with 20.6% of patients (48 of 233) with malignant nodules (P≤0.0001). TgAb (OR=2.24: CI=1.57, 3.19) and TSH ≥1 μIU/ml (OR (95% CI)) OR: 1.49 (1.09, 2.03) were significant predictors of TC in multivariate analysis controlling for age and gender. TC was not associated with serum concentrations of TPOAb. In patients with TN, elevated serum concentration of TgAb and TSH ≥1 μIU/ml are independent predictors for TC. The association between HT and TC is antibody specific.
TL;DR: The results showed that crh, slc5a5, tg and tshβ mRNA levels were significantly up-regulated in the larvae, but the gene expression of trα and trβ was down- regulated in a concentration-dependent manner, indicating that Cd(2+) could alter gene expression in the HPT axis that might subsequently contribute to thyroid disruption.
Abstract: Cadmium is a heavy metal abundant in the environment that can induce endocrine disorder and toxicity in aquatic organisms at low levels. However, its effects on the thyroid system in fish are still unclear. In this study, the thyroid hormone (TH) levels and the expression profiles of genes related to hypothalamic– pituitary–thyroid (HPT) axis, including corticotropin-releasing hormone (crh), thyroid stimulating hormone beta (tshβ), solute carrier family 5 (sodium iodide symporter) member 5 (slc5a5), thyroglobulin (tg), thyroid hormone receptor alpha (trα) and thyroid hormone receptor beta (trβ), were determined in whole body of Chinese rare minnow (Gobiocypris rarus) larvae after exposure to different levels of Cd2 + (0, 0.5 and 2.5 mg/L) for 4 days. And the 96-h lethal concentration of Cd2 + on rare minnow larvae was determined as 2.59 mg/L. The results showed that crh, slc5a5, tg and tshβ mRNA levels were significantly up-regulated in the larvae, but the gene expression of trα and trβ was down-regulated in a concentration-dependent manner. Besides, the THs levels decreased in the whole-body of fish, especially the thyroxine (T4) level. The above results indicated that Cd2 + could alter gene expression in the HPT axis that might subsequently contribute to thyroid disruption.
TL;DR: Low-dose RAI therapy is sufficient to treat DTC patients classified as intermediate risk just by the presence of microscopic ETE, and no patient had clinical recurrences during the median 7.2 years of follow-up.
Abstract: Background: It is unclear whether differentiated thyroid cancer (DTC) patients classified as intermediate risk based on the presence of microscopic extrathyroidal extension (ETE) should be treated with low or high doses of radioiodine (RAI) after surgery. We evaluated success rates and long-term clinical outcomes of patients with DTC of small tumor size, microscopic ETE, and no cervical lymph node (LN) metastasis treated either with a low (1.1 GBq) or high RAI dose (5.5 GBq). Methods: This is a retrospective analysis of a historical cohort from 2000 to 2010 in a tertiary referral hospital. A total of 176 patients with small (≤2 cm) DTC, microscopic ETE, and no cervical LN metastasis were included. Ninety-six patients were treated with 1.1 GBq (LO group) and 80 patients with 5.5 GBq (HI group). Successful RAI therapy was defined as (i) negative stimulated thyroglobulin (Tg) in the absence of Tg antibodies, and (ii) absence of remnant thyroid tissue and of abnormal cervical LNs on ultrasonography. Clinical ...
TL;DR: The data confirm that quercetin can act as a thyroid disruptor, and they suggest that caution is needed in its supplemental and therapeutic use.
TL;DR: The results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.
Abstract: The role Hsp60 might play in various inflammatory and autoimmune diseases is under investigation, but little information exists pertaining to Hashimoto’s thyroiditis (HT). With the aim to fill this gap, in the present work, we directed our attention to Hsp60 participation in HT pathogenesis. We found Hsp60 levels increased in the blood of HT patients compared to controls. The chaperonin was immunolocalized in thyroid tissue specimens from patients with HT, both in thyrocytes and oncocytes (Hurthle cells) with higher levels compared to controls (goiter). In oncocytes, we found Hsp60 not only in the cytoplasm but also on the plasma membrane, as shown by double immunofluorescence performed on fine needle aspiration cytology. By bioinformatics, we found regions in the Hsp60 molecule with remarkable structural similarity with the thyroglobulin (TG) and thyroid peroxidase (TPO) molecules, which supports the notion that autoantibodies against TG and TPO are likely to recognize Hsp60 on the plasma membrane of oncocytes. This was also supported by data obtained by ELISA, showing that anti-TG and anti-TPO antibodies cross-react with human recombinant Hsp60. Antibody-antigen (Hsp60) reaction on the cell surface could very well mediate thyroid cell damage and destruction, perpetuating inflammation. Experiments with recombinant Hsp60 did not show stimulation of cytokine production by peripheral blood mononuclear cells from HT patients. All together, these results led us to hypothesize that Hsp60 may be an active player in HT pathogenesis via an antibody-mediated immune mechanism.
TL;DR: The measurement of thyroglobulin in the fine-needle aspiration biopsy washout fluid (FNAB-Tg) increases the diagnostic performance of cytology to up to 100% sensitivity and specificity, even when the latter is unable to diagnose LN metastases.
Abstract: Background: The clinical evaluation of enlarged local lymph nodes (LNs) is difficult at the beginning and throughout the follow-up of differentiated thyroid carcinoma (DTC). Although the examination of samples collected from LNs by fine-needle aspiration biopsy cytology (FNAB-C) is extremely specific for the diagnosis of metastases, its sensitivity is low, especially in paucicellular samples. Summary: The measurement of thyroglobulin (Tg) in the fine-needle aspiration biopsy (FNAB) washout fluid (FNAB-Tg) increases the diagnostic performance of cytology to up to 100% sensitivity and specificity. However, the application of FNAB-Tg is currently hindered by the absence of methodological standardization, a lack of definite cutoff points, and the ongoing debate regarding its accuracy in nonthyroidectomized patients, those with elevated serum Tg, and those with circulating anti-Tg antibodies. Conclusion: FNAB-Tg improves the diagnostic performance of FNAB-C in LN metastases, even when the latter is unable to d...
TL;DR: It is suggested that ERp29 acts as an escort factor for ATF6 and promotes its transport from ER to Golgi apparatus under ER stress conditions and does not alter thyroglobulin expression levels.
Abstract: Endoplasmic reticulum protein 29 (ERp29) belongs to the redox-inactive PDI-Dβ-subfamily of PDI-proteins. ERp29 is expressed in all mammalian tissues examined. Especially high levels of expression were observed in secretory tissues and in some tumors. However, the biological role of ERp29 remains unclear. In the present study we show, by using thyrocytes and primary dermal fibroblasts from adult ERp29−/− mice, that ERp29 deficiency affects the activation of the ATF6–CHOP-branch of unfolded protein response (UPR) without influencing the function of other UPR branches, like the ATF4-eIF2α-XBP1 signaling pathway. As a result of impaired ATF6 activation, dermal fibroblasts and adult thyrocytes from ERp29−/− mice display significantly lower apoptosis sensitivities when treated with tunicamycin and hydrogen peroxide. However, in contrast to previous reports, we could demonstrate that ERp29 deficiency does not alter thyroglobulin expression levels. Therefore, our study suggests that ERp29 acts as an escort factor for ATF6 and promotes its transport from ER to Golgi apparatus under ER stress conditions.
TL;DR: It was showed that TgAb positivity was an independent risk factor for PTC, and a positive correlation between T gAb and PTC in patients with indeterminate nodules was existed, indicating the potential role of positive serum Tg Ab in the prediction of PTC.
Abstract: Hashimoto thyroiditis (HT) is associated with an increased risk of developing papillary thyroid carcinoma (PTC). The relationship between thyroid autoimmunity and cancer remains controversial. The purpose of this study was to investigate whether the preoperative TgAb could be a potential predictor of PTC in patients with thyroid nodules and to assess whether there is an association of preoperative TgAb with lymph node metastases. This retrospective, nonrandomised study included 854 patients who underwent standard total thyroidectomy. Benign thyroid nodules were diagnosed in 447 patients, and 407 presented with malignant nodules. The examined parameters included the clinical characteristics, preoperative TSH and TgAb levels, and the histopathological characteristics of the tumour. Tumour size >10 mm (p = 0.01), the presence of PTC (p 10 mm (p 3.4 μU/ml, p = 0.038) were independent risk factors for PTC based on the multivariate logistic regression analysis. This study showed that TgAb positivity was an independent risk factor for PTC. A positive correlation between TgAb and PTC in patients with indeterminate nodules was existed. Additionally, a positive correlation existed between TgAb and lymph node metastases in patients with PTC. Prospective studies with a larger number of patients and long-term follow-up are needed clarify the potential role of positive serum TgAb in the prediction of PTC.
TL;DR: A high molecular weight precursor of the much smaller thyroid hormones, triiodothyronine and thyroxine, is presented that acts as a ‘spatially aggregating agent’ to form thyroglobulin.
Abstract: Background: The established paradigm for thyroglobulin (Tg) function is that of a high molecular weight precursor of the much smaller thyroid hormones, triiodothyronine (T3) and thyroxine (T4). How...
TL;DR: Fibrocytes express four proteins, the aggregate expression of which was previously thought to be restricted to thyroid epithelium, and these proteins represent the necessary molecular biosynthetic machinery necessary for thyroid hormone production.
Abstract: Context: CD34+ fibrocytes, bone marrow-derived progenitor cells, infiltrate orbital connective tissue in thyroid-associated ophthalmopathy, a manifestation of Graves' disease. In the orbit, they become CD34+ fibroblasts and coexist with native CD34− fibroblasts. Fibrocytes have been shown to express TSH receptor and thyroglobulin. Objective: The objective of the study was to determine whether a broader repertoire of thyroid protein expression can be detected in fibrocytes and whether a common factor is responsible. Design/Setting/Participants: Fibrocytes and fibroblasts were collected and analyzed from healthy individuals and those with Graves' disease in an academic clinical practice. Main Outcome Measures: Real-time PCR, Western blot analysis, gene promoter analysis, cell transfections, and flow cytometric cell sorting were performed. Results: We detect two additional thyroid proteins expressed by fibrocytes, namely sodium-iodide symporter and thyroperoxidase. The autoimmune regulator (AIRE) protein app...
TL;DR: Prognostic factors have been identified that provide relevant information for owners and clinicians and independent negative predictors for disease‐free survival were found.
Abstract: BACKGROUND
Prognostic markers for dogs with thyroid tumors are limited.
HYPOTHESIS/OBJECTIVES
To identify clinical, pathologic, and immunohistochemical prognostic factors for dogs with thyroid tumors.
ANIMALS
Seventy dogs with thyroid neoplasia.
METHODS
Retrospective study. Dogs with thyroid neoplasia were included when follow-up information and formalin-fixed paraffin-embedded tumor samples were available. Immunohistochemistry (IHC) was performed for thyroglobulin, calcitonin, Ki-67, and E-cadherin. Correlation of tumor variables (diameter, volume, localization, scintigraphic uptake, thyroid function, IHC) with local invasiveness and metastatic disease was performed on all tumor samples. Forty-four dogs treated by thyroidectomy were included in a survival analysis.
RESULTS
Fifty dogs (71%) had differentiated follicular cell thyroid carcinoma (dFTC) and 20 (29%) had medullary thyroid carcinoma (MTC). At diagnosis, tumor diameter (P = .007; P = .038), tumor volume (P = .020), tumor fixation (P = .002), ectopic location (P = .002), follicular cell origin (P = .044), and Ki-67 (P = .038) were positively associated with local invasiveness; tumor diameter (P = .002), tumor volume (P = .023), and bilateral location (P = .012) were positively associated with presence of distant metastases. Forty-four dogs (28 dFTC, 16 MTC; stage I-III) underwent thyroidectomy. Outcome was comparable between dogs with dFTC and MTC. Macroscopic (P = .007) and histologic (P = .046) vascular invasion were independent negative predictors for disease-free survival. Although time to presentation, histologic vascular invasion and Ki-67 were negatively associated with time to metastases, and time to presentation was negatively associated with time to recurrence, no independent predictors were found. E-cadherin expression was not associated with outcome.
CONCLUSIONS AND CLINICAL IMPORTANCE
Prognostic factors have been identified that provide relevant information for owners and clinicians.
TL;DR: Sequential TgAb change is a good predictor of disease prognosis and is helpful for clinical decision making, especially for patients with undetectable thyroglobulin.
Abstract: Objective: To investigate whether elevated and sequential changes in serum antithyroglobulin antibody (TgAb) levels are indicators of recurrence or persistence of papillary thyroid cancer (PTC) in patients with undetectable thyroglobulin Methods: In 56 patients followed for more than 7 years, we recorded all serum TgAb levels (except the ones determined within one year after 131I therapy or diagnostic scans) and evaluated their disease status All patients had undergone total thyroidectomy and remnant ablation by 131I, and they were positive for TgAb and had undetectable thyroglobulin during follow-up The sequential changes of TgAb were defined as persistently high, increasing, persistently medium, decreasing, and decreasing to negative Recurrence or persistence of PTC was defined as active disease as assessed by 131I scanning, 18F-fluorodeoxyglucose positron emission tomography, ultrasonography, computed tomography, or surgical examination Results: Of the 56 patients enrolled, 10 patients had persist
TL;DR: Serum positive TgAb or TPOAb is an independent predictor for PTC regardless of AITD, and is correlated with elevated TSH level and advanced PTC stage.
Abstract: The correlation between thyroglobulin antibodies (TgAb) or thyroid peroxidase antibodies (TPOAb) and papillary thyroid cancer (PTC) remains controversial. This histological study aimed to explore the correlation between thyroid autoantibodies (TAb), thyroid-stimulating hormone (TSH), and PTC in patients with thyroid nodules (TN). This was a retrospective study. 2,132 non-autoimmune thyroid diseases (AITD) patients who underwent thyroidectomy were subdivided into: TgAb or TPOAb single positive (TgAb+ or TPOAb+) TN group; TgAb and TPOAb double positive or negative (TAb+ or TAb−) TN group. PTC patients showed a higher rate of TAb+ TN (10.24 vs. 4.89 %; P = 0.000) and a higher TSH level (1.83 ± 0.07 vs. 1.39 ± 0.03 mIU/L; P = 0.000) than patients with benign nodules. TAb+ TN patients showed a higher TSH level and PTC frequency than those with TAb− TN (1.91 ± 0.17 vs. 1.47 ± 0.03 mIU/L; P = 0.011) (41.35 vs. 22.08 %; P = 0.000). In PTC, TAb+ TN patients showed a higher TSH level (2.57 ± 0.35 vs. 1.79 ± 0.07 mIU/L; P = 0.032), a greater frequency of lymph node metastasis (52.73 vs. 36.51 %, P = 0.026), and a lower micro-PTC frequency (16.36 vs. 39.51 %; P = 0.001) than TAb− TN patients. PTC was correlated with TgAb+ TN (OR = 1.921, CI 1.431–2.580; P = 0.000), TPOAb+ TN (OR = 1.945, CI 1.195–3.165; P = 0.007), TAb+ TN (OR = 2.393, CI 1.635–3.501; P = 0.000), and serum TSH >1.35 mIU/L (OR = 1.742, CI 1.089–2.786; P = 0.021). Serum positive TgAb or TPOAb is an independent predictor for PTC regardless of AITD. The coexistence of TgAb and TPOAb confers a greater risk for PTC than isolated positive TgAb or TPOAb, and is correlated with elevated TSH level and advanced PTC stage.
TL;DR: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and goiter were common in subjects living in a mild to moderate iodine-deficient area and screening could be reasonable in subjects at a higher risk.
Abstract: Objective: To assess thyroid function, the presence of thyroid antibodies, as well as the presence of goiter and/or nodules in subjects without a prior diagnosis of thyroid disorders, in a region with mild to moderate iodine deficiency. Design and methods: This cross-sectional study is based on data obtained from first and third visits of participants in the Sardinian survey. We performed two different analyses. In one, we assessed the prevalence of unknown thyroid dysfunctions among 6252 subjects who had a medical examination and blood collection for assays of thyrotropin, free thyroxine, and antibodies against thyroperoxidase (AbTPO) and against thyroglobulin (AbTG). In a second analysis, we evaluated the frequency of undiagnosed goiter and nodules among 3377 subjects who had a thyroid ultrasound scan. Subjects were excluded if they had a previous history of thyroid disorders or presence of goiter and/or nodules, or thyroid surgery, or if they were taking drugs that could impair thyroid function. Results: We found a low prevalence of overt thyroid dysfunction (hyperthyroidism 0.4% and hypothyroidism 0.7%). The rates of subclinical hypothyroidism and hyperthyroidism were 4.7 and 2.4% respectively. Almost 16% of participants were positive for at least one antibody and 5.2% for both AbTG and AbTPO. Nodules were detected in 17.4% of subjects and the prevalence of goiter was 22.1%. Conclusions: Undiagnosed biochemical thyroid dysfunctions, unknown nodules, and goiter were common in subjects living in a mild to moderate iodine-deficient area. In this community, thyroid disorders often go undetected and screening could be reasonable in subjects at a higher risk.