[Thyroid emergencies : Thyroid storm and myxedema coma].

PubMed

Spitzweg, C; Reincke, M; Gärtner, R

2017-10-01

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of a long-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (β-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

Competitive inhibition of thyroidal uptake of dietary iodide by perchlorate does not describe perturbations in rat serum total T4 and TSH.

PubMed

McLanahan, Eva D; Andersen, Melvin E; Campbell, Jerry L; Fisher, Jeffrey W

2009-05-01

Perchlorate (ClO4(-)) is an environmental contaminant known to disrupt the thyroid axis of many terrestrial and aquatic species. ClO4(-) competitively inhibits iodide uptake into the thyroid at the sodium/iodide symporter and disrupts hypothalamic-pituitary-thyroid (HPT) axis homeostasis in rodents. We evaluated the proposed mode of action for ClO4(-)-induced rat HPT axis perturbations using a biologically based dose-response (BBDR) model of the HPT axis coupled with a physiologically based pharmacokinetic model of ClO4(-). We configured a BBDR-HPT/ClO4(-) model to describe competitive inhibition of thyroidal uptake of dietary iodide by ClO4(-) and used it to simulate published adult rat drinking water studies. We compared model-predicted serum thyroid-stimulating hormone (TSH) and total thyroxine (TT4) concentrations with experimental observations reported in these ClO4(-) drinking water studies. The BBDR-HPT/ClO4(-) model failed to predict the ClO4(-)-induced onset of disturbances in the HPT axis. Using ClO4(-) inhibition of dietary iodide uptake into the thyroid, the model underpredicted both the rapid decrease in serum TT4 concentrations and the rise in serum TSH concentrations. Assuming only competitive inhibition of thyroidal uptake of dietary iodide, BBDR-HPT/ClO4(-) model calculations were inconsistent with the rapid decrease in serum TT4 and the corresponding increase in serum TSH. Availability of bound iodide in the thyroid gland governed the rate of hormone secretion from the thyroid. ClO4(-) is translocated into the thyroid gland, where it may act directly or indirectly on thyroid hormone synthesis/secretion in the rat. The rate of decline in serum TT4 in these studies after 1 day of treatment with ClO4(-) appeared consistent with a reduction in thyroid hormone production/secretion. This research demonstrates the utility of a biologically based model to evaluate a proposed mode of action for ClO4(-) in a complex biological process.

Celebrating 10 Years of Delivering EarthScope USArray Transportable Array Data from the Array Network Facility (ANF)

NASA Astrophysics Data System (ADS)

Eakins, J. A.; Vernon, F.; Astiz, L.; Davis, G. A.; Reyes, J. C.; Martynov, V. G.; Tytell, J.; Cox, T. A.; Meyer, J.

2013-12-01

Since 2004, the Array Network Facility (ANF) has been responsible for generation and delivery of the metadata as well as collection and initial quality control and the transmission of the seismic, and more recently infrasound and meteorological data, for the Earthscope USArray Transportable Array. As of August 2013, we have managed data from over 1600 stations. Personnel at the ANF provide immediate eyes on the data to improve quality control as well as interact with the individual stations via calibrations, mass recentering, baler data retrieval and event analysis. Web-based tools have been developed, and rewritten over the years, to serve the needs of both station engineers and the public. Many lessons on the needs for scalability have been learned. Analysts continue to review all seismic events recorded on 7 or more TA stations making associations against externally available bulletins and/or generating ANF authored locations which are available at both the ANF and IRIS-DMC. The US Array pressure data have several unique characteristics that are allowing us to conduct a rigorous analysis of the spatio-temporal variations in the pressure field on time scales of less than an hour across the eastern United States. With the installation of the infrasound and atmospheric pressure sensors, starting in 2010, observations of gust fronts, near misses of tornados at individual stations, and of the mesoscale gravity waves showing the value and utility of the US Array pressure data will be presented.

Molecular characterization of thyroid hormone-inhibited atrial L-type calcium channel expression: implication for atrial fibrillation in hyperthyroidism.

PubMed

Chen, Wei-Jan; Yeh, Yung-Hsin; Lin, Kwang-Huei; Chang, Gwo-Jyh; Kuo, Chi-Tai

2011-03-01

Atrial fibrillation (AF) is a common complication in hyperthyroidism. Earlier studies demonstrate that thyroid hormone decreases L-type calcium channel (LCC) current expression with resultant shortening of action potential duration (APD), providing a substrate for AF. The aim of this study was to investigate the potential mechanism underlying the regulatory effect of thyroid hormone on LCC. In a hyperthyroid rat model, thyroid hormone (triiodothyronine [T3]) administration down-regulated atrial LCC expression. In vitro, treatment of murine atrial myocytes (HL-1) with T3 decreased the expression of LCC and its current, resulting in abbreviation of APD. Furthermore, T3 inhibited the activation of cyclic AMP response element (CRE)-binding protein (CREB), including phosphorylation at Ser133 and its nuclear translocation. Transient transfection studies in HL-1 cells indicated that T3 reduced LCC promoter activity. Deletion and mutation analysis of the LCC promoter region along with chromatin immunoprecipitation using anti-CREB antibody showed that CRE was essential for T3-mediated LCC gene expression. Transfection of dominant-negative CREB (mutated Ser133) and mutant thyroid hormone receptor (TR, mutated Cys51) abolished the T3-dependent effects, suggesting an association between both transcriptional factors. Co-immunoprecipitation documented an increased binding of TR with CREB after T3 treatment. The transcriptional cross-talk 3 between TR and CREB bound to CRE mediates T3-inhibited CREB activity and LCC expression. Thyroid hormone-induced TR binding of CREB inhibits CREB activity and LCC current expression, which may contribute to AF. These findings provide an important mechanistic insight into hyperthyroidism-induced AF.

The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia.

PubMed

Contreras-Jurado, Constanza; Alonso-Merino, Elvira; Saiz-Ladera, Cristina; Valiño, Arturo José; Regadera, Javier; Alemany, Susana; Aranda, Ana

2016-08-03

Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)-induced endotoxic shock in animals as well as in critically ill patients. Here we studied the role of the thyroid hormone receptors (TRs) in activation of STAT3, NF-κB and ERK, which play a key role in the response to inflammatory cytokines during sepsis. TR knockout mice showed down-regulation of hepatic inflammatory mediators, including interleukin 6 (IL-6) in response to LPS. Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act as endogenous repressors of these pathways. Furthermore, hyperthyroidism increased cytokine production and mortality in response to LPS, despite decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly repress the response of the cells to inflammatory mediators. Indeed, we found that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3 recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs are potent regulators of inflammatory responses and immune homeostasis during sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism for preventing deleterious effects of excessive hormone signaling during infections.

The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia

PubMed Central

Contreras-Jurado, Constanza; Alonso-Merino, Elvira; Saiz-Ladera, Cristina; Valiño, Arturo José; Regadera, Javier; Alemany, Susana; Aranda, Ana

2016-01-01

Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)-induced endotoxic shock in animals as well as in critically ill patients. Here we studied the role of the thyroid hormone receptors (TRs) in activation of STAT3, NF-κB and ERK, which play a key role in the response to inflammatory cytokines during sepsis. TR knockout mice showed down-regulation of hepatic inflammatory mediators, including interleukin 6 (IL-6) in response to LPS. Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act as endogenous repressors of these pathways. Furthermore, hyperthyroidism increased cytokine production and mortality in response to LPS, despite decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly repress the response of the cells to inflammatory mediators. Indeed, we found that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3 recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs are potent regulators of inflammatory responses and immune homeostasis during sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism for preventing deleterious effects of excessive hormone signaling during infections. PMID:27484112

Inhibition of Tumorigenesis by the Thyroid Hormone Receptor β in Xenograft Models

PubMed Central

Kim, Won Gu; Zhao, Li; Kim, Dong Wook; Willingham, Mark C.

2014-01-01

Background: Previous studies showed a close association between several types of human cancers and somatic mutations of thyroid hormone receptor β (TRβ) and reduced expression of TRβ due to epigenetic inactivation and/or deletion of the THRB gene. These observations suggest that TRβ could act as a tumor suppressor in carcinogenesis. However, the mechanisms by which TRβ could function to inhibit tumorigenesis are less well understood. Methods: We used the human follicular thyroid cancer cell lines (FTC-133 and FTC-236 cells) to elucidate how functional expression of the THRB gene could affect tumorigenesis. We stably expressed the THRB gene in FTC cells and evaluated the effects of the expressed TRβ on cancer cell proliferation, migration, and tumor growth in cell-based studies and xenograft models. Results: Expression of TRβ in FTC-133 cells, as compared with control FTC cells without TRβ, reduced cancer cell proliferation and impeded migration of tumor cells through inhibition of the AKT-mTOR-p70 S6K pathway. TRβ expression in FTC-133 and FTC-236 led to less tumor growth in xenograft models. Importantly, new vessel formation was significantly suppressed in tumors induced by FTC cells expressing TRβ compared with control FTC cells without TRβ. The decrease in vessel formation was mediated by the downregulation of vascular endothelial growth factor in FTC cells expressing TRβ. Conclusions: These findings indicate that TRβ acts as a tumor suppressor through downregulation of the AKT-mTOR-p70 S6K pathway and decreased vascular endothelial growth factor expression in FTC cells. The present results raise the possibility that TRβ could be considered as a potential therapeutic target for thyroid cancer. PMID:23731250

Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways.

PubMed

Vickers, Alison E M; Heale, Jason; Sinclair, John R; Morris, Stephen; Rowe, Josh M; Fisher, Robyn L

2012-04-01

Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24-48 h) and human (24 h) with ≥ 10 μM MMI. Thyroid from rats treated with single doses of MMI (30-1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (~15-84 μM), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24h with MMI (≥ 10 μM) and PTU (100 μM). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ~2-fold) and only at higher MMI concentrations (≥ 1500 μM, 24h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. Copyright © 2012 Elsevier Inc. All rights reserved.

Thyroid organotypic rat and human cultures used to investigate drug effects on thyroid function, hormone synthesis and release pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vickers, Alison E.M., E-mail: vickers_alison@allergan.com; Heale, Jason; Sinclair, John R.

Drug induced thyroid effects were evaluated in organotypic models utilizing either a rat thyroid lobe or human thyroid slices to compare rodent and human response. An inhibition of thyroid peroxidase (TPO) function led to a perturbation in the expression of key genes in thyroid hormone synthesis and release pathways. The clinically used thiourea drugs, methimazole (MMI) and 6-n-propyl-2-thioruacil (PTU), were used to evaluate thyroid drug response in these models. Inhibition of TPO occurred early as shown in rat thyroid lobes (2 h) and was sustained in both rat (24–48 h) and human (24 h) with ≥ 10 μM MMI. Thyroidmore » from rats treated with single doses of MMI (30–1000 mg/kg) exhibited sustained TPO inhibition at 48 h. The MMI in vivo thyroid concentrations were comparable to the culture concentrations (∼ 15–84 μM), thus demonstrating a close correlation between in vivo and ex vivo thyroid effects. A compensatory response to TPO inhibition was demonstrated in the rat thyroid lobe with significant up-regulation of genes involved in the pathway of thyroid hormone synthesis (Tpo, Dio1, Slc5a5, Tg, Tshr) and the megalin release pathway (Lrp2) by 24 h with MMI (≥ 10 μM) and PTU (100 μM). Similarly, thyroid from the rat in vivo study exhibited an up-regulation of Dio1, Slc5a5, Lrp2, and Tshr. In human thyroid slices, there were few gene expression changes (Slc5a5, ∼ 2-fold) and only at higher MMI concentrations (≥ 1500 μM, 24 h). Extended exposure (48 h) resulted in up-regulation of Tpo, Dio1 and Lrp2, along with Slc5a5 and Tshr. In summary, TPO was inhibited by similar MMI concentrations in rat and human tissue, however an increased sensitivity to drug treatment in rat is indicated by the up-regulation of thyroid hormone synthesis and release gene pathways at concentrations found not to affect human tissue. -- Highlights: ► Novel model of rat thyroid or human thyroid slices to evaluate pathways of injury. ► TPO inhibition by MMI or PTU

Inhibition of the Growth of Papillary Thyroid Carcinoma Cells by CI-1040

PubMed Central

Henderson, Ying C.; Ahn, Soon-Hyun; Clayman, Gary L.

2015-01-01

Background Papillary thyroid carcinoma (PTC), the most common type of thyroid malignancy, usually possesses mutations, either RET/PTC rearrangement or BRAF mutation. Both mutations can activate the mitogen-activated protein kinase kinase/extracellular signal–related kinase signaling transduction pathway, which results in activation of transcription factors that regulate cellular proliferation, differentiation, and apoptosis. Objective To test the effects of CI-1040 (PD184352), a specific MEK1/2 inhibitor, on PTC cells carrying either an RET/PTC1 rearrangement or a BRAF mutation. Design The effects of CI-1040 on PTC cells were evaluated in vitro and in vivo. Main Outcome Measures The effects of CI-1040 on PTC cells were evaluated in vitro using a cell proliferation assay, cell cycle analysis, and immunoblotting. The antitumor effects of CI-1040 in vivo were evaluated in an orthotopic mouse model. Results The concentrations of CI-1040 needed to inhibit 50% cell growth were 0.052μM for PTC cells with a BRAF mutation and 1.1μM for PTC cells with the RET/PTC1 rearrangement. After 3 weeks of oral administration of CI-1040 (300 mg/kg/d) to mice with orthotopic tumor implants of PTC cells, the mean tumor volume of implants bearing the RET/PTC1 rearrangement (n=5) was reduced 47.5% compared with untreated mice (from 701.9 to 368.5 mm3), and the mean volume of implants with a BRAF mutation (n=8) was reduced 31.3% (from 297.3 to 204.2 mm3). Conclusions CI-1040 inhibits PTC cell growth in vitro and in vivo. Because RET/PTC rearrangements are unique to thyroid carcinomas and a high percentage of PTCs possess either mutation, these findings support the clinical evaluation of CI-1040 for patients with PTC. PMID:19380355

Inhibition of thyroid hormone sulfotransferase activity by brominated flame retardants and halogenated phenolics

PubMed Central

Butt, Craig M.; Stapleton, Heather M.

2013-01-01

Many halogenated organic contaminants (HOCs) are considered endocrine disruptors and affect the hypothalamic-pituitary-thyroid axis, often by interfering with circulating levels of thyroid hormones (THs). This study investigated one potential mechanism for TH disruption, inhibition of sulfotransferase activity. One of the primary roles of TH sulfation is to support the regulation of biologically active T3 through the formation of inactive THs. This study investigated TH sulfotransferase inhibition by 14 hydroxylated polybrominated diphenyl ethers (OH-BDEs), BDE 47, triclosan, and fluorinated, chlorinated, brominated and iodinated analogues of 2,4,6-trihalogenated phenol and BPA. A new mass spectrometry-based method was also developed to measure the formation rates of 3,3′-T2 sulfate (3,3′-T2S). Using pooled human liver cytosol we investigated the influence of these HOCs on the sulfation of 3,3′-T2, a major substrate for TH sulfation. For the formation of 3,3′-T2 sulfate, the Michaelis constant (Km) was 1070 ± 120 nM and the Vmax was 153 ± 6.6 pmol/min.mg protein. All chemicals investigated inhibited sulfotransferase activity with the exception of BDE 47. The 2,4,6-trihalogenated phenols were the most potent inhibitors followed by the OH-BDEs and then halogenated BPAs. The IC50 concentrations for the OH-BDEs were primarily in the low nM range, which may be environmentally relevant. In silico molecular modeling techniques were also used to simulate OH-BDE binding with SULT1A1. This study suggests that some HOCs, including anti-microbial chemicals and metabolites of flame retardants, may interfere with TH regulation through inhibition of sulfotransferase activity. PMID:24089703

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1

PubMed Central

Zhang, Yue; Sun, Bin; Huang, Zhi

2018-01-01

Background Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes. Material/Methods The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro. A transwell motility assay was used to analyze the migration of TPC-1 cells. Western blot was performed to determine the expression levels of PTEN and DNMT1 genes. A methylation-specific polymerase chain reaction (PCR) (MSP) assay was used to evaluate the methylation of PTEN. Results Following treatment with shikonin, the cell survival rate of TPC-1 cells decreased in a dose-dependent manner; the inhibitory effects on HTori-3 cells were less marked. Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner. The methylation of PTEN was suppressed by shikonin, which also reduced the expression of DNMT1 in a dose-dependent manner, and increased the expression of PTEN. Overexpression of DNMT1 promoted the migration of TPC-1 cells and the methylation of PTEN. Levels of protein expression of PTEN in TPC-1 cells treated with shikonin decreased, and were increased by DNMT1 knockdown. Conclusions Shikonin suppressed the expression of DNMT1, reduced PTEN gene methylation, and increased PTEN protein expression, leading to the inhibition of TPC-1 cell migration. PMID:29389913

A Selective TSH Receptor Antagonist Inhibits Stimulation of Thyroid Function in Female Mice

PubMed Central

Neumann, Susanne; Nir, Eshel A.; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E.

2014-01-01

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease. PMID:24169564

A selective TSH receptor antagonist inhibits stimulation of thyroid function in female mice.

PubMed

Neumann, Susanne; Nir, Eshel A; Eliseeva, Elena; Huang, Wenwei; Marugan, Juan; Xiao, Jingbo; Dulcey, Andrés E; Gershengorn, Marvin C

2014-01-01

Because the TSH receptor (TSHR) plays an important role in the pathogenesis of thyroid disease, a TSHR antagonist could be a novel treatment. We attempted to develop a small molecule, drug-like antagonist of TSHR signaling that is selective and active in vivo. We synthesized NCGC00242364 (ANTAG3) by chemical modification of a previously reported TSHR antagonist. We tested its potency, efficacy, and selectivity in a model cell system in vitro by measuring its activity to inhibit stimulation of cAMP production stimulated by TSH, LH, or FSH. We tested the in vivo activity of ANTAG3 by measuring its effects to lower serum free T4 and thyroid gene expression in female BALB/c mice continuously treated with ANTAG3 for 3 days and given low doses of TRH continuously or stimulated by a single administration of a monoclonal thyroid-stimulating antibody M22. ANTAG3 was selective for TSHR inhibition; half-maximal inhibitory doses were 2.1 μM for TSHR and greater than 30 μM for LH and FSH receptors. In mice treated with TRH, ANTAG3 lowered serum free T4 by 44% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 75% and 83%, respectively. In mice given M22, ANTAG3 lowered serum free T4 by 38% and lowered mRNAs for sodium-iodide cotransporter and thyroperoxidase by 73% and 40%, respectively. In conclusion, we developed a selective TSHR antagonist that is effective in vivo in mice. This is the first report of a small-molecule TSHR antagonist active in vivo and may lead to a drug to treat Graves' disease.

Comparison of Performance of AN-F-58 Fuel and Gasoline in J34-WE-22 Turbojet Engine

NASA Technical Reports Server (NTRS)

Dowman, Harry W; Younger, George G

1949-01-01

As part of an investigation of the performance of AN-F-58 fuel in various types of turbojet engine, the performance of this fuel in a 3000-pound-thrust turbojet engine has been investigated in an altitude test chamber together with the comparative performance of 62-octane gasoline. The investigation of normal engine performance, which covered a range of engine speeds at altitudes from 5000 to 50,000 feet and flight Mach numbers up to 1.00, showed that both the net thrust and average turbine-outlet temperatures were approximately the same for both fuels. The specific fuel consumption and the combustion efficiency at the maximum engine speeds investigated were approximately the same for both fuels at altitudes up to 35,000 feet, but at an altitude of 50,000 feet the specific fuel consumption was about 9 percent higher and the combustion efficiency was correspondingly lower with the AN-F-58 fuel than with gasoline. The low-engine-speed blow-out limits were about the same for both fuels. Ignition of AN-F-58 fuel with the standard spark plug was possible only with the spark plug in a clean condition; ignition was impossible at all flight conditions investigated when the plug was fouled by an accumulation of liquid fuel from a preceding false start. Use of an extended-electrode spark plug provided satisfactory ignition over a slightly smaller range of altitudes and flight Mach numbers than for gasoline with the standard spark plug.

A study of the time-resolved fluorescence spectrum and red edge effect of ANF in a room-temperature ionic liquid.

PubMed

Hu, Zhonghan; Margulis, Claudio J

2006-06-15

In a recent article, we have analyzed using molecular dynamics simulations the steady-state red edge effect (REE) observed by Samanta and co-workers when the fluorescent probe 2-amino-7-nitrofluorene (ANF) is photoexcited at different wavelengths in 1-butyl-3-methylimidazolium ([BMIM+]) hexafluorophosphate ([PF6-]). In this letter, we predict the time- and wavelength-dependent emission spectra of ANF in the same ionic solvent. From the analysis of our simulated data, we are able to derive an approximate time scale for reorganization of the solvent around the solute probe. The effect that slow varying local liquid environments have on the overall time-dependent signal is also discussed.

Hydrogen peroxide inhibits iodide influx and enhances iodide efflux in cultured FRTL-5 rat thyroid cells.

PubMed

Sugawara, M; Yamaguchi, D T; Lee, H Y; Yanagisawa, K; Murakami, S; Summer, C N; Johnson, D G; Levin, S R

1990-05-01

This study describes the effects of hydrogen peroxide on the two iodide transport systems, I influx and I efflux, in the cultured FRTL-5 rat thyroid cells. I influx was measured by the amount of I taken up by the cells during incubation with Na125I and NaI for 7 min, and I efflux was measured by calculating the rate of 125I release from the 125I-loaded cells in the presence and absence of 5 mmol/l H2O2. Exposure to greater than 100 mumol/l H2O2 for 40 min caused a significant inhibition of I influx; the inhibition was reversible and non-competitive with iodide. Thyroid Na+K+ ATPase activity, a major mechanism to drive I influx, decreased by 40% after the cells were exposed to 5 mmol/l H2O2 for 10 min. H2O2 enhanced I efflux only when Ca2+ was present in the medium. The mechanism of an enhanced I efflux by H2O2 appears to be mediated through the elevation of free cytosolic Ca2+ concentration. Our data indicate that H2O2 can affect I transport by inhibiting I influx and enhancing I efflux.

Recent developments in the investigation of thyroid regulation and thyroid carcinogenesis.

PubMed Central

Hard, G C

1998-01-01

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in

Effect of adrenal hormones on thyroid secretion and thyroid hormones on adrenal secretion in the sheep.

PubMed Central

Falconer, I R; Jacks, F

1975-01-01

1. Previous work has shown that after stressful stimuli, sheep initially secrete increased amounts of thyroid hormone, at a time when adrenal secretion is also elevated. 2. This study was designed to evaluate (a) any short-term activation or inhibition of thyroid secretion by exogenous cortisol or ACTH administered in quantities comparable to those secreted after stress in sheep and (b) any short-term effect that exogenous thyroxine or triiodothyronine may have on the concentration of plasma cortisol in the sheep. 3. Thyroid activity was measured by determination of plasma protein bound 125I (PB125I) and total 125I in thyroid vein and mixed venous (jugular) blood. Plasma cortisol and thyroxine concentrations were measured by a competitive protein-binding assay at intervals for up to 5 hr after commencement of the experiment. 4. No evidence of an activation of thyroid secretion was found during cortisol or ACTH infusion, as monitored by thyroid vein PB125I. Similarly there was no evidence of any inhibition of thyroid function, as measured by continued secretion of thyroid hormones into thyroid vein blood. 5. No effect on plasma cortisol concentration due to thyroid hormone treatment was observed. 6. It was concluded that (a) elevated circulating corticosteroids in physiological concentrations have no short-term effects on thyroid activity in the sheep and (b) the short-term alterations in thyroid and adrenal cortical secretion observed during stress in the sheep could not be attributed to direct interaction of elevated thyroid hormone concentrations with adrenal cortical secretion. PMID:170400

Sympathovagal imbalance in thyroid dysfunctions in females: correlation with thyroid profile, heart rate and blood pressure.

PubMed

Karthik, S; Pal, G K; Nanda, Nivedita; Hamide, Abdoul; Bobby, Zachariah; Amudharaj, D; Pal, Pravati

2009-01-01

The aim of the study was to investigate the role of spectral analysis of heart rate variability (HRV) for assessing the type and degree of sympathovagal imbalance (SVI) and their link to cardiovascular morbidities in thyroid dysfunctions. Forty-five female subjects (15 control subjects and freshly diagnosed untreated 15 hypothyroid and 15 hyperthyroid patients) were recruited for the study. Thyroid profile, body mass index (BMI), basal heart rate (BHR), blood pressure (BP) and spectral indices of HRV (TP, LFnu, HFnu and LF-HF ratio, mean RR, SDNN and RMSSD) were assessed in all the three groups. LF-HF ratio was correlated with thyroid profile, BMI, BHR and BP. SVI was more prominent in hyperthyroid (P < 0.001) compared to hypothyroid (P < 0.05) subjects. LF-HF ratio was correlated with thyroid profile in both hypo and hyperthyroid subjects; but correlation with BHR and BP was significant only in hyperthyroidism. Though the SVI was found to be due to both vagal withdrawal and sympathetic activation, especially in hyperthyroidism, contribution by vagal inhibition was prominent. Vagal inhibition contributes significantly to SVI in thyroid dysfunctions, especially in hyperthyroidism. As the present study indicates poor cardiovascular health due to vagal inhibition in patients suffering from thyroid dysfunctions, attempt should be made to improve vagal tone especially in hyperthyroid subjects to attain a stable sympathovagal and cardiovascular homeostasis.

GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 kinase (PI3K) and hypoxia-inducible factor-1α (HIF-1α) pathways.

PubMed

Burrows, Natalie; Babur, Muhammad; Resch, Julia; Ridsdale, Sophie; Mejin, Melissa; Rowling, Emily J; Brabant, Georg; Williams, Kaye J

2011-12-01

Phosphoinositide 3-kinase (PI3K) regulates the transcription factor hypoxia-inducible factor-1 (HIF-1) in thyroid carcinoma cells. Both pathways are associated with aggressive phenotype in thyroid carcinomas. Our objective was to assess the effects of the clinical PI3K inhibitor GDC-0941 and genetic inhibition of PI3K and HIF on metastatic behavior of thyroid carcinoma cells in vitro and in vivo. Vascular endothelial growth factor ELISA, HIF activity assays, proliferation studies, and scratch-wound migration and cell spreading assays were performed under various O(2) tensions [normoxia, hypoxia (1 and 0.1% O(2)), and anoxia] with or without GDC-0941 in a panel of four thyroid carcinoma cell lines (BcPAP, WRO, FTC133, and 8505c). Genetic inhibition was achieved by overexpressing phosphatase and tensin homolog (PTEN) into PTEN-null cells and by using a dominant-negative variant of HIF-1α (dnHIF). In vivo, human enhanced green fluorescence protein-expressing follicular thyroid carcinomas (FTC) were treated with GDC-0941 (orally). Spontaneous lung metastasis was confirmed by viewing enhanced green fluorescence protein-positive colonies cultured from lung tissue. GDC-0941 inhibited hypoxia/anoxia-induced HIF-1α and HIF-2α expression and HIF activity in thyroid carcinoma cells. Basal (three of four cell lines) and/or hypoxia-induced (four of four) secreted vascular endothelial growth factor was inhibited by GDC-0941, whereas selective HIF targeting predominantly affected hypoxia/anoxia-mediated secretion (P < 0.05-0.0001). Antiproliferative effects of GDC-0941 were more pronounced in PTEN mutant compared with PTEN-restored cells (P < 0.05). Hypoxia increased migration in papillary cells and cell spreading/migration in FTC cells (P < 0.01). GDC-0941 reduced spreading and migration in all O(2) conditions, whereas dnHIF had an impact only on hypoxia-induced migration (P < 0.001). In vivo, GDC-0941 reduced expression of HIF-1α, phospho-AKT, GLUT-1, and lactate

Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.

PubMed

Yu, Yang; Yu, Xiaohui; Fan, Chenling; Wang, Hong; Wang, Renee; Feng, Chen; Guan, Haixia

2018-06-25

Papillary thyroid cancer is a prevalent endocrine malignancy. Although alterations in glutamine metabolism have been reported in several types of hematological and solid tumors, little is known about the functions of glutamine and glutaminolysis-associated proteins in papillary thyroid cancer. Here, we demonstrated the glutamine dependence of papillary thyroid cancer cells, and with the use of RT 2 -PCR arrays, we screened for the aberrant overexpression of glutaminase in human papillary thyroid cancer tissues and cells. These results were later confirmed via real-time PCR, Western blots, and immunohistochemical staining. We found that the levels of glutaminase were significantly correlated with extrathyroidal extension. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. The proliferative, viable, migratory, and invasive abilities of papillary thyroid cancer cells were impaired by both the pharmacological inhibition and the genetic knockdown of glutaminase. Additionally, the inhibition of glutaminase deactivated the mechanistic target of the rapamycin complex 1 (mTORC1) signaling pathway, promoting autophagy and apoptosis. Collectively, these findings show that glutaminase-mediated glutamine dependence may be a potential therapeutic target for papillary thyroid cancer. PTC cells are glutamine-dependent, and GLS is aberrantly overexpressed in PTC. Inhibition of GLS suppressed glutaminolysis and reduced mitochondrial respiration. Inhibition of GLS impairs the viability of PTC cells. GLS blockade causes deactivation of mTORC1 and induction of autophagy and apoptosis. GLS may be a potential therapeutic target for PTC.

Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

PubMed

Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

1996-05-01

Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

A Network of AOPs for reduced thyroid hormone synthesis derived from inhibition of Thyroperoxidase - A common Molecular Initiating Event Leading to Species-Specific Indices of Adversity.

EPA Science Inventory

This collection of 3 AOPs describe varying outcomes of adversity dependent upon species in response to inhibition of thyroperoxidase (TPO) during development. Chemical inhibition of TPO, the molecular-initiating event (MIE), results in decreased thyroid hormone (TH) synthesis, a...

Inhibition of the Thyroid Hormone Pathway in Xenopus by Mercaptobenzothiazole

EPA Science Inventory

Amphibian metamorphosis is a thyroid hormone-dependent process that provides a potential model system to assess chemicals for their ability to disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Several studies have demonstrated the sensitivity of this system to a variety of ...

MARGINAL IODINE DEFICIENCY EXACERBATES PERCHLORATE THYROID TOXICITY.

EPA Science Inventory

The environmental contaminant perchlorate disrupts thyroid homeostasis via inhibition of iodine uptake into the thyroid. This work tested whether iodine deficiency exacerbates the effects of perchlorate. Female 27 day-old LE rats were fed a custom iodine deficient diet with 0, 50...

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib

PubMed Central

Wang, Weibin; Kang, Helen; Zhao, Yinu; Min, Irene; Wyrwas, Brian; Moore, Maureen; Teng, Lisong; Zarnegar, Rasa; Jiang, Xuejun

2017-01-01

Context: The RAF inhibitor vemurafenib has provided a major advance for the treatment of patients with BRAF-mutant metastatic melanoma. However, BRAF-mutant thyroid cancer is relatively resistant to vemurafenib, and the reason for this disparity remains unclear. Anticancer therapy–induced autophagy can trigger adaptive drug resistance in a variety of cancer types and treatments. To date, role of autophagy during BRAF inhibition in thyroid cancer remains unknown. Objective: In this study, we investigate if autophagy is activated in vemurafenib-treated BRAF-mutant thyroid cancer cells, and whether autophagy inhibition improves or impairs the treatment efficacy of vemurafenib. Design: Autophagy level was determined by western blot assay and transmission electron microscopy. The combined effects of autophagy inhibitor and vemurafenib were assessed in terms of cell viability in vitro and tumor growth rate in vivo. Whether the endoplasmic reticulum (ER) stress was in response to vemurafenib-induced autophagy was also analyzed. Results: Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells. Inhibition of autophagy by either a pharmacological inhibitor or interfering RNA knockdown of essential autophagy genes augmented vemurafenib-induced cell death. Vemurafenib-induced autophagy was independent of MAPK signaling pathway and was mediated through the ER stress response. Finally, administration of vemurafenib with the autophagy inhibitor hydroxychloroquine promoted more pronounced tumor suppression in vivo. Conclusions: Our data demonstrate that vemurafenib induces ER stress response–mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. PMID:27754804

Targeting Autophagy Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.

PubMed

Wang, Weibin; Kang, Helen; Zhao, Yinu; Min, Irene; Wyrwas, Brian; Moore, Maureen; Teng, Lisong; Zarnegar, Rasa; Jiang, Xuejun; Fahey, Thomas J

2017-02-01

The RAF inhibitor vemurafenib has provided a major advance for the treatment of patients with BRAF-mutant metastatic melanoma. However, BRAF-mutant thyroid cancer is relatively resistant to vemurafenib, and the reason for this disparity remains unclear. Anticancer therapy-induced autophagy can trigger adaptive drug resistance in a variety of cancer types and treatments. To date, role of autophagy during BRAF inhibition in thyroid cancer remains unknown. In this study, we investigate if autophagy is activated in vemurafenib-treated BRAF-mutant thyroid cancer cells, and whether autophagy inhibition improves or impairs the treatment efficacy of vemurafenib. Autophagy level was determined by western blot assay and transmission electron microscopy. The combined effects of autophagy inhibitor and vemurafenib were assessed in terms of cell viability in vitro and tumor growth rate in vivo. Whether the endoplasmic reticulum (ER) stress was in response to vemurafenib-induced autophagy was also analyzed. Vemurafenib induced a high level of autophagy in BRAF-mutant thyroid cancer cells. Inhibition of autophagy by either a pharmacological inhibitor or interfering RNA knockdown of essential autophagy genes augmented vemurafenib-induced cell death. Vemurafenib-induced autophagy was independent of MAPK signaling pathway and was mediated through the ER stress response. Finally, administration of vemurafenib with the autophagy inhibitor hydroxychloroquine promoted more pronounced tumor suppression in vivo. Our data demonstrate that vemurafenib induces ER stress response-mediated autophagy in thyroid cancer and autophagy inhibition may be a beneficial strategy to sensitize BRAF-mutant thyroid cancer to vemurafenib. Copyright © 2017 by the Endocrine Society

Comparison of in vitro and ex vivo thyroid hormone synthesis inhibition results and in vivo outcomes for a series of benzothiazoles

EPA Science Inventory

Assessing how in vitro data may be used to predict adverse effects in vivo is critical as efforts are advanced to incorporate in vitro assays into a risk assessment framework. Within the context of a thyroid hormone (TH) synthesis inhibition adverse outcome pathway (AOP), in vitr...

Thyroid stimulating antibodies in sarcoidosis.

PubMed

Attali, J R; Valensi, P; Valeyre, D; Sandre-Banon, D; Sebaoun, J; Battesti, J P

1994-06-01

Thyroid disorders, particularly euthyroid goiters and hyperthyroidism, can be observed in sarcoidosis. The aim of this study was to analyze the presence of thyroid stimulating antibodies (TSAb) in 21 patients with sarcoidosis. 12 patients out of 21 had simultaneous euthyroid goiter. The others were euthyroid and free of goiter. The TSAb testing was carried out using the rat thyroid fragment perifusion technique. Thyroid response to IgG was determined by the mean rate of T4 release (R) during a 30-min perifusion and the secretion peak (Imax). Antibodies inhibiting TSH binding to its receptors were also looked for. Ten patients were TSAb+ and eleven were TSAb-. There was no difference between the TSAb+ and TSAb- groups in the clinical parameters for sarcoidosis, nor in the number of goiters found (n = 6 for both groups). In 5 out of the 6 cases where goiter was present in the TSAb+ group it was homogeneous and diagnosed at the same time as or after the first signs of sarcoidosis, whereas in 5 out of the 6 cases of goiter in TSAb- patients, it was nodular, diagnosed before sarcoidosis in 3 of them, endemic in one of them, and familial in another. The search for antibodies inhibiting TSH binding to its receptors was negative in 10 out of 21 patients tested. Although the presence of thyroid-stimulating antibodies in the serum of patients with sarcoidosis, found here for the first time, remains to be explained, it pleads in favor of the immunologic nature of the association of sarcoidosis with thyroid disorders.

Curcumin induces G2/M arrest, apoptosis, NF-κB inhibition, and expression of differentiation genes in thyroid carcinoma cells.

PubMed

Schwertheim, Suzan; Wein, Frederik; Lennartz, Klaus; Worm, Karl; Schmid, Kurt Werner; Sheu-Grabellus, Sien-Yi

2017-07-01

The therapy of unresectable advanced thyroid carcinomas shows unfavorable outcome. Constitutive nuclear factor-κB (NF-κB) activation in thyroid carcinomas frequently contributes to therapeutic resistance; the radioiodine therapy often fails due to the loss of differentiated functions in advanced thyroid carcinomas. Curcumin is known for its anticancer properties in a series of cancers, but only few studies have focused on thyroid cancer. Our aim was to evaluate curcumin's molecular mechanisms and to estimate if curcumin could be a new therapeutic option in advanced thyroid cancer. Human thyroid cancer cell lines TPC-1 (papillary), FTC-133 (follicular), and BHT-101 (anaplastic) were treated with curcumin. Using real-time PCR analysis, we investigated microRNA (miRNA) and mRNA expression levels. Cell cycle, Annexin V/PI staining, and caspase-3 activity analysis were performed to detect apoptosis. NF-κB p65 activity and cell proliferation were analyzed using appropriate ELISA-based colorimetric assay kits. Treatment with 50 μM curcumin significantly increased the mRNA expression of the differentiation genes thyroglobulin (TG) and sodium iodide symporter (NIS) in all three cell lines and induced inhibition of cell proliferation, apoptosis, and decrease of NF-κB p65 activity. The miRNA expression analyses showed a significant deregulation of miRNA-200c, -21, -let7c, -26a, and -125b, known to regulate cell differentiation and tumor progression. Curcumin arrested cell growth at the G2/M phase. Curcumin increases the expression of redifferentiation markers and induces G2/M arrest, apoptosis, and downregulation of NF-κB activity in thyroid carcinoma cells. Thus, curcumin appears to be a promising agent to overcome resistance to the conventional cancer therapy.

Inhibition of miR-146b expression increases radioiodine-sensitivity in poorly differential thyroid carcinoma via positively regulating NIS expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Luchuan; Lv, Bin; Chen, Bo

2015-07-10

Dedifferentiated thyroid carcinoma (DTC) with the loss of radioiodine uptake (RAIU) is often observed in clinical practice under radioiodine therapy, indicating the challenge for poor prognosis. MicroRNA (miRNA) has emerged as a promising therapeutic target in many diseases; yet, the role of miRNAs in RAIU has not been generally investigated. Based on recent studies about miRNA expression in papillary or follicular thyroid carcinomas, the expression profiles of several thyroid relative miRNAs were investigated in one DTC cell line, derived from normal DTC cells by radioiodine treatment. The top candidate miR-146b, with the most significant overexpression profiles in dedifferentiated cells, wasmore » picked up. Further research found that miR-146b could be negatively regulated by histone deacetylase 3 (HDAC3) in normal cells, indicating the correlation between miR-146b and Na{sup +}/I{sup −} symporter (NIS)-mediated RAIU. Fortunately, it was confirmed that miR-146b could regulate NIS expression/activity; what is more important, miR-146b interference would contribute to the recovery of radioiodine-sensitivity in dedifferentiated cells via positively regulating NIS. In the present study, it was concluded that NIS-mediated RAIU could be modulated by miR-146b; accordingly, miR-146b might serve as one of targets to enhance efficacy of radioactive therapy against poorly differential thyroid carcinoma (PDTC). - Highlights: • Significant upregulated miR-146b was picked up from thyroid relative miRNAs in DTC. • MiR-146b was negatively regulated by HDAC3 in normal thyroid carcinoma cells. • NIS activity and expression could be regulated by miR-146b in thyroid carcinoma. • MiR-146b inhibition could recover the decreased radioiodine-sensitivity of DTC cells.« less

Mutationally activated BRAF(V600E) elicits papillary thyroid cancer in the adult mouse.

PubMed

Charles, Roch-Philippe; Iezza, Gioia; Amendola, Elena; Dankort, David; McMahon, Martin

2011-06-01

Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC). To model PTC, we bred mice with adult-onset, thyrocyte-specific expression of BRAF(V600E). One month following BRAF(V600E) expression, mice displayed increased thyroid size, widespread alterations in thyroid architecture, and dramatic hypothyroidism. Over 1 year, without any deliberate manipulation of tumor suppressor genes, all mice developed PTC displaying nuclear atypia and marker expression characteristic of the human disease. Pharmacologic inhibition of MEK1/2 led to decreased thyroid size, restoration of thyroid form and function, and inhibition of tumorigenesis. Mice with BRAF(V600E)-induced PTC will provide an excellent system to study thyroid tumor initiation and progression and the evaluation of inhibitors of oncogenic BRAF signaling.

Blocks to thyroid cancer cell apoptosis can be overcome by inhibition of the MAPK and PI3K/AKT pathways.

PubMed

Gunda, V; Bucur, O; Varnau, J; Vanden Borre, P; Bernasconi, M J; Khosravi-Far, R; Parangi, S

2014-03-06

Current treatment for recurrent and aggressive/anaplastic thyroid cancers is ineffective. Novel targeted therapies aimed at the inhibition of the mutated oncoprotein BRAF(V600E) have shown promise in vivo and in vitro but do not result in cellular apoptosis. TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a tumor-selective manner by activating the extrinsic apoptotic pathway. Here, we show that a TRAIL-R2 agonist antibody, lexatumumab, induces apoptosis effectively in some thyroid cancer cell lines (HTh-7, TPC-1 and BCPAP), while more aggressive anaplastic cell lines (8505c and SW1736) show resistance. Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAF(V600E) inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo. A decrease in anti-apoptotic proteins, pAkt, Bcl-xL, Mcl-1 and c-FLIP, coupled with an increase in the activator proteins, Bax and Bim, results in an increase in the Bax to Bcl-xL ratio that appears to be critical for sensitization and subsequent apoptosis of these resistant cells. Our results suggest that targeting the death receptor pathway in thyroid cancer can be a promising strategy for inducing apoptosis in thyroid cancer cells, although combination with other kinase inhibitors may be needed in some of the more aggressive tumors initially resistant to apoptosis.

Fluoride caused thyroid endocrine disruption in male zebrafish (Danio rerio).

PubMed

Jianjie, Chen; Wenjuan, Xue; Jinling, Cao; Jie, Song; Ruhui, Jia; Meiyan, Li

2016-02-01

Excessive fluoride in natural water ecosystem has the potential to detrimentally affect thyroid endocrine system, but little is known of such effects or underlying mechanisms in fish. In the present study, we evaluated the effects of fluoride on growth performance, thyroid histopathology, thyroid hormone levels, and gene expressions in the HPT axis in male zebrafish (Danio rerio) exposed to different determined concentrations of 0.1, 0.9, 2.0 and 4.1 M of fluoride to investigate the effects of fluoride on thyroid endocrine system and the potential toxic mechanisms caused by fluoride. The results indicated that the growth of the male zebrafish used in the experiments was significantly inhibited, the thyroid microtrastructure was changed, and the levels of T3 and T4 were disturbed in fluoride-exposed male fish. In addition, the expressional profiles of genes in HPT axis displayed alteration. The expressions of all studied genes were significantly increased in all fluoride-exposed male fish after exposure for 45 days. The transcriptional levels of corticotrophin-releasing hormone (CRH), thyroid-stimulating hormone (TSH), thyroglobulin (TG), sodium iodide symporter (NIS), iodothyronine I (DIO1), and thyroid hormone receptor alpha (TRα) were also elevated in all fluoride-exposed male fish after 90 days of exposure, while the inconsistent expressions were found in the mRNA of iodothyronineⅡ (DIO2), UDP glucuronosyltransferase 1 family a, b (UGT1ab), transthyretin (TTR), and thyroid hormone receptor beta (TRβ). These results demonstrated that fluoride could notably inhibit the growth of zebrafish, and significantly affect thyroid endocrine system by changing the microtrastructure of thyroid, altering thyroid hormone levels and endocrine-related gene expressions in male zebrafish. All above indicated that fluoride could pose a great threat to thyroid endocrine system, thus detrimentally affected the normal function of thyroid of male zebrafish. Copyright © 2015

Transient thyrotoxicosis from thyroiditis induced by sibutramine overdose: a case report.

PubMed

Kim, S K; Lee, S M; Yoo, S S; Hahm, J R; Jung, J H; Kim, H S; Kim, S; Chung, S I; Jung, T S

2013-08-01

Sibutramine is an antiobesity drug that inhibits the reuptake of serotonin and noradrenalin in the hypothalamus. A 37-year-old Korean man presented to the emergency room for the oral intake of 280 mg of sibutramine. The patient was in thyrotoxic state. The (99m)Technetium-pertechnetate thyroid scan showed irregular uptake of radioisotope and thyroid-stimulating hormone receptor antibody and thyroperoxidase antibody were negative. Thyroid function normalized after that. The patient had transient thyrotoxicosis with thyroiditis. We report a case of thyrotoxicosis accompanied by thyroiditis resulting from the intentional overdose of sibutramine.

A tiered approach to evaluate an iodine recycling inhibition ...

EPA Pesticide Factsheets

The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces thyroid hormone synthesis, which leads to insufficiency in tissues and subsequent negative developmental consequences. Iodide recycling by IYD is especially critical for low iodine diets and low iodine environments, including most freshwater ecosystems. We developed a putative adverse outcome pathway for IYD inhibition in amphibians and evaluated IYD inhibition with a tiered approach: 1) development of an in vitro IYD enzyme inhibition assay for chemical screening of compounds of interest to the US EPA, 2) ex vivo thyroid culture to establish thyroglobulin iodination as a biomarker of IYD inhibition, and 3) in vivo bioassays to characterize an organismal adverse outcome and test essentiality of IYD activity. An in vitro colorimetric assay was developed to measure activity of recombinant human IYD enzyme in a 96-well format, establishing the feasibility of medium to high throughput screening of chemicals for IYD inhibition. In ex vivo thyroid culture studies, thyroxine (T4), monoiodotyrosine (MIT), and diiodotyrosine (DIT) were quantified in individual thyroid glands and the media using a ultrahigh performance LC-MS/MS. In vivo exposure of developing Xenopus laevis to a suspected IYD inhibitor (3-L-nitro-tyrosine) resulted in markedly delayed metamorphosis and glandular

Thyroid hormones and thyroid disease in relation to perchlorate dose and residence near a superfund site.

PubMed

Gold, Ellen B; Blount, Benjamin C; O'Neill Rasor, Marianne; Lee, Jennifer S; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-07-01

Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Residential blocks were randomly selected from areas: (1) with potential perchlorate exposure via drinking water; (2) with potential exposure to environmental contaminants; and (3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20-50 years during 1988-1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone and free thyroxine) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Residential location and current perchlorate dose were not associated with thyroid function or disease. No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped.

Developmental neurotoxicity of monocrotophos and lead is linked to thyroid disruption

PubMed Central

Kumar, B. Kala; Reddy, A. Gopala; Krishna, A. Vamsi; Quadri, S. S. Y. H.; Kumar, P. Shiva

2016-01-01

Aim: A role of thyroid disruption in developmental neurotoxicity of monocrotophos (MCP) and lead is studied. Materials and Methods: A total of 24 female rats after conception were randomized into four groups of six each and treated as follows: Group I - Sham was administered distilled water orally. Group II - A positive control was administered methyl methimazole at 0.02% orally in drinking water. Group III - MCP orally at 0.3 mg/kg and Group IV - Lead acetate at 0.2% orally in drinking water. The drug was administered from gestation day 3 through post-natal day 21 in all the groups. Acetylcholinesterase (AChE) inhibition, thyroid profile (thyroid stimulating hormone, T3 and T4), neurodevelopment (brain wet weights, DNA, RNA and protein), and neurobehavioral (elevated plus maze, photoactometry, and Morris water maze) parameters were assessed in pups. A histopathology of thyroid of dams and brain of progeny was conducted. Results: Inhibition of AChE was <20%. Thyroid profile decreased in the treatment groups. Neurodevelopmental and neurobehavioral parameters did not reveal any significant changes. Thyroid architecture was affected significantly with MCP and lead. Cortical layers too were affected. The three layers of cerebellum either had abnormal arrangement or decreased cellularity in all treated groups relating to thyroid disruption. Conclusion: MCP and lead might have affected the development of cerebrum and cerebellum via thyroid disruption leading to developmental neurotoxicity. PMID:27051198

Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.

PubMed

López, Miguel; Varela, Luis; Vázquez, María J; Rodríguez-Cuenca, Sergio; González, Carmen R; Velagapudi, Vidya R; Morgan, Donald A; Schoenmakers, Erik; Agassandian, Khristofor; Lage, Ricardo; Martínez de Morentin, Pablo Blanco; Tovar, Sulay; Nogueiras, Rubén; Carling, David; Lelliott, Christopher; Gallego, Rosalía; Oresic, Matej; Chatterjee, Krishna; Saha, Asish K; Rahmouni, Kamal; Diéguez, Carlos; Vidal-Puig, Antonio

2010-09-01

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib.

PubMed

Hanly, Elyse K; Bednarczyk, Robert B; Tuli, Neha Y; Moscatello, Augustine L; Halicka, H Dorota; Li, Jiangwei; Geliebter, Jan; Darzynkiewicz, Zbigniew; Tiwari, Raj K

2015-11-24

Treatment options for advanced metastatic thyroid cancer patients are limited. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials although cellular resistance occurs. Combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. We used an in vitro model to examine combination treatment with vemurafenib and mammalian target of rapamycin (mTOR) inhibitors, metformin and rapamycin. Cellular viability and apoptosis were analyzed in thyroid cell lines by trypan blue exclusion and TUNEL assays. Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells. This combination was also found to be active in vemurafenib-resistant BCPAP cells. Changes in expression of signaling molecules such as decreased mTOR expression in BCPAP and enhanced inhibition of phospho-MAPK in resistant BCPAP and 8505c were observed. The second combination of vemurafenib and rapamycin amplified cell death in BCPAP cells. We conclude that combination of BRAFV600E and mTOR inhibition forms the basis of a treatment regimen that should be further investigated in in vivo model systems. Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zadunaisky, J.A.; Scheide, J.I.

Whole killifish efflux of /sup 36/Cl was increased more than 2x with the addition of 1.4 x 10/sup -7/ M atriopeptin (ANF) to the seawater bath. Atriopeptin II (10/sup -7/ M) added serosally to the isolated Fundulus heteroclitus opercular epithelium resulted in a consistent stimulation of the short-circuit current, from 129.5 +/- 12.3 to 153.5 +/- 13.4 ..mu..A/cm/sup 2/. Tissue resistance was decreased 10% from 114.9 +/- 14.2 to 103.9 +/- 11.8 Omega x cm/sup 2/ indicating a change in chloride conductance. The effect of ANF was maximal at 10/sup -7/M and mucosal addition of ANF was ineffective in stimulatingmore » the opercular current. The ANF current stimulation did not interfere with the isoproterenol (10/sup -6/ M) response but ANF did not stimulate the current if added after isoproterenol. Serosal addition of propranolol (10/sup -5/ M), sufficient to inhibit 10/sup -6/ M isoproterenol, had no effect on the ANF response. The serosal addition of 10/sup -6/ M tetrodotoxin or 10/sup -4/ M diltiazem did not inhibit the ANF response. The stimulatory effect observed by ANF did not involve the isoproterenol receptor or nerve activation; however, it was a distinct stimulatory response on the isolated opercular epithelium.« less

Thyroid Hormones and Thyroid Disease in Relation to Perchlorate Dose and Residence Near a Superfund Site

PubMed Central

Gold, Ellen B.; Blount, Benjamin C.; Rasor, Marianne O’Neill; Lee, Jennifer S.; Alwis, Udeni; Srivastav, Anup; Kim, Kyoungmi

2013-01-01

Background Perchlorate is a widely occurring contaminant, which can competitively inhibit iodide uptake and thus thyroid hormone production. The health effects of chronic low dose perchlorate exposure are largely unknown. Objectives In a community-based study, we compared thyroid function and disease in women with differing likelihoods of prior and current perchlorate exposure. Methods Residential blocks were randomly selected from areas: 1) with potential perchlorate exposure via drinking water; 2) with potential exposure to environmental contaminants; and 3) neighboring but without such exposures. Eligibility included having lived in the area for ≥6 months and aged 20–50 years during 1988–1996 (during documented drinking water well contamination). We interviewed 814 women and collected blood samples (assayed for thyroid stimulating hormone [TSH] and free thyroxine [fT4]) from 431 interviewed women. Daily urine samples were assayed for perchlorate and iodide for 178 premenopausal women with blood samples. We performed multivariable regression analyses comparing thyroid function and disease by residential area and by urinary perchlorate dose adjusted for urinary iodide levels. Results Residential location and current perchlorate dose were not associated with thyroid function or disease. Conclusions No persistent effect of perchlorate on thyroid function or disease was found several years after contaminated wells were capped. PMID:22968349

Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases

PubMed Central

Fröhlich, Eleonore; Wahl, Richard

2017-01-01

Autoimmune diseases have a high prevalence in the population, and autoimmune thyroid disease (AITD) is one of the most common representatives. Thyroid autoantibodies are not only frequently detected in patients with AITD but also in subjects without manifest thyroid dysfunction. The high prevalence raises questions regarding a potential role in extra-thyroidal diseases. This review summarizes the etiology and mechanism of AITD and addresses prevalence of antibodies against thyroid peroxidase, thyroid-stimulating hormone receptor (TSHR), and anti-thyroglobulin and their action outside the thyroid. The main issues limiting the reliability of the conclusions drawn here include problems with different specificities and sensitivities of the antibody detection assays employed, as well as potential confounding effects of altered thyroid hormone levels, and lack of prospective studies. In addition to the well-known effects of TSHR antibodies on fibroblasts in Graves’ disease (GD), studies speculate on a role of anti-thyroid antibodies in cancer. All antibodies may have a tumor-promoting role in breast cancer carcinogenesis despite anti-thyroid peroxidase antibodies having a positive prognostic effect in patients with overt disease. Cross-reactivity with lactoperoxidase leading to induction of chronic inflammation might promote breast cancer, while anti-thyroid antibodies in manifest breast cancer might be an indication for a more active immune system. A better general health condition in older women with anti-thyroid peroxidase antibodies might support this hypothesis. The different actions of the anti-thyroid antibodies correspond to differences in cellular location of the antigens, titers of the circulating antibodies, duration of antibody exposure, and immunological mechanisms in GD and Hashimoto’s thyroiditis. PMID:28536577

Quantitative Adverse Outcome Pathway for Neurodevelopmental Effects of Thyroid Peroxidase-Induced Thyroid Hormone Synthesis Inhibition

EPA Science Inventory

Adequate levels of thyroid hormones (TH) are needed for proper brain development and deficiencies lead to adverse neurological outcomes in humans and in animal models. Environmental chemicals have been shown to disrupt TH levels, yet the relationship between developmental exposur...

Prolonged weightlessness effect on postflight plasma thyroid hormones

NASA Technical Reports Server (NTRS)

Leach, C. S.; Johnson, P. C.; Driscoll, T. B.

1977-01-01

Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 micro g/dl and in thyroid-stimulating hormone (TSH) of 4 microunits ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.

EFFECT OF HYPOTHYROIDISM AND THYROID GRAFTS ON LYMPHOID TUMOR DEVELOPMENT IN IRRADIATED C57BL MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagareda, C.S.; Kaplan, H.S.

1959-04-01

Studies on the effect of radiothyroidectomy and thyroid grafts on the incidence of thymic implant lymphomas in thymectomized-irradiated CS7BL mice are reported. Hypothyroidism significantly inhibited thymic implant tumor development in females. A similar reduction of lymphoma incidence in hypothyroid males was not statistically significant. When thyroid activity was restored by grafting normal thyroids to radiothyroidectomized animals, lymphoma incidence returned to the level seen in euthyroid animals. I/sup 131/ uptake measurements were made on a representative number of thyroids and thyroid grafts. There was no significant uptake by the I/sup 131/-treated thyroids. Thyroid grafts were just as active as thyroids frommore » control animals. Body weight decreased significantiy in hypothyroid animals and was restored to control euthyroid levels in radiothyroidectomized animals by thyroid grafts. The possible influence of secondary nutritional and endocrine disturbances on leukemogenesis are discussed; it seems likely that the observed inhibition is attributable to hypothyroidism per se, rather than to secondary influences on nutrition or other endocrine imbalances. Incidental observations on pituitary tumor development in lymphoma- free radiothyroldectomized animals are also reported. Pituitary tumor development was completely prevented by thyroid grafts after radiothyroidectomy. (auth)« less

Glycyrrhizin, a Direct HMGB1 Antagonist, Ameliorates Inflammatory Infiltration in a Model of Autoimmune Thyroiditis via Inhibition of TLR2-HMGB1 Signaling.

PubMed

Li, Chenyan; Peng, Shiqiao; Liu, Xin; Han, Cheng; Wang, Xinyi; Jin, Ting; Liu, Shanshan; Wang, Weiwei; Xie, Xiaochen; He, Xue; Zhang, Hanyi; Shan, Ling; Fan, Chenling; Shan, Zhongyan; Teng, Weiping

2017-05-01

decreased in the NaI + GL group. GL administration also significantly reduced the protein expression of TLR2, MyD88, HMGB1 and nuclear transcription factor κB in the thyroid gland and attenuated the severity of thyroiditis. HMGB1 may play a crucial role in autoimmune thyroiditis by causing inflammatory infiltration, thus increasing the severity of autoimmune thyroiditis. GL effectively attenuated thyroiditis in the iodine-induced NOD.H-2 h4 mice via a molecular mechanism related to the inhibition of TLR2-HMGB1 signaling.

Amphibian (Xenopus sp.) iodothyronine deiodinase production for screening of thyroid-disrupting chemicals

EPA Science Inventory

The U.S. EPA-MED amphibian thyroid group is currently screening chemicals for inhibition of human iodothyronine deiodinase activity as components of the thyroid system important in human development. Amphibians are a bellwether taxonomic group to gauge toxicity of chemicals in th...

mTOR inhibitors sensitize thyroid cancer cells to cytotoxic effect of vemurafenib

PubMed Central

Hanly, Elyse K.; Bednarczyk, Robert B.; Tuli, Neha Y.; Moscatello, Augustine L.; Halicka, H. Dorota; Li, Jiangwei; Geliebter, Jan; Darzynkiewicz, Zbigniew; Tiwari, Raj K.

2015-01-01

Treatment options for advanced metastatic thyroid cancer patients are limited. Vemurafenib, a BRAFV600E inhibitor, has shown promise in clinical trials although cellular resistance occurs. Combination therapy that includes BRAFV600E inhibition and avoids resistance is a clinical need. We used an in vitro model to examine combination treatment with vemurafenib and mammalian target of rapamycin (mTOR) inhibitors, metformin and rapamycin. Cellular viability and apoptosis were analyzed in thyroid cell lines by trypan blue exclusion and TUNEL assays. Combination of vemurafenib and metformin decreased cell viability and increased apoptosis in both BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells. This combination was also found to be active in vemurafenib-resistant BCPAP cells. Changes in expression of signaling molecules such as decreased mTOR expression in BCPAP and enhanced inhibition of phospho-MAPK in resistant BCPAP and 8505c were observed. The second combination of vemurafenib and rapamycin amplified cell death in BCPAP cells. We conclude that combination of BRAFV600E and mTOR inhibition forms the basis of a treatment regimen that should be further investigated in in vivo model systems. Metformin or rapamycin adjuvant treatment may provide clinical benefits with minimal side effects to BRAFV600E-positive advanced thyroid cancer patients treated with vemurafenib. PMID:26284586

[Hashimoto's thyroiditis(chronic thyroiditis), IgG4-related thyroiditis].

PubMed

Itoh, Mitsuyasu

2012-11-01

Hashimoto's thyroiditis emerges in patients who have genetic preponderance such as SNPs of CTLA-4 and risk factors such as excess intake of iodine, pregnancy or postpartum period, and smoking. Such risk factors also affect the entire clinical course. One of the major outcomes in Hashimoto's thyroiditis appears to be increased in cardio-vascular risks through subclinical hypothyroidism and concomitant metabolic syndrome, but in most cases, treatment with L-T4 has little effects on cardio-vascular benefit or quality of life. The pregnant women also have risks for obstetric complications and postpartum thyroid dysfunction. The women who have anti-TPO antibodies, type 1 diabetes, or previous history of post-partum thyroid dysfunction are recommended to be measured their TSH. It is noteworthy that Hashimoto's thyroiditis is sometimes complicated with encephalopathy, papillary carcinoma, or IgG4-related thyroiditis. IgG4-related thyroiditis is partly similar but partly discerned from a variant of Hashimoto's thyroiditis. The pathogenetic roles of this variant on autoimmune-based thyroiditis remain unclear.

Comparison of in vitro and in vivo bioassays to measure thyroid hormone disrupting activity in water extracts.

PubMed

Leusch, Frederic D L; Aneck-Hahn, Natalie H; Cavanagh, Jo-Anne E; Du Pasquier, David; Hamers, Timo; Hebert, Armelle; Neale, Peta A; Scheurer, Marco; Simmons, Steven O; Schriks, Merijn

2018-01-01

Environmental chemicals can induce thyroid disruption through a number of mechanisms including altered thyroid hormone biosynthesis and transport, as well as activation and inhibition of the thyroid receptor. In the current study six in vitro bioassays indicative of different mechanisms of thyroid disruption and one whole animal in vivo assay were applied to 9 model compounds and 4 different water samples (treated wastewater, surface water, drinking water and ultra-pure lab water; both unspiked and spiked with model compounds) to determine their ability to detect thyroid active compounds. Most assays correctly identified and quantified the model compounds as agonists or antagonists, with the reporter gene assays being the most sensitive. However, the reporter gene assays did not detect significant thyroid activity in any of the water samples, suggesting that activation or inhibition of the thyroid hormone receptor is not a relevant mode of action for thyroid endocrine disruptors in water. The thyroperoxidase (TPO) inhibition assay and transthyretin (TTR) displacement assay (FITC) detected activity in the surface water and treated wastewater samples, but more work is required to assess if this activity is a true measure of thyroid activity or matrix interference. The whole animal Xenopus Embryonic Thyroid Assay (XETA) detected some activity in the unspiked surface water and treated wastewater extracts, but not in unspiked drinking water, and appears to be a suitable assay to detect thyroid activity in environmental waters. Copyright © 2017 Elsevier Ltd. All rights reserved.

THYROID AXIS INHIBITION IN XENOPUS LAEVIS: DEVELOPMENT OF AN AMPHIBIAN-BASED SCREENING ASSAY FOR THYROID DISRUPTION

EPA Science Inventory

In response to the initial EDSTAC recommendations, research was conducted on the development of a Xenopus laevis based tail resorption assay for evaluating thyroid axis disruption. These experiments highlighted key limitations associated with reliance on tail resorption as a meas...

Excess thyroid hormone inhibits embryonic neural stem/progenitor cells proliferation and maintenance through STAT3 signalling pathway.

PubMed

Chen, Chunhai; Zhou, Zhou; Zhong, Min; Li, Maoquan; Yang, Xuesen; Zhang, Yanwen; Wang, Yuan; Wei, Aimin; Qu, Mingyue; Zhang, Lei; Xu, Shangcheng; Chen, Shude; Yu, Zhengping

2011-07-01

Hyperthyroidism is prevalent during pregnancy, but little is known about the effects of excess thyroid hormone on the development of embryonic neural stem/progenitor cells (NSCs), and the mechanisms underlying these effects. Previous studies indicate that STAT3 plays a crucial role in determining NSC fate during neurodevelopment. In this study, we investigated the effects of a supraphysiological dose of 3,5,3'-L-triiodothyronine (T3) on the proliferation and maintenance of NSCs derived from embryonic day 13.5 mouse neocortex, and the involvement of STAT3 in this process. Our results suggest that excess T3 treatment inhibits NSC proliferation and maintenance. T3 decreased tyrosine phosphorylation of JAK1, JAK2 and STAT3, and subsequently inhibited STAT3-DNA binding activity. Furthermore, proliferation and maintenance of NSCs were decreased by inhibitors of JAKs and STAT3, indicating that the STAT3 signalling pathway is involved in the process of NSC proliferation and maintenance. Taken together, these results suggest that the STAT3 signalling pathway is involved in the process of T3-induced inhibition of embryonic NSC proliferation and maintenance. These findings provide data for understanding the effects of hyperthyroidism during pregnancy on fetal brain development, and the mechanisms underlying these effects.

[Thyroiditis].

PubMed

Buffet, Camille; Groussin, Lionel

2013-02-01

The diagnosis of thyroiditis encompasses a broad spectrum of thyroid disorders. Analysis of signs and symptoms, biochemical changes, neck ultrasound characteristics and radioactive iodine uptake values allows an accurate diagnosis. Recent studies of the whole genome have helped to identify many susceptibility genes for autoimmune thyroiditis. However, none of these genes contribute to a significant increase in risk of developing this thyroiditis. Clinical awareness of the characteristic presentations of exceptional thyroiditis (acute suppurative thyroiditis, Riedel's thyroiditis) is an important issue. Selenium administration seems to be beneficial for reducing the incidence of thyroiditis. Finally, certain drug-induced thyroiditis remains a therapeutic challenge for the physician.

Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.

1988-09-01

To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific bindingmore » of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.« less

Inhibition of Thyroid Hormone Release from Cultured Amphibian Thyroid Glands by Methimazole, 6-Propylthiouracil, and Perchlorate

EPA Science Inventory

The research presented here is the development of an in vitro thyroid gland culture system to test the effect of chemicals directly on the gland without influence of other parts of the HPT axis. . . This information can then be used to select chemicals for further evaluation in v...

Synthetic gene network restoring endogenous pituitary–thyroid feedback control in experimental Graves’ disease

PubMed Central

Saxena, Pratik; Charpin-El Hamri, Ghislaine; Folcher, Marc; Zulewski, Henryk; Fussenegger, Martin

2016-01-01

Graves’ disease is an autoimmune disorder that causes hyperthyroidism because of autoantibodies that bind to the thyroid-stimulating hormone receptor (TSHR) on the thyroid gland, triggering thyroid hormone release. The physiological control of thyroid hormone homeostasis by the feedback loops involving the hypothalamus–pituitary–thyroid axis is disrupted by these stimulating autoantibodies. To reset the endogenous thyrotrophic feedback control, we designed a synthetic mammalian gene circuit that maintains thyroid hormone homeostasis by monitoring thyroid hormone levels and coordinating the expression of a thyroid-stimulating hormone receptor antagonist (TSHAntag), which competitively inhibits the binding of thyroid-stimulating hormone or the human autoantibody to TSHR. This synthetic control device consists of a synthetic thyroid-sensing receptor (TSR), a yeast Gal4 protein/human thyroid receptor-α fusion, which reversibly triggers expression of the TSHAntag gene from TSR-dependent promoters. In hyperthyroid mice, this synthetic circuit sensed pathological thyroid hormone levels and restored the thyrotrophic feedback control of the hypothalamus–pituitary–thyroid axis to euthyroid hormone levels. Therapeutic plug and play gene circuits that restore physiological feedback control in metabolic disorders foster advanced gene- and cell-based therapies. PMID:26787873

Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance

PubMed Central

López, Miguel; Varela, Luis; Vázquez, María J.; Rodríguez-Cuenca, Sergio; González, Carmen R.; Velagapudi, Vidya R.; Morgan, Donald A.; Schoenmakers, Erik; Agassandian, Khristofor; Lage, Ricardo; de Morentin, Pablo Blanco Martínez; Tovar, Sulay; Nogueiras, Rubén; Carling, David; Lelliott, Christopher; Gallego, Rosalía; Orešič, Matej; Chatterjee, Krishna; Saha, Asish K.; Rahmouni, Kamal; Diéguez, Carlos; Vidal-Puig, Antonio

2010-01-01

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here, we demonstrate that either whole body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly inhibition of thyroid hormone receptors (TRs) in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation as genetic ablation of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid-hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is an important regulator of energy homeostasis. PMID:20802499

Thyroid Hormone Receptor β (THRB) Is a Major Target Gene for MicroRNAs Deregulated in Papillary Thyroid Carcinoma (PTC)

PubMed Central

Boguslawska, Joanna; Jendrzejewski, Jaroslaw; Liyanarachchi, Sandya; Pachucki, Janusz; Wardyn, Kazimierz A.; Nauman, Alicja

2011-01-01

Context: Loss of the thyroid hormone receptor is common in tumors. In mouse models, a truncated THRB gene leads to thyroid cancer. Previously, we observed up-regulation of the expression of eight microRNAs (miRs) in papillary thyroid carcinoma (PTC) tumors. Objective: Our objective was to determine whether THRB might be inhibited by miRs up-regulated in PTC. Design: The potential binding of miR to the 3′-untranslated region of THRB was analyzed in silico. Direct inhibition by miRs binding to the cloned 3′-untranslated region of THRB was evaluated using luciferase assays. Inhibition of endogenous THRB and its target genes (DIO1 and APP) was examined in cell lines transfected by pre-miRs. The impact on thyroid hormone response element (TRE) was evaluated in promoter assays. Correlations between the expression of THRB and miRs was evaluated in 13 PTC tumor/normal tissue pairs. Results: THRB contains binding sites for the top seven miRs up-regulated in PTC (P = 0.0000002). Direct interaction with THRB was shown for miR-21 and miR-146a. We observed lower levels of THRB transcripts in cell lines transfected with miR-21, -146a, and -221 (down-regulation of 37–48%; P < 0.0001), but not with miR-181a. THRB protein was suppressed down to 10–28% by each of four miRs. Concomitant expression of DIO1 and APP was affected (down-regulation of 32–66%, P < 0.0034 and up-regulation of 48–57%, P < 0.0002, respectively). All four miRs affected TRE activity in promoter assays. Down-regulation of luciferase occurred after transfection with pTRE-TK-Luc construct and each of four miRs. The analysis of tumor/normal tissue pairs revealed down-regulation of THRB in 11 of 13 pairs (1.3- to 9.1-fold), and up-regulation of miR-21, -146a, -181a, and -221 in almost all pairs. Conclusions: MiRs up-regulated in PTC tumors directly inhibit the expression of THRB, an important tumor suppressor gene. PMID:21159845

TRIADIMEFON INDUCES RAT THYROID TUMORS THROUGH A NON-TSH MEDIATED MODE OF ACTION

EPA Science Inventory

Conazoles are a class of fungicides used as agricultural and pharmaceutical products which inhibit ergosterol biosynthesis. Members of this class are hepatotoxic and cause mouse hepatocellular tumors and/or rat thyroid follicular cell tumors. Triadimefon-induced rat thyroid tumor...

Foetal and neonatal thyroid disorders.

PubMed

Radetti, G; Zavallone, A; Gentili, L; Beck-Peccoz, P; Bona, G

2002-10-01

Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes

Dual ectopic thyroid associated with thyroid hemiagenesis.

PubMed

Nakamura, Shigenori; Masuda, Teruyuki; Ishimori, Masatoshi

2018-01-01

We report a case of a 15-year-old girl with a midline neck mass that was first noted 2 or 3 years previously. She had been treated with levothyroxine (L-T4) for congenital hypothyroidism until 11 years of age. Ultrasonography revealed an atrophic right thyroid (1.0 × 1.6 × 2.6 cm in size) and a mass (2.3 × 1.0 × 3.5 cm in size) in the upper part of the neck. No left lobe of the thyroid was detected. On further evaluation, Tc-99m pertechnetate thyroid scintigraphy and CT showed ectopic thyroid tissue in the lingual region and infrahyoid region. Thus, she was diagnosed as having dual ectopic thyroid and thyroid hemiagenesis. The atrophic right thyroid was thought be non-functional. Treatment with L-T4 was started to reduce the size of the dual ectopic thyroid tissue. This may be the first reported case of dual ectopic thyroid associated with hemiagenesis detected only by ultrasonography. Ultrasonography can confirm the presence or absence of orthotopic thyroid tissue in patients with ectopic thyroid.The cause of congenital hypothyroidism should be examined.Clinical manifestation of ectopic thyroid may appear when the treatment with L-T4 is discontinued.Annual follow-up is needed in all children when their thyroid hormone replacement is stopped.

Thyroiditis

MedlinePlus

... 12-18 months, 20% possibility of permanent hypothyroidism. Post partum thyroiditis Anti-thyroid antibodies, autoimmune disease Thyrotoxicosis followed by hypothyroidism. Thyroid function tests, thyroid antibody tests, radioactive iodine uptake (contraindicated if ...

Recurrent Silent Thyroiditis as a Sequela of Postpartum Thyroiditis

PubMed Central

Kim, Paul

2014-01-01

Thyroiditis encompasses a group of disorders characterized by thyroid inflammation. Though clinically indistinguishable from silent thyroiditis, postpartum thyroiditis occurs in women within 12 months after delivery. Recurrent postpartum thyroiditis in subsequent pregnancies is common, but recurrent silent thyroiditis is rare. We reported a case of patient with recurrent episodes of thyroiditis, unrelated to pregnancy, after an episode of postpartum thyroiditis. It is of interest that postpartum thyroiditis and silent thyroiditis could occur closely to each other; however, the link between these disorders is not well established. This report is to remind physicians of the possibility of recurrent silent thyroiditis in women with a history of postpartum thyroiditis. PMID:24987536

Submandibular ectopic thyroid with normally located thyroid gland.

PubMed

Yılmaz, Mahmut Sinan; Aytürk, Semra; Güven, Mehmet; Dilek, Fatma Hüsniye

2014-01-01

Ectopic thyroid is a rare developmental anomaly of the thyroid gland which is defined as the presence of thyroid tissue at a site other than the pretracheal area. Nearly 1 to 3% of all ectopic thyroids are located in the lateral neck. Simultaneous submandibular ectopic thyroid tissue presenting with a functional orthotopic thyroid gland is extremely rare. In this article, we report a 37-year-old female case admitted to our clinic with a complaint of swollen neck in whom ultrasonography revealed submandibular ectopic thyroid tissue presenting with an orthotopic thyroid gland.

Computational modeling of the amphibian thyroid axis ...

EPA Pesticide Factsheets

In vitro screening of chemicals for bioactivity together with computational modeling are beginning to replace animal toxicity testing in support of chemical risk assessment. To facilitate this transition, an amphibian thyroid axis model has been developed to describe thyroid homeostasis during Xenopus laevis pro-metamorphosis. The model simulates the dynamic relationships of normal thyroid biology throughout this critical period of amphibian development and includes molecular initiating events (MIEs) for thyroid axis disruption to allow in silico simulations of hormone levels following chemical perturbations. One MIE that has been formally described using the adverse outcome pathway (AOP) framework is thyroperoxidase (TPO) inhibition. The goal of this study was to refine the model parameters and validate model predictions by generating dose-response and time-course biochemical data following exposure to three TPO inhibitors, methimazole, 6-propylthiouracil and 2-mercaptobenzothiazole. Key model variables including gland and blood thyroid hormone (TH) levels were compared to empirical values measured in biological samples at 2, 4, 7 and 10 days following initiation of exposure at Nieuwkoop and Faber (NF) stage 54 (onset of pro-metamorphosis). The secondary objective of these studies was to relate depleted blood TH levels to delayed metamorphosis, the adverse apical outcome. Delayed metamorphosis was evaluated by continuing exposure with a subset of larvae until a

Estrogen Induced Metastatic Modulators MMP-2 and MMP-9 Are Targets of 3,3′-Diindolylmethane in Thyroid Cancer

PubMed Central

Rajoria, Shilpi; Suriano, Robert; George, Andrea; Shanmugam, Arulkumaran; Schantz, Stimson P.; Geliebter, Jan; Tiwari, Raj K.

2011-01-01

Background Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3′-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor. Methodology/Principal Findings Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E2 enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9. Conclusion/Significance Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease. PMID:21267453

Zebrafish bcl2l is a survival factor in thyroid development.

PubMed

Porreca, Immacolata; De Felice, Elena; Fagman, Henrik; Di Lauro, Roberto; Sordino, Paolo

2012-06-15

Regulated cell death, defined in morphological terms as apoptosis, is crucial for organ morphogenesis. While differentiation of the thyroid gland has been extensively studied, nothing is yet known about the survival mechanisms involved in the development of this endocrine gland. Using the zebrafish model system, we aim to understand whether genes belonging to the Bcl-2 family that control apoptosis are implicated in regulation of cell survival during thyroid development. Evidence of strong Bcl-2 gene expression in mouse thyroid precursors prompted us to investigate the functions played by its zebrafish homologs during thyroid development. We show that the bcl2-like (bcl2l) gene is expressed in the zebrafish thyroid primordium. Morpholino-mediated knockdown and mutant analyses revealed that bcl2l is crucial for thyroid cell survival and that this function is tightly modulated by the transcription factors pax2a, nk2.1a and hhex. Also, the bcl2l gene appears to control a caspase-3-dependent apoptotic mechanism during thyroid development. Thyroid precursor cells require an actively maintained survival mechanism to properly proceed through development. The bcl2l gene operates in the inhibition of cell death under direct regulation of a thyroid specific set of transcription factors. This is the first demonstration of an active mechanism to ensure survival of the thyroid primordium during morphogenesis. Copyright © 2012 Elsevier Inc. All rights reserved.

Development of a thyroperoxidase inhibition assay for high-throughput screening

EPA Science Inventory

High-throughput screening (HTPS) assays to detect inhibitors of thyroperoxidase (TPO), the enzymatic catalyst for thyroid hormone (TH) synthesis, are not currently available. Herein we describe the development of a HTPS TPO inhibition assay. Rat thyroid microsomes and a fluores...

Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas.

PubMed

Burrows, Natalie; Williams, Joseph; Telfer, Brian A; Resch, Julia; Valentine, Helen R; Fitzmaurice, Richard J; Eustace, Amanda; Irlam, Joely; Rowling, Emily J; Hoang-Vu, Cuong; West, Catharine M; Brabant, Georg; Williams, Kaye J

2016-09-27

Anaplastic (ATC) and certain follicular thyroid-carcinomas (FTCs) are radioresistant. The Phosphatidylinositide 3-kinase (PI3K) pathway is commonly hyperactivated in thyroid-carcinomas. PI3K can modify the PI3K-related kinases (PIKKs) in response to radiation: How PIKKs interact with PI3K and contribute to radioresistance in thyroid-carcinomas is unknown. Further uncertainties exist in how these interactions function under the radioresistant hypoxic microenvironment. Under normoxia/anoxia, ATC (8505c) and FTC (FTC-133) cells were irradiated, with PI3K-inhibition (via GDC-0941 and PTEN-reconstitution into PTEN-null FTC-133s) and effects on PIKK-activation, DNA-damage, clonogenic-survival and cell cycle, assessed. FTC-xenografts were treated with 5 × 2 Gy, ± 50 mg/kg GDC-0941 (twice-daily; orally) for 14 days and PIKK-activation and tumour-growth assessed. PIKK-expression was additionally assessed in 12 human papillary thyroid-carcinomas, 13 FTCs and 12 ATCs. GDC-0941 inhibited radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inhibition of ATM and DNA-PKcs was PI3K-dependent, since activation was reduced in PTEN-reconstituted FTC-133s. Inhibition of PIKK-activation was greater under anoxia: Consequently, whilst DNA-damage was increased and prolonged under both normoxia and anoxia, PI3K-inhibition only reduced clonogenic-survival under anoxia. GDC-0941 abrogated radiation-induced cell cycle arrest, an effect most likely linked to the marked inhibition of ATR-activation. Importantly, GDC-0941 inhibited radiation-induced PIKK-activation in FTC-xenografts leading to a significant increase in time taken for tumours to triple in size: 26.5 ± 5 days (radiation-alone) versus 31.5 ± 5 days (dual-treatment). PIKKs were highly expressed across human thyroid-carcinoma classifications, with ATM scoring consistently lower. Interestingly, some loss of ATM and DNA

Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas

PubMed Central

Burrows, Natalie; Williams, Joseph; Telfer, Brian A; Resch, Julia; Valentine, Helen R; Fitzmaurice, Richard J; Eustace, Amanda; Irlam, Joely; Rowling, Emily J; Hoang-Vu, Cuong; West, Catharine M; Brabant, Georg; Williams, Kaye J

2016-01-01

Anaplastic (ATC) and certain follicular thyroid-carcinomas (FTCs) are radioresistant. The Phosphatidylinositide 3-kinase (PI3K) pathway is commonly hyperactivated in thyroid-carcinomas. PI3K can modify the PI3K-related kinases (PIKKs) in response to radiation: How PIKKs interact with PI3K and contribute to radioresistance in thyroid-carcinomas is unknown. Further uncertainties exist in how these interactions function under the radioresistant hypoxic microenvironment. Under normoxia/anoxia, ATC (8505c) and FTC (FTC-133) cells were irradiated, with PI3K-inhibition (via GDC-0941 and PTEN-reconstitution into PTEN-null FTC-133s) and effects on PIKK-activation, DNA-damage, clonogenic-survival and cell cycle, assessed. FTC-xenografts were treated with 5 × 2 Gy, ± 50 mg/kg GDC-0941 (twice-daily; orally) for 14 days and PIKK-activation and tumour-growth assessed. PIKK-expression was additionally assessed in 12 human papillary thyroid-carcinomas, 13 FTCs and 12 ATCs. GDC-0941 inhibited radiation-induced activation of Ataxia-telangiectasia mutated (ATM), ATM-and Rad3-related (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Inhibition of ATM and DNA-PKcs was PI3K-dependent, since activation was reduced in PTEN-reconstituted FTC-133s. Inhibition of PIKK-activation was greater under anoxia: Consequently, whilst DNA-damage was increased and prolonged under both normoxia and anoxia, PI3K-inhibition only reduced clonogenic-survival under anoxia. GDC-0941 abrogated radiation-induced cell cycle arrest, an effect most likely linked to the marked inhibition of ATR-activation. Importantly, GDC-0941 inhibited radiation-induced PIKK-activation in FTC-xenografts leading to a significant increase in time taken for tumours to triple in size: 26.5 ± 5 days (radiation-alone) versus 31.5 ± 5 days (dual-treatment). PIKKs were highly expressed across human thyroid-carcinoma classifications, with ATM scoring consistently lower. Interestingly, some loss of ATM and DNA

[Intracellular signaling mechanisms in thyroid cancer].

PubMed

Mondragón-Terán, Paul; López-Hernández, Luz Berenice; Gutiérrez-Salinas, José; Suárez-Cuenca, Juan Antonio; Luna-Ceballos, Rosa Isela; Erazo Valle-Solís, Aura

2016-01-01

Thyroid cancer is the most common malignancy of the endocrine system, the papillary variant accounts for 80-90% of all diagnosed cases. In the development of papillary thyroid cancer, BRAF and RAS genes are mainly affected, resulting in a modification of the system of intracellular signaling proteins known as «protein kinase mitogen-activated» (MAPK) which consist of «modules» of internal signaling proteins (Receptor/Ras/Raf/MEK/ERK) from the cell membrane to the nucleus. In thyroid cancer, these signanling proteins regulate diverse cellular processes such as differentiation, growth, development and apoptosis. MAPK play an important role in the pathogenesis of thyroid cancer as they are used as molecular biomarkers for diagnostic, prognostic and as possible therapeutic molecular targets. Mutations in BRAF gene have been correlated with poor response to treatment with traditional chemotherapy and as an indicator of poor prognosis. To review the molecular mechanisms involved in intracellular signaling of BRAF and RAS genes in thyroid cancer. Molecular therapy research is in progress for this type of cancer as new molecules have been developed in order to inhibit any of the components of the signaling pathway (RET/PTC)/Ras/Raf/MEK/ERK; with special emphasis on the (RET/PTC)/Ras/Raf section, which is a major effector of ERK pathway. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

The transcriptional repressor DREAM is involved in thyroid gene expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Andrea, Barbara; Di Palma, Tina; Mascia, Anna

2005-04-15

Downstream regulatory element antagonistic modulator (DREAM) was originally identified in neuroendocrine cells as a calcium-binding protein that specifically binds to downstream regulatory elements (DRE) on DNA, and represses transcription of its target genes. To explore the possibility that DREAM may regulate the endocrine activity of the thyroid gland, we analyzed its mRNA expression in undifferentiated and differentiated thyroid cells. We demonstrated that DREAM is expressed in the normal thyroid tissue as well as in differentiated thyroid cells in culture while it is absent in FRT poorly differentiated cells. In the present work, we also show that DREAM specifically binds tomore » DRE sites identified in the 5' untranslated region (UTR) of the thyroid-specific transcription factors Pax8 and TTF-2/FoxE1 in a calcium-dependent manner. By gel retardation assays we demonstrated that thapsigargin treatment increases the binding of DREAM to the DRE sequences present in Pax8 and TTF-2/Foxe1 5' UTRs, and this correlates with a significant reduction of the expression of these genes. Interestingly, in poorly differentiated thyroid cells overexpression of exogenous DREAM strongly inhibits Pax8 expression. Moreover, we provide evidence that a mutated form of DREAM unable to bind Ca{sup 2+} interferes with thyroid cell proliferation. Therefore, we propose that in thyroid cells DREAM is a mediator of the calcium-signaling pathway and it is involved in the regulation of thyroid cell function.« less

CETUXIMAB AND IRINOTECAN INTERACT SYNERGISTICALLY TO INHIBIT THE GROWTH OF ORTHOTOPIC ANAPLASTIC THYROID CARCINOMA XENOGRAFTS IN NUDE MICE

PubMed Central

Kim, Seungwon; Prichard, Christopher N.; Younes, Maher N.; Yazici, Yasemin D.; Jasser, Samar A.; Bekele, B. Nebiyou; Myers, Jeffrey N.

2006-01-01

Objective Anaplastic thyroid carcinoma (ATC) remains one of the most lethal known human cancers. Targeted molecular therapy with cetuximab, a monoclonal antibody against EGFR, offers new treatment potentials for patient with ATC. Cetuximab has also been reported to have synergistic effects when combined with irinotecan, a topoisomerase inhibitor. Therefore, we hypothesized that cetuximab and irinotecan would be effective in inhibiting the growth and progression of ATC in a murine orthotopic model. Design The in vitro anti-proliferative effects of cetuximab and irinotecan on ATC cell line ARO were examined. We also studied the in vivo effects of cetuximab and irinotecan on the growth, invasion, and metastasis of orthotopic ATC tumors in nude mice. The in vivo antitumor efficacy of cetuximab/irinotecan combination was also compared with that of doxorubicin. Results Cetuximab alone did not show any anti-proliferative or pro-apoptotic effect on this cell line. However, when combined with irinotecan, cetuximab potentiated the in vitro anti-proliferative and pro-apoptotic effect of irinotecan. Cetuximab, irinotecan, and cetuximab/irinotecan combination resulted in 77%, 79%, and 93% in vivo inhibition of tumor growth, respectively. Incidences of lymph node metastasis, laryngeal invasion, and tumor microvessel density were also significantly decreased in these treatment groups. Furthermore, the cetuximab/irinotecan combination was significantly more effective than doxorubicin in inhibiting the growth of orthotopic ATC xenografts. Conclusions Combination therapy with cetuximab/irinotecan inhibits the growth and progression of orthotopic ATC xenografts in nude mice. Given the lack of curative options for patients with ATC, combination therapy with cetuximab and irinotecan treatment warrants further study. PMID:16428506

The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors.

PubMed

Woodmansee, W W; Gordon, D F; Dowding, J M; Stolz, B; Lloyd, R V; James, R A; Wood, W M; Ridgway, E C

2000-07-01

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.

Effects of environmental chemicals on fish thyroid function: Implications for fisheries and aquaculture in Australia.

PubMed

Nugegoda, Dayanthi; Kibria, Golam

2017-04-01

Numerous environmental stressors exert acute or chronic effects on the fish thyroid cascade. Such effects could be mediated via thyroidal alterations, imbalance of plasma T4 and T3 levels or damage to the structure of the thyroidal tissues (thyroid hypertrophy, hyperplasia). The thyroidal system is intricately linked to other endocrine systems in vertebrates including the control of reproduction. Disruption of fish thyroid function by environmental stressors has the potential to result in deleterious effects including the inhibition of sperm production, reduction in egg production, gonad development, ovarian growth, swimming activity, fertilisation and increase in larval mortality. Thyroid hormones play a major role in the development and growth of fish, particularly during their early life stages, thus, thyroid disruption by environmental stressors could inhibit the growth of fish larvae and juveniles in wild fish and cultured species, limit fish seed production and result in a decline in wild fisheries. This review highlights the effects of several environmental toxicants including PBDE, PCBs, PCDD and PCDF, PAH/oil, phthalates, metals, pesticides, mixed pollutants/chemicals, cyanide; and other stressors including acid (low pH) and ammonia, on fish thyroid function. Environmental sources of chemical stressors and appropriate water quality guidelines to protect the freshwater and marine species for the relevant pollutants are also discussed including (when available) the Australian guidelines (2000) and Canadian water quality guidelines (where Australian guidelines are not available). To date there has been no published research on the effects of anthropogenic environmental pollutants on the thyroid system of any native Australian fish species. However, the detection of high risk chemicals (notably PBDEs, PCBs, PAHs, metals and pesticides) in Australian waterways and Australian fish and shellfish implies that thyroid disruption of Australian wild fish and

Mutual regulation of TGF-β1, TβRII and ErbB receptors expression in human thyroid carcinomas

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mincione, Gabriella, E-mail: g.mincione@unich.it; Center of Excellence on Aging, Ce.S.I., ‘G. d'Annunzio’ University Foundation, Chieti; Tarantelli, Chiara

2014-09-10

The role of EGF and TGF-β1 in thyroid cancer is still not clearly defined. TGF-β1 inhibited the cellular growth and migration of follicular (FTC-133) and papillary (B-CPAP) thyroid carcinoma cell lines. Co-treatments of TGF-β1 and EGF inhibited proliferation in both cell lines, but displayed opposite effect on their migratory capability, leading to inhibition in B-CPAP and promotion in FTC-133 cells, by a MAPK-dependent mechanism. TGF-β1, TβRII and EGFR expressions were evaluated in benign and malignant thyroid tumors. Both positivity (51.7% and 60.0% and 80.0% in FA and PTC and FTC) and overexpression (60.0%, 77.7% and 75.0% in FA, PTC andmore » FTC) of EGFR mRNA correlates with the aggressive tumor behavior. The moderate overexpression of TGF-β1 and TβRII mRNA in PTC tissues (61.5% and 62.5%, respectively), counteracted their high overexpression in FTC tissues (100% and 100%, respectively), while EGFR overexpression was similar in both carcinomas. Papillary carcinomas were positive to E-cadherin expression, while the follicular carcinomas lose E-cadherin staining. Our findings of TGF-β1/TβRII and EGFR overexpressions together with a loss of E-cadherin observed in human follicular thyroid carcinomas, and of increased migration ability MAPK-dependent after EGF/TGF-β1 treatments in the follicular thyroid carcinoma cell line, reinforced the hypothesis of a cross-talk between EGF and TGF-β1 systems in follicular thyroid carcinomas phenotype. - Highlights: • We reinforce the hypothesis of a cross talk between EGF and TGF-β1 in follicular thyroid carcinoma. • Increased migration MAPK-dependent is observed after EGF+TGF-β1 treatment in follicular thyroid carcinoma cells. • EGF and TGF-β1 caused opposite effect on the migratory ability in B-CPAP and in FTC-133 cells. • TGF-β1, TβRII and EGFR are overexpressed in follicular thyroid carcinoma.« less

Effects of 3-nitro-l-tyrosine on thyroid function in the rat: an experimental model for the dehalogenase defect

PubMed Central

Green, William L.

1971-01-01

The effects on thyroid function of an inhibitor of tyrosine dehalogenase, 3-nitro-L-tyrosine (MNT) have been investigated in rats. In preliminary studies, marked inhibition of iodotyrosine deiodination was demonstrated in rats drinking 8 mM MNT. A series of experiments was then performed in which rats received Remington low iodine diet and 8 mM MNT as drinking fluid. This regimen had the following effects, compared to the effects of a low iodine diet alone: (a) a decrease in serum protein-bound iodine, elevation of serum thyrotropin level, goiter, and growth inhibition all prevented or reversed by iodine supplements: (b) on initiation of MNT, a 2- to 3-fold increase in the rate of release of radioiodine from the thyroid and concomitant urinary excretion of large amounts of organic iodine: and (c) after 2 wk of MNT, a greatly increased rate of thyroidal uptake and release of 131I, an increase in the ratio of monoiodotyrosine-131I to diiodotyrosine-131I in thyroid proteolysates and the appearance of labeled iodotyrosines in serum. Acute administration of MNT intraperitoneally to rats on either an iodine-deficient or iodine-sufficient diet did not inhibit thyroidal uptake of 131I or alter the distribution of 131I among thyroidal iodoamino acids. It is concluded that MNT is an effective inhibitor of iodotyrosine deiodination in vivo, without other important actions on thyroid function. Thus, MNT treatment affords a model for the human dehalogenase defect. By provoking iodotyrosine secretion and consequent urinary loss of iodine, MNT can exaggerate the effects of a low iodine intake, producing goitrous hypothyroidism despite a rapid rate of iodine turnover in the thyroid. Images PMID:5129302

Thyroid

MedlinePlus

Thyroid is used to treat the symptoms of hypothyroidism (a condition where the thyroid gland does not produce enough thyroid hormone). Symptoms of hypothyroidism include lack of energy, depression, constipation, weight gain, ...

Defective ciliogenesis in thyroid hürthle cell tumors is associated with increased autophagy

PubMed Central

Lee, Junguee; Yi, Shinae; Kang, Yea Eun; Chang, Joon Young; Kim, Jung Tae; Sul, Hae Joung; Kim, Jong Ok; Kim, Jin Man; Kim, Joon; Porcelli, Anna Maria; Kim, Koon Soon; Shong, Minho

2016-01-01

Primary cilia are found in the apical membrane of thyrocytes, where they may play a role in the maintenance of follicular homeostasis. In this study, we examined the distribution of primary cilia in the human thyroid cancer to address the involvement of abnormal ciliogenesis in different thyroid cancers. We examined 92 human thyroid tissues, including nodular hyperplasia, Hashimoto's thyroiditis, follicular tumor, Hürthle cell tumor, and papillary carcinoma to observe the distribution of primary cilia. The distribution and length of primary cilia facing the follicular lumen were uniform across variable-sized follicles in the normal thyroid gland. However, most Hürthle cells found in benign and malignant thyroid diseases were devoid of primary cilia. Conventional variant of papillary carcinoma (PTC) displayed longer primary cilia than those of healthy tissue, whereas both the frequency and length of primary cilia were decreased in oncocytic variant of PTC. In addition, ciliogenesis was markedly defective in primary Hürthle cell tumors, including Hürthle cell adenomas and carcinomas, which showed higher level of autophagosome biogenesis. Remarkably, inhibition of autophagosome formation by Atg5 silencing or treatment with pharmacological inhibitors of autophagosome formation restored ciliogenesis in the Hürthle cell carcinoma cell line XTC.UC1 which exhibits a high basal autophagic flux. Moreover, the inhibition of autophagy promoted the accumulation of two factors critical for ciliogenesis, IFT88 and ARL13B. These results suggest that abnormal ciliogenesis, a common feature of Hürthle cells in diseased thyroid glands, is associated with increased basal autophagy. PMID:27816963

Management of hyper and hypo thyroid conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Locke, W.

1982-03-01

In hyperthyroidism, the primary objective of therapy is to reduce secretion of thyroid hormone, which can be accomplished in various ways. The stimulus to hypersecretion can be removed in some causes of hyperthyroidism; in others, hormone synthesis and release can be inhibited by drugs such as thioamides, adrenergic blocking agents, or possibly lithium or glucocorticoids. Radioactive iodine is indicated for primary therapy of uncomplicated hyperthyroidism due to Graves' disease in persons over 30 years of age (myxedema may be a complication) and for treatment of autonomous thyroid adenoma in patients who are not suitable candidates for surgery. Surgical ablation ismore » preferred for some causes of hyperthyroidism but may induce postoperative hypothyroidism. Hypothyroidism due to thyroid failure usually presents few therapeutic difficulties and can be managed simply by long-term hormone replacement. Before hormone replacement is prescribed for secondary or tertiary hypothyroidism, the other pituitary functions should be assessed.« less

Human herpes simplex viruses in benign and malignant thyroid tumours.

PubMed

Jensen, Kirk; Patel, Aneeta; Larin, Alexander; Hoperia, Victoria; Saji, Motoyasu; Bauer, Andrew; Yim, Kevin; Hemming, Val; Vasko, Vasyl

2010-06-01

To test the hypothesis that herpes viruses may have a role in thyroid neoplasia, we analysed thyroid tissues from patients with benign (44) and malignant (65) lesions for HSV1 and HSV2 DNA. Confirmatory studies included direct sequencing, analysis of viral gene expression, and activation of viral-inducible signalling pathways. Expression of viral entry receptor nectin-1 was examined in human samples and in cancer cell lines. In vitro experiments were performed to explore the molecular mechanisms underlying thyroid cancer cell susceptibility to HSV. HSV DNA was detected in 43/109 (39.4%) examined samples. HSV capsid protein expression correlated with HSV DNA status. HSV-positive tumours were characterized by activation of virus-inducible signalling such as interferon-beta expression and nuclear NFkappaB expression. Lymphocyte infiltration and oncocytic cellular features were common in HSV-positive tumours. HSV1 was detected with the same frequency in benign and malignant thyroid tumours. HSV2 was significantly associated with papillary thyroid cancer and the presence of lymph node metastases. The expression of HSV entry receptor nectin-1 was increased in thyroid tumours compared to normal thyroid tissue and further increased in papillary thyroid cancer. Nectin-1 expression was detected in all examined thyroid cancer cell lines. Nectin-1 expression in cancer cells correlated with their susceptibility to HSV. Inhibition of PI3K/AKT or MAPK/ERK signalling did not affect the level of nectin-1 expression but decreased thyroid cancer cell susceptibility to HSV. These findings showed that HSV is frequently detected in thyroid cancer. During tumour progression, thyroid cells acquire increased susceptibility to HSV due to increased expression of viral entry mediator nectin-1 and activation of mitogenic signalling in cancer cells.

Thyroid Diseases

MedlinePlus

... beats. All of these activities are your body's metabolism. Thyroid problems include Goiter - enlargement of the thyroid gland Hyperthyroidism - when your thyroid gland makes more thyroid hormones ...

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer

PubMed Central

Alexander, Erik K.; Bible, Keith C.; Doherty, Gerard M.; Mandel, Susan J.; Nikiforov, Yuri E.; Pacini, Furio; Randolph, Gregory W.; Sawka, Anna M.; Schlumberger, Martin; Schuff, Kathryn G.; Sherman, Steven I.; Sosa, Julie Ann; Steward, David L.; Tuttle, R. Michael; Wartofsky, Leonard

2016-01-01

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy

2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer.

PubMed

Haugen, Bryan R; Alexander, Erik K; Bible, Keith C; Doherty, Gerard M; Mandel, Susan J; Nikiforov, Yuri E; Pacini, Furio; Randolph, Gregory W; Sawka, Anna M; Schlumberger, Martin; Schuff, Kathryn G; Sherman, Steven I; Sosa, Julie Ann; Steward, David L; Tuttle, R Michael; Wartofsky, Leonard

2016-01-01

Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression

Statins and Thyroid Carcinoma: a Meta-Analysis.

PubMed

Zhao, Junyu; Xu, Chunmei; Yao, Jinming; Yu, Changzhen; Liao, Lin; Dong, Jianjun

2018-06-19

Experimental studies have reported the antineoplastic effects of statins in thyroid carcinoma; however, observational studies suggested that statins might increase the risk of thyroid carcinoma. Therefore, this study evaluated the antineoplastic effects of statins in both in vitro studies and animal models, as well as the epidemiological evidence. Databases-PubMed, Cochrane Library, SinoMed, CNKI, Wanfang, and clinical trial registries- were searched. A meta-analysis was performed with sufficiently homogeneous studies. Eighteen articles were involved. In in vitro studies, statins showed a concentration-dependent inhibition of cell line growth (weighted mean difference -34.68, 95% confidence interval -36.53 to -32.83). A significant efficacy of statin-induced apoptosis was observed (weighted mean difference [95% confidence interval]: 24 h, 57.50 [55.98-59.03]; 48 h, 23.43 [22.19-24.66]; 72 h, 51.29 [47.52-55.07]). Early apoptosis was increased in a dose- and time-dependent manner. In in vivo antitumor studies, lovastatin inhibited tumor growth, as shown by a reduction in tumor volume. However, two clinical studies showed discordant results from the experimental studies. Experimental studies revealed the antineoplastic efficacy of statins but statins were associated with thyroid carcinoma in clinical studies. This discrepancy may be due to the different concentrations of statins used and the effects of hyperlipidemia interventions, and thus further study is required. © 2018 The Author(s). Published by S. Karger AG, Basel.

[Autoimmune thyroiditis and thyroid cancer].

PubMed

Krátký, Jan; Jiskra, Jan

2015-10-01

Association between autoimmune thyroiditis (CLT) and thyroid cancer remains not clear. Although both diseases often occur simultaneously in histological samples, it is not yet clear whether CLT can be regarded as a risk factor for thyroid malignancy. This review focus on the known epidemiological and molecular genetics links between both diseases. Most studies have shown a significant association between thyroid cancer and positive antibodies to thyroglobulin and histological evidence of CLT, as well. Both disorders share some risk factors (greater incidence in women, in areas with adequate supply of iodine and in patients after radiotherapy of the neck) and molecular genetics linkage. For example: RET/PTC rearrangements could be more often found in carcinomas associated with CLT, but this mutation could be found in benign lesions such as CLT, as well. CLT seems to be a positive prognostic factor in patients with differentiated thyroid cancer. It is associated with less invasive forms of tumor, lower occurrence of infiltrated lymphatic nodes and a lower risk of recurrence.

[Effect of combined oral contraceptives on the hypophyseo-thyroid and hypophyseo-adrenal systems in women with various anatomy of the thyroid gland].

PubMed

Zigizmund, V A; Sadykova, M Sh; Samoĭlova, O N; Moiseeva, O M

1988-11-01

Potential therapeutic effects of combined oral contraceptives (COC) rigevidon and ovidon (estrogen:gestagen ratio of 1:5) were studied in 97 women aged 19-35 years. With respect to the anatomical state of the thyroid, the patients were divided into two groups: group 1 included 42 women with normal thyroid function and group 2 included 55 women with euthyroid hyperplasia of the thyroid gland of stage I-II (the anatomical state of the thyroid gland was ranked according to the five-point Swiss scale adopted by WHO in 1975). All patients had a history of pregnancy, normal delivery, or abortion. The state of the pituitary-thyroid system was estimated by absorption of iodine isotopes in the thyroid tissue, and by the blood levels of thyrotropic hormone, thyroxine-binding globulin, thyroxine, and triiodothyronine. Activity of the pituitary- adrenal system was estimated by the blood levels of adrenocorticotropic hormone (ACTH) and cortisol. Blood samples were withdrawn 9 and 10 hours prior to the onset of COC administration, and after 24 and 48 weeks of COC use. The changes in the functional state of the pituitary- thyroid system in groups 1 and 2 were identical throughout the entire period of COC administration. Progressive increase in the levels of thyroxine and triiodothyronine was associated with inhibition of the thyrotropic function of the pituitary seen as decrease in thyrotropin levels. COC administration caused decrease in size of hyperplastic tyroid gland. Prior to COC administration, women in group 2 showed significant elevation of ACTH levels and marked decrease in ACTH levels and increase in cortisol levels in both groups. Normalization of the size of thyroid gland indicated that COC be used therapeutically in patients with thyroid hyperplasia.

Cross-species analysis of thyroperoxidase inhibition by xenobiotics demonstrates conservation of response between pig and rat

EPA Science Inventory

Thyroperoxidase (TPO), the enzyme that catalyzes the synthesis of thyroid hormone (TH), is a known target for thyroid-disrupting chemicals (TDC). In vivo toxicological evidence supporting TPO-inhibition as one molecular-initiating event that leads to thyroid disruption is derive...

Thyroid Tests

MedlinePlus

... calories and how fast your heart beats. Thyroid tests check how well your thyroid is working. They ... thyroid diseases such as hyperthyroidism and hypothyroidism. Thyroid tests include blood tests and imaging tests. Blood tests ...

CHIP promotes thyroid cancer proliferation via activation of the MAPK and AKT pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Li; Liu, Lianyong; Department of Endocrinology, Shanghai Punan Hospital, Shanghai 200125

The carboxyl terminus of Hsp70-interacting protein (CHIP) is a U box-type ubiquitin ligase that plays crucial roles in various biological processes, including tumor progression. To date, the functional mechanism of CHIP in thyroid cancer remains unknown. Here, we obtained evidence of upregulation of CHIP in thyroid cancer tissues and cell lines. CHIP overexpression markedly enhanced thyroid cancer cell viability and colony formation in vitro and accelerated tumor growth in vivo. Conversely, CHIP knockdown impaired cell proliferation and tumor growth. Notably, CHIP promoted cell growth through activation of MAPK and AKT pathways, subsequently decreasing p27 and increasing cyclin D1 and p-FOXO3a expression. Ourmore » findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. - Highlights: • CHIP is significantly upregulated in thyroid cancer cells. • Overexpression of CHIP facilitates proliferation and tumorigenesis of thyroid cancer cells. • Silencing of CHIP inhibits the proliferation and tumorigenesis of thyroid cancer cells. • CHIP promotes thyroid cancer cell proliferation via activating the MAPK and AKT pathways.« less

Thyroid Surgery

MedlinePlus

... thyroid surgery, requiring treatment with thyroid hormone (see Hypothyroidism brochure ). This is especially true if you had ... Disease Graves’ Eye Disease Hashimoto’s Thyroiditis Hyperthyroidism (Overactive) Hypothyroidism (Underactive) Iodine Deficiency Low Iodine Diet Medullary Thyroid ...

[Non-autoimmune thyroiditis].

PubMed

Rizzo, Leonardo F L; Mana, Daniela L; Bruno, Oscar D

2014-01-01

The term thyroiditis comprises a group of thyroid diseases characterized by the presence of inflammation, including autoimmune and non-autoimmune entities. It may manifest as an acute illness with severe thyroid pain (subacute thyroiditis and infectious thyroiditis), and conditions in which the inflammation is not clinically evident evolving without pain and presenting primarily thyroid dysfunction and/or goiter (drug-induced thyroiditis and Riedel thyroiditis). The aim of this review is to provide an updated approach on non-autoimmune thyroiditis and its clinical, diagnostic and therapeutic aspects.

Estimating Margin of Exposure to Thyroid Peroxidase Inhibitors Using High-throughput In Vitro Data, High-throughput Exposure Modeling, and Physiologically-Based Pharmacokinetic/Pharmacodynamic Modeling

EPA Science Inventory

Some pharmaceuticals and environmental chemicals bind the thyroid peroxidase (TPO) enzyme and disrupt thyroid hormone production. The potential for TPO inhibition is a function of both the binding affinity and concentration of the chemical within the thyroid gland. The former can...

In vivo deiodinase inhibition by iopanoic acid causes thyroid axis disruption and dysmorphogenesis in model amphibian species Xenopus laevis

EPA Science Inventory

Deiodinase (DIO) enzymes activate, deactivate and catabolize thyroid hormones (THs) and play an important role in thyroid-mediated amphibian metamorphosis. DIOs have been implicated as putative targets of xenobiotics leading to thyroid disruption. In an effort to characterize bi...

Painless thyroiditis associated to thyroid carcinoma: role of initial ultrasonography evaluation.

PubMed

Valentini, Raisa Bressan; Macedo, Bruno Mussoi de; Izquierdo, Rogério Friedrich; Meyer, Erika Laurini Souza

2016-04-01

Even though it is a rare event, most associations of thyroid carcinoma with subacute thyroiditis described in the literature are related to its granulomatous form (Quervain's thyroiditis). We present a patient with subacute lymphocytic thyroiditis (painless thyroiditis) and papillary thyroid cancer that was first suspected in an initial ultrasound evaluation. A 30-year old female patient who was referred to the emergency room due to hyperthyroidism symptoms was diagnosed with painless thyroiditis established by physical examination and laboratory findings. With the presence of a palpable painless thyroid nodule an ultrasound was prescribed and the images revealed a suspicious thyroid nodule, microcalcification focus in the heterogeneous thyroid parenquima and cervical lymphadenopathy. Fine needle aspiration biopsy was taken from this nodule; cytology was assessed for compatibility with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a multicentric papillary carcinoma and lymphocytic infiltration. Subacute thyroiditis, regardless of type, may produce transitory ultrasound changes that obscure the coexistence of papillary carcinoma. Due to this, initial thyroid ultrasound evaluation should be delayed until clinical recovery. We recommended a thyroid ultrasound exam for initial evaluation of painless thyroiditis, particularly in patients with palpable thyroid nodule. Further cytological examination is recommended in cases presenting with suspect thyroid nodule and/or non-nodular hypoechoic (> 1 cm) or heterogeneous areas with microcalcification focus.

Sonographic features of thyroid nodules that may help distinguish clinically atypical subacute thyroiditis from thyroid malignancy.

PubMed

Pan, Fu-shun; Wang, Wei; Wang, Yan; Xu, Ming; Liang, Jin-yu; Zheng, Yan-ling; Xie, Xiao-yan; Li, Xiao-xi

2015-04-01

The purpose of this study was to evaluate sonographic features for distinguishing clinically atypical subacute thyroiditis from malignant thyroid nodules. A total of 165 hypoechoic thyroid nodules without calcification in 135 patients with histologic diagnosis were included in this study. These nodules were classified into 2 groups: a thyroiditis group (55 nodules in 36 patients) and a malignancy group (110 nodules in 99 patients). The sonographic features of the groups were retrospectively reviewed. No significant differences were detected for the variables of marked echogenicity, a taller-than-wide shape, and mixed vascularity. However, a poorly defined margin was detected more frequently in the thyroiditis group than the malignancy group (P < .05); it yielded a high capability for differential diagnosis of atypical subacute thyroiditis, with sensitivity and specificity of 87.3% and 80.9%, respectively. Centripetal reduction echogenicity was observed exclusively in the thyroiditis group, with high specificity (100%) but low sensitivity (21.8%) for atypical subacute thyroiditis diagnosis. All of the thyroiditis nodules with a positive color signal showed noninternal vascularity (negative predictive value, 100%). There is a considerable overlap between the sonographic features of atypical subacute thyroiditis and thyroid malignancy. However, the margin, echogenicity, and vascularity type are helpful indicators for differential diagnosis of atypical subacute thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Apatinib Inhibits Angiogenesis Via Suppressing Akt/GSK3β/ANG Signaling Pathway in Anaplastic Thyroid Cancer.

PubMed

Jin, Zhijian; Cheng, Xi; Feng, Haoran; Kuang, Jie; Yang, Weiping; Peng, Chenghong; Shen, Baiyong; Qiu, Weihua

2017-01-01

Anaplastic thyroid carcinoma (ATC) is one of the most lethal human malignancies, and there is no efficient method to slow its process. Apatinib, a novel tyrosine kinase inhibitor (TKI), has been confirmed for its efficacy and safety in the treatment of advanced gastric carcinoma patients. However, the effects of Apatinib in ATC are still unknown. In this study, we explored the effects and mechanisms of Apatinib on tumor growth and angiogenesis in vitro and in vitro in ATC cells. Angiogenesis antibodies array was utilized to detect the expression of angiogenesis-related genes after Apatinib treatment in ATC cells. In addition, we used Akt activator, Akt inhibitor and GSK3β inhibitor to further study the mechanism for how Apatinib suppressed angiogenesis. Apatinib treatment could suppress the growth of ATC cells in a dose- and time-dependent manner via inducing apoptosis and blocking cell cycle progression at G0/G1 phase. Moreover, Apatinib treatment decreased the expression of angiogenin (ANG) and inhibited angiogenesis of ATC cells in vitro and in vitro. We further confirmed that recombinant human ANG (rhANG) significantly abrogated Apatinib-mediated anti-angiogenic ability in ATC cells. Additionally, Apatinib treatment decreased the level of p-Akt and p-GSK3β. Moreover, the Apatinib-mediated decrease of ANG and anti-angiogenic ability were partly reversed when an Akt activator, SC79, was administered. Furthermore, the anti-angiogenic ability of Apatinib can be enhanced in the presence of Akt inhibitor, and the inhibition of GSK3β attenuated the anti-angiogenic ability of Apatinib. Our results demonstrated that Apatinib treatment inhibited tumor growth, and Apatinib-induced suppression of Akt/GSK3β/ANG signaling pathway may play an important role in the inhibition of angiogenesis in ATC, supporting a potential therapeutic approach for using Apatinib in the treatment of ATC. © 2017 The Author(s). Published by S. Karger AG, Basel.

Thyroid gland disorder emergencies: thyroid storm and myxedema coma.

PubMed

Hampton, Jessica

2013-01-01

Although thyroid dysfunction will develop in more than 12% of the US population during their lifetimes, true thyroid emergencies are rare. Thyroid storm and myxedema coma are endocrine emergencies resulting from thyroid hormone dysregulation, usually coupled with an acute illness as a precipitant. Careful assessment of risk and rapid action, once danger is identified, are essential for limiting morbidity and mortality related to thyroid storm and myxedema coma. This article reviews which patients are at risk, explains thyroid storm and myxedema coma, and describes pharmacological treatment and supportive cares.

Thyroid Cancer

MedlinePlus

... are here Home > Types of Cancer > Thyroid Cancer Thyroid Cancer This is Cancer.Net’s Guide to Thyroid Cancer. Use the menu below to choose the Overview/ ... social workers, and patient advocates. Cancer.Net Guide Thyroid Cancer Introduction Statistics Medical Illustrations Risk Factors Symptoms and ...

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

PubMed

Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

Overview of the 2015 American Thyroid Association guidelines for managing thyroid nodules and differentiated thyroid cancer.

PubMed

Matti, Bashar; Cohen-Hallaleh, Ruben

2016-09-09

The last few years have witnessed numerous publications addressing the management of thyroid nodules and differentiated thyroid cancers. The purpose of this review is to provide a simplified summary of the newly released guidelines by the American Thyroid Association. A systematic approach has been recommended to evaluate a thyroid nodule through clinical assessment, measurement of serum Thyroid Stimulating Hormone, neck ultrasonography and Fine Needle Aspiration where appropriate. This is followed by cytology analysis using the Bethesda scoring system to detect malignancy. Once diagnosed, thyroid cancers need to be staged and risk stratification needs to be applied to develop further treatment plans. Lastly, several recommendations have been presented to assure proper follow-up and support for thyroid cancer patients regardless of the treatment received.

Pazopanib Enhances Paclitaxel-Induced Mitotic Catastrophe in Anaplastic Thyroid Cancer

PubMed Central

Isham, Crescent R.; Bossou, Ayoko R.; Negron, Vivian; Fisher, Kelly E.; Kumar, Rakesh; Marlow, Laura; Lingle, Wilma L.; Smallridge, Robert C.; Sherman, Eric J.; Suman, Vera J.; Copland, John A.; Bible, Keith C.

2014-01-01

Anaplastic thyroid cancer (ATC) has perhaps the worst prognosis of any cancer, with a median survival of only about 5 months regardless of stage. Pazopanib monotherapy has promising clinical activity in differentiated thyroid cancers (generally attributed to vascular endothelial growth factor receptor inhibition), yet has less effective single-agent activity in ATC. We now report that combining pazopanib with microtubule inhibitors such as paclitaxel produced heightened and synergistic antitumor effects in ATC cells and xenografts that were associated with potentiated mitotic catastrophe. We hypothesized that combined effects may reflect enhanced paclitaxel-induced cytotoxicity mediated by cell cycle regulatory kinase inhibition by pazopanib. Indeed, pazopanib potently inhibited aurora A, with pazopanib/paclitaxel synergy recapitulated by aurora A short hairpin RNA knockdown or by specific aurora A pharmacological inhibition. Pazopanib/paclitaxel synergy was reversed by aurora A knockdown. Moreover, aurora A (but not B or C) message and protein levels were significantly increased in patient ATCs, and durable benefit resulted from pilot clinical translation of pazopanib/paclitaxel therapy in a patient with metastatic ATC. Collectively, these results suggest that the pazopanib/paclitaxel combination is a promising candidate therapeutic approach in ATC and that aurora A may represent a potentially viable therapeutic molecular target in ATC. PMID:23283368

Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening.

PubMed

Anania, Maria; Gasparri, Fabio; Cetti, Elena; Fraietta, Ivan; Todoerti, Katia; Miranda, Claudia; Mazzoni, Mara; Re, Claudia; Colombo, Riccardo; Ukmar, Giorgio; Camisasca, Stefano; Pagliardini, Sonia; Pierotti, Marco; Neri, Antonino; Galvani, Arturo; Greco, Angela

2015-10-27

The incidence of thyroid carcinoma is rapidly increasing. Although generally associated with good prognosis, a fraction of thyroid tumors are not cured by standard therapy and progress to aggressive forms for which no effective treatments are currently available. In order to identify novel therapeutic targets for thyroid carcinoma, we focused on the discovery of genes essential for sustaining the oncogenic phenotype of thyroid tumor cells, but not required to the same degree for the viability of normal cells (non-oncogene addiction paradigm). We screened a siRNA oligonucleotide library targeting the human druggable genome in thyroid cancer BCPAP cell line in comparison with immortalized normal human thyrocytes (Nthy-ori 3-1). We identified a panel of hit genes whose silencing interferes with the growth of tumor cells, while sparing that of normal ones. Further analysis of three selected hit genes, namely Cyclin D1, MASTL and COPZ1, showed that they represent common vulnerabilities for thyroid tumor cells, as their inhibition reduced the viability of several thyroid tumor cell lines, regardless the histotype or oncogenic lesion. This work identified non-oncogenes essential for sustaining the phenotype of thyroid tumor cells, but not of normal cells, thus suggesting that they might represent promising targets for new therapeutic strategies.

Bexarotene via CBP/p300 induces suppression of NF-κB-dependent cell growth and invasion in thyroid cancer.

PubMed

Cras, Audrey; Politis, Béatrice; Balitrand, Nicole; Darsin-Bettinger, Diane; Boelle, Pierre Yves; Cassinat, Bruno; Toubert, Marie-Elisabeth; Chomienne, Christine

2012-01-15

Retinoic acid (RA) treatment has been used for redifferentiation of metastatic thyroid cancer with loss of radioiodine uptake. The aim of this study was to improve the understanding of RA resistance and investigate the role of bexarotene in thyroid cancer cells. A model of thyroid cancer cell lines with differential response to RA was used to evaluate the biological effects of retinoid and rexinoid and to correlate this with RA receptor levels. Subsequently, thyroid cancer patients were treated with 13-cis RA and bexarotene and response evaluated on radioiodine uptake reinduction on posttherapy scan and conventional imaging. In thyroid cancer patients, 13-cis RA resistance can be bypassed in some tumors by bexarotene. A decreased tumor growth without differentiation was observed confirming our in vitro data. Indeed, we show that ligands of RARs or RXRs exert different effects in thyroid cancer cell lines through either differentiation or inhibition of cell growth and invasion. These effects are associated with restoration of RARβ and RXRγ levels and downregulation of NF-κB targets genes. We show that bexarotene inhibits the transactivation potential of NF-κB in an RXR-dependent manner through decreased promoter permissiveness without interfering with NF-κB nuclear translocation and binding to its responsive elements. Inhibition of transcription results from the release of p300 coactivator from NF-κB target gene promoters and subsequent histone deacetylation. This study highlights dual mechanisms by which retinoids and rexinoids may target cell tumorigenicity, not only via RARs and RXRs, as expected, but also via NF-κB pathway. ©2011 AACR.

Latent childhood thyroid carcinoma in diffuse lymphocytic thyroiditis.

PubMed

Siegal, A; Mimouni, M; Kovalivker, M; Griffel, B

1983-07-01

Diffuse thyroid enlargement in a child is a rare presenting symptom of thyroid carcinoma. A papillary carcinoma may be hidden in a diffuse lymphocytic thyroiditis and should be carefully searched for during surgery. Furthermore, the finding, in frozen sections, of psammoma bodies in a lymphocytic thyroiditis should raise the suspicion of an occult malignant neoplasm. A case illustrating these diagnostic difficulties in a 5-year-old child is presented.

[Painless thyroiditis].

PubMed

Okamura, Ken; Fujikawa, Megumi; Bandai, Sachiko

2006-12-01

Painless thyroiditis is characterized by painless low-uptake thyrotoxicosis (thyrotoxicosis without hyperthyroidism). Destructive damage of the thyroid has been thought to be the mechanism for self-limited thyrotoxicosis. However, hydrolysis of thyroglobulin must be responsible for the release of excessive thyroid hormone. Low-uptake of iodine and excessive release of thyroid hormone suggest the uncoupling of hormone synthesis and hormone secretion in the thyroid gland. Suppressed serum TSH level, various cytokines or growth factors including TGFbeta1, and thyroglobulin itself may be responsible for the suppressed hormone synthesis. The mechanism for persistent hormone release despite suppressed hormone synthesis should be clarified. Quantitative TSH binding inhibitor immunoglobulin assay is helpful for the differential diagnosis of painless thyroiditis and Graves' hyperthyroidism.

[Thyroid nodules and differentiated thyroid cancer: Brazilian consensus].

PubMed

Maia, Ana Luiza; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa M Zanini; Rosário, Pedro W; Vaisman, Mario

2007-07-01

Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.

EXPERIMENTAL THYROIDISM

PubMed Central

Cunningham, R. H.

1898-01-01

From the results of the various experiments already detailed I feel justified in drawing the following conclusions: (1) Absolutely fresh thyroid gland is not poisonous, in the usual sense of the term, when absorbed through the alimentary canal. (2) The symptoms of induced thyroidism are manifestations of an intoxication resulting from the ingestion of decomposed thyroid material, a conclusion that agrees in part with the previously related observations of Lanz. (3) The so-called experimental thyroidism is not specific for the thyroid only, for the ingestion of many substances derived from animal tissues other than the thyroid gland may produce an intoxication strikingly similar in every respect to that of experimental thyroidism. (4) Most, if not all, animal tissues yield substances which, if injected in large quantities directly into the circulation or beneath the skin, will produce an intoxication often very similar to that produced by injections of various substances derived from the fresh thyroid tissue. (5) The effects resulting from the intravascular or subcutaneous injections of aqueous extracts, decoctions and the concentrated extractives of the thyroid tissue, of the thymus, of muscle, etc., are by no means necessarily indicative of the function and the action of the hypothetical internal secretions of the same tissues during life. (6) The utilization of the fact that ingestion of decomposed thyroid material produces on certain occasions an intoxication with certain symptoms similar to some of those of G-raves' disease is not justifiable for the furtherance of the theory that the symptoms of exophthalmic goitre result from an over-production of the thyroid secretion. (7) Our results lead us to conclude with Drechsel that the fresh thyroid tissue yields at least probably two substances that are capable of palliating the symptoms of the acute cachexia in totally thyroidless dogs. (8) The thymus tissue also yields one and probably two substances that are as

Thyroid scan

MedlinePlus

... thyroid; Radioactive iodine uptake and scan test - thyroid; Nuclear scan - thyroid ... the test. Ask your provider or the radiology/nuclear medicine team performing the scan about taking precautions.

Case of concurrent Riedel's thyroiditis, acute suppurative thyroiditis, and micropapillary carcinoma.

PubMed

Hong, Ji Taek; Lee, Jung Hwan; Kim, So Hun; Hong, Seong Bin; Nam, Moonsuk; Kim, Yong Seong; Chu, Young Chae

2013-03-01

Riedel's thyroiditis (RT) is a rare chronic inflammatory disease of the thyroid gland. It is characterized by a fibroinflammatory process that partially destroys the gland and extends into adjacent neck structures. Its clinical manifestation can mask an accompanying thyroid neoplasm and can mimic invasive thyroid carcinoma. Therefore, diagnosis can be difficult prior to surgical removal of the thyroid, and histopathologic examination of the thyroid is necessary for a definite diagnosis. The concurrent presence of RT and other thyroid diseases has been reported. However, to our knowledge, the association of RT with acute suppurative thyroiditis and micropapillary carcinoma has not been reported. We report a rare case of concurrent RT, acute suppurative thyroiditis, and micropapillary carcinoma in a 48-year-old patient.

Thyroid Echography-induced Thyroid Storm and Exacerbation of Acute Heart Failure.

PubMed

Nakabayashi, Keisuke; Nakazawa, Naomi; Suzuki, Toshiaki; Asano, Ryotaro; Saito, Hideki; Nomura, Hidekimi; Isomura, Daichi; Okada, Hisayuki; Sugiura, Ryo; Oka, Toshiaki

2016-01-01

Hyperthyroidism and thyroid storm affect cardiac circulation in some conditions. Several factors including trauma can induce thyroid storms. We herein describe the case of a 57-year-old woman who experienced a thyroid storm and exacerbation of acute heart failure on thyroid echography. She initially demonstrated a good clinical course after medical rate control for atrial fibrillation; however, thyroid echography for evaluating hyperthyroidism led to a thyroid storm and she collapsed. A multidisciplinary approach stabilized her thyroid hormone levels and hemodynamics. Thus, the medical staff should be prepared for a deterioration in the patient's condition during thyroid echography in heart failure patients with hyperthyroidism.

Inhibition of oncogene-induced inflammatory chemokines using a farnesyltransferase inhibitor

PubMed Central

DeGeorge, Katharine C; DeGeorge, Brent R; Testa, James S; Rothstein, Jay L

2008-01-01

Background Farnesyltransferase inhibitors (FTI) are small molecule agents originally formulated to inhibit the oncogenic functions of Ras. Although subsequent analysis of FTI activity revealed wider effects on other pathways, the drug has been demonstrated to reduce Ras signaling by direct measurements. The purpose of the current study was to determine if FTI could be used to inhibit the inflammatory activities of a known Ras-activating human oncoprotein, RET/PTC3. RET/PTC3 is a fusion oncoprotein expressed in the thyroid epithelium of patients afflicted with thyroid autoimmune disease and/or differentiated thyroid carcinoma. Previous studies have demonstrated that RET/PTC3 signals through Ras and can provoke nuclear translocation of NFκB and the downstream release of pro-inflammatory mediators from thyroid follicular cells in vitro and in vivo, making it an ideal target for studies using FTI. Methods For the studies described here, an in vitro assay was developed to measure FTI inhibition of RET/PTC3 pro-inflammatory effects. Rat thyrocytes transfected with RET/PTC3 or vector control cDNA were co-cultured with FTI and examined for inhibition of chemokine expression and secretion measured by RT-PCR and ELISA. Immunoblot analysis was used to confirm the level at which FTI acts on RET/PTC3-expressing cells, and Annexin V/PI staining of cells was used to assess cell death in RET/PTC3-expressing cells co-cultured with FTI. Results These analyses revealed significant mRNA and protein inhibition of chemokines Ccl2 and Cxcl1 with nanomolar doses of FTI. Neither RET/PTC3 protein expression nor apoptosis were affected at any dose of FTI investigated. Conclusion These data suggest that FTI may be applied as an effective inhibitor for RET/PTC3-oncogene induced pro-inflammatory mediators. PMID:18304343

Pre-operative ultrasound identification of thyroiditis helps predict the need for thyroid hormone replacement after thyroid lobectomy.

PubMed

Morris, Lilah F; Iupe, Isabella M; Edeiken-Monroe, Beth S; Warneke, Carla L; Hansen, Mandy O; Evans, Douglas B; Lee, Jeffrey E; Grubbs, Elizabeth G; Perrier, Nancy D

2013-01-01

To evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy. Data from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had ≥1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR. During follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 μ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 μIU/mL and US-identified thyroiditis had a 5.8-fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001). A pre-operative TSH level >2.5 μIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months).

Thyroid Emergencies

PubMed Central

Leung, Angela M

2017-01-01

Myxedema coma and thyroid storm are thyroid emergencies associated with increased mortality. Prompt recognition of these states—which represent the severe, life-threatening conditions of extremely reduced or elevated circulating thyroid hormone concentrations, respectively—is necessary to initiate treatment. Management of myxedema coma and thyroid storm requires both medical and supportive therapies and should be treated in an intensive care unit setting. PMID:27598067

Silent thyroiditis

MedlinePlus

... gland. The disorder can cause hyperthyroidism, followed by hypothyroidism. The thyroid gland is located in the neck, ... Later symptoms may be of an underactive thyroid ( hypothyroidism ), including fatigue and cold intolerance, until the thyroid ...

Thyroid Nodules

MedlinePlus

... disorder, can cause thyroid inflammation resulting in nodular enlargement. This often is associated with reduced thyroid gland ... Goiter" is a term used to describe any enlargement of the thyroid gland, which can be caused ...

Thyroiditis: an integrated approach.

PubMed

Sweeney, Lori B; Stewart, Christopher; Gaitonde, David Y

2014-09-15

Thyroiditis is a general term that encompasses several clinical disorders characterized by inflammation of the thyroid gland. The most common is Hashimoto thyroiditis; patients typically present with a nontender goiter, hypothyroidism, and an elevated thyroid peroxidase antibody level. Treatment with levothyroxine ameliorates the hypothyroidism and may reduce goiter size. Postpartum thyroiditis is transient or persistent thyroid dysfunction that occurs within one year of childbirth, miscarriage, or medical abortion. Release of preformed thyroid hormone into the bloodstream may result in hyperthyroidism. This may be followed by transient or permanent hypothyroidism as a result of depletion of thyroid hormone stores and destruction of thyroid hormone-producing cells. Patients should be monitored for changes in thyroid function. Beta blockers can treat symptoms in the initial hyperthyroid phase; in the subsequent hypothyroid phase, levothyroxine should be considered in women with a serum thyroid-stimulating hormone level greater than 10 mIU per L, or in women with a thyroid-stimulating hormone level of 4 to 10 mIU per L who are symptomatic or desire fertility. Subacute thyroiditis is a transient thyrotoxic state characterized by anterior neck pain, suppressed thyroid-stimulating hormone, and low radioactive iodine uptake on thyroid scanning. Many cases of subacute thyroiditis follow an upper respiratory viral illness, which is thought to trigger an inflammatory destruction of thyroid follicles. In most cases, the thyroid gland spontaneously resumes normal thyroid hormone production after several months. Treatment with high-dose acetylsalicylic acid or nonsteroidal anti-inflammatory drugs is directed toward relief of thyroid pain.

Thyroid dysfunction and thyroid autoimmunity in euthyroid women in achieving fertility.

PubMed

Medenica, S; Nedeljkovic, O; Radojevic, N; Stojkovic, M; Trbojevic, B; Pajovic, B

2015-01-01

Thyroid disease is the second most common endocrine condition in women of childbearing age. Thyroid hormones are involved in control of menstrual cycle and in achieving fertility affecting the actions of follicle-stimulating hormone and luteinizing hormone on steroid biosynthesis by specific triiodothyronine sites on oocytes; therefore, affect all aspects of reproduction. It remains controversial if pregnant women should be screened for thyroid dysfunction. Purpose of this review was to examine recent studies on the assessment of thyroid dysfunction in pregnancy, its treatment and newly perspective of thyroid autoimmunity in pregnant euthyroid women in achieving fertility. An electronic search was conducted using the internet medical databases: Medline/PubMed, EMBASE, EBSCO, and the Cochrane library. Thyroid gland faces great challenge in pregnancy when many hormonal changes occur. Precondition for normal follicular development and ovulation is pulsate gonadothropin realizing hormone secretion. Thyroid dysfunction in pregnancy is classified as forms of hypothyroidism (positivity of thyroid autoantibody, isolated hypothyroidism, and subclinical or overt hypothyroidism), hyperthyroidism, and autoimmune disease, but also thyroid nodules and cancer, iodine insufficiency and postpartum thyroiditis. These conditions can cause adverse effects on mother and fetus including pregnancy loss, gestational hypertension, or pre-eclampsia, pre-term delivery, low birth weight, placental abruption and postpartum hemorrhage. There is an evidence that thyroid autoimmunity, in thyroid dysfunction adversely affects conception and pregnancy outcomes, but it is unclear what impact has isolated eumetabolic thyroid autoimmunity in achieving fertility, especially in women undergoing in vitro fertilization. Treatment of euthyroid pregnant women with positive thyroid peroxides antibodies is still controverse, but not few studies show that levothyroxine substitution is able to lower the chance

[Clinico-pathological features of papillary thyroid cancer coexistent with Hashimoto's thyroiditis].

PubMed

Molnár, Sarolta; Győry, Ferenc; Nagy, Endre; Méhes, Gábor; Molnár, Csaba

2017-02-01

Former studies suggest the frequent coexistence of Hashimoto's thyreoditis with papillary thyroid cancer, frequently featured by multifocal carcinogenesis but lower clinical stages compared to thyroid cancers lacking thyroiditis. We examined the clinico-pathological correlations between Hashimoto's thyroditis and papillary thyroid cancer in our region in the North-Eastern part of Hungary. We included a total of 230 patients with papillary thyroid cancer who underwent thyroid surgery at the Surgical Department of the University of Debrecen. Patients' sex, age, multifocality of thyroid cancer and clinical stage were evaluated. Cases included 40 patients (17.4%) with (4 male, 36 female) and 190 (82.6%) patients without HT (44 male, 146 female). Hashimoto's thyroiditis related thyroid cancer was almost exclusively associated with the papillary histological type. Multifocality of papillary cancer was significantly more frequent with coexisting Hashimoto's thyroiditis (16/40; 40.0%) compared to cases uninvolved (45/190; 23.7%; p = 0.034). In contrast, lymph node metastasis was significantly less frequent among patients with Hashimoto's thyroiditis (4 pN1 [36.4%]; 7 pN0 [63.6%]) then without it (34 pN1 [82.9%]; 7 pN0 [17.1%]; p = 0.002). Higher frequency and multifocality of papillary thyroid cancer might be the consequence of preexisting Hashimoto's thyroiditis to be considered as a preneoplastic stimulus supporting carcinogenesis, though the exact pathomechanism of this correlation is not clear yet. Orv. Hetil., 2017, 158(5), 178-182.

Optimized FPGA Implementation of the Thyroid Hormone Secretion Mechanism Using CAD Tools.

PubMed

Alghazo, Jaafar M

2017-02-01

The goal of this paper is to implement the secretion mechanism of the Thyroid Hormone (TH) based on bio-mathematical differential eqs. (DE) on an FPGA chip. Hardware Descriptive Language (HDL) is used to develop a behavioral model of the mechanism derived from the DE. The Thyroid Hormone secretion mechanism is simulated with the interaction of the related stimulating and inhibiting hormones. Synthesis of the simulation is done with the aid of CAD tools and downloaded on a Field Programmable Gate Arrays (FPGAs) Chip. The chip output shows identical behavior to that of the designed algorithm through simulation. It is concluded that the chip mimics the Thyroid Hormone secretion mechanism. The chip, operating in real-time, is computer-independent stand-alone system.

Thyroid and parathyroid imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandler, M.P.; Patton, J.A.; Partain, C.L.

1986-01-01

This book describes the numerous modalities currently used in the diagnosis and treatment of both thyroid and parathyroid disorders. Each modality is fully explained and then evaluated in terms of benefits and limitations in the clinical context. Contents: Production and Quality Control of Radiopharmaceutics Used for Diagnosis and Therapy in Thyroid and Parathyroid Disorders. Basic Physics. Nuclear Instrumentation. Radioimmunoassay: Thyroid Function Tests. Quality Control. Embryology, Anatomy, Physiology, and Thyroid Function Studies. Scintigraphic Thyroid Imaging. Neonatal and Pediatric Thyroid Imaging. Radioiodine Thyroid Uptake Measurement. Radioiodine Treatment of Thyroid Disorders. Radiation Dosimetry of Diagnostic Procedures. Radiation Safety Procedures for High-Level I-131 Therapies.more » X-Ray Fluorescent Scanning. Thyroid Sonography. Computed Tomography in Thyroid Disease. Magnetic Resonance Imaging in Thyroid Disease. Parathyroid Imaging.« less

Thyroid profiles in a patient with resistance to thyroid hormone and episodes of thyrotoxicosis, including repeated painless thyroiditis.

PubMed

Taniyama, Matsuo; Otsuka, Fumiko; Tozaki, Teruaki; Ban, Yoshiyuki

2013-07-01

Thyrotoxic disease can be difficult to recognize in patients with resistance to thyroid hormone (RTH) because the clinical symptoms of thyrotoxicosis cannot be observed, and thyrotropin (TSH) may not be suppressed because of hormone resistance. Painless thyroiditis is a relatively common cause of thyrotoxicosis, but its occurrence in RTH has not been reported. We assessed the thyroid profile in a patient with RTH and episodes of thyrotoxicosis who experienced repeated painless thyroiditis. A 44-year-old Japanese woman with RTH, which was confirmed by the presence of a P453A mutation in the thyroid hormone receptor β (TRβ) gene, showed a slight elevation of the basal levels of thyroid hormones, which indicated that her pituitary RTH was mild. She experienced a slight exacerbation of hyperthyroxinemia concomitant with TSH suppression. A diagnosis of painless thyroiditis was made because of the absence of TSH receptor antibodies, low Tc-99m pertechnetate uptake by the thyroid gland, and transient suppression followed by a slight elevation of TSH following the elevation of thyroid hormones. The patient's complaints of general malaise and occasional palpitations did not change throughout the course of painless thyroiditis. Three years later, painless thyroiditis occurred again without any deterioration of the clinical manifestations. Mild pituitary RTH can be overcome by slight exacerbation of hyperthyroxinemia during mild thyrotoxicosis. When pituitary resistance is severe and TSH is not suppressed, thyrotoxicosis may be overlooked.

Pediatric Thyroid Cancer

MedlinePlus

... Marketplace Find an ENT Doctor Near You Pediatric Thyroid Cancer Pediatric Thyroid Cancer Patient Health Information News media ... and neck issues, should be consulted. Types of thyroid cancer in children: Papillary : This form of thyroid cancer ...

[Characteristics of thyroid carcinoma in Grave's disease Hashimoto's thyroiditis and nodular goiter].

PubMed

Filipović, A; Paunović, I

2003-01-01

The biology of thyroid cancer represents a spectrum of behavior ranging from well-differentiated lesions with an excellent prognosis to anaplastic carcinoma, which is almost fatal. For this reason, it is important that clinicians have methods at their disposal to asses the characteristics of patient's thyroid malignancy. In this work we discuss the behavior of differentiated thyroid cancer in associated diseases of thyroid as: Graves' disease, chronic lymphocytic thyroiditis--Hashimoto and nodular goiter. This is retrospectively reviewing of 50 patients treated for differentiated thyroid carcinoma at Department of surgery, Clinical Centre of Montenegro in Podgorica from 1998 until 2003. We evaluated occurrence, as well as the role of this diseases in patients with thyroid cancer. We found a more favorable course of thyroid cancer in the presence of chronic lymphocytic thyroiditis and nodular goiter, a contrary Graves' disease. In associated diseases of thyroid, a significantly greater proportion of patients with thyroid cancer, have modular goiter.

Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis.

PubMed

Solak, Y; Atalay, H; Nar, A; Ozbek, O; Turkmen, K; Erekul, S; Turk, S

2011-04-01

Fungal pathogens are increasingly encountered after renal transplantation. Aspergillus causes significant morbidity and mortality in transplant patients. Fungal thyroiditis is a rare occurrence owing to unique features of the thyroid gland. Most cases are caused by Aspergillus species and have been described in immunocompromised patients. Presentation may be identical with that of subacute thyroiditis, in which hyperthyroidism features and painful thyroid are the prominent findings. Diagnosis can be ascertained by fine-needle aspiration of thyroid showing branching hyphae of Aspergillus. We describe a renal transplant patient who developed Aspergillus thyroiditis as part of a disseminated infection successfully treated with voriconazole. © 2010 John Wiley & Sons A/S.

Correlation between serum lead and thyroid diseases: papillary thyroid carcinoma, nodular goiter, and thyroid adenoma.

PubMed

Li, Hui; Li, Xiang; Liu, Jie; Jin, Langping; Yang, Fan; Wang, Junbo; Wang, Ouchen; Gao, Ying

2017-10-01

Studies have showed that lead was associated with human health. However, the effects of lead on thyroid functions are inconsistent, and studies based on Chinese population are fragmentary. To evaluate the correlation between lead and thyroid functions of Chinese with different thyroid diseases, we conducted a hospital-based study. Ninety-six papillary thyroid carcinoma (PTC), 10 nodular goiter (NG), and 7 thyroid adenoma (TA) patients were recruited from the First Affiliated Hospital of Wenzhou Medical University, China. Serum triiodothyronine (T3), free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone (TSH) were evaluated with chemiluminescent microparticle immunoassay. Serum lead was assessed with ICP-MASS. Partial correlation was used to explore the correlations of serum lead and thyroid diseases. Compared to PTC, the level of lead was significantly higher in TA, and lower in NG (p < 0.05). This difference remained significant in females when stratified by sex. Serum lead was negatively correlated with TSH (r s  =  - 0.27, p < 0.05) in PTC group. T3 was positively related to lead at quartile4 (r s  = 0.61, p < 0.05) in PTC group. No significant correlations were observed between lead and FT3 or FT4 in any group. The results suggested that lead might have different etiological roles in these three thyroid diseases.

A tiered approach to evaluate an iodine recycling inhibition adverse outcome pathway (AOP) in amphibians

EPA Science Inventory

The enzyme iodotyrosine deiodinase (dehalogenase, IYD) catalyzes iodide recycling and promotes iodide retention in thyroid follicular cells. Loss of function or chemical inhibition of IYD reduces thyroid hormone synthesis, which leads to insufficiency in tissues and subsequent ne...

Sonographic appearance of thyroid cancer in patients with Hashimoto thyroiditis.

PubMed

Durfee, Sara M; Benson, Carol B; Arthaud, Dylan M; Alexander, Erik K; Frates, Mary C

2015-04-01

To determine whether the sonographic appearance of thyroid cancer differs in patients with and without Hashimoto thyroiditis. Patients with histologically proven thyroid cancer who had thyroid peroxidase (TPO) antibodies measured and sonography performed preoperatively were included. We evaluated each nodule for size, echogenicity, composition, margins, halo, and vascularity and evaluated the background heterogeneity of the gland. There were 162 thyroid cancers in 145 patients. Forty-two patients (29.0%) had Hashimoto thyroiditis with positive TPO antibodies, and 103 patients (71.0%) had negative TPO antibodies. The background echogenicity was more often heterogeneous in TPO antibody-positive patients compared to those who had negative TPO antibodies (57.1% versus 26.2%; P= .0005). Comparing cancers in TPO antibody-positive to TPO antibody-negative patients, there was no significant difference in the size, echogenicity, composition, margins, halo presence, calcification presence and type, or vascularity of the cancerous nodule (P > .05). Among TPO antibody-positive patients, comparing thyroid cancerous nodules in patients with heterogeneous glands to those with homogeneous glands, there was no significant difference in any sonographic characteristic except the margin of the nodule, which was more often irregular or poorly defined in heterogeneous glands and more often smooth in homogeneous glands (P< .05). Sonographic features of thyroid cancer are similar in patients with and without Hashimoto thyroiditis. Among patients with Hashimoto thyroiditis and thyroid cancer, the sonographic appearance of the cancerous nodule is similar, except that cancerous nodule margins are more likely to be irregular or poorly defined when the gland is heterogeneous. © 2015 by the American Institute of Ultrasound in Medicine.

Radiofrequency ablation for postsurgical thyroid removal of differentiated thyroid carcinoma

PubMed Central

Xu, Dong; Wang, Lipin; Long, Bin; Ye, Xuemei; Ge, Minghua; Wang, Kejing; Guo, Liang; Li, Linfa

2016-01-01

Differentiated thyroid carcinoma (DTC) is the most common endocrine malignancy. Surgical removal with radioactive iodine therapy is recommended for recurrent thyroid carcinoma, and the postsurgical thyroid removal is critical. This study evaluated the clinical values of radiofrequency ablation (RFA) in the postsurgical thyroid removal for DTC. 35 DTC patients who had been treated by subtotal thyroidectomy received RFA for postsurgical thyroid removal. Before and two weeks after RFA, the thyroid was examined by ultrasonography and 99mTcO4 - thyroid imaging, and the serum levels of free triiodothyronine (FT3), free thyroxin (FT4), thyroid stimulating hormone (TSH) and thyroglobulin (Tg) were detected. The efficacy and complications of RFA were evaluated. Results showed that, the postsurgical thyroid removal by RFA was successfully performed in 35 patients, with no significant complication. After RFA, the average largest diameter and volume were significantly decreased in 35 patients (P > 0.05), and no obvious contrast media was observed in ablation area in the majority of patients. After RFA, the serum FT3, FT4 and Tg levels were markedly decreased (P < 0.05), and TSH level was significantly increased (P < 0.05). After RFA, radioiodine concentration in the ablation area was significantly reduced in the majority of patients. The reduction rate of thyroid update was 0.69±0.20%. DTC staging and interval between surgery and RFA had negative correlation (Pearson coefficient = -0.543; P = 0.001), with no obvious correlation among others influential factors. RFA is an effective and safe method for postsurgical thyroid removal of DTC. PMID:27186311

Assessment of petroleum streams for thyroid toxicity.

PubMed

Fowles, Jeff R; Banton, Marcy I; Boogaard, Peter J; Ketelslegers, Hans B; Rohde, Arlean M

2016-07-08

in the JP-8 or F-179 products than in studies in which thyroid effects were not observed. Thus, a few products may carry a weak potential to affect the thyroid at high doses in rodents, possibly through secondary effects on the rodent liver or possibly through a pathway involving the inhibition of TPO by specific members of the PAH family. Human epidemiology evidence found weak and inconsistent effects on the thyroid but without identification of specific chemicals involved. Two studies in petroleum workers, which found a lower rate of morbidity and mortality overall, reported a statistically significant increase in thyroid cancer, but the small number of cases could not exclude confounding variables as possible explanations for the statistical findings. Overall, the available data indicates a low potential for thyroid hormone effects from exposure to petroleum streams, especially when the aromatic content is low. Because regulatory studies for most chemicals do not include detailed thyroid function or receptor studies, it remains possible that subclinical effects on this system may exist that were not detectable using conventional pathology or hormone measurements. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Thyroid nodules and thyroid autoimmunity in the context of environmental pollution.

PubMed

Benvenga, Salvatore; Antonelli, Alessandro; Vita, Roberto

2015-12-01

Evidence suggests that in most industrialized countries autoimmune disorders, including chronic lymphocytic thyroiditis, are increasing. This increase parallels the one regarding differentiated thyroid cancer, the increment of which is mainly due to the papillary histotype. A number of studies have pointed to an association between chronic lymphocytic thyroiditis and differentiated thyroid cancer. The upward trend of these two thyroid diseases is sustained by certain environmental factors, such as polluting substances acting as endocrine disrupting chemicals. Herein we will review the experimental and clinical literature that highlights the effects of environmental and occupational exposure to polluting chemicals in the development of autoimmune thyroid disease or differentiated thyroid cancer. Stakeholders, starting from policymarkers, should become more sensitive to the consequences for the thyroid resulting from exposure to EDC. Indeed, the economic burden resulting from such consequences has not been quantified thus far.

Increased Prevalence of Chronic Lymphocytic Thyroiditis in Korean Patients with Papillary Thyroid Cancer

PubMed Central

Oh, Chang-Mo; Park, Sohee; Lee, Joo Young; Won, Young-Joo; Shin, Aesun; Kong, Hyun-Joo; Choi, Kui-Sun; Lee, You Jin; Chung, Ki- Wook; Jung, Kyu-Won

2014-01-01

Background In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. PMID:24927027

Thyroid nodules, thyroid function and dietary iodine in the Marshall islands.

PubMed

Takahashi, T; Fujimori, K; Simon, S L; Bechtner, G; Edwards, R; Trott, K R

1999-08-01

Thyroid nodules have been found to be common in the population of the Marshall Islands. This has been attributed to potential exposure of radioiodines from the nuclear weapons tests on Bikini and Eniwetok between 1946 and 1958. In order to get a full picture of thyroid pathology in the Marshallese population potentially exposed to radioactive fallout we performed a large thyroid screening programme using palpation, high resolution ultrasound and fine needle biopsies of palpable nodules. In addition, various parameters of thyroid function (free T3, free T4, thyroid stimulating hormone [TSH]) and anti-thyroid antibodies were examined in large proportions of the total population at risk. Since dietary iodine deficiency is an established risk factor for thyroid nodules, iodine concentration in urine samples of 362 adults and 119 children was measured as well as the iodine content of selected staple food products. The expected high prevalence of thyroid nodules was confirmed. There was no indication of an increased rate of impaired thyroid function in the Marshallese population. A moderate degree of iodine deficiency was found which may be responsible for some of the increased prevalence of thyroid nodules in the Marshallese population. Studies on the relationship between exposure to radioiodines and thyroid nodules need to take dietary iodine deficiency into account in the interpretation of findings.

Benign Thyroid Diseases and Risk of Thyroid Cancer: A Nationwide Cohort Study.

PubMed

Kitahara, Cari M; K Rmendiné Farkas, Dóra; Jørgensen, Jens Otto L; Cronin-Fenton, Deirdre; Sørensen, Henrik Toft

2018-06-01

Thyroid nodules, adenomas, and goiter have consistently been associated with thyroid cancer risk. Few studies have assessed whether thyroid dysfunction and thyroid autoimmunity influence this risk. To examine thyroid cancer risk after diagnoses of a wide range of benign thyroid conditions. Hospital and cancer registry linkage cohort study for the years 1978 to 2013. Nationwide (Denmark). Patients diagnosed with hyperthyroidism (n = 85,169), hypothyroidism (n = 63,143), thyroiditis (n = 12,532), nontoxic nodular goiter (n = 65,782), simple goiter (n = 11,582), other/unspecified goiter (n = 21,953), or adenoma (n = 6,481) among 8,258,807 residents of Denmark during the study period. We computed standardized incidence ratios (SIRs) for differentiated thyroid cancer, excluding the first 12 months of follow-up after benign thyroid disease diagnosis. SIRs were significantly elevated for all benign thyroid diseases apart from hypothyroidism. SIRs were higher for men than women and in the earlier follow-up periods. Elevated SIRs were observed for localized and regional/distant thyroid cancer. After excluding the first 10 years of follow-up, hyperthyroidism [n = 27 thyroid cancer cases; SIR = 2.00; 95% confidence interval (CI): 1.32 to 2.92], nontoxic nodular goiter (n = 83; SIR = 4.91; 95% CI: 3.91 to 6.09), simple goiter (n = 8; SIR = 4.33; 95% CI: 1.87 to 8.53), other/unspecified goiter (n = 20; SIR = 3.94; 95% CI: 2.40 to 6.08), and adenoma (n = 9; SIR = 6.02; 95% CI: 2.76 to 11.5) remained positively associated with thyroid cancer risk. We found an unexpected increased risk of differentiated thyroid cancer, including regional/distant disease, following diagnosis of hyperthyroidism and thyroiditis that could not be solely attributed to increased medical surveillance. Hypothyroidism was less clearly associated with thyroid cancer risk.

CD8+ T cells induce thyroid epithelial cell hyperplasia and fibrosis.

PubMed

Yu, Shiguang; Fang, Yujiang; Sharav, Tumenjargal; Sharp, Gordon C; Braley-Mullen, Helen

2011-02-15

CD8(+) T cells can be important effector cells in autoimmune inflammation, generally because they can damage target cells by cytotoxicity. This study shows that activated CD8(+) T cells induce thyroid epithelial cell hyperplasia and proliferation and fibrosis in IFN-γ(-/-) NOD.H-2h4 SCID mice in the absence of CD4(+) T cells. Because CD8(+) T cells induce proliferation rather than cytotoxicity of target cells, these results describe a novel function for CD8(+) T cells in autoimmune disease. In contrast to the ability of purified CD8(+) T cells to induce thyrocyte proliferation, CD4(+) T cells or CD8 T cell-depleted splenocytes induced only mild thyroid lesions in SCID recipients. T cells in both spleens and thyroids highly produce TNF-α. TNF-α promotes proliferation of thyrocytes in vitro, and anti-TNF-α inhibits development of thyroid epithelial cell hyperplasia and proliferation in SCID recipients of IFN-γ(-/-) splenocytes. This suggests that targeting CD8(+) T cells and/or TNF-α may be effective for treating epithelial cell hyperplasia and fibrosis.

Mechanism of iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase.

PubMed

Magnusson, R P; Taurog, A; Dorris, M L

1984-01-10

Mechanisms that have been proposed for peroxidase-catalyzed iodination require the utilization of 1 mol of H2O2 for organic binding of 1 mol of iodide. When we measured the stoichiometry of this reaction using thyroid peroxidase or lactoperoxidase at pH 7.0, we consistently obtained a ratio less than 1.0. This was shown to be attributable to catalase-like activity of these enzymes, resulting in unproductive cleavage of H2O2. This catalatic activity was completely iodide-dependent. To elucidate the mechanism of the iodide-dependent catalatic activity, the effects of various agents were investigated. The major observations may be summarized as follows: 1) The catalatic activity was inhibited in the presence of an iodine acceptor such as tyrosine. 2) The pseudohalide, SCN-, could not replace I- as a promoter of catalatic activity. 3) The inhibitory effects of the thioureylene drugs, methimazole and carbimazole, on the iodide-dependent catalatic activity were very similar to those reported previously for thyroid peroxidase-catalyzed iodination. 4) High concentrations of I- inhibited the catalatic activity of thyroid peroxidase and lactoperoxidase in a manner similar to that described previously for peroxidase-catalyzed iodination. On the basis of these observations and other findings, we have proposed a scheme which offers a possible explanation for iodide-dependent catalatic activity of thyroid peroxidase and lactoperoxidase. Compound I of the peroxidases is represented as EO, and oxidation of I- by EO is postulated to form enzyme-bound hypoiodite, represented in our scheme as [EOI]-. We suggest that the latter can react with H2O2 in a catalase-like reaction, with evolution of O2. We postulate further that the same form of oxidized iodine is also involved in iodination of tyrosine, oxidation of thioureylene drugs, and oxidation of I-, and that inhibition of catalatic activity by these agents occurs through competition with H2O2 for oxidized iodine.

THYROID AXIS INHIBITION IN XENOPUS LAEVIS: DEVELOPMENT OF AN AMPHIBIAN-BASED SCREENING ASSAY

EPA Science Inventory

In response to the initial EDSTAC recommendations, research was conducted on the development of a Xenopus laevis based tail resorption assay for evaluating thyroid axis disruption. These experiments highlighted key limitations associated with relying on tail resorption as a measu...

[Effect of aceclofenac on thyroid hormone binding and thyroid function].

PubMed

Nadler, K; Buchinger, W; Semlitsch, G; Pongratz, R; Rainer, F

2000-01-01

Influences of non-steroidal anti-inflammatory drugs (NSAID) on concentrations of thyroid hormones are known for a long time. These effects could be explained with interference between NSAIDs and thyroid hormone binding. We investigated the effects of a single dose of aceclofenac on thyroid function and thyroid hormone binding in 18 healthy volunteers. Serum levels of free thyroid hormones (FT3, FT4) and thyrotropin (TSH) were measured with commercial available kids and thyroid hormone binding was estimated with a specially modified horizontal argarose-gel-electrophoresis prior to and 2 hours after receiving a single dose of aceclofenac. We found a significant decrease in T3 binding on TBG and a significant increase of albumin-bound T3. All other investigated thyroid hormone binding parameters, FT3 and FT4, showed no significant changes. We conclude that aceclofenac leads to a significant redistribution of T3 protein binding. These effects seem to be explained by T3 displacement from TBG induced by aceclofenac.

[Thyroid nodule].

PubMed

Clerc, Jérôme

2005-01-31

The thyroid nodule is a frequent, most often benign, chronic, multifocal and slowly progressive disease. The first line strategy is to diagnose cancerous nodules (<5%) and relies upon fine needle aspiration (FNA), a specialised technique which in trained hands has a false negative rate of below 5%. The interest to explore small thyroid nodules is controversial since the prognosis of thyroid cancer is excellent for lesions measuring less than 20 mm. Though imaging accuracy is quite limited in assessing the diagnosis of thyroid cancer, both ultrasounds (US) and thyroid scan are helpful to enhance nodular identification (>30%), to sort the nodules relevant for cytological sampling and to optimize the follow-up, the major source of health costs. Suspicious and non contributive FNAs must have a control FNA within 6 months. Nodules with a non suspicious FNA (>85%) require long term follow-up. This follow-up is mainly morphological. New or evolutive nodules, as assessed by palpation or US, will require iterative FNAs or should be considered for surgery. In patients with hyperfunctioning nodules on the scan (10 to 20%), a yearly evaluation of the TSH level is sufficient. These nodules account either for autonomously functioning ones, which slowly develop towards thyrotoxicosis, or for hyperplastic nodules frequently disclosing a lymphocytic thyroiditis. Morbidity due to thyroid autonomy is still underestimated especially in aging patients with TSH levels < or =0.60 mU/L. An algorithmic approach to the diagnostic and follow-up evaluation of thyroid nodule is suggested.

MiR-34a targets GAS1 to promote cell proliferation and inhibit apoptosis in papillary thyroid carcinoma via PI3K/Akt/Bad pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Yanfei; Qin, Huadong; Cui, Yunfu, E-mail: yfma77@126.com

Highlights: •MiR-34a is up- and GAS1 is down-regulated in papillary thyroid carcinoma. •GAS1 is a direct target for miR-34a. •MiR-34a promotes PTC cells proliferation and inhibits apoptosis through PI3K/Akt/Bad pathway. -- Abstract: MicroRNAs (miRNAs) are fundamental regulators of cell proliferation, differentiation, and apoptosis, and are implicated in tumorigenesis of many cancers. MiR-34a is best known as a tumor suppressor through repression of growth factors and oncogenes. Growth arrest specific1 (GAS1) protein is a tumor suppressor that inhibits cancer cell proliferation and induces apoptosis through inhibition of RET receptor tyrosine kinase. Both miR-34a and GAS1 are frequently down-regulated in various tumors.more » However, it has been reported that while GAS1 is down-regulated in papillary thyroid carcinoma (PTC), miR-34a is up-regulated in this specific type of cancer, although their potential roles in PTC tumorigenesis have not been examined to date. A computational search revealed that miR-34a putatively binds to the 3′-UTR of GAS1 gene. In the present study, we confirmed previous findings that miR-34a is up-regulated and GAS1 down-regulated in PTC tissues. Further studies indicated that GAS1 is directly targeted by miR-34a. Overexpression of miR-34a promoted PTC cell proliferation and colony formation and inhibited apoptosis, whereas knockdown of miR-34a showed the opposite effects. Silencing of GAS1 had similar growth-promoting effects as overexpression of miR-34a. Furthermore, miR-34a overexpression led to activation of PI3K/Akt/Bad signaling pathway in PTC cells, and depletion of Akt reversed the pro-growth, anti-apoptotic effects of miR-34a. Taken together, our results demonstrate that miR-34a regulates GAS1 expression to promote proliferation and suppress apoptosis in PTC cells via PI3K/Akt/Bad pathway. MiR-34a functions as an oncogene in PTC.« less

The effect of chronic lymphocytic thyroiditis on patients with thyroid cancer.

PubMed

Zhang, Yi; Ma, Xiao-Peng; Deng, Fu-Sheng; Liu, Zheng-Rong; Wei, Hou-Qing; Wang, Xi-Hong; Chen, Hao

2014-09-01

The purpose of this study was to investigate the association between chronic lymphocytic thyroiditis (CLT) and malignant tumors of the thyroid. A retrospective review of 647 patients who underwent thyroid surgery at the Department of Breast and Thyroid Surgery in Anhui Provincial Hospital, China in 2012 was performed. The clinicopathological characteristics of patients with thyroid malignancies and CLT were collected. CLT was diagnosed by histopathological method. Among 647 patients, 144 patients had thyroid malignancies and 108 patients had been diagnosed with CLT. Moreover, in total, 44 patients had thyroid malignancies coexistent with CLT: forty-one (93.2%) patients had been diagnosed with the papillary thyroid cancer (PTC); two (4.5%) patients suffered from medullary carcinoma; and one (2.3%) patient suffered from lymphoma. The morbidity of thyroid malignancies in patients with CLT was significantly higher than that in patients without CLT (40.7% versus 18.6%; P <0.001). A female preponderance was observed in the patients with CLT compared with those without CLT (P <0.001). There was no statistically significant difference in the tumor size (P = 0.073), multifocality (P = 0.0871), neck lymph node metastasis (P = 0.350), age (P = 0.316), microcarcinoma (P = 0.983) and tumor-node-metastasis (TNM) stage (P = 0.949) between the patients of thyroid malignancies with CLT and without CLT. Female predominance was observed in patients with CLT. CLT may have no effect on the progression of thyroid malignant tumor. Nevertheless, the influences of CLT on the prognosis of the thyroid carcinoma still need to be investigated with a larger sample size.

Nivolumab-induced thyroid dysfunction in patients with lung cancer.

PubMed

Ramos-Levi, Ana M; Rogado, Jacobo; Sanchez-Torres, Jose Miguel; Colomer, Ramón; Marazuela, Mónica

2018-06-14

Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab. Potential risk factors are analyzed, and strategies for IRAE management are proposed. Forty consecutive patients treated with nivolumab for advanced non-small cell lung cancer (NSCLC) were studied, paying particular attention to development of endocrine IRAEs (thyroid, hypophyseal, adrenal, or pancreatic) and clinical outcome. Thyroid function changes were found in 9 patients (22.5%), of which six developed hypothyroidism and three had hyperthyroidism after a median of 3.8 and 2.3 cycles of nivolumab respectively. Only one patient had thyroid-related symptoms. Thyroid autoimmunity was negative in all cases. Hyperthyroid patients showed no uptake in iodine scintigraphy, and their hormone values returned to normal in less than six months. Nivolumab was discontinued for toxicity in one patient. One patient with hyperthyroidism also developed autoimmune diabetes, and one patient with hypothyroidism also had hypogonadism. After a median follow-up of 7.6 months, 25 patients (62.5%) showed response to nivolumab. Univariate and multivariate analyses showed no differences between patients who developed thyroid changes and those who did not. Thyroid changes after treatment with nivolumab are common and warrant active laboratory monitoring. The underlying mechanisms and their relevance deserve further research. Copyright © 2018 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

Risk of Thyroid Cancer in Euthyroid Asymptomatic Patients with Thyroid Nodules with an Emphasis on Family History of Thyroid Cancer.

PubMed

Hwang, Shin Hye; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Kwak, Jin Young

2016-01-01

To determine the factors associated with thyroid cancer, focusing on first-degree family history and ultrasonography (US) features, in euthyroid asymptomatic patients with thyroid nodules. This retrospective study included 1310 thyroid nodules of 1254 euthyroid asymptomatic patients who underwent US-guided fine-needle aspiration biopsy between November 2012 and August 2013. Nodule size and clinical risk factors-such as patient age, gender, first-degree family history of thyroid cancer, multiplicity on US and serum thyroid stimulating hormone (TSH) levels-were considered together with US features to compare benign and malignant nodules. Multiple logistic regression analysis was performed to assess the risk of thyroid malignancy according to clinical and US characteristics. Although all of the clinical factors and US findings were significantly different between patients with benign and malignant nodules, a solitary lesion on US (p = 0.041-0.043), US features and male gender (p < 0.001) were significant independent risk factors for thyroid malignancy in a multivariate analysis. Patient age, a first-degree family history of thyroid cancer and high normal serum TSH levels did not independently significantly increase the risk of thyroid cancer. However, multicollinearity existed between US assessment and patient age, first-degree family history of thyroid cancer and serum TSH values. Ultrasonography findings should be the primary criterion used to decide the management of euthyroid asymptomatic patients with thyroid nodules. The concept of first-degree family history as a risk factor for thyroid malignancy should be further studied in asymptomatic patients.

Thyroid nodules.

PubMed

Knox, Mark A

2013-08-01

Thyroid nodules are a common finding in the general population. They may present with symptoms of pressure in the neck or may be discovered during physical examination. Although the risk of cancer is small, it is the main reason for workup of these lesions. Measurement of thyroid-stimulating hormone can identify conditions that may cause hyperfunctioning of the thyroid. For all other conditions, ultrasonography and fine-needle aspiration are central to the diagnosis. Lesions larger than 1 cm should be biopsied. Lesions with features suggestive of malignancy and those in patients with risk factors for thyroid cancer should be biopsied, regardless of size. Smaller lesions and those with benign histology can be followed and reevaluated if they grow. The evaluation of thyroid nodules in euthyroid and hypothyroid pregnant women is the same as in other adults. Thyroid nodules are uncommon in children, but the malignancy rate is much higher than in adults. Fine-needle aspiration is less accurate in children, so more aggressive surgical excision may be preferable.

Likelihood ratio-based differentiation of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in patients with sonographically evident diffuse hashimoto thyroiditis: preliminary study.

PubMed

Wang, Liang; Xia, Yu; Jiang, Yu-Xin; Dai, Qing; Li, Xiao-Yi

2012-11-01

To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for

Breaking Tolerance to Thyroid Antigens: Changing Concepts in Thyroid Autoimmunity

PubMed Central

Rapoport, Basil

2014-01-01

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

Thyroid Ultrasound Pitfalls: Esophageal Fibrovascular Polyp Mimicking Thyroid Nodule

PubMed Central

Brigante, G.; Madeo, B.

2016-01-01

Background. Ultrasound (US) is the most accurate tool in the diagnosis of thyroid nodules if performed by expert physician. Misdiagnosis due to extrathyroidal lesions mimicking thyroid nodules is reported in literature. We describe the first case of an esophageal fibrovascular polyp misdiagnosed as a thyroid nodule on US examination. Patient Findings. A 54-year-old woman presented to emergency department for headache and underwent carotid Doppler extended to neck ultrasound with incidental finding of a nodule in the posterior side of the left thyroid lobe. A following thyroid US performed by an endocrinologist allowed the characterization of the lesion as an esophageal pathology, considering the extrathyroidal position, the typical peripheral hyperechoic spots and hypoechoic rim, the connection to the esophagus, and the swallowing connected movement. The patient was addressed to further investigations and finally to anterior pharyngotomy with histological diagnosis of esophageal fibrovascular polyp. Summary. Differential diagnosis between thyroid nodules and other neck lesions is important to prevent an unnecessary fine needle aspiration biopsy and to treat the extrathyroidal pathology. In this case, an US performed by an expert endocrinologist allowed detecting an esophageal fibrovascular polyp requiring surgical removal. In conclusion, the possibility of an esophageal pathology, and even fibrovascular polyp, should be considered during US thyroid examination. PMID:27022492

Risk of thyroid cancer in patients with thyroiditis: a population-based cohort study.

PubMed

Liu, Chien-Liang; Cheng, Shih-Ping; Lin, Hui-Wen; Lai, Yuen-Liang

2014-03-01

The causative relationship between autoimmune thyroiditis and thyroid cancer remains a controversial issue. The aim of this population-based study was to investigate the risk of thyroid cancer in patients with thyroiditis. From the Longitudinal Health Insurance Database 2005 (LHID2005) of Taiwan, we identified adult patients newly diagnosed with thyroiditis between 2004 and 2009 (n = 1,654). The comparison cohort (n = 8,270) included five randomly selected age- and sex-matched controls for each patient in the study cohort. All patients were followed up from the date of cohort entry until they developed thyroid cancer or to the end of 2010. Multivariate Cox regression was used to assess the risk of developing thyroid cancer. A total of 1,000 bootstrap replicates were created for internal validation. A total of 35 patients developed thyroid cancer during the study period, of whom 24 were from the thyroiditis cohort and 11 were from the comparison cohort (incidence 353 and 22 per 100,000 person-years, respectively). After adjusting for potential confounding factors, the hazard ratio (HR) for thyroid cancer in patients with thyroiditis was 13.24 (95 % CI 6.40-27.39). Excluding cancers occurring within 1 year of follow-up, the HR remained significantly increased (6.64; 95 % CI 2.35-18.75). Hypothyroidism was not an independent factor associated with the occurrence of thyroid cancer. We found an increased risk for the development of thyroid cancer after a diagnosis of thyroiditis, independent of comorbidities.

RNA interference targeting CD147 inhibits the proliferation, invasiveness, and metastatic activity of thyroid carcinoma cells by down-regulating glycolysis

PubMed Central

Huang, Peng; Chang, Shi; Jiang, Xiaolin; Su, Juan; Dong, Chao; Liu, Xu; Yuan, Zhengtai; Zhang, Zhipeng; Liao, Huijun

2015-01-01

A high rate of glycolytic flux, even in the presence of oxygen, is a key metabolic hallmark of cancer cells. Lactate, the end product of glycolysis, decreases the extracellular pH and contributes to the proliferation, invasiveness and metastasis of tumor cells. CD147 play a crucial role in tumorigenicity, invasion and metastasis; and CD147 also interacts strongly and specifically with monocarboxylate transporter1 (MCT1) that mediates the transport of lactate. The objective of this study was to determine whether CD147 is involved, via its association with MCT1 to transport lactate, in glycolysis, contributing to the progression of thyroid carcinoma. The expression levels of CD147 in surgical specimens of normal thyroid, nodular goiter (NG), well-differentiated thyroid carcinoma (WDTC), and undifferentiated thyroid carcinoma (UDTC) were determined using immunohistochemical techniques. The effects of CD147 silencing on cell proliferation, invasiveness, metastasis, co-localization with MCT1, glycolysis rate and extracellular pH of thyroid cancer cells (WRO and FRO cell lines) were measured after CD147 was knocked-down using siRNA targeting CD147. Immunohistochemical analysis of thyroid carcinoma (TC) tissues revealed significant increases in signal for CD147 compared with normal tissue or NG, while UDTC expressed remarkably higher levels of CD147 compared with WDTC. Furthermore, silencing of CD147 in TC cells clearly abrogated the expression of MCT1 and its co-localization with CD147 and dramatically decreased both the glycolysis rate and extracellular pH. Thus, cell proliferation, invasiveness, and metastasis were all significantly decreased by siRNA. These results demonstrate in vitro that the expression of CD147 correlates with the degree of dedifferentiation of thyroid cancer, and show that CD147 interacts with MCT1 to regulate tumor cell glycolysis, resulting in the progression of thyroid carcinoma. PMID:25755717

Thyroid cancer - medullary carcinoma

MedlinePlus

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

IL-1β a potential factor for discriminating between thyroid carcinoma and atrophic thyroiditis.

PubMed

Kammoun-Krichen, Maha; Bougacha-Elleuch, Noura; Mnif, Mouna; Bougacha, Fadia; Charffedine, Ilhem; Rebuffat, Sandra; Rebai, Ahmed; Glasson, Emilie; Abid, Mohamed; Ayadi, Fatma; Péraldi-Roux, Sylvie; Ayadi, Hammadi

2012-01-01

Interactions between cytokines and others soluble factors (hormones, antibodies...) can play an important role in the development of thyroid pathogenesis. The purpose of the present study was to examine the possible correlation between serum cytokine concentrations, thyroid hormones (FT4 and TSH) and auto-antibodies (Tg and TPO), and their usefulness in discriminating between different thyroid conditions. In this study, we investigated serum from 115 patients affected with a variety of thyroid conditions (44 Graves' disease, 17 Hashimoto's thyroiditis, 11 atrophic thyroiditis, 28 thyroid nodular goitre and 15 papillary thyroid cancer), and 30 controls. Levels of 17 cytokines in serum samples were measured simultaneously using a multiplexed human cytokine assay. Thyroid hormones and auto-antibodies were measured using ELISA. Our study showed that IL-1β serum concentrations allow the discrimination between atrophic thyroiditis and papillary thyroid cancer groups (p = 0.027).

Hyperactive ERK and persistent mTOR signaling characterize vemurafenib resistance in papillary thyroid cancer cells.

PubMed

Hanly, Elyse K; Tuli, Neha Y; Bednarczyk, Robert B; Suriano, Robert; Geliebter, Jan; Moscatello, Augustine L; Darzynkiewicz, Zbigniew; Tiwari, Raj K

2016-02-23

Clinical studies evaluating targeted BRAFV600E inhibitors in advanced thyroid cancer patients are currently underway. Vemurafenib (BRAFV600E inhibitor) monotherapy has shown promising results thus far, although development of resistance is a clinical challenge. The objective of this study was to characterize development of resistance to BRAFV600E inhibition and to identify targets for effective combination therapy. We created a line of BCPAP papillary thyroid cancer cells resistant to vemurafenib by treating with increasing concentrations of the drug. The resistant BCPAP line was characterized and compared to its sensitive counterpart with respect to signaling molecules thought to be directly related to resistance. Expression and phosphorylation of several critical proteins were analyzed by Western blotting and dimerization was evaluated by immunoprecipitation. Resistance to vemurafenib in BCPAP appeared to be mediated by constitutive overexpression of phospho-ERK and by resistance to inhibition of both phospho-mTOR and phospho-S6 ribosomal protein after vemurafenib treatment. Expression of potential alternative signaling molecule, CRAF, was not increased in the resistant line, although formation of CRAF dimers appeared increased. Expression of membrane receptors HER2 and HER3 was greatly amplified in the resistant cancer cells. Papillary thyroid cancer cells were capable of overcoming targeted BRAFV600E inhibition by rewiring of cell signal pathways in response to prolonged vemurafenib therapy. Our study suggests that in vitro culture of cancer cells may be useful in assessing molecular resistance pathways. Potential therapies in advanced thyroid cancer patients may combine vemurafenib with inhibitors of CRAF, HER2/HER3, ERK, and/or mTOR to delay or abort development of resistance.

Assessment of the value of quantitative thyroid scintigraphy for determination of thyroid function in dogs.

PubMed

Shiel, R E; Pinilla, M; McAllister, H; Mooney, C T

2012-05-01

To assess the value of thyroid scintigraphy to determine thyroid status in dogs with hypothyroidism and various non-thyroidal illnesses. Thyroid hormone concentrations were measured and quantitative thyroid scintigraphy performed in 21 dogs with clinical and/or clinicopathological features consistent with hypothyroidism. In 14 dogs with technetium thyroidal uptake values consistent with euthyroidism, further investigations supported non-thyroidal illness. In five dogs with technetium thyroidal uptake values within the hypothyroid range, primary hypothyroidism was confirmed as the only disease in four. The remaining dog had pituitary-dependent hyperadrenocorticism. Two dogs had technetium thyroidal uptake values in the non-diagnostic range. One dog had iodothyronine concentrations indicative of euthyroidism. In the other, a dog receiving glucocorticoid therapy, all iodothyronine concentrations were decreased. Markedly asymmetric technetium thyroidal uptake was present in two dogs. All iodothyronine concentrations were within reference interval but canine thyroid stimulating hormone concentration was elevated in one. Non-thyroidal illness was identified in both cases. In dogs, technetium thyroidal uptake is a useful test to determine thyroid function. However, values may be non-diagnostic, asymmetric uptake can occur and excess glucocorticoids may variably suppress technetium thyroidal uptake and/or thyroid hormone concentrations. Further studies are necessary to evaluate quantitative thyroid scintigraphy as a gold standard method for determining canine thyroid function. © 2012 British Small Animal Veterinary Association.

Insights into Enzyme Catalysis and Thyroid Hormone Regulation of Cerebral Ketimine Reductase/μ-Crystallin Under Physiological Conditions.

PubMed

Hallen, André; Cooper, Arthur J L; Jamie, Joanne F; Karuso, Peter

2015-06-01

Mammalian ketimine reductase is identical to μ-crystallin (CRYM)-a protein that is also an important thyroid hormone binding protein. This dual functionality implies a role for thyroid hormones in ketimine reductase regulation and also a reciprocal role for enzyme catalysis in thyroid hormone bioavailability. In this research we demonstrate potent sub-nanomolar inhibition of enzyme catalysis at neutral pH by the thyroid hormones L-thyroxine and 3,5,3'-triiodothyronine, whereas other thyroid hormone analogues were shown to be far weaker inhibitors. We also investigated (a) enzyme inhibition by the substrate analogues pyrrole-2-carboxylate, 4,5-dibromopyrrole-2-carboxylate and picolinate, and (b) enzyme catalysis at neutral pH of the cyclic ketimines S-(2-aminoethyl)-L-cysteine ketimine (owing to the complex nomenclature trivial names are used for the sulfur-containing cyclic ketimines as per the original authors' descriptions) (AECK), Δ(1)-piperideine-2-carboxylate (P2C), Δ(1)-pyrroline-2-carboxylate (Pyr2C) and Δ(2)-thiazoline-2-carboxylate. Kinetic data obtained at neutral pH suggests that ketimine reductase/CRYM plays a major role as a P2C/Pyr2C reductase and that AECK is not a major substrate at this pH. Thus, ketimine reductase is a key enzyme in the pipecolate pathway, which is the main lysine degradation pathway in the brain. In silico docking of various ligands into the active site of the X-ray structure of the enzyme suggests an unusual catalytic mechanism involving an arginine residue as a proton donor. Given the critical importance of thyroid hormones in brain function this research further expands on our knowledge of the connection between amino acid metabolism and regulation of thyroid hormone levels.

Diffuse sclerosing variant of thyroid carcinoma presenting as Hashimoto thyroiditis: a case report.

PubMed

Vukasović, Anamarija; Kuna, Sanja Kusacić; Ostović, Karmen Trutin; Prgomet, Drago; Banek, Tomislav

2012-11-01

The aim of report is to present a case of a rare diffuse sclerosing variant of a papillary thyroid carcinoma. A 15-year old girl referred for ultrasound examination because of painless thyroid swelling lasting 10 days before. An ultrasound of the neck showed diffusely changed thyroid parenchyma, without nodes, looking as lymphocytic thyroiditis Hashimoto at first, but with snow-storm appearance, predominantly in the right lobe. Positive thyroid peroxidase antibodies (TPO-AT) also suggested Hashimoto thyroiditis. Repeated US-FNAB (fine needle-aspiration biopsy) of the right lobe revealed diffuse sclerosing variant of papillary thyroid carcinoma and patient underwent total thyreoidectomy. Patohistologic finding confirmed diffuse sclerosing variant of a papillary thyroid carcinoma in the both thyroid lobes and several metastatic lymph nodes. Two months later patient recived radioablative therapy with 3700 MBq (100 mCi) of 1-131 followed by levothyroxine replacement. At the moment, patient is without evidence of local or distant metastases and next regular control is scheduled in 6 months. In conclusion, a diffuse sclerosing variant is rare form of papillary thyroid carcinoma that echographically looks similar to Hashimoto thyroiditis and sometimes could be easily overlooked.

The MEK1/2 Inhibitor AZD6244 Sensitizes BRAF-Mutant Thyroid Cancer to Vemurafenib.

PubMed

Song, Hao; Zhang, Jinna; Ning, Liang; Zhang, Honglai; Chen, Dong; Jiao, Xuelong; Zhang, Kejun

2018-05-08

highest level at 24-48 h. Combined treatment for 48 h completely inhibited pERK1/2 expression. Combination treatment with vemurafenib and AZD6244 inhibited cell growth and induced apoptosis by causing cell-cycle arrest, with the corresponding changes in the expression of the cell cycle regulators p27Kip1 and cyclin D1. Co-administration of vemurafenib and AZD6244 [i]in vivo[/i] had a significant synergistic antitumor effect in a nude mouse model. CONCLUSIONS Vemurafenib activated pERK1/2 and induced vemurafenib resistance in thyroid cancer cells. Combination treatment with vemurafenib and AZD6244 inhibited ERK signaling and caused cell cycle arrest, resulting in cell growth inhibition. Combination treatment in patients with thyroid cancer harboring the [i]BRAFV600E[/i] mutation may overcome vemurafenib resistance and enhance the therapeutic effect.

Ultrasound sonoelastography in the evaluation of thyroiditis and autoimmune thyroid disease.

PubMed

Ruchała, Marek; Szmyt, Krzysztof; Sławek, Sylwia; Zybek, Ariadna; Szczepanek-Parulska, Ewelina

2014-01-01

Sonoelastography (USE) is a constantly evolving imaging technique used for the noninvasive and objective estimation of tissue stiffness. Several USE methods have been developed, including Quasi-Static or Strain Elastography and Shear Wave Elastography. The utility of USE has been demonstrated in differentiating between malignant and benign thyroid lesions. Recently, USE has been applied in the evaluation of thyroiditis and autoimmune thyroid disease (AITD).Thyroid inflammatory illnesses constitute a diverse group of diseases and may manifest various symptoms. These conditions may share some parallel clinical, biochemical, and ultrasonographic features, which can lead to diagnostic difficulties. USE may be an additional tool, supporting other methods in the diagnosis and treatment monitoring of thyroid diseases, other than thyroid nodular disease.The aim of this article was to analyse and summarise the available literature on the applicability of different elastographic techniques in the diagnosis, differentiation and monitoring of various types of thyroiditis and AITD. Advantages and limitations of this technique are also discussed.

Small-molecule MAPK inhibitors restore radioiodine incorporation in mouse thyroid cancers with conditional BRAF activation

PubMed Central

Chakravarty, Debyani; Santos, Elmer; Ryder, Mabel; Knauf, Jeffrey A.; Liao, Xiao-Hui; West, Brian L.; Bollag, Gideon; Kolesnick, Richard; Thin, Tin Htwe; Rosen, Neal; Zanzonico, Pat; Larson, Steven M.; Refetoff, Samuel; Ghossein, Ronald; Fagin, James A.

2011-01-01

Advanced human thyroid cancers, particularly those that are refractory to treatment with radioiodine (RAI), have a high prevalence of BRAF (v-raf murine sarcoma viral oncogene homolog B1) mutations. However, the degree to which these cancers are dependent on BRAF expression is still unclear. To address this question, we generated mice expressing one of the most commonly detected BRAF mutations in human papillary thyroid carcinomas (BRAFV600E) in thyroid follicular cells in a doxycycline-inducible (dox-inducible) manner. Upon dox induction of BRAFV600E, the mice developed highly penetrant and poorly differentiated thyroid tumors. Discontinuation of dox extinguished BRAFV600E expression and reestablished thyroid follicular architecture and normal thyroid histology. Switching on BRAFV600E rapidly induced hypothyroidism and virtually abolished thyroid-specific gene expression and RAI incorporation, all of which were restored to near basal levels upon discontinuation of dox. Treatment of mice with these cancers with small molecule inhibitors of either MEK or mutant BRAF reduced their proliferative index and partially restored thyroid-specific gene expression. Strikingly, treatment with the MAPK pathway inhibitors rendered the tumor cells susceptible to a therapeutic dose of RAI. Our data show that thyroid tumors carrying BRAFV600E mutations are exquisitely dependent on the oncoprotein for viability and that genetic or pharmacological inhibition of its expression or activity is associated with tumor regression and restoration of RAI uptake in vivo in mice. These findings have potentially significant clinical ramifications. PMID:22105174

Coexistence of papillary thyroid cancer and Hashimoto thyroiditis in children: report of 3 cases.

PubMed

Koibuchi, Harumi; Omoto, Kiyoka; Fukushima, Noriyoshi; Toyotsuji, Tomonori; Taniguchi, Nobuyuki; Kawano, Mikihiko

2014-07-01

This report documents 3 pediatric papillary thyroid carcinoma cases with associated Hashimoto thyroiditis. In all 3 cases, hypoechoic nodules accompanied by multiple echogenic spots were noted on sonography of the thyroid. Hashimoto thyroiditis was suspected on the basis of positive thyroid autoantibody test results and pathologic examinations of thyroidectomy specimens, which revealed chronic thyroiditis with lymphocytic infiltration as the background of papillary thyroid carcinoma development. The potential for papillary carcinoma development warrants close follow-up, and meticulous sonographic examinations must be performed in children with Hashimoto thyroiditis. © 2014 by the American Institute of Ultrasound in Medicine.

Co-Existence of Thyroid Nodule and Thyroid Cancer in Children and Adolescents with Hashimoto Thyroiditis: A Single-Center Study.

PubMed

Keskin, Meliksah; Savas-Erdeve, Senay; Aycan, Zehra

2016-01-01

Currently, there is an inadequate number of studies on nodule and malignancy development in children and adolescents with Hashimoto thyroiditis (HT). Patients who were diagnosed with HT between 2004 and 2013 were included in the study. The HT diagnosis was made with a heterogeneous appearance on thyroid ultrasonography and the elevation of antithyroid peroxidase and/or anti-thyroglobulin antibodies. Fine-needle aspiration biopsy (FNAB) was performed in cases with a nodule size >1 cm or who had ultrasonography findings indicating malignancy. A total of 39 (13%) thyroid nodules were detected in 300 patients with a diagnosis of HT. Papillary thyroid carcinoma (PTC) was diagnosed in 2 of the 12 cases in whom FNAB was performed. The thyroid nodule was detected at the same time as HT in the 2 cases with malignancy. The PTC diagnosis was made 2 years after the HT diagnosis in the first case and 3 years later in the second case. The largest diameter of the thyroid nodule was 5 mm in both cases. The thyroid nodule rate on an HT background was found to be 13%, and the thyroid malignancy rate was 0.67% in our study. © 2016 S. Karger AG, Basel.

Thyroid C-Cell Biology and Oncogenic Transformation

PubMed Central

Cote, Gilbert J.; Grubbs, Elizabeth G.; Hofmann, Marie-Claude

2017-01-01

The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that Multiple Endocrine Neoplasia, type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma. Thyroid C-cells are known to express RET at high levels relative to most cell types, therefore aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations has uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation will help in the development of novel molecular targeted therapies. PMID:26494382

TSH Compensates Thyroid-Specific IGF-I Receptor Knockout and Causes Papillary Thyroid Hyperplasia

PubMed Central

Müller, Kathrin; Führer, Dagmar; Mittag, Jens; Klöting, Nora; Blüher, Matthias; Weiss, Roy E.; Many, Marie-Christine; Schmid, Kurt Werner

2011-01-01

Although TSH stimulates all aspects of thyroid physiology IGF-I signaling through a tyrosine kinase-containing transmembrane receptor exhibits a permissive impact on TSH action. To better understand the importance of the IGF-I receptor in the thyroid in vivo, we inactivated the Igf1r with a Tg promoter-driven Cre-lox system in mice. We studied male and female mice with thyroidal wild-type, Igf1r+/−, and Igf1r−/− genotypes. Targeted Igf1r inactivation did transiently reduce thyroid hormone levels and significantly increased TSH levels in both heterozygous and homozygous mice without affecting thyroid weight. Histological analysis of thyroid tissue with Igf1r inactivation revealed hyperplasia and heterogeneous follicle structure. From 4 months of age, we detected papillary thyroid architecture in heterozygous and homozygous mice. We also noted increased body weight of male mice with a homozygous thyroidal null mutation in the Igf1r locus, compared with wild-type mice, respectively. A decrease of mRNA and protein for thyroid peroxidase and increased mRNA and protein for IGF-II receptor but no significant mRNA changes for the insulin receptor, the TSH receptor, and the sodium-iodide-symporter in both Igf1r+/− and Igf1r−/− mice were detected. Our results suggest that the strong increase of TSH benefits papillary thyroid hyperplasia and completely compensates the loss of IGF-I receptor signaling at the level of thyroid hormones without significant increase in thyroid weight. This could indicate that the IGF-I receptor signaling is less essential for thyroid hormone synthesis but maintains homeostasis and normal thyroid morphogenesis. PMID:21980075

Development of a thyroperoxidase inhibition assay for high ...

EPA Pesticide Factsheets

High-throughput screening (HTPS) assays to detect inhibitors of thyroperoxidase (TPO), the enzymatic catalyst for thyroid hormone (TH) synthesis, are not currently available. Herein we describe the development of a HTPS TPO inhibition assay. Rat thyroid microsomes and a fluorescent peroxidase substrate, Amplex UltraRed (AUR, LifeTechnologies), were employed in an endpoint assay for comparison to the existing kinetic guaiacol (GUA) oxidation assay. Following optimization of assay metrics including Z’, dynamic range, and activity using methimazole (MMI), the assay was tested with a 21-chemical training set. The potency of MMI-induced TPO inhibition was greater with AUR compared to GUA. The dynamic range and Z’ score with MMI were as follows: 127-fold and 0.62 for the GUA assay, 18-fold and 0.86 for the 96-well AUR assay, and 11.5-fold and 0.93 for the 384-well AUR assay. The 384-well AUR assay drastically reduced animal use, requiring one-tenth of the rat thyroid microsomal protein needed for the GUA 96-well format assay. Fourteen chemicals inhibited TPO, with a relative potency ranking of MMI > ethylene thiourea > 6-propylthiouracil > 2,2’,4,4’-tetrahydroxy-benzophenone > 2-mercaptobenzothiazole > 3-amino-1,2,4-triazole > genistein > 4-propoxyphenol > sulfamethazine > daidzein > 4-nonylphenol > triclosan > iopanoic acid > resorcinol. These data demonstrate the capacity of this assay to detect diverse TPO inhibitors. Seven chemicals acted as negati

Thyroid Hypoplasia in Congenital Hypothyroidism Associated with Thyroid Peroxidase Mutations.

PubMed

Stoupa, Athanasia; Chaabane, Rim; Guériouz, Manelle; Raynaud-Ravni, Catherine; Nitschke, Patrick; Bole-Feyset, Christine; Mnif, Mouna; Ammar Keskes, Leila; Hachicha, Mongia; Belguith, Neila; Polak, Michel; Carré, Aurore

2018-05-23

Primary congenital hypothyroidism (CH) affects about 1:3000 newborns worldwide and is mainly caused by defects in thyroid gland development (thyroid dysgenesis, TD) or hormone synthesis. A genetic cause is identified in less than 10% of TD patients. Our aim was to identify novel candidate genes in patients with TD using next-generation sequencing tools. We used whole exome sequencing (WES) to study two families, a consanguineous Tunisian family (one child with severe thyroid hypoplasia) and a French family (two newborn siblings, with a thyroid in situ that was not enlarged on ultrasound at diagnosis). Variants in candidate genes were filtered according to type of variation, frequency in public and in-house databases, in silico prediction tools, and inheritance mode. We unexpectedly identified three different variants of the thyroid peroxidase (TPO) gene. A homozygous missense mutation (c.875C>T, p.S292F) was found in the Tunisian patient with severe thyroid hypoplasia. The two French siblings were compound heterozygotes (c.387delC/c.2578G>A, p.N129Kfs*80/p.G860R) for TPO mutations. All three mutations have been previously described in patients with goitrous CH. In our patients treatment was initiated immediately after diagnosis and the effect, if any, of TSH stimulation of these thyroids remains unclear. We report the first cases of thyroid hypoplasia at diagnosis during neonatal period in patients with CH and TPO mutations. These cases highlight the importance of screening for TPO mutations not only in goitrous CH, but also in thyroids of normal or small size, and they broaden the clinical spectrum of described phenotypes.

The relationship between procalcitonin and thyroid autoantibodies in patients with autoimmune thyroiditis.

PubMed

Oncul, Ali; Ates, Ihsan; Arikan, Mehmet Fettah; Yilmaz, Nisbet; Topcuoglu, Canan; Yilmaz, Fatma Meric; Altay, Mustafa

2017-11-01

The aim of this study is to investigate the serum levels of procalcitonin and its association with autoantibodies in patients with euthyroid Hashimoto's thyroiditis. A total of 80 participants were included in the study; 40 of which were newly diagnosed with Hashimoto's thyroiditis, aged over 18, and 40 of which were healthy volunteers. The serum levels of procalcitonin were measured by enzyme-linked immunosorbent assay kit. Thyroid function tests were analyzed in hormone laboratory with Electro-chemiluminescence immunoassay. Hashimoto's thyroiditis patients had higher median procalcitonin levels than those of the control group (34.3 pg/mL vs 27.8 pg/mL respectively; P=.037). Also, male patients had higher median procalcitonin levels as compared to female patients (37 pg/mL vs 27 pg/mL respectively; P=.013). In the Hashimoto's thyroiditis group, procalcitonin level was positively correlated with anti-thyroglobulin and anti-thyroid peroxidase levels (r=.559, P<.001; r=634, P<.001, respectively). The procalcitonin and anti-thyroid peroxidase levels were identified to be an independent predictor in diagnosis of Hashimoto's thyroiditis. The fact that procalcitonin was found to be correlated with thyroid autoantibodies and found to be an independent risk factor for Hashimoto's thyroiditis in the regression analysis in the framework of this study urges us to think that procalcitonin may be associated with the autoimmunity. © 2017 Wiley Periodicals, Inc.

Hashimoto's thyroiditis following Graves' disease.

PubMed

Umar, Husaini; Muallima, Nur; Adam, John M F; Sanusi, Harsinen

2010-01-01

Both Graves' disease and chronic thyroiditis (Hashimoto's thyroiditis) are autoimmune diseases of thyroid gland. Graves' disease is caused by stimulation of TSH receptor located on the thyroid gland by an antibody, which is known as TSH receptor antibody (TRAb). Furthermore, this may lead to hyperplasia and hyperfunction of the thyroid gland. On the contrary, the cause of Hashimoto's thyroiditis is thought due to a TSH stimulation-blocking antibody (TSBAb) which blocks the action of TSH hormone and subsequently brings damage and atrophy to thyroid gland. Approximately 15-20% of patients with Graves' disease had been reported to have spontaneous hypothyroidism resulting from the chronic thyroiditis (Hashimoto's disease). Pathogenesis for chronic thyroiditis following anti-thyroid drug treatment in patients with Graves' disease remains unclear. It has been estimated that chronic thyroiditis or Hashimoto's disease, which occurs following the Graves' disease episode is due to extended immune response in Graves' disease. It includes the immune response to endogenous thyroid antigens, i.e. thyroid peroxidase and thyroglobulin, which may enhance lymphocyte infiltration and finally causes Hashimoto's thyroiditis. We report four cases of chronic thyroiditis (Hashimoto's disease) in patients who have been previously diagnosed with Graves' hyperthyroidism. In three cases, Hashimoto's thyroiditis occurs in 7 to 25 years after the treatment of Grave's disease; while the other case has it only after few months of Grave's disease treatment. The diagnosis of Hashimoto's disease (chronic thyroiditis) was based on clinical manifestation, high TSHs level, positive thyroid peroxidase antibody and thyroglobulin antibody, and supported by positive results of fine needle aspiration biopsy. Moreover, the result of histopathological test has also confirmed the diagnosis in two cases. All cases have been successfully treated by levothyroxine treatment.

A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature.

PubMed

Mirfakhraee, Sasan; Mathews, Dana; Peng, Lan; Woodruff, Stacey; Zigman, Jeffrey M

2013-05-04

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant "hot" nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules.

A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature

PubMed Central

2013-01-01

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant “hot” nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules. PMID:23641736

Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis.

PubMed

González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René

2015-01-01

Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis.

Project Overview: Inhibition of the Sodium-Iodide Symporter by Perchlorate: Evaluation of Lifestage Sensitivity Using PBPK Modeling

EPA Science Inventory

Perchlorate (ClO4-) competitively inhibits uptake of iodide by the sodium-iodide symporter (NIS) in laboratory animals and humans. NIS is found in many tissues, but is primarily responsible for sequestering iodide into the thyroid, enabling biosynthesis of thyroid hormones. The N...

Benign Thyroid Conditions Associated with Increased Risk of Thyroid Cancer Later in Life

Cancer.gov

In a new study from the National Cancer Institute and Aarhus University Hospital in Denmark, researchers report an association between diagnosis of hyperthyroidism and thyroiditis (inflammation of the thyroid gland), two benign thyroid conditions, and increased risk of differentiated thyroid cancer.

Thyroid Cancer—Patient Version

Cancer.gov

Thyroid cancer can be of four main types. Anaplastic thyroid cancer is hard to cure with current treatments, whereas papillary (the most common), follicular, and medullary thyroid cancer can usually be cured. Start here to find information on thyroid cancer treatment, screening, research, and statistics.

Hyperfunction thyroid nodules: their risk for becoming or being associated with thyroid cancers.

PubMed

Lee, Eun Sun; Kim, Ji-Hoon; Na, Dong Gyu; Paeng, Jin Chul; Min, Hye Sook; Choi, Seung Hong; Sohn, Chul Ho; Chang, Ki-Hyun

2013-01-01

To retrospectively evaluate the risk of thyroid cancer in patients with hyperfunctioning thyroid nodules through ultrasonographic-pathologic analysis. Institutional review board approval was obtained and informed consent was waived. From 2003 to 2007, 107 patients consecutively presented with hot spots on thyroid scans and low serum thyroid-stimulating hormone levels. Among them, 32 patients who had undergone thyroid ultrasonography were analyzed in this study. Thyroid nodules depicted on ultrasonography were classified based on size and categorized as benign, indeterminate, or suspicious malignant nodules according to ultrasonographic findings. The thyroid nodules were determined as either hyperfunctioning or coexisting nodules and were then correlated with pathologic results. In 32 patients, 42 hyperfunctioning nodules (mean number per patient, 1.31; range, 1-6) were observed on thyroid scans and 68 coexisting nodules (mean, 2.13; range, 0-7) were observed on ultrasonography. Twenty-five patients (78.1%) had at least one hyperfunctioning (n = 17, 53.1%) or coexisting (n = 16, 50.0%) nodule that showed a suspicious malignant feature larger than 5 mm (n = 8, 25.0%), or an indeterminate feature 1 cm or greater (n = 20, 62.5%) in diameter, which could have been indicated by using fine needle aspiration (FNA). Seven patients were proven to have 11 thyroid cancers in 3 hyperfunctioning and 8 coexisting nodules. All of these had at least one thyroid cancer, which could have been indicated by using FNA. The estimated minimal risk of thyroid cancer was 6.5% (7/107). Patients with hyperfunctioning nodules may not be safe from thyroid cancer because hyperfunctioning nodules can coexist with thyroid cancer nodules. To screen out these cancers, ultrasonography should be performed.

Hashimoto thyroiditis, anti-thyroid antibodies and systemic lupus erythematosus.

PubMed

Posselt, Rayana T; Coelho, Vinícius N; Skare, Thelma L

2018-01-01

To study the prevalence of Hashimoto thyroiditis (HT), anti-thyroid autoantibodies (anti-thyroglobulin or TgAb and thyroperoxidase or TPOAb) in systemic lupus erythematosus (SLE) patients. To analyze if associated HT, TgAb and/or TPOAb influence clinical or serological profiles, disease activity and/or its cumulative damage. Three hundred and one SLE patients and 141 controls were studied for thyroid stimulating hormone, thyroxin, TgAb and TPOAb by chemiluminescence and immunometric assays. Patients' charts were reviewed for serological and clinical profiles. Activity was measured by SLE Disease Activity Index and cumulative damage by Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index for SLE. SLE patients were divided into: (i) with HT; (ii) with anti-thyroid antibodies but without HT; and (iii) without HT and without anti-thyroid antibodies, and were then compared. Furthermore, SLE patients were compared according to the number of positive anti-thyroid antibodies. Hashimoto thyroiditis prevalence in SLE was 12.6% and 5.6% in controls (P = 0.02; odds ratio = 2.4; 95% CI = 1.09-5.2). Lupus patients with HT had less malar rash (P = 0.02) and more anti-Sm (P = 0.04). Anti-Sm was more common in those with two anti-thyroid antibodies than in those with one or negative. The presence of HT or the number of positive autoantibodies did not associate either with disease activity (P = 0.95) or with cumulative damage (P = 0.98). There is a two-fold increased risk of HT in SLE patients. Anti-Sm antibodies favor this association and also double antibody positivity. Disease activity and cumulative damage are not related to HT or with autoantibodies. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat.

PubMed

Sultanian, R; Deng, Y; Kaufman, S

2001-05-15

The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min(-1)) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min(-1)) increase in microvascular pressure from 11.3 +/- 0.7 to 14.9 +/- 0.5 mmHg and in post-capillary resistance from 7.2 +/- 0.6 to 10.1 +/- 1.1 mmHg ml(-1). ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min(-1)) caused a sustained increase in intrasplenic fluid efflux from 0.1 +/- 0.1 to 0.3 +/- 0.1 ml min(-1), and in capillary filtration coefficient (Kf) from 1.2 +/- 0.5 to 2.4 +/- 0.6 ml mmHg-1 min-1 (100 g tissue)-1. Mechanical elevation of splenic intravascular pressure (from 11.3 +/- 0.7 to 22.4 +/- 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 +/- 0.3 to 1.4 +/- 0.3 ml min(-1)). The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min(-1)) did not alter splenic intravascular pressure or pre-/post-capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min-1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

Thyroid hormone and obesity.

PubMed

Pearce, Elizabeth N

2012-10-01

To review several of the most recent and most important clinical studies regarding the effects of thyroid treatments on weight change, associations between thyroid status and weight, and the effects of obesity and weight change on thyroid function. Weight decreases following treatment for hypothyroidism. However, following levothyroxine treatment for overt hypothyroidism, weight loss appears to be modest and mediated primarily by loss of water weight rather than fat. There is conflicting evidence about the effects of thyroidectomy on weight. In large population studies, even among euthyroid individuals, serum thyroid-stimulating hormone is typically positively associated with body weight and BMI. Both serum thyroid-stimulating hormone and T3 are typically increased in obese compared with lean individuals, an effect likely mediated, at least in part, by leptin. Finally, there is no consistent evidence that thyroid hormone treatment induces weight loss in obese euthyroid individuals, but thyroid hormone analogues may eventually be useful for weight loss. The interrelationships between body weight and thyroid status are complex.

Thyroid hormone receptor inhibits hepatoma cell migration through transcriptional activation of Dickkopf 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chi, Hsiang-Cheng; Liao, Chen-Hsin; Huang, Ya-Hui

Highlights: •T{sub 3} affects DKK4 mRNA and protein expression in HepG2-TR cells. •Regulation of DKK4 by T{sub 3} is at transcriptional level. •DKK4 overexpression suppresses hepatoma cell metastasis. -- Abstract: Triiodothyronine (T{sub 3}) is a potent form of thyroid hormone mediates several physiological processes including cellular growth, development, and differentiation via binding to the nuclear thyroid hormone receptor (TR). Recent studies have demonstrated critical roles of T{sub 3}/TR in tumor progression. Moreover, long-term hypothyroidism appears to be associated with the incidence of human hepatocellular carcinoma (HCC), independent of other major HCC risk factors. Dickkopf (DKK) 4, a secreted protein thatmore » antagonizes the canonical Wnt signaling pathway, is induced by T{sub 3} at both mRNA and protein levels in HCC cell lines. However, the mechanism underlying T{sub 3}-mediated regulation of DKK4 remains unknown. In the present study, the 5′ promoter region of DKK4 was serially deleted, and the reporter assay performed to localize the T{sub 3} response element (TRE). Consequently, we identified an atypical direct repeat TRE between nucleotides −1645 and −1629 conferring T{sub 3} responsiveness to the DKK4 gene. This region was further validated using chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA). Stable DKK4 overexpression in SK-Hep-1 cells suppressed cell invasion and metastatic potential, both in vivo andin vitro, via reduction of matrix metalloproteinase-2 (MMP-2) expression. Our findings collectively suggest that DKK4 upregulated by T{sub 3}/TR antagonizes the Wnt signal pathway to suppress tumor cell progression, thus providing new insights into the molecular mechanism underlying thyroid hormone activity in HCC.« less

Expression of stanniocalcin 1 in thyroid side population cells and thyroid cancer cells.

PubMed

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S; Hewitt, Stephen M; Ward, Jerrold M; Kimura, Shioko

2015-04-01

Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma-derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer.

Thyroid Dysfunction and Autoimmune Thyroid Diseases Among Atomic Bomb Survivors Exposed in Childhood.

PubMed

Imaizumi, Misa; Ohishi, Waka; Nakashima, Eiji; Sera, Nobuko; Neriishi, Kazuo; Yamada, Michiko; Tatsukawa, Yoshimi; Takahashi, Ikuno; Fujiwara, Saeko; Sugino, Keizo; Ando, Takao; Usa, Toshiro; Kawakami, Atsushi; Akahoshi, Masazumi; Hida, Ayumi

2017-07-01

The risk of thyroid cancer increases and persists for decades among individuals exposed to ionizing radiation in childhood, although the long-term effects of childhood exposure to medium to low doses of radiation on thyroid dysfunction and autoimmune thyroid diseases have remained unclear. To evaluate radiation dose responses for the prevalence of thyroid dysfunction and autoimmune thyroid disease among atomic bomb survivors exposed in childhood. Hiroshima and Nagasaki atomic bomb survivors who were younger than 10 years old at exposure underwent thyroid examinations at the Radiation Effects Research Foundation between 2007 and 2011, which was 62 to 66 years after the bombing. Data from 2668 participants (mean age, 68.2 years; 1455 women) with known atomic bomb thyroid radiation doses (mean dose, 0.182 Gy; dose range, 0 to 4.040 Gy) were analyzed. Dose-response relationships between atomic bomb radiation dose and the prevalence of hypothyroidism, hyperthyroidism (Graves' disease), and positive for antithyroid antibodies. Prevalences were determined for hypothyroidism (129 cases, 7.8%), hyperthyroidism (32 cases of Graves' disease, 1.2%), and positive for antithyroid antibodies (573 cases, 21.5%). None of these was associated with thyroid radiation dose. Neither thyroid antibody-positive nor -negative hypothyroidism was associated with thyroid radiation dose. Additional analyses using alternative definitions of hypothyroidism and hyperthyroidism found that radiation dose responses were not significant. Radiation effects on thyroid dysfunction and autoimmune thyroid diseases were not observed among atomic bomb survivors exposed in childhood, at 62 to 66 years earlier. The cross-sectional design and survival bias were limitations of this study. Copyright © 2017 Endocrine Society

Sarcoma of the thyroid region mimicking Riedel's thyroiditis

PubMed Central

Torres-Montaner, A; Beltran, M; d Romero; Oliva, H

2001-01-01

Because sarcomas of the anterior lower neck region occur so infrequently, they are not usually considered in the differential diagnosis of Riedel's thyroiditis. Riedel's thyroiditis itself may be confused on clinical grounds alone with malignant neoplasms because of its invasive features. Sarcomatoid carcinoma is the main entity to be discarded in this regard. This is accomplished through histological examination by the finding of carcinomatous areas and/or reactivity with epithelial markers. These features also set apart sarcomatoid carcinoma from true sarcomas. This report concerns a patient with a sarcoma of the anterior lower neck region which was initially suspected to be Riedel's thyroiditis or sarcomatoid carcinoma on clinical and radiological grounds. A peroperative biopsy was interpreted by two independent pathologists as consistent with Riedel's thyroiditis. The subsequent clinical course and postmortem examination demonstrated a high grade sarcoma with metastasis to both lungs and the pleura, and invasion of adjacent neck structures. Nevertheless, some areas of the postmortem material showed a microscopic pattern similar to mediastinal fibrosis, raising the possibility of the malignant transformation of a fibrosclerotic lesion. Key Words: Riedel's thyroiditis • sarcomatoid carcinoma • fibrous histiocytoma • differential diagnosis PMID:11429435

GNAq mutations are not identified in papillary thyroid carcinomas and hyperfunctioning thyroid nodules.

PubMed

Cassol, Clarissa A; Guo, Miao; Ezzat, Shereen; Asa, Sylvia L

2010-12-01

Activating mutations of GNAq protein in a hotspot at codon 209 have been recently described in uveal melanomas. Since these neoplasms share with thyroid carcinomas a high frequency of MAP kinase pathway-activating mutations, we hypothesized whether GNAq mutations could also play a role in the development of thyroid carcinomas. Additionally, activating mutations of another subtype of G protein (GNAS1) are frequently found in hyperfunctioning thyroid adenomas, making it plausible that GNAq-activating mutations could also be found in some of these nodules. To investigate thyroid papillary carcinomas and thyroid hyperfunctioning nodules for GNAq mutations in exon 5, codon 209, a total of 32 RET/PTC, BRAF, and RAS negative thyroid papillary carcinomas and 13 hyperfunctioning thyroid nodules were evaluated. No mutations were identified. Although plausible, GNAq mutations seem not to play an important role in the development of thyroid follicular neoplasms, either benign hyperfunctioning nodules or malignant papillary carcinomas. Our results are in accordance with the literature, in which no GNAq hotspot mutations were found in thyroid papillary carcinomas, as well as in an extensive panel of other tumors. The molecular basis for MAP-kinase pathway activation in RET-PTC/BRAF/RAS negative thyroid carcinomas remains to be determined.

[Thyroid and pregnancy].

PubMed

Iwen, K A; Lehnert, H

2018-05-17

During pregnancy thyroid hormones have profound effects on embryonal/fetal development and maternal health. Therefore, thyroid gland disorders should be immediately diagnosed and adequately treated. Pregnancy-specific physiological alterations during pregnancy cause changes in the reference interval for thyroid-stimulating hormone levels and trimester-specific thresholds must be taken into account. This article summarizes the most important diagnostic and therapeutic aspects before, during and after pregnancy. With reference to the period prior to pregnancy, the article discusses iodide supplementation, preconceptional examination of thyroid gland metabolism and the importance of thyroid gland functional disorders for fertility and fulfilling the desire to have children. With a view to the period during pregnancy, the effect of hypothyroxinemia, hypothyroidism, and hyperthyroidism as well as the effects of their treatment on the development of the child are explained. Finally, a description is given of what must be paid attention to in the breast-feeding period and in postpartum thyroiditis.

Endocrinology Update: Thyroid Disorders.

PubMed

Kelley, Scott

2016-12-01

Thyroid disease affects nearly every organ system in the body. Hypothyroidism is a state of thyroid hormone insufficiency that results in decreased metabolism and secondary effects including fatigue and weight gain. Primary hypothyroidism typically is a result of autoimmune thyroiditis or iodine deficiency and is assessed by measurement of the thyroid-stimulating hormone (TSH) level. This level usually is elevated in patients with hypothyroidism and low in patients with hyperthyroidism. Levothyroxine is the treatment of choice for hypothyroidism. Hyperthyroidism is a state of thyroid hormone excess, which increases the metabolic rate and causes symptoms including anxiety and tremor. Graves disease is the most common etiology in developed countries. Patients with hyperthyroidism are evaluated with measurement of TSH and free thyroxine levels. Management options include antithyroid drugs, radioactive iodine, and surgery. Thyroid nodules are detected commonly in family medicine, and may or may not be associated with thyroid hormone abnormalities. Patients with thyroid nodules should be evaluated with TSH level measurement and thyroid ultrasonography to guide further testing. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Hyperfunction Thyroid Nodules: Their Risk for Becoming or Being Associated with Thyroid Cancers

PubMed Central

Lee, Eun Sun; Na, Dong Gyu; Paeng, Jin Chul; Min, Hye Sook; Choi, Seung Hong; Sohn, Chul Ho; Chang, Ki-Hyun

2013-01-01

Objective To retrospectively evaluate the risk of thyroid cancer in patients with hyperfunctioning thyroid nodules through ultrasonographic-pathologic analysis. Materials and Methods Institutional review board approval was obtained and informed consent was waived. From 2003 to 2007, 107 patients consecutively presented with hot spots on thyroid scans and low serum thyroid-stimulating hormone levels. Among them, 32 patients who had undergone thyroid ultrasonography were analyzed in this study. Thyroid nodules depicted on ultrasonography were classified based on size and categorized as benign, indeterminate, or suspicious malignant nodules according to ultrasonographic findings. The thyroid nodules were determined as either hyperfunctioning or coexisting nodules and were then correlated with pathologic results. Results In 32 patients, 42 hyperfunctioning nodules (mean number per patient, 1.31; range, 1-6) were observed on thyroid scans and 68 coexisting nodules (mean, 2.13; range, 0-7) were observed on ultrasonography. Twenty-five patients (78.1%) had at least one hyperfunctioning (n = 17, 53.1%) or coexisting (n = 16, 50.0%) nodule that showed a suspicious malignant feature larger than 5 mm (n = 8, 25.0%), or an indeterminate feature 1 cm or greater (n = 20, 62.5%) in diameter, which could have been indicated by using fine needle aspiration (FNA). Seven patients were proven to have 11 thyroid cancers in 3 hyperfunctioning and 8 coexisting nodules. All of these had at least one thyroid cancer, which could have been indicated by using FNA. The estimated minimal risk of thyroid cancer was 6.5% (7/107). Conclusion Patients with hyperfunctioning nodules may not be safe from thyroid cancer because hyperfunctioning nodules can coexist with thyroid cancer nodules. To screen out these cancers, ultrasonography should be performed. PMID:23901323

What is the real significance and management of major thyroid disorders in bipolar patients?

PubMed

Sierra, Pilar; Cámara, Rosa; Tobella, Helena; Livianos, Lorenzo

2014-01-01

Thyroid disfunction affects negatively emotional stability and worsens the clinical course of bipolar affective disorder. The main stabilizer used in this illness, lithium carbonate has numerous effects on the physiology of the thyroid, with the most significant being the inhibition of thyroid hormone release that may occur at therapeutic levels. These dysfunctions have also been reported most frequently in bipolar patients not undergoing treatment with lithium, and was not completely explained by the effects of this drug. Apart from the numerous medical complications and mood disturbances, the cognitive or perceptual system may also be affected. In fact, the presence of thyroid disease increases the rates of obsessive compulsive disorder, phobias, panic disorder, major depressive disorder, cyclothymia, or bipolar disorder. In severe cases of hypothyroidism, the clinical symptoms and signs can be similar to a melancholic depression or dementia. It is therefore important to know well all these possible complications in daily clinical practice. This review will cover the main thyroid dysfunctions present in bipolar patients, whether ot not produced by treatment with lithium carbonate, and will provide a series of recommendations for clinical management. Copyright © 2013 SEP y SEPB. Published by Elsevier España. All rights reserved.

Warthin-Like Papillary Thyroid Carcinoma Associated with Lymphadenopathy and Hashimoto's Thyroiditis

PubMed Central

González-Colunga, Karla Judith; Loya-Solis, Abelardo; Ceceñas-Falcón, Luis Ángel; Barboza-Quintana, Oralia; Rodríguez-Gutiérrez, René

2015-01-01

Defining the histologic variant of thyroid carcinoma is an important clinical implication as their progression, recurrence, aggressiveness, and prognosis differ. Warthin-like variant is one of the rarest histologic variants of papillary thyroid cancer. A 36-year-old female sought consult for assessment of a painless right neck tumor. High-resolution neck ultrasound revealed a right hypoechoic, 1.71 × 1.05 cm thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy report was a Bethesda grade III. Thyroid function tests showed Hashimoto's thyroiditis. The patient underwent right hemithyroidectomy. Microscopically, the tumor was composed of papillae lined by cells with eosinophilic cytoplasm, nuclear chromatin clearing, grooves, and pseudoinclusions and a characteristic lymphoplasmacytic infiltrate of the papillae cores. Extension into the perithyroidal soft tissue and 3 ipsilateral lymph nodes was found to be positive for cancer. Warthin-like variant is an uncommon and relatively unknown variant of papillary thyroid carcinoma that has been usually associated with an excellent prognosis. Interestingly, BRAF mutations have been reported to be present in up to 75% of the patients. It is frequently associated with Hashimoto's thyroiditis and presents unique morphological features that make it recognizable on histologic examination. The cytological diagnosis is difficult to assess due to the overlap in its findings with the classical variant and Hashimoto's thyroiditis. PMID:25821606

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women.

PubMed

Horton, Megan K; Blount, Benjamin C; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

2015-11-01

Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4-0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Co-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

PubMed Central

Horton, Megan K.; Blount, Benjamin C.; Valentin-Blasini, Liza; Wapner, Ronald; Whyatt, Robin; Gennings, Chris; Factor-Litvak, Pam

2015-01-01

Background Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy. Objectives We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (± 2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results Individual analyte concentrations in urine were significantly correlated (Spearman’s r 0.4–0.5, p < 0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. PMID:26408806

A progress report of the Marshall Islands nationwide thyroid study: an international cooperative scientific study.

PubMed

Takahashi, T; Simon, S L; Trott, K R; Fujimori, K; Nakashima, N; Arisawa, K; Schoemaker, M J

1999-04-01

The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer.

Expression of Stanniocalcin 1 in Thyroid Side Population Cells and Thyroid Cancer Cells

PubMed Central

Hayase, Suguru; Sasaki, Yoshihito; Matsubara, Tsutomu; Seo, Daekwan; Miyakoshi, Masaaki; Murata, Tsubasa; Ozaki, Takashi; Kakudo, Kennichi; Kumamoto, Kensuke; Ylaya, Kris; Cheng, Sheue-yann; Thorgeirsson, Snorri S.; Hewitt, Stephen M.; Ward, Jerrold M.

2015-01-01

Background: Mouse thyroid side population (SP) cells consist of a minor population of mouse thyroid cells that may have multipotent thyroid stem cell characteristics. However the nature of thyroid SP cells remains elusive, particularly in relation to thyroid cancer. Stanniocalcin (STC) 1 and 2 are secreted glycoproteins known to regulate serum calcium and phosphate homeostasis. In recent years, the relationship of STC1/2 expression to cancer has been described in various tissues. Method: Microarray analysis was carried out to determine genes up- and down-regulated in thyroid SP cells as compared with non-SP cells. Among genes up-regulated, stanniocalcin 1 (STC1) was chosen for study because of its expression in various thyroid cells by Western blotting and immunohistochemistry. Results: Gene expression analysis revealed that genes known to be highly expressed in cancer cells and/or involved in cancer invasion/metastasis were markedly up-regulated in SP cells from both intact as well as partial thyroidectomized thyroids. Among these genes, expression of STC1 was found in five human thyroid carcinoma–derived cell lines as revealed by analysis of mRNA and protein, and its expression was inversely correlated with the differentiation status of the cells. Immunohistochemical analysis demonstrated higher expression of STC1 in the thyroid tumor cell line and thyroid tumor tissues from humans and mice. Conclusion: These results suggest that SP cells contain a population of cells that express genes also highly expressed in cancer cells including Stc1, which warrants further study on the role of SP cells and/or STC1 expression in thyroid cancer. PMID:25647164

Development of the thyroid gland.

PubMed

Nilsson, Mikael; Fagman, Henrik

2017-06-15

Thyroid hormones are crucial for organismal development and homeostasis. In humans, untreated congenital hypothyroidism due to thyroid agenesis inevitably leads to cretinism, which comprises irreversible brain dysfunction and dwarfism. Elucidating how the thyroid gland - the only source of thyroid hormones in the body - develops is thus key for understanding and treating thyroid dysgenesis, and for generating thyroid cells in vitro that might be used for cell-based therapies. Here, we review the principal mechanisms involved in thyroid organogenesis and functional differentiation, highlighting how the thyroid forerunner evolved from the endostyle in protochordates to the endocrine gland found in vertebrates. New findings on the specification and fate decisions of thyroid progenitors, and the morphogenesis of precursor cells into hormone-producing follicular units, are also discussed. © 2017. Published by The Company of Biologists Ltd.

The thyroid axis in ageing.

PubMed

Leitol, Holger; Behrends, Jens; Brabant, Georg

2002-01-01

The hypothalmo-pituitary thyroid axis, among various endocrine systems, undergoes physiological alterations associated with the ageing process. Directly age-related changes have to be distinguished from indirect modifications which are caused by simultaneous thyroidal or non-thyroidal illness or other physiological or pathophysiological states whose incidence increases with age. In summary, direct changes of the hypothalmo-pituitary-thyroid axis seem to be subtle and suggestive of a decreased hypothalamic stimulation of thyroid function. In parallel, disease-specific alterations such as the development of thyroid autonomy or changes in energy intake or sleep lead to pronounced alterations of thyroid function with age which may dominate the underlying ageing of the hypothalmo-pituitary thyroid axis itself. The following article attempts to delineate some aspects of the interplay of the regulation of thyroid function and the ageing process.

Human a-L-fucosidase-1 attenuates the invasive properties of thyroid cancer.

PubMed

Vecchio, Giancarlo; Parascandolo, Alessia; Allocca, Chiara; Ugolini, Clara; Basolo, Fulvio; Moracci, Marco; Strazzulli, Andrea; Cobucci-Ponzano, Beatrice; Laukkanen, Mikko O; Castellone, Maria Domenica; Tsuchida, Nobuo

2017-04-18

Glycans containing α-L-fucose participate in diverse interactions between cells and extracellular matrix. High glycan expression on cell surface is often associated with neoplastic progression. The lysosomal exoenzyme, α-L-fucosidase-1 (FUCA-1) removes fucose residues from glycans. The FUCA-1 gene is down-regulated in highly aggressive and metastatic human tumors. However, the role of FUCA-1 in tumor progression remains unclear. It is speculated that its inactivation perturbs glycosylation of proteins involved in cell adhesion and promotes cancer. FUCA-1 expression of various thyroid normal and cancer tissues assayed by immunohistochemical (IHC) staining was high in normal thyroids and papillary thyroid carcinomas (PTC), whereas it progressively decreased in poorly differentiated, metastatic and anaplastic thyroid carcinomas (ATC). FUCA-1 mRNA expression from tissue samples and cell lines and protein expression levels and enzyme activity in thyroid cancer cell lines paralleled those of IHC staining. Furthermore, ATC-derived 8505C cells adhesion to human E-selectin and HUVEC cells was inhibited by bovine α-L-fucosidase or Lewis antigens, thus pointing to an essential role of fucose residues in the adhesive phenotype of this cancer cell line. Finally, 8505C cells transfected with a FUCA-1 containing plasmid displayed a less invasive phenotype versus the parental 8505C. These results demonstrate that FUCA-1 is down-regulated in ATC compared to PTC and normal thyroid tissues and cell lines. As shown for other human cancers, the down-regulation of FUCA-1 correlates with increased aggressiveness of the cancer type. This is the first report indicating that the down-regulation of FUCA-1 is related to the increased aggressiveness of thyroid cancer.

Thyroid Function and Obesity

PubMed Central

Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

2012-01-01

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail. PMID:24783015

Thyroid function and obesity.

PubMed

Laurberg, Peter; Knudsen, Nils; Andersen, Stig; Carlé, Allan; Pedersen, Inge Bülow; Karmisholt, Jesper

2012-10-01

Important interaction exists between thyroid function, weight control, and obesity. Several mechanisms seem to be involved, and in studies of groups of people the pattern of thyroid function tests depends on the balance of obesity and underlying thyroid disease in the cohort studied. Obese people with a normal thyroid gland tend to have activation of the hypothalamic-pituitary-thyroid axis with higher serum TSH and thyroid hormones in serum. On the other hand, small differences in thyroid function are associated with up to 5 kg difference in body weight. The weight loss after therapy of overt hypothyroidism is caused by excretion of water bound in tissues (myxoedema). Many patients treated for hyperthyroidism experience a gain of more weight than they lost during the active phase of the disease. The mechanism for this excessive weight gain has not been fully elucidated. New studies on the relation between L-T3 therapy and weight control are discussed. The interaction between weight control and therapy of thyroid disease is important to many patients and it should be studied in more detail.

Thyroid Cancer

MedlinePlus

... body work normally. There are several types of cancer of the thyroid gland. You are at greater ... imaging tests, and a biopsy to diagnose thyroid cancer. Treatment depends on the type of cancer you ...

Autoimmune Thyroid Disorders

PubMed Central

Iddah, M. A.; Macharia, B. N.

2013-01-01

Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice. PMID:23878745

A Case of Painful Hashimoto Thyroiditis that Mimicked Subacute Thyroiditis

PubMed Central

Seo, Hye Mi; Kim, Miyeon; Bae, Jaeseok; Kim, Jo-Heon; Lee, Jeong Won; Lee, Sang Ah; Koh, Gwanpyo

2012-01-01

Hashimoto thyroiditis (HT) is an autoimmune thyroid disorder that usually presents as a diffuse, nontender goiter, whereas subacute thyroiditis (SAT) is an uncommon disease that is characterized by tender thyroid enlargement, transient thyrotoxicosis, and an elevated erythrocyte sedimentation rate (ESR). Very rarely, patients with HT can present with painful, tender goiter or fever, a mimic of SAT. We report a case of painful HT in a 68-year-old woman who presented with pain and tenderness in a chronic goiter. Her ESR was definitely elevated and her thyroid laboratory tests suggested subclinical hypothyroidism of autoimmune origin. 99mTc pertechnetate uptake was markedly decreased. Fine needle aspiration biopsy revealed reactive and polymorphous lymphoid cells and occasional epithelial cells with Hürthle cell changes. Her clinical symptoms showed a dramatic response to glucocorticoid treatment. She became hypothyroid finally and is now on levothyroxine therapy. PMID:22570820

Long noncoding RNA AB074169 inhibits cell proliferation via modulation of KHSRP-mediated p21 expression in papillary thyroid carcinoma.

PubMed

Gou, Qiheng; Gao, Linbo; Nie, Xinwen; Pu, Wenchen; Zhu, Jingqiang; Wang, Yichao; Liu, Xuesha; Tan, Shuangyan; Zhou, Jian-Kang; Gong, Yanqiu; He, Juan; Wu, Ke; Xie, Yuxin; Zhao, Wanjun; Dai, Lunzhi; Liu, Lunxu; Xiang, Rong; Wei, Yu-Quan; Zhang, Lin; Peng, Yong

2018-05-07

Long noncoding RNAs (lncRNAs) are emerging as a novel class of regulators in gene expression associated with tumorigenesis. However, the role of lncRNAs in papillary thyroid carcinoma (PTC) is poorly understood. Here we conducted global lncRNA profiling and identified lncRNA AB074169 (lncAB) as significantly downregulated in PTC. Decreased expression of lncAB in PTC was caused by CpG hypermethylation within its gene promoter. Functional studies showed that lncAB overexpression led to cell cycle arrest and tumor growth inhibition in vitro and in vivo, whereas lncAB knockdown promoted cell proliferation. Mechanistic analyses revealed that lncAB bound KH-type splicing regulatory protein (KHSRP) and also decreased expression of KHSRP, thus increasing CDKN1a (p21) expression and decreasing CDK2 expression to repress cell proliferation. Taken together, these findings demonstrate that lncAB functions as a tumor suppressor during PTC tumorigenesis. Copyright ©2018, American Association for Cancer Research.

Thyroid Problems

MedlinePlus

... treated differently. Common thyroid disorders and problems include: Hypothyroidism Hypothyroidism is a disorder in which your thyroid doesn’ ... normal after you get better. If you have hypothyroidism, however, the levels of T4 in your blood ...

Thyroid disease in pustulosis palmoplantaris.

PubMed

Agner, T; Sindrup, J H; Høier-Madsen, M; Hegedüs, L

1989-10-01

An increased frequency of thyroid autoantibodies has been reported in patients with palmar and plantar pustulosis (PPP). This study was undertaken to determine the frequency and type of thyroid disease in 32 patients with this disease compared with a control group. Thyroid disease was demonstrated in 53% of the patients with PPP as compared to 16% in the matched control group. Fourteen patients with PPP had an enlarged thyroid and in six there were thyroid autoantibodies. There appears to be an increased incidence of goitre and thyroid autoantibodies in PPP with a decrease in the level of the thyroid hormones.

Poorly Differentiated Thyroid Carcinoma.

PubMed

Setia, Namrata; Barletta, Justine A

2014-12-01

Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.

Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination.

PubMed

Köhrle, Josef

2007-06-01

Thyroid hormone metabolism by the three deiodinase selenoproteins -- DIO1, DIO2, and DIO3 -- regulates the local availability of various iodothyronine metabolites and thus mediates their effects on gene expression, thermoregulation, energy metabolism, and many key reactions during the development and maintenance of an adult organism. Circulating serum levels of thyroid hormone and thyroid-stimulating hormone, used as a combined indicator of thyroid hormone status, reflect a composite picture of: thyroid secretion; tissue-specific production of T(3) by DIO1 and DIO2 activity, which both contribute to circulating levels of T(3); and degradation of the prohormone T4, of the thyromimetically active T(3), of the inactive rT(3), of other iodothyronines metabolites with a lower iodine content and of thyroid hormone conjugates. Degradation reactions are catalyzed by either DIO1 or DIO3. Aberrant expression of individual deiodinases in disease, single nucleotide polymorphisms in their genes, and novel regulators of DIO gene expression (such as bile acids) provide a more complex picture of the fine tuning and the adaptation of systemic and local bioavailability of thyroid hormones.

Painless giant cell thyroiditis diagnosed by fine needle aspiration and associated with intense thyroidal uptake of gallium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sanders, L.R.; Moreno, A.J.; Pittman, D.L.

1986-05-01

A 52-year-old woman presented with fever, goiter, and no evidence of pain or tenderness in the thyroid. A diagnosis of silent thyroiditis was made after obtaining evidence of biochemical thyrotoxicosis, intense gallium-67 citrate thyroidal localization, and cytologic thyroiditis. Fine needle aspiration biopsy of the thyroid revealed numerous giant cells in all areas of the thyroid, typical of subacute thyroiditis. This is believed to be the first time painless thyroiditis is reported with the classic cytologic feature of painful subacute thyroiditis.

Thyroid Antibodies

MedlinePlus

... been associated with reproductive difficulties, such as miscarriage, pre-eclampsia , premature delivery, and in-vitro fertilization failure Thyroglobulin antibody TgAb Thyroid cancer ; Hashimoto thyroiditis Whenever a thyroglobulin test is performed to see if the antibody is ...

[Riedel thyroiditis: two cases report].

PubMed

Zhou, Rongjin; Wang, Junguo

2014-10-01

Riedel thyroiditis is a benign disease, which is often self-limited. Examinations, such as CT and histologic diagnosis can distinguish it from malignant neoplasms and hashimoto's thyroiditis. Riedel thyroiditis is an uncommon form of chronic thyroiditis in which the thyroid gland is replaced by fibrous tissue. It can be cured by surgery and medicine.

Development and Characterization of a Differentiated Thyroid Cancer Cell Line Resistant to VEGFR-Targeted Kinase Inhibitors

PubMed Central

Isham, Crescent R.; Netzel, Brian C.; Bossou, Ayoko R.; Milosevic, Dragana; Cradic, Kendall W.; Grebe, Stefan K.

2014-01-01

Background: Vascular endothelial growth factor-targeted kinase inhibitors have emerged as highly promising therapies for radioiodine-refractory metastatic differentiated thyroid cancer. Unfortunately, drug resistance uniformly develops, limiting their therapeutic efficacies and thereby constituting a major clinical problem. Approach and Methods: To study acquired drug resistance and elucidate underlying mechanisms in this setting, BHP2–7 human differentiated thyroid cancer cells were subjected to prolonged continuous in vitro selection with 18 μM pazopanib, a clinically relevant concentration; acquisition of pazopanib resistance was serially assessed, with the resulting resistant cells thereafter subcloned and characterized to assess potential mechanisms of acquired pazopanib resistance. Results: Stable 2- to 4-fold in vitro pazopanib resistance emerged in response to pazopanib selection associated with similar in vitro growth characteristics but with markedly more aggressive in vivo xenograft growth. Selected cells were cross-resistant to sunitinib and to a lesser extent sorafenib but not to MAPK kinase (MEK1/2) inhibition by GSK1120212. Genotyping demonstrated acquisition of a novel activating KRAS codon 13 GGC to GTT (glycine to valine) mutation, consistent with the observed resistance to upstream vascular endothelial growth factor receptor inhibition yet sensitivity to downstream MAPK kinase (MEK1/2) inhibition. Conclusions: Selection of thyroid cancer cells with clinically utilized therapeutics can lead to acquired drug resistance and altered in vivo xenograft behavior that can recapitulate analogous drug resistance observed in patients. This approach has the potential to lead to insights into acquired treatment-related drug resistance in thyroid cancers that can be subjected to subsequent validation in serially collected patient samples and that has the potential to yield preemptive and responsive approaches to dealing with this important clinical problem

Diffuse Thyroid Metastasis From Lung Cancer Mimicking Thyroiditis on 99mTc-Pertechnetate Scintigraphy.

PubMed

Gao, Rui; Gao, Shan; Feng, Jinteng; Wang, Yuanbo; Zhang, Guangjian

2017-09-01

Possible thyroiditis was suspected in a 56-year-old man who initially presented sore throat because laboratory examinations revealed decreased serum thyroid hormone and the Tc-pertechnetate scintigraphy showed no tracer uptake by the thyroid gland. However, subsequent examination demonstrated that the absence of pertechnetate activity in the thyroid was due to complete replacement of thyroid gland by the metastasis from lung adenocarcinoma, which was unknown at the initial presentation.

Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes.

PubMed

Paolino, Donatella; Cosco, Donato; Gaspari, Marco; Celano, Marilena; Wolfram, Joy; Voce, Pasquale; Puxeddu, Efisio; Filetti, Sebastiano; Celia, Christian; Ferrari, Mauro; Russo, Diego; Fresta, Massimo

2014-08-01

Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Decitabine in Treating Patients With Metastatic Papillary Thyroid Cancer or Follicular Thyroid Cancer Unresponsive to Iodine I 131

ClinicalTrials.gov

2014-08-20

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Hashimoto thyroiditis: Part 1, sonographic analysis of the nodular form of Hashimoto thyroiditis.

PubMed

Anderson, Lauren; Middleton, William D; Teefey, Sharlene A; Reading, Carl C; Langer, Jill E; Desser, Terry; Szabunio, Margaret M; Hildebolt, Charles F; Mandel, Susan J; Cronan, John J

2010-07-01

The purpose of this article is to analyze the sonographic appearance of nodular Hashimoto thyroiditis. As part of an ongoing multiinstitutional study, patients who underwent ultrasound examination and fine-needle aspiration of one or more thyroid nodules were analyzed for multiple predetermined sonographic features. Patients completed a questionnaire, including information about thyroid function and thyroid medication. Patients (n = 61) with fine-needle aspiration cytologic results consistent with nodular Hashimoto thyroiditis (n = 64) were included in the study. The mean (+/- SD) diameter of nodular Hashimoto thyroiditis was 15 +/- 7.33 mm. Nodular Hashimoto thyroiditis occurred as a solitary nodule in 36% (23/64) of cases and in the setting of five or more nodules in 23% (15/64) of cases. Fifty-five percent (35/64) of the cases of nodular Hashimoto thyroiditis occurred within a sonographic background of diffuse Hashimoto thyroiditis, and 45% (29/64) of cases occurred within normal thyroid parenchyma. The sonographic appearance was extremely variable. It was most commonly solid (69% [42/61] of cases) and hypoechoic (47% [27/58] of cases). Twenty percent (13/64) of nodules had calcifications (seven with nonspecific bright reflectors, four with macrocalcifications, and three eggshell), and 5% (3/64) of nodules had colloid. Twenty-seven percent (17/64) of nodules had a hypoechoic halo. The margins were well defined in 60% (36/60) and ill defined in 40% (24/60) of nodules. On Doppler analysis, 35% (22/62) of nodules were hypervascular, 42% (26/62) were isovascular or hypovascular, and 23% (14/62) were avascular. The sonographic features and vascularity of nodular Hashimoto thyroiditis were extremely variable.

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer

PubMed Central

Waguespack, Steven G.; Bauer, Andrew J.; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M.; Dinauer, Catherine A.; Hamilton, Jill; Hay, Ian D.; Luster, Markus; Parisi, Marguerite T.; Rachmiel, Marianna; Thompson, Geoffrey B.; Yamashita, Shunichi

2015-01-01

Background: Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. Methods: A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. Results: These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. Conclusions: In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the

Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer.

PubMed

Francis, Gary L; Waguespack, Steven G; Bauer, Andrew J; Angelos, Peter; Benvenga, Salvatore; Cerutti, Janete M; Dinauer, Catherine A; Hamilton, Jill; Hay, Ian D; Luster, Markus; Parisi, Marguerite T; Rachmiel, Marianna; Thompson, Geoffrey B; Yamashita, Shunichi

2015-07-01

Previous guidelines for the management of thyroid nodules and cancers were geared toward adults. Compared with thyroid neoplasms in adults, however, those in the pediatric population exhibit differences in pathophysiology, clinical presentation, and long-term outcomes. Furthermore, therapy that may be recommended for an adult may not be appropriate for a child who is at low risk for death but at higher risk for long-term harm from overly aggressive treatment. For these reasons, unique guidelines for children and adolescents with thyroid tumors are needed. A task force commissioned by the American Thyroid Association (ATA) developed a series of clinically relevant questions pertaining to the management of children with thyroid nodules and differentiated thyroid cancer (DTC). Using an extensive literature search, primarily focused on studies that included subjects ≤18 years of age, the task force identified and reviewed relevant articles through April 2014. Recommendations were made based upon scientific evidence and expert opinion and were graded using a modified schema from the United States Preventive Services Task Force. These inaugural guidelines provide recommendations for the evaluation and management of thyroid nodules in children and adolescents, including the role and interpretation of ultrasound, fine-needle aspiration cytology, and the management of benign nodules. Recommendations for the evaluation, treatment, and follow-up of children and adolescents with DTC are outlined and include preoperative staging, surgical management, postoperative staging, the role of radioactive iodine therapy, and goals for thyrotropin suppression. Management algorithms are proposed and separate recommendations for papillary and follicular thyroid cancers are provided. In response to our charge as an independent task force appointed by the ATA, we developed recommendations based on scientific evidence and expert opinion for the management of thyroid nodules and DTC in

Thyroid Hormones and Moderate Exposure to Perchlorate during Pregnancy in Women in Southern California.

PubMed

Steinmaus, Craig; Pearl, Michelle; Kharrazi, Martin; Blount, Benjamin C; Miller, Mark D; Pearce, Elizabeth N; Valentin-Blasini, Liza; DeLorenze, Gerald; Hoofnagle, Andrew N; Liaw, Jane

2016-06-01

Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring. We evaluated the potential effects of low environmental exposures to perchlorate on thyroid function. Serum thyroid hormones and anti-thyroid antibodies and urinary perchlorate, thiocyanate, nitrate, and iodide concentrations were measured in 1,880 pregnant women from San Diego County, California, during 2000-2003, a period when much of the area's water supply was contaminated from an industrial plant with perchlorate at levels near the 2007 California regulatory standard of 6 μg/L. Linear regression was used to evaluate associations between urinary perchlorate and serum thyroid hormone concentrations in models adjusted for urinary creatinine and thiocyanate, maternal age and education, ethnicity, and gestational age at serum collection. The median urinary perchlorate concentration was 6.5 μg/L, about two times higher than in the general U.S. Adjusted associations were identified between increasing log10 perchlorate and decreasing total thyroxine (T4) [regression coefficient (β) = -0.70; 95% CI: -1.06, -0.34], decreasing free thyroxine (fT4) (β = -0.053; 95% CI: -0.092, -0.013), and increasing log10 thyroid-stimulating hormone (β = 0.071; 95% CI: 0.008, 0.133). These results suggest that environmental perchlorate exposures may affect thyroid hormone production during pregnancy. This could have implications for public health given widespread perchlorate exposure and the importance of thyroid hormone in fetal neurodevelopment. Steinmaus C, Pearl M, Kharrazi M, Blount BC, Miller MD, Pearce EN, Valentin-Blasini L, DeLorenze G, Hoofnagle AN, Liaw J. 2016. Thyroid

The impact of N- and O-glycosylation on the functions of Glut-1 transporter in human thyroid anaplastic cells.

PubMed

Samih, Nezha; Hovsepian, Sonia; Notel, Frédéric; Prorok, Maëlle; Zattara-Cannoni, Hélène; Mathieu, Sylvie; Lombardo, Dominique; Fayet, Guy; El-Battari, Assou

2003-04-07

It has been previously shown that glucose transporter Glut-1 expression was detectable by immunostaining in tissue sections from anaplastic carcinoma, but not in normal thyroid tissue. Using human thyroid anaplastic carcinoma cells, we studied the mechanism by which Glut-1 molecules are translocated from the endoplasmic reticulum to the cell surface. The contribution of N- and O-linked glycans for the translocation and activity of Glut-1 transporter is emphasized. The inhibition of N-glycosylation with tunicamycin (TM) led to a 50% decrease in glucose transport while glycosylated and unglycosylated forms of Glut-1 were found at the cell surface. However, the inhibition of N-linked oligosaccharide processing with deoxymannojirimycin (dMJ) and swainsonine (SW) influenced neither the intracellular trafficking nor the activity of the transporter. On the other hand, Glut-1 bound to the O-linked glycan-specific lectin jacalin and the O-glycosylation inhibitor benzyl-N-acetylgalactosamine dramatically inhibited glucose transport. These results show that O- and N-linked oligosaccharides arbored by Glut-1 are essential for glucose transport in anaplastic carcinoma cells. The quantitative and qualitative alterations of Glut-1 glycosylation and the increase in glucose transport are associated with the anaplastic phenotype of human thyroid cells.

The p65 Subunit of NF-κB Inhibits COL1A1 Gene Transcription in Human Dermal and Scleroderma Fibroblasts through Its Recruitment on Promoter by Protein Interaction with Transcriptional Activators (c-Krox, Sp1, and Sp3)*

PubMed Central

Beauchef, Gallic; Bigot, Nicolas; Kypriotou, Magdalini; Renard, Emmanuelle; Porée, Benoît; Widom, Russell; Dompmartin-Blanchere, Anne; Oddos, Thierry; Maquart, François-Xavier; Demoor, Magali; Boumediene, Karim; Galera, Philippe

2012-01-01

Transcriptional mechanisms regulating type I collagen genes expression in physiopathological situations are not completely known. In this study, we have investigated the role of nuclear factor-κB (NF-κB) transcription factor on type I collagen expression in adult normal human (ANF) and scleroderma (SF) fibroblasts. We demonstrated that NF-κB, a master transcription factor playing a major role in immune response/apoptosis, down-regulates COL1A1 expression by a transcriptional control involving the −112/−61 bp sequence. This 51-bp region mediates the action of two zinc fingers, Sp1 (specific protein-1) and Sp3, acting as trans-activators of type I collagen expression in ANF and SF. Knockdown of each one of these trans factors by siRNA confirmed the trans-activating effect of Sp1/Sp3 and the p65 subunit of NF-κB trans-inhibiting effect on COL1A1 expression. Despite no existing κB consensus sequence in the COL1A1 promoter, we found that Sp1/Sp3/c-Krox and NF-κB bind and/or are recruited on the proximal promoter in chromatin immunoprecipitation (ChIP) assays. Attempts to elucidate whether interactions between Sp1/Sp3/c-Krox and p65 are necessary to mediate the NF-κB inhibitory effect on COL1A1 in ANF and SF were carried out; in this regard, immunoprecipitation assays revealed that they interact, and this was validated by re-ChIP. Finally, the knockdown of Sp1/Sp3/c-Krox prevents the p65 inhibitory effect on COL1A1 transcription in ANF, whereas only the siRNAs targeting Sp3 and c-Krox provoked the same effect in SF, suggesting that particular interactions are characteristic of the scleroderma phenotype. In conclusion, our findings highlight a new mechanism for COL1A1 transcriptional regulation by NF-κB, and these data could allow the development of new antifibrotic strategies. PMID:22139845

Graves' disease following subacute thyroiditis.

PubMed

Nakano, Yoshishige; Kurihara, Hideo; Sasaki, Jun

2011-12-01

Subacute thyroiditis is a painful, inflammatory disease frequently accompanied with fever. It is suspected to be a viral infectious disease, while Graves' disease is an autoimmune disease. Thus, there appears to be no etiological relationship between the two diseases. A total of 25,267 thyroid disease patients made their first visits to our thyroid clinic during a period of 24 years between 1985 and 2008. Among them, subacute thyroiditis and Graves' disease accounted for 918 patients (3.6%) and 4,617 patients (18.2%), respectively. We have encountered 7 patients (one male and six female) with subacute thyroiditis followed by Graves' disease in this period (0.15% of the 4,617 patients with Graves' disease and 0.76% of the 918 patients with subacute thyroiditis). The age ranges were 40~66 years (mean 48.7 years) at the onset of subacute thyroiditis. The intervals between the onsets of subacute thyroiditis and Graves' disease were 1~8 months (mean 4.7 months). Because Graves' disease was preceded by subacute thyroiditis, the signs and symptoms of both diseases were evident together in the intervening period. The diagnosis of Graves' disease in those patients is always difficult because of atypical signs and symptoms and an unclear onset time. The causes of the Graves'disease that followed subacute thyroiditis are still unknown. However, the inflammatory nature of subacute thyroiditis may lead to the activation of the autoimmune response in susceptible subjects, resulting in the onset of Graves' disease. Graves' disease should be suspected when a high blood level of thyroid hormone persists after subacute thyroiditis.

Evodiamine Inhibits Angiotensin II-Induced Rat Cardiomyocyte Hypertrophy.

PubMed

He, Na; Gong, Qi-Hai; Zhang, Feng; Zhang, Jing-Yi; Lin, Shu-Xian; Hou, Hua-Hua; Wu, Qin; Sun, An-Sheng

2018-05-01

To investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa (Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms. Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.1 μmol/L), and Evo (0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium ([Ca 2+ ] i ) concentration, activity of nitric oxide synthase (NOS) and content of nitric oxide (NO) were measured, respectively. The mRNA expressions of atrial natriuretic factor (ANF), calcineurin (CaN), extracellular signal-regulated kinase-2 (ERK-2), and endothelial nitric oxide synthase (eNOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit (CnA) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by Western blot analysis. Compared with the control group, Ang II induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF mRNA expression; increased intracellular free calcium ([Ca 2+ ] i ) concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but decreased MKP-1 protein expression (P<0.05 or P<0.01). Compared with Ang II, Evo (0.3, 3 μmol/L) significantly attenuated Ang II-induced cardiomyocyte hypertrophy, decreased the [Ca 2+ ] i concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but increased MKP-1 protein expression (P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the eNOS mRNA expression (P<0.05). Evo signifificantly attenuated Ang II-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca 2+ ]i concentration, and inhibition of Ca

Neurotoxicity of Thyroid Disrupting Contaminants

EPA Science Inventory

Thyroid hormones playa critical role in the normal development ofthe mammalian brain. Thyroid disrupting chemicals (TDCs) are environmental contaminants that alter the structure or function ofthe thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeost...

GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation

PubMed Central

Kang, Hong Soon; Kumar, Dhirendra; Liao, Grace; Lichti-Kaiser, Kristin; Gerrish, Kevin; Liao, Xiao-Hui; Refetoff, Samuel; Jothi, Raja; Jetten, Anton M.

2017-01-01

Deficiency in Krüppel-like zinc finger transcription factor GLI-similar 3 (GLIS3) in humans is associated with the development of congenital hypothyroidism. However, the functions of GLIS3 in the thyroid gland and the mechanism by which GLIS3 dysfunction causes hypothyroidism are unknown. In the current study, we demonstrate that GLIS3 acts downstream of thyroid-stimulating hormone (TSH) and TSH receptor (TSHR) and is indispensable for TSH/TSHR-mediated proliferation of thyroid follicular cells and biosynthesis of thyroid hormone. Using ChIP-Seq and promoter analysis, we demonstrate that GLIS3 is critical for the transcriptional activation of several genes required for thyroid hormone biosynthesis, including the iodide transporters Nis and Pds, both of which showed enhanced GLIS3 binding at their promoters. The repression of cell proliferation of GLIS3-deficient thyroid follicular cells was due to the inhibition of TSH-mediated activation of the mTOR complex 1/ribosomal protein S6 (mTORC1/RPS6) pathway as well as the reduced expression of several cell division–related genes regulated directly by GLIS3. Consequently, GLIS3 deficiency in a murine model prevented the development of goiter as well as the induction of inflammatory and fibrotic genes during chronic elevation of circulating TSH. Our study identifies GLIS3 as a key regulator of TSH/TSHR-mediated thyroid hormone biosynthesis and proliferation of thyroid follicular cells and uncovers a mechanism by which GLIS3 deficiency causes neonatal hypothyroidism and prevents goiter development. PMID:29083325

Thyroid Cancer—Health Professional Version

Cancer.gov

There are four types of thyroid cancer. These are papillary, follicular, medullary, and anaplastic thyroid cancer. Papillary is the most common type of thyroid cancer. Find evidence-based information on thyroid cancer treatment, screening, research, genetics, and statistics.

Thyroid Radiation Dose and Other Risk Factors of Thyroid Carcinoma Following Childhood Cancer.

PubMed

de Vathaire, Florent; Haddy, Nadia; Allodji, Rodrigue S; Hawkins, Mike; Guibout, Catherine; El-Fayech, Chiraz; Teinturier, Cécile; Oberlin, Odile; Pacquement, Hélène; Diop, Fara; Kalhouche, Amar; Benadjaoud, Mohamedamine; Winter, David; Jackson, Angela; Bezin Mai-Quynh, Giao; Benabdennebi, Aymen; Llanas, Damien; Veres, Cristina; Munzer, Martine; Nguyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Deutsch, Eric; Lefkopoulos, Dimitri; Schlumberger, Martin; Diallo, Ibrahima; Rubino, Carole

2015-11-01

Thyroid carcinoma is a frequent complication of childhood cancer radiotherapy. The dose response to thyroid radiation dose is now well established, but the potential modifier effect of other factors requires additional investigation. This study aimed to investigate the role of potential modifiers of the dose response. We followed a cohort of 4338 5-year survivors of solid childhood cancer treated before 1986 over an average of 27 years. The dose received by the thyroid gland and some other anatomical sites during radiotherapy was estimated after reconstruction of the actual conditions in which irradiation was delivered. Fifty-five patients developed thyroid carcinoma. The risk of thyroid carcinoma increased with a radiation dose to the thyroid of up to two tenths of Gy, then leveled off for higher doses. When taking into account the thyroid radiation dose, a surgical or radiological splenectomy (>20 Gy to the spleen) increased thyroid cancer risk (relative risk [RR] = 2.3; 95% confidence interval [CI], 1.3-4.0), high radiation doses (>5 Gy) to pituitary gland lowered this risk (RR = 0.2; 95% CI, 0.1-0.6). Patients who received nitrosourea chemotherapy had a 6.6-fold (95% CI, 2.5-15.7) higher risk than those who did not. The excess RR per Gy of radiation to the thyroid was 4.7 (95% CI, 1.7-22.6). It was 7.6 (95% CI, 1.6-33.3) if body mass index at time of interview was equal or higher than 25 kg/m(2), and 4.1 (95% CI, 0.9-17.7) if not (P for interaction = .1). Predicting thyroid cancer risk following childhood cancer radiation therapy probably requires the assessment of more than just the radiation dose to the thyroid. Chemotherapy, splenectomy, radiation dose to pituitary gland, and obesity also play a role.

[Subclinical thyroid diseases].

PubMed

Zamrazil, V

2007-01-01

Subclinical thyroids disease (STD) is recently defined term in clinical thyroidology, which includes mainly functional disorders. Basic diagnostic signs are: normal values of thyroid hormones (fT4, fT3) and elevated TSH level (subclinical hypothyroidism) or suppresed TSH level (subclinical hyperthyroidism). In a category of STD may be included subclinical autoimunne thyroiditis (elevated level of thyroid antigens antibodies and/or hypoechogenity in sonographic screen, increased volume of the thyroid without clinical symptoms and/or autoimminity) and microscopic lesions of papillary thyroid carcinoma. Subclinical hypothyroidism may be dangerous for tendency to development of manifest hypothyroidism and for risk of disorders of lipid profile and development of atherosclerosis and its organ complication (esp. myocardial infarction). Subclinical hyperthyroidism is a risk factor of cardiac arythmias and probably can increase a risk of cardiovascular mortality) as well for osteoporosis (esp. in peri- and post-climacteric women), and last but not least for degenerative diseases of brain (?). Indication of treatment of STD is a matter of controversies. Recomendations of experts, varied from "no therapy, monitoring only" to "treat always". Treatment of risk groups (esp. pregnant women) is probably nowadays a most rationale recommendations since results of sofisticated prospective studies will be available.

Thyroid associated orbitopathy

PubMed Central

Verma, Rajesh; Gupta, Mani; Mehta, Vinod Kumar

2013-01-01

Thyroid-associated orbitopathy (TAO) is a self-limiting auto-immune condition usually associated with Grave's disease. It is characterised by ocular pain, eyelid swelling, chemosis, proptosis and keratopathy. As the mechanism for ophthamoplegia and optic neuropathy is the orbital swelling leading to mechanical restriction of ocular muscles and compression of optic nerve, one expects proptosis rather than ptosis in TAO. We describe a case of a young adult woman who presented with acute onset restriction of movement along with partial ptosis and severe diminution of vision in left eye. The MRI of orbit revealed significant swelling of recti along with signal alteration consistent with TAO. The radio-isotope thyroid scan revealed thyroiditis, and thyroid peroxidase (TPO) antibody was significantly high; hence, the diagnosis of Hashimoto thyroiditis was considered. A course of intravenous methylprednisolone followed by oral steroid was administered, which produced marked improvement in vision and extraocular movement. PMID:23737589

The Clinical and Thyroid Function Studies of Lymphocytic Thyroiditis with Spontaneously Resolving Hyperthyroidism: Comparison to Subacute Thyroiditis

PubMed Central

Koh, Eun Hee; Park, Yong Joon; Lee, Hyun Chul; Hong, Chein Soo; Huh, Kap Bum; Lee, Sang Yong; Ryu, Kyung Za

1986-01-01

Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (LT-SRH) has been reported in the past years, and is referred to as “silent thyroiditis.” It is characterized by a low or decreased radioactive iodine uptake (RAIU) of thyroid in a patient with hyperthyroidism in whom initial diagnosis is generally thought to be Graves’ disease. Thirty-five patients who had hyperthyroidism or goiter with decreased RAIU have been assessed. Twenty-four (68.6%) of 35 patients had LT-SRH and the remaining patients, subacute thyroiditis (SAT). The clinical characteristics of the patients with LT-SRH were a history of delivery, painless goiter, elevated T3 and T4 levels and positive anti-microsomal antibodies. Anti-microsomal antibodies were positive in 70.8% of the LT-SRH group, whereas 12.5% in the SAT group. Resolution of the hyperthyroidism took 8 to 12 months. It is considered that LT-SRH is an autoimmune thyroiditis with spontaneously resolving hyperthyroidism and determination of the RAIU is very useful in differentiating from other forms of hyperthyroidism. PMID:15759376

Molecular Aspects of Thyroid Hormone Actions

PubMed Central

Cheng, Sheue-Yann; Leonard, Jack L.; Davis, Paul J.

2010-01-01

ion transport systems, such as the Na+/H+ exchanger, or complex cellular events such as cell proliferation. Concentration of the integrin on cells of the vasculature and on tumor cells explains recently described proangiogenic effects of iodothyronines and proliferative actions of thyroid hormone on certain cancer cells, including gliomas. Thus, hormonal events that begin nongenomically result in effects in DNA-dependent effects. l-T4 is an agonist at the plasma membrane without conversion to T3. Tetraiodothyroacetic acid is a T4 analog that inhibits the actions of T4 and T3 at the integrin, including angiogenesis and tumor cell proliferation. T3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytoplasmic in origin or may begin at integrin αvβ3. Downstream consequences of phosphatidylinositol 3-kinase activation by T3 include specific gene transcription and insertion of Na, K-ATPase in the plasma membrane and modulation of the activity of the ATPase. Thyroid hormone, chiefly T3 and diiodothyronine, has important effects on mitochondrial energetics and on the cytoskeleton. Modulation by the hormone of the basal proton leak in mitochondria accounts for heat production caused by iodothyronines and a substantial component of cellular oxygen consumption. Thyroid hormone also acts on the mitochondrial genome via imported isoforms of nuclear TRs to affect several mitochondrial transcription factors. Regulation of actin polymerization by T4 and rT3, but not T3, is critical to cell migration. This effect has been prominently demonstrated in neurons and glial cells and is important to brain development. The actin-related effects in neurons include fostering neurite outgrowth. A truncated TRα1 isoform that resides in the extranuclear compartment mediates the action of thyroid hormone on the cytoskeleton. PMID:20051527

WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

PubMed

Nieto, Hannah; Boelaert, Kristien

2016-11-01

Differentiated thyroid cancer is the most common endocrine malignancy and the incidence is increasing rapidly worldwide. Appropriate diagnosis and post-treatment monitoring of patients with thyroid tumours are critical. Fine needle aspiration cytology remains the gold standard for diagnosing thyroid cancer, and although there have been significant refinements to this technique, diagnostic surgery is often required for patients suspected to have malignancy. Serum thyroid-stimulating hormone (TSH) is higher in patients with malignant thyroid nodules than in those with benign disease, and TSH is proportionally increased in more aggressive tumours. Importantly, we have shown that the pre-operative serum TSH concentration independently predicts the presence of malignancy in subjects presenting with thyroid nodules. Establishing the use of TSH measurements in algorithms identifying high-risk thyroid nodules in routine clinical practice represents an exciting, cost-efficient and non-invasive approach to optimise thyroid cancer diagnosis. Binding of TSH to receptors on thyrocytes stimulates a number of growth promoting pathways both in normal and malignant thyroid cells, and TSH suppression with high doses of levothyroxine is routinely used after thyroidectomy to prevent cancer recurrence, especially in high-risk tumours. This review examines the relationship between serum TSH and thyroid cancer and reflects on the clinical potential of TSH measurements in diagnosis and disease monitoring. © 2016 Society for Endocrinology.

The association between thyroid malignancy and chronic lymphocytic thyroiditis: should it alter the surgical approach?

PubMed

Büyükaşık, Oktay; Hasdemir, Ahmet Oğuz; Yalçın, Erol; Celep, Bahadır; Sengül, Serkan; Yandakçı, Kemal; Tunç, Gündüz; Küçükpınar, Tevfik; Alkoy, Seval; Cöl, Cavit

2011-01-01

The relation between thyroid neoplasms and chronic lymphocytic thyroiditis (CLT) is controversial. While it is accepted that focal lymphocytic thyroiditis develops secondarily to malignancy, it is not clear whether diffuse lymphocytic thyroiditis has a tendency to develop into thyroid cancer. The aim of this study was to investigate the relation between CLT and malignant tumours of the thyroid and evaluate the surgical approach to CLT cases. In this study, 917 patients operated on for thyroid diseases were investigated retrospectively. Seventy-seven (8.4%) patients histopathologically diagnosed as having CLT (either non-specific or Hashimoto's thyroiditis) were investigated for any concurrent malignant neoplasm. Fifteen patients in whom CLT and thyroid malignancy were coexisting were included in the study. In the pathological evaluation of 917 cases, malignancy in the thyroid was found in 97 (10.6%) cases. Seventy-seven cases were categorised as CLT. Of these 77, 16 (20.8%) were Hashimoto's thyroiditis (specific CLT) and the other 61 (79.2%) were non-specific CLT. In 15 cases, thyroid malignancy was found to be concurrent with CLT. Of the malignities, nine (60%) were papillary carcinoma, three (20%) medullar carcinoma, one (6.6%) follicular carcinoma, one (6.6%) Hurthle cell carcinoma, and one (6.6%) lymphoma. In our series, the rate of the development of malignancy against the background of CLT was 19.48%, while the rate in the groups without CLT was 9.76%, with a statistically significant difference between the groups (p = 0.008). CLT cases should be evaluated more carefully in terms of malignancy. If a nodule is detected on thyroiditis, the minimal surgical intervention should be lobectomy. Total thyroidectomy should be considered as preferable to subtotal thyroidectomy because of its many advantages such as controlling thyroiditis, removing the probability of reoperation, and hormonal stability.

Pheochromocytoma, papillary thyroid carcinoma.

PubMed

Nasser, Tariq; Qari, Faiza

2009-08-01

A 53-year-old woman presented with labile and difficult to control hypertension on 3 different anti-hypertensive medications. Abdominal computed tomography and ultrasonography of the thyroid gland showed a 1.8 cm thyroid nodule. Fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. Serum thyroid stimulating hormone and free thyroxine, calcitonin, carcinoembryonic antigen, intact parathyroid hormone, and calcium levels were within normal limits. A 24-hour urine metanephrine showed significant elevation in urine metanephrine of approximately 3 times the upper limit of normal, and the result of 131I-metaiodobenzyleguanjdjne (131I-MIBG) scintigraphy confirmed that the adrenal mass was pheochromocytoma. Right adrenalectomy and total thyroidectomy were performed. The final pathology was pheochromocytoma and papillary thyroid carcinoma. An analysis of c-ret porto-oncogene mutation yielded a negative result. This unusual association of 2 tumors represents a new entity.

Thyroid and the Heart

PubMed Central

Grais, Ira Martin; Sowers, James R.

2015-01-01

Thyroid hormones modulate every component of the cardiovascular system necessary for normal cardiovascular development and function. When cardiovascular disease is present, thyroid function tests are characteristically indicated to determine if overt thyroid disorders or even subclinical dysfunction exists. As hypothyroidism, hypertension and cardiovascular disease all increase with advancing age monitoring of TSH, the most sensitive test for hypothyroidism, is important in this expanding segment of our population. A better understanding of the impact of thyroid hormonal status on cardiovascular physiology will enable health care providers to make decisions regarding thyroid hormone evaluation and therapy in concert with evaluating and treating hypertension and cardiovascular disease. The goal of this review is to access contemporary understanding of the effects of thyroid hormones on normal cardiovascular function and the potential role of overt and subclinical hypothyroidism and hyperthyroidism in a variety of cardiovascular diseases. PMID:24662620

Hyperfunctioning thyroid nodules in children.

PubMed

Abe, K; Konno, M; Sato, T; Matsuura, N

1980-10-01

We studied two cases of hyperfunctioning thyroid nodules in children. A 9-year-old girl and an 11-year-old girl had thyroid masses in otherwise nonpalpable thyroid glands. Scintiscan showed hyperfunctioning thyroid nodules. The former patient had elevated values for T4 and T3, and plasma thyrotropin (TSH) level failed to respond to stimulation with thyrotropin releasing hormone (TRH), whereas the latter patient had normal values for T4, and T3 and plasma TSH response to TRH was normal. After the surgical removal of nodules, scintiscan exhibited radioactivity in the contralateral lobe of the thyroid gland in the former and in the ectopic thyroid tissue in the latter. Results of microscopic examinations of thyroid nodules were consistent with adenomatous goiter.

Differentiated thyroid carcinoma with functional autonomy.

PubMed

Yaturu, Subhashini; Fowler, Marjorie R

2002-01-01

To present a case of papillary carcinoma in an autonomously hyperfunctioning thyroid nodule. We chronicle the clinical and laboratory findings in a patient with a painless neck mass, with a particular focus on the pathologic findings after surgical removal of the right thyroid lobe. A 39-year-old woman had an enlarging nodule of the right thyroid lobe. Results of thyroid function tests suggested subclinical hyperthyroidism. Two months later, the patient complained of increasing swelling in the neck (but still had no symptoms suggestive of hyperthyroidism). Thus, resection of the right thyroid lobe was performed. Pathologic analysis disclosed low-grade papillary thyroid carcinoma within the nodule, with a small rim of compressed inactive-appearing thyroid tissue surrounding the nodule. Subsequently, she underwent total thyroidectomy and follow-up care for thyroid carcinoma. Although solitary hyperfunctioning nodules of the thyroid gland are usually considered benign, the current case suggests that the diagnosis of autonomous thyroid nodules does not preclude thyroid carcinoma in a functioning nodule.

Regional variation in thyroid cancer incidence in Belgium is associated with variation in thyroid imaging and thyroid disease management.

PubMed

Van den Bruel, Annick; Francart, Julie; Dubois, Cecile; Adam, Marielle; Vlayen, Joan; De Schutter, Harlinde; Stordeur, Sabine; Decallonne, Brigitte

2013-10-01

Increased thyroid cancer incidence is at least partially attributed to increased detection and shows considerable regional variation. We investigated whether regional variation in cancer incidence was associated with variations in thyroid disease management. We conducted a retrospective population-based cohort study that involved linking data from the Belgian Health Insurance database and the Belgian Cancer Registry to compare thyroid-related procedures between regions with high and low cancer incidence. Primary outcome measures were rates of TSH testing, imaging, fine-needle aspiration cytology (FNAC), and thyroid surgery. Secondary study outcomes were proportions of subjects with thyrotoxicosis and nodular disease treated with surgery, of subjects treated with surgery preceded by FNAC or with synchronous lymph node dissection, and of thyroid cancer diagnosis after surgery. The rate of TSH testing was similar, but the rate of imaging was lower in the low incidence region. The rate of FNAC was similar, whereas the rate of surgery was lower in the low incidence region (34 [95% CI 33; 35 ] vs 80 [95% CI 79; 81 ] per 100,000 person years in the high incidence region; P < .05). In the low incidence region compared to the high incidence region, surgery represented a less chosen therapy for euthyroid nodular disease patients (47% [95% CI 46; 48] vs 69% [95% CI 68; 70]; P < .05), proportionally more surgery was preceded by FNAC, more cancer was diagnosed after total thyroidectomy, and thyroid cancer patients had more preoperative FNAC and synchronous lymph node dissection. Regional variation in thyroid cancer incidence, most marked for low-risk disease, is associated with different usage of thyroid imaging and surgery, supporting variable detection as a key determinant in geographic variation.

[Malignant tumors of thyroid gland].

PubMed

Uhliarová, B; Bugová, G; Hajtman, A

2015-01-01

The incidence of thyroid cancer has been increasing. The aim of this work was to determine risk factors, diagnostic methods and extent of surgical treatment of malignant goiter. The authors retrospectively analyzed patients who were surgically treated for thyroid disease at the Department of Otorhinolaryngology, Head and Neck Surgery, Comenius University, Jessenius Faculty of Medicine, Teaching Hospital in Martin, Slovakia, from the January 1st, 2006 to December 31st, 2013, for thyroid disease. The incidence, risk factors of malignant thyroid tumors, indication for surgery and its complications were evaluated. A total of 1,620 adult patients were surgically treated for thyroid disease at the Department of ENT, Head and Neck Surgery, CU JMF, UH in Martin, Slovakia, between 2006- 2013. Malignant tumors were identified in 238 patients (15%). Microcarcinoma (incidentally detected malignant tumor 1 cm) occurred in 78 cases (5%). Malignant thyroid tumor was more common in younger patients (p = 0.002). Newly created and larger nodules positively correlated with the occurrence of malignancy (p = 0.003, p = 0.041, resp.). Gender, family history of thyroid disorder, previous radiation therapy, and previous malignancy did not affect the incidence of malignant tumor of thyroid gland. High sensitivity and specificity in the dia-gnosis of malignant thyroid nodule was observed using aspiration cytology (75%, 97%, resp.) and intraoperative histopathological examination (88%, 100%, resp.). Malignant tumor of thyroid gland is more common in younger patients with newly developed nodule. The risk factors of malignancy increase with the size of the thyroid nodule. Aspiration cytology and peroperative histopathology have high sensitivity and specificity in the dia-gnosis of malignant thyroid tumor; therefore, they should be a standard method in the dia-gnosis of nodular goiter. The method of choice in the treatment of thyroid malignancy is total thyroidectomy.

Reactivity of thyroid papillary carcinoma cells to thyroid stimulating hormone-dominated endocrine therapy

PubMed Central

Ma, Yuqin; Zhang, Xia; Wang, Yutao

2017-01-01

This study investigated the effect of thyroid stimulating hormone (TSH) on the proliferation of papillary thyroid carcinoma (PTC) cells and the therapeutic effect of levothyroxine sodium (TH). PTC cells (TPC-1) were cultured using 0.1, 1.0 and 10 U/l TSH and 10−2, 10−4 and 10−6 mol/l TH. After the appropriate concentration was screened, TPC-1 cells were further divided into control group, TSH group, TH group and TSH+TH group. The cell proliferation was detected via methyl thiazolyl tetrazolium (MTT) method, TPC-1 cell cycle was detected via flow cytometer, and the mRNA and protein expression of cyclin D1 were detected via real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Compared with control group, TSH significantly promoted the proliferation of TPC-1 cells (P<0.05 or P<0.01), obviously promoted the transition of TPC-1 cells from G1 phase to S phase (P<0.01) and remarkably increased the mRNA and protein expression of cyclin D1 (P<0.01); but TH had a significant inhibitory effect on these results of TSH (P<0.05 or P<0.01). TSH can promote the proliferation of PTC cells, and the appropriate complement of TH can inhibit its proliferation. PMID:29250166

Thyroid dysfunction: an autoimmune aspect.

PubMed

Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera

2015-01-01

Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins.

Hyperkalemia develops in some thyroidectomized patients undergoing thyroid hormone withdrawal in preparation for radioactive iodine ablation for thyroid carcinoma.

PubMed

Horie, Ichiro; Ando, Takao; Imaizumi, Misa; Usa, Toshiro; Kawakami, Atsushi

2015-05-01

Hyponatremia is observed in hypothyroidism, but it is not known if hypo- or hyperkalemia is associated with hypothyroidism. To study these questions, we determined serum potassium (K(+)) levels in thyroidectomized patients undergoing levothyroxine withdrawal before radioactive iodine (RAI) therapy for thyroid carcinoma. We retrospectively studied the records of 108 patients who had undergone total thyroidectomy for thyroid carcinoma followed by levothyroxine withdrawal and then ablation with RAI at Nagasaki University Hospital from 2009-2013. Blood samples were analyzed for serum K(+) concentrations when patients were euthyroid just before levothyroxine withdrawal and hypothyroid 21 days after levothyroxine withdrawal. We determined the proportion of patients who developed hyperkalemia (K(+) ≥5 mEq/L) and hypokalemia (K(+) ≤3.5 mEq/L). Five (4.6%) patients developed hyperkalemia and 2 (1.9%) patients developed hypokalemia after levothyroxine withdrawal. The mean serum K(+) level after levothyroxine withdrawal was significantly higher than before levothyroxine withdrawal (4.23 ± 0.50 mEq/L vs. 4.09 ± 0.34 mEq/L; P<.001). After levothyroxine withdrawal, serum K(+) values were significantly correlated with age, serum sodium and creatinine levels, and the estimated glomerular filtration rate but not with serum free thyroxine or thyroid-stimulating hormone concentrations. The finding of an elevated serum K(+) of >0.5 mEq/L after levothyroxine withdrawal was more prevalent with age >60 years (odds ratio [OR], 4.66; P = .026) and with the use of angiotensin-II receptor blockers or angiotensin-converting enzyme inhibitors (OR, 3.53; P = .033) in a multivariate analysis. Hyperkalemia develops in a small percentage of hypothyroid patients after thyroid hormone withdrawal, especially in patients over 60 years of age who are using antihypertensive agents that inhibit the reninangiotensin-aldosterone system.

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

PubMed Central

2014-01-01

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

Flavonoids, Thyroid Iodide Uptake and Thyroid Cancer—A Review

PubMed Central

Gonçalves, Carlos F. L.; de Freitas, Mariana L.; Ferreira, Andrea C. F.

2017-01-01

Thyroid cancer is the most common malignant tumor of the endocrine system and the incidence has been increasing in recent years. In a great part of the differentiated carcinomas, thyrocytes are capable of uptaking iodide. In these cases, the main therapeutic approach includes thyroidectomy followed by ablative therapy with radioiodine. However, in part of the patients, the capacity to concentrate iodide is lost due to down-regulation of the sodium-iodide symporter (NIS), the protein responsible for transporting iodide into the thyrocytes. Thus, therapy with radioiodide becomes ineffective, limiting therapeutic options and reducing the life expectancy of the patient. Excessive ingestion of some flavonoids has been associated with thyroid dysfunction and goiter. Nevertheless, studies have shown that some flavonoids can be beneficial for thyroid cancer, by reducing cell proliferation and increasing cell death, besides increasing NIS mRNA levels and iodide uptake. Recent data show that the flavonoids apingenin and rutin are capable of increasing NIS function and expression in vivo. Herein we review literature data regarding the effect of flavonoids on thyroid cancer, besides the effect of these compounds on the expression and function of the sodium-iodide symporter. We will also discuss the possibility of using flavonoids as adjuvants for therapy of thyroid cancer. PMID:28604619

Thyroid hormone stimulates progesterone release from human luteal cells by generating a proteinaceous factor.

PubMed

Datta, M; Roy, P; Banerjee, J; Bhattacharya, S

1998-09-01

Blood samples collected from 29 women (aged between 19 and 35 years) during the luteal phase of the menstrual cycle (between days 18 and 23 of the cycle) showed that deficiency in thyroid hormone level is related to a decrease in progesterone (P4) secretion. To observe the effect of thyroid hormone on human ovarian luteal cells, 3,5,3'-triiodothyronine (T3; 125 ng/ml) was added to luteal cells in vitro. T3 significantly stimulated progesterone release (P < 0.01) from luteal cells and this could be blocked by cycloheximide, indicating a protein mediator for the T3 effect. The T3 stimulatory effect was inhibited by anti-T3 antibody suggesting specificity of T3 action. Addition of T3 caused a more than threefold increase in cellular protein synthesis which was inhibited by cycloheximide. Preparation of partially purified thyroid hormone-induced factor (TIF) (from peak II of Sephadex G 100 chromatography of T3-incubated cells), and its addition to luteal cell incubations caused a significant increase in P4 release (P < 0.05). Incubation with trypsin or treatment with heat destroyed the stimulatory effect of TIF on P4 release, indicating the proteinaceous nature of TIF. Purified thyroid hormone-induced protein. (TIP) from rat granulosa cells and fish ovarian follicles greatly stimulated P4 release from human luteal cells. These results suggest that T3 stimulation of P4 release from human luteal cells is not direct, but is mediated through a putative protein factor, which appears to be a protein conserved through evolution as far as its biological activity is concerned.

Papillary thyroid carcinoma in an autonomous hyperfunctioning thyroid nodule: case report and review of the literature.

PubMed

Tfayli, Hala M; Teot, Lisa A; Indyk, Justin A; Witchel, Selma Feldman

2010-09-01

Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy.

Papillary Thyroid Carcinoma in an Autonomous Hyperfunctioning Thyroid Nodule: Case Report and Review of the Literature

PubMed Central

Tfayli, Hala M.; Teot, Lisa A.; Indyk, Justin A.

2010-01-01

Background Whereas thyroid nodules are less common among children than among adults, the anxiety generated by the finding of a thyroid nodule is high because 20% of nodules found in children contain thyroid cancer. Discovery of a nodule in the context of hyperthyroidism is usually comforting due to the presumption that the nodule represents a benign toxic adenoma. Summary An 11-year-old girl presented with heavy menses, fatigue, and a right thyroid mass. Laboratory evaluation revealed elevated triiodothyronine and undetectable thyroid-stimulating hormone. Thyroid ultrasonography revealed a 3.5 cm nonhomogenous nodule, and scintigraphy was consistent with an autonomous hyper-functioning nodule. Fine-needle aspiration biopsy could not rule out malignancy, and patient underwent right hemithyroidectomy and isthmusectomy. Pathology was consistent with papillary thyroid carcinoma. Conclusions We report the discovery of papillary thyroid carcinoma in an autonomously hyperfunctioning nodule in an 11-year-old girl. Detection of an autonomously functioning thyroid nodule in children and adolescents does not exclude the possibility of thyroid carcinoma and warrants careful evaluation and appropriate therapy. PMID:20718686

Viruses and thyroiditis: an update

PubMed Central

Desailloud, Rachel; Hober, Didier

2009-01-01

Viral infections are frequently cited as a major environmental factor involved in subacute thyroiditis and autoimmune thyroid diseases This review examines the data related to the role of viruses in the development of thyroiditis. Our research has been focused on human data. We have reviewed virological data for each type of thyroiditis at different levels of evidence; epidemiological data, serological data or research on circulating viruses, direct evidence of thyroid tissue infection. Interpretation of epidemiological and serological data must be cautious as they don't prove that this pathogen is responsible for the disease. However, direct evidence of the presence of viruses or their components in the organ are available for retroviruses (HFV) and mumps in subacute thyroiditis, for retroviruses (HTLV-1, HFV, HIV and SV40) in Graves's disease and for HTLV-1, enterovirus, rubella, mumps virus, HSV, EBV and parvovirus in Hashimoto's thyroiditis. However, it remains to determine whether they are responsible for thyroid diseases or whether they are just innocent bystanders. Further studies are needed to clarify the relationship between viruses and thyroid diseases, in order to develop new strategies for prevention and/or treatment. PMID:19138419

Inhibition of AMPK and Krebs cycle gene expression drives metabolic remodeling of Pten-deficient preneoplastic thyroid cells.

PubMed

Antico Arciuch, Valeria G; Russo, Marika A; Kang, Kristy S; Di Cristofano, Antonio

2013-09-01

Rapidly proliferating and neoplastically transformed cells generate the energy required to support rapid cell division by increasing glycolysis and decreasing flux through the oxidative phosphorylation (OXPHOS) pathway, usually without alterations in mitochondrial function. In contrast, little is known of the metabolic alterations, if any, which occur in cells harboring mutations that prime their neoplastic transformation. To address this question, we used a Pten-deficient mouse model to examine thyroid cells where a mild hyperplasia progresses slowly to follicular thyroid carcinoma. Using this model, we report that constitutive phosphoinositide 3-kinase (PI3K) activation caused by PTEN deficiency in nontransformed thyrocytes results in a global downregulation of Krebs cycle and OXPHOS gene expression, defective mitochondria, reduced respiration, and an enhancement in compensatory glycolysis. We found that this process does not involve any of the pathways classically associated with the Warburg effect. Moreover, this process was independent of proliferation but contributed directly to thyroid hyperplasia. Our findings define a novel metabolic switch to glycolysis driven by PI3K-dependent AMPK inactivation with a consequent repression in the expression of key metabolic transcription regulators. ©2013 AACR.

[Thyroid and cardiovascular disorders].

PubMed

Zyśko, Dorota; Gajek, Jacek

2004-05-01

In this study three problems concerning interactions between thyroid and cardiovascular system are discussed. Cardiac arrhythmias, congestive heart failure, pleural effusion, hyperlipidaemia, arterial hypertension may be consequences of thyroid disorders leading to inappropriate hormone secretion. During such illnesses as heart failure, myocardial infarction and in patients undergoing coronary artery bypass surgery profound changes may occur in thyroid hormone metabolism known as sick euthyroid syndrome. Treatment with amiodarone may lead to changes in thyroid tests results and to development of hypothyroidism or thyrotoxicosis.

Breaking tolerance in transgenic mice expressing the human TSH receptor A-subunit: thyroiditis, epitope spreading and adjuvant as a 'double edged sword'.

PubMed

McLachlan, Sandra M; Aliesky, Holly A; Chen, Chun-Rong; Chong, Gao; Rapoport, Basil

2012-01-01

Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a "double-edged sword". On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the

Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis.

PubMed

Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

2016-01-01

Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as "MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node." Total thyroidectomy specimen showed "MTC with coexisting HT." At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists.

Identification of metastatic papillary thyroid carcinoma in FNA specimens using thyroid peroxidase immunohistochemistry.

PubMed

Shield, P W; Crouch, S J; Papadimos, D J; Walsh, M D

2018-06-01

We evaluated immunohistochemical staining for thyroid peroxidase (TPO), a glycoprotein found in the apical plasma membrane of thyroid follicular cells, as a marker for metastatic PTC in FNA samples and compared results with thyroglobulin (Tg) and thyroid transcription factor 1 (TTF1) staining. Cell block sections prepared from 100 FNA specimens were stained with a rabbit monoclonal antibody to TPO (EP159). The FNAs included 64 metastatic malignancies from non-thyroid primary sites, including 18 lung, and 36 cases of thyroid tumours (29 PTC, six cases of medullary thyroid carcinoma and one thyroid anaplastic carcinoma). Thyroid tumours were stained with TTF1 and Tg in addition to TPO. All cases of metastatic lung carcinoma also had TTF-1 staining results. TPO staining was negative in all non-thyroid malignancies. Ninety percent (26/29) of PTC were positive. All positive cases showed strong cytoplasmic staining, although 54% (14/26) showed positivity in less than half of the cells. By comparison, Tg staining of TPC cases was present in 62% and TTF-1 in 100%. In addition to showing higher sensitivity, interpretation of staining results with TPO was generally easier with than Tg. All metastatic lung adenocarcinomas were positive for TTF-1 and TPO negative. The six medullary cancers showed positivity in 17%, 0% and 83% with TPO, Tg and TTF-1, respectively. TPO (mAb EP159) may be a useful addition to immunohistochemical panels for FNA specimens where metastatic PTC is a consideration, particularly in cases where metastatic lung carcinoma features in the differential diagnosis. © 2018 John Wiley & Sons Ltd.

Thyroid Disorders Overview

MedlinePlus

... state, with many body systems developing abnormal function. Hypothyroidism Too little thyroid hormone from an underactive thyroid gland is called hypothyroidism. In hypothyroidism, the body's metabolism is slowed. Several ...

Precipitation of the thyrotropin receptor and identification of thyroid autoantigens using Graves' disease immunoglobulins.

PubMed Central

Heyma, P; Harrison, L C

1984-01-01

The thyrotropin (TSH) receptor is a putative target for autoantibodies in Graves' hyperthyroidism and therefore, should be capable of being identified, isolated, and structurally characterized by immunological means. To this end, four sera from patients with hyperthyroidism, three of which inhibited the binding of 125I-TSH to Triton-solubilized human thyroid membranes, were used to isolate TSH receptors by immunoprecipitation. To account for an effect of TSH binding or receptor occupancy on the ability of Graves' immunoglobulins to precipitate TSH receptors, two approaches were taken: (a) specific 125I-TSH binding activity was measured after solubilized thyroid membranes had been incubated with Graves' sera followed by precipitation with Staphylococcus protein A ("receptor depletion"); (b) TSH binding sites were labeled with 125I-TSH and the complexes were precipitated using Graves' sera and Staphylococcus protein A ("receptor precipitation"). The three sera which inhibited 125I-TSH binding depleted 125I-TSH binding activity between 30-80%. Preformed complexes between Staphylococcus protein A and immunoglobulins in these sera were also able to deplete 125I-TSH binding activity. However, after receptor depletion, the one serum that did not inhibit 125I-TSH binding was associated with a significant increase in 125I-TSH binding. All four sera specifically precipitated 80-100% of receptors identified by prelabeling with 125I-TSH. The dilutions of sera that precipitated 50% of 125I-TSH-receptor complexes ranged from 1:150-1:20. Complexes were partially precipitated by high concentrations of control sera (1:20), but the relative potency of control sera was at least fourfold less than Graves' sera. Immunoprecipitates of 125I-labeled thyroid membranes were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography to reveal Graves'-specific bands of reduced molecular weights of 100-110,000, 80-90,000, and 70-75,000. These bands were similar

The BRAF{sup T1799A} mutation confers sensitivity of thyroid cancer cells to the BRAF{sup V600E} inhibitor PLX4032 (RG7204)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xing, Joanna; Liu, Ruixin; Xing, Mingzhao

2011-01-28

Research highlights: {yields} Exciting therapeutic potential has been recently reported for the BRAF{sup V600E} inhibitor PLX4032 in melanoma. {yields} We tested the effects of PLX4032 on the growth of thyroid cancer cells which often harbor the BRAF{sup V600E} mutation. {yields} We observed a potent BRAF{sup V600E}-dependent inhibition of thyroid cancer cells by PLX4032. {yields} We thus demonstrated an important therapeutic potential of PLX4032 for thyroid cancer. -- Abstract: Aberrant signaling of the Ras-Raf-MEK-ERK (MAP kinase) pathway driven by the mutant kinase BRAF{sup V600E}, as a result of the BRAF{sup T1799A} mutation, plays a fundamental role in thyroid tumorigenesis. This studymore » investigated the therapeutic potential of a BRAF{sup V600E}-selective inhibitor, PLX4032 (RG7204), for thyroid cancer by examining its effects on the MAP kinase signaling and proliferation of 10 thyroid cancer cell lines with wild-type BRAF or BRAF{sup T1799A} mutation. We found that PLX4032 could effectively inhibit the MAP kinase signaling, as reflected by the suppression of ERK phosphorylation, in cells harboring the BRAF{sup T1799A} mutation. PLX4032 also showed a potent and BRAF mutation-selective inhibition of cell proliferation in a concentration-dependent manner. PLX4032 displayed low IC{sub 50} values (0.115-1.156 {mu}M) in BRAF{sup V600E} mutant cells, in contrast with wild-type BRAF cells that showed resistance to the inhibitor with high IC{sub 50} values (56.674-1349.788 {mu}M). Interestingly, cells with Ras mutations were also sensitive to PLX4032, albeit moderately. Thus, this study has confirmed that the BRAF{sup T1799A} mutation confers cancer cells sensitivity to PLX4032 and demonstrated its specific potential as an effective and BRAF{sup T1799A} mutation-selective therapeutic agent for thyroid cancer.« less

Increases in thyroid nodule fine-needle aspirations, operations, and diagnoses of thyroid cancer in the United States.

PubMed

Sosa, Julie Ann; Hanna, John W; Robinson, Karen A; Lanman, Richard B

2013-12-01

To provide population-based estimates of trends in thyroid nodule fine-needle aspirations (FNA) and operative volumes, we used multiple claims databases to quantify rates of these procedures and their association with the increasing incidence of thyroid cancer in the United States. Private and public insurance claims databases were used to estimate procedure volumes from 2006 to 2011. Rates of FNA and thyroid operations related to thyroid nodules were defined by CPT4 codes associated with International Classification of Diseases, Ninth Revision Clinical Modification codes for nontoxic uni- or multinodular goiter and thyroid neoplasms. Use of thyroid FNA more than doubled during the 5-year study period (16% annual growth). The number of thyroid operations performed for thyroid nodules increased by 31%. Total thyroidectomies increased by 12% per year, whereas lobectomies increased only 1% per year. In 2011, total thyroidectomies accounted for more than half (56%) of the operations for thyroid neoplasms in the United States. Thyroid operations became increasingly (62%) outpatient procedures. Thyroid FNA and operative procedures have increased rapidly in the United States, with an associated increase in the incidence of thyroid cancer. The more substantial increase in number of total versus partial thyroid resections suggests that patients undergoing thyroid operation are perceived to have a greater risk of cancer as determined by preoperative assessments, but this trend could also increase detection of incidental microcarcinomas. Copyright © 2013 Mosby, Inc. All rights reserved.

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet and Health Study

PubMed Central

Kilfoy, Briseis A.; Zhang, Yawei; Park, Yikyung; Holford, Theodore R.; Schatzkin, Arthur; Hollenbeck, Albert; Ward, Mary H.

2010-01-01

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50–71 years in 1995–1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk (RR) for the highest quintile versus lowest quintile RR=2.28, 95% CI: 1.29–4.04l; p-trend <0.001); however, we observed no trend with intake among women (p-trend=0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95%CI: 1.09–4.05; p-trend=0.05) and follicular thyroid cancer (RR= 3.42; 95%CI: 1.03–11.4; p-trend=0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR= 2.74; 95%CI: 0.86–8.77; p-trend=0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted. PMID:20824705

Dietary nitrate and nitrite and the risk of thyroid cancer in the NIH-AARP Diet and Health Study.

PubMed

Kilfoy, Briseis A; Zhang, Yawei; Park, Yikyung; Holford, Theodore R; Schatzkin, Arthur; Hollenbeck, Albert; Ward, Mary H

2011-07-01

During the past several decades, an increasing incidence of thyroid cancer has been observed worldwide. Nitrate inhibits iodide uptake by the thyroid, potentially disrupting thyroid function. An increased risk of thyroid cancer associated with nitrate intake was recently reported in a cohort study of older women in Iowa. We evaluated dietary nitrate and nitrite intake and thyroid cancer risk overall and for subtypes in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study, a large prospective cohort of 490,194 men and women, ages 50-71 years in 1995-1996. Dietary intakes were assessed using a 124-item food frequency questionnaire. During an average of 7 years of follow-up we identified 370 incident thyroid cancer cases (170 men, 200 women) with complete dietary information. Among men, increasing nitrate intake was positively associated with thyroid cancer risk (relative risk [RR] for the highest quintile versus lowest quintile RR = 2.28, 95% confidence interval [CI]: 1.29-4.041; p-trend <0.001); however, we observed no trend with intake among women (p-trend = 0.61). Nitrite intake was not associated with risk of thyroid cancer for either men or women. We evaluated risk for the two main types of thyroid cancer. We found positive associations for nitrate intake and both papillary (RR = 2.10; 95% CI: 1.09-4.05; p-trend = 0.05) and follicular thyroid cancer (RR = 3.42; 95% CI: 1.03-11.4; p-trend = 0.01) among men. Nitrite intake was associated with increased risk of follicular thyroid cancer (RR = 2.74; 95%CI: 0.86-8.77; p-trend = 0.04) among men. Our results support a role of nitrate in thyroid cancer risk and suggest that further studies to investigate these exposures are warranted. Published 2010 UICC.

Thyroid Disease Around the World.

PubMed

Maniakas, Anastasios; Davies, Louise; Zafereo, Mark E

2018-06-01

Thyroid disease is one of the most common pathologies in the world, with two of the most clinically important subgroups being iodine deficiency and thyroid goiter, and thyroid cancer. This review looks at the current state of thyroid disease in the world and evaluates the future direction in terms of thyroid disease treatment and prevention. Several of the most impactful epidemiologic studies are presented and analyzed, as well as a brief overview of the current socioeconomic burden of disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Disguised Thyroid Disorders

PubMed Central

Tsao, John M.; Catz, Boris

1965-01-01

In six cases of hyperthyroidism and two of chronic thyroiditis herein described, the initial features of the diseases were misinterpreted as attributable to other kinds of illness such as myocardial infarction, gastrointestinal malignant disease, malabsorption syndrome, psychosis, simple exophthalmos and endemic goiter. The characteristic signs and symptoms of hyperthyroidism (in six patients) and chronic thyroiditis (in two patients) were present at the outset but were not identified. Intensive questioning and alertness were required to elicit these characteristics. The symptoms improved or disappeared after the true disease was controlled. In the studies of these cases, the usefulness of a number of laboratory tests was illustrated—thyroid suppression studies, 4 to 6-hour and 24-hour radioactive iodine uptake, T3 uptake by the red cells and determinations of 24-hour urine creatine, antithyroglobulin antibody titer and long-acting thyroid stimulating hormone. The manifestations of thyroid diseases are many and varied. The term “masked hyperthyroidism” may in part be a reflection of the “masked physician” unless he uses his clinical detective abilities. PMID:14347981

Change of body height is regulated by thyroid hormone during metamorphosis in flatfishes and zebrafish.

PubMed

Xu, Juan; Ke, Zhonghe; Xia, Jianhong; He, Fang; Bao, Baolong

2016-09-15

Flatfishes with more body height after metamorphosis should be better adapted to a benthic lifestyle. In this study, we quantified the changes in body height during metamorphosis in two flatfish species, Paralichthys olivaceus and Platichthys stellatus. The specific pattern of cell proliferation along the dorsal and ventral edge of the body to allow fast growth along the dorsal/ventral axis might be related to the change of body height. Thyroid hormone (T4 and T3) and its receptors showed distribution or gene expression patterns similar to those seen for the cell proliferation. 2-Mercapto-1-methylimidazole, an inhibitor of endogenous thyroid hormone synthesis, inhibited cell proliferation and decreased body height, suggesting that the change in body shape was dependent on the local concentration of thyroid hormone to induce cell proliferation. In addition, after treatment with 2-mercapto-1-methylimidazole, zebrafish larvae were also shown to develop a slimmer body shape. These findings enrich our knowledge of the role of thyroid hormone during flatfish metamorphosis, and the role of thyroid hormone during the change of body height during post-hatching development should help us to understand better the biology of metamorphosis in fishes. Copyright © 2016 Elsevier Inc. All rights reserved.

Thyroid storm: an updated review.

PubMed

Chiha, Maguy; Samarasinghe, Shanika; Kabaker, Adam S

2015-03-01

Thyroid storm, an endocrine emergency first described in 1926, remains a diagnostic and therapeutic challenge. No laboratory abnormalities are specific to thyroid storm, and the available scoring system is based on the clinical criteria. The exact mechanisms underlying the development of thyroid storm from uncomplicated hyperthyroidism are not well understood. A heightened response to thyroid hormone is often incriminated along with increased or abrupt availability of free hormones. Patients exhibit exaggerated signs and symptoms of hyperthyroidism and varying degrees of organ decompensation. Treatment should be initiated promptly targeting all steps of thyroid hormone formation, release, and action. Patients who fail medical therapy should be treated with therapeutic plasma exchange or thyroidectomy. The mortality of thyroid storm is currently reported at 10%. Patients who have survived thyroid storm should receive definite therapy for their underlying hyperthyroidism to avoid any recurrence of this potentially fatal condition. © The Author(s) 2013.

[Alternative approaches in thyroid surgery].

PubMed

Maurer, E; Wächter, S; Bartsch, D K

2017-08-01

In thyroid surgery multiple different cervical minimally invasive (partly endoscopically assisted) and extracervical endoscopic (partly robot-assisted) approaches have been developed in the last 20 years. The aim of all these alternative approaches to the thyroid gland is optimization of the cosmetic result. The indications for the use of alternative and conventional approaches are principally the same. Important requirements for the use of alternative methods are nevertheless a broad experience in conventional thyroid operations of the thyroid and adequate patient selection under consideration of the size of the thyroid and the underlying pathology. Contraindications for the use of alternative approaches are a large size of the thyroid gland including local symptoms, advanced carcinomas, reoperations and previous radiations of the anterior neck. The current article gives an overview of the clinically implemented alternative approaches for thyroid surgery. Of those the majority must still be considered as experimental. The alternative approaches to the thyroid gland can be divided in cervical minimally invasive, extracervical endosopic (robot-assisted) and transoral operations (natural orifice transluminal endoscopic surgery, NOTES). Since conventional thyroid operations are standardized procedures with low complication rates, alternative approaches to the thyroid gland are considered critically in Germany. The request for a perfect cosmetic result should not overweigh patients' safety. Only a few alternative approaches (e. g. MIVAT, RAT) can yet be considered as a safe addition in experienced hands in highly selected patients.

Iodine deficiency and thyroid disorders.

PubMed

Zimmermann, Michael B; Boelaert, Kristien

2015-04-01

Iodine deficiency early in life impairs cognition and growth, but iodine status is also a key determinant of thyroid disorders in adults. Severe iodine deficiency causes goitre and hypothyroidism because, despite an increase in thyroid activity to maximise iodine uptake and recycling in this setting, iodine concentrations are still too low to enable production of thyroid hormone. In mild-to-moderate iodine deficiency, increased thyroid activity can compensate for low iodine intake and maintain euthyroidism in most individuals, but at a price: chronic thyroid stimulation results in an increase in the prevalence of toxic nodular goitre and hyperthyroidism in populations. This high prevalence of nodular autonomy usually results in a further increase in the prevalence of hyperthyroidism if iodine intake is subsequently increased by salt iodisation. However, this increase is transient because iodine sufficiency normalises thyroid activity which, in the long term, reduces nodular autonomy. Increased iodine intake in an iodine-deficient population is associated with a small increase in the prevalence of subclinical hypothyroidism and thyroid autoimmunity; whether these increases are also transient is unclear. Variations in population iodine intake do not affect risk for Graves' disease or thyroid cancer, but correction of iodine deficiency might shift thyroid cancer subtypes toward less malignant forms. Thus, optimisation of population iodine intake is an important component of preventive health care to reduce the prevalence of thyroid disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Management of hyperfunctioning single thyroid nodules in the era of minimally invasive thyroid surgery.

PubMed

Tan, Charles; Sidhu, Stan; Sywak, Mark; Delbridge, Leigh

2009-05-01

Both surgical excision and radioiodine ablation are effective modalities in the management of hyperfunctioning thyroid nodules. Minimally invasive thyroid surgery (MITS) using the lateral mini-incision approach has previously been demonstrated to be a safe and effective technique for thyroid lobectomy. As such MITS may offer advantages as a surgical approach to hyperfunctioning thyroid nodules without the need for a long cervical incision or extensive dissection associated with formal open hemithyroidectomy. The aim of the present study was to assess the safety and efficacy of MITS for the treatment of hyperfunctioning thyroid nodules. This is a retrospective case study. Data were obtained from the University of Sydney Endocrine Surgical Unit Database from 2002 to 2007. There were 86 cases of hyperfunctioning thyroid nodules surgically removed during the study period, of which 10 (12%) were managed using the MITS approach. The ipsilateral recurrent laryngeal nerve was identified and preserved in all cases with no incidence of temporary or permanent nerve palsy. The external branch of the superior laryngeal nerve was visualized and preserved in eight cases (80%). There were no cases of postoperative bleeding. There was one clinically significant follicular thyroid carcinoma in the series (10%). In nine of 10 cases (90%) normalization of thyroid function followed surgery. MITS is a safe and effective procedure, achieving the benefits of a minimally invasive procedure with minimal morbidity. As such it now presents an attractive alternative to radioiodine ablation for the management of small hyperfunctioning thyroid nodules.

Thyroid Swelling and Thyroiditis in the Setting of Recent hCG Injections and Fine Needle Aspiration

PubMed Central

Lamos, Elizabeth M.; Munir, Kashif M.

2016-01-01

A 60-year-old woman presented with a neck mass and underwent fine needle aspiration of a left thyroid nodule. During this time, she had been injected with hCG for weight loss. Soon after, she developed rapid diffuse thyroid growth with pain. She was ultimately diagnosed with thyrotoxicosis due to postaspiration subacute thyroiditis and subsequently became hypothyroid. This condition is rare in the nonpregnant state in noncystic nodules with a smaller needle gauge approach. The incidence of thyroid nodule discovery and evaluation is increasing. As more procedures are undertaken, understanding of potential complications is important. This case highlights potential complications of thyroid fine needle aspiration including diffuse thyroid swelling and thyroiditis. The role of hCG injections is speculated to have potentially stimulated thyroid follicular epithelium via cross-reactivity with the TSH receptor and contributed to the acute inflammatory response after fine needle aspiration. PMID:26942022

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

PubMed Central

Anderson, Grant; Forrest, Douglas; Galton, Valerie Anne; Gereben, Balázs; Kim, Brian W.; Kopp, Peter A.; Liao, Xiao Hui; Obregon, Maria Jesus; Peeters, Robin P.; Refetoff, Samuel; Sharlin, David S.; Simonides, Warner S.; Weiss, Roy E.; Williams, Graham R.

2014-01-01

Background: An in-depth understanding of the fundamental principles that regulate thyroid hormone homeostasis is critical for the development of new diagnostic and treatment approaches for patients with thyroid disease. Summary: Important clinical practices in use today for the treatment of patients with hypothyroidism, hyperthyroidism, or thyroid cancer are the result of laboratory discoveries made by scientists investigating the most basic aspects of thyroid structure and molecular biology. In this document, a panel of experts commissioned by the American Thyroid Association makes a series of recommendations related to the study of thyroid hormone economy and action. These recommendations are intended to promote standardization of study design, which should in turn increase the comparability and reproducibility of experimental findings. Conclusions: It is expected that adherence to these recommendations by investigators in the field will facilitate progress towards a better understanding of the thyroid gland and thyroid hormone dependent processes. PMID:24001133

Thyroid Function Tests

MedlinePlus

... problem that is directly affecting the thyroid (primary hypothyroidism). The opposite situation, in which the TSH level ... making enough TSH to stimulate the thyroid (secondary hypothyroidism). In most healthy individuals, a normal TSH value ...

A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo

PubMed Central

Machado, Danielle S.; Sabet, Amin; Santiago, Leticia A.; Sidhaye, Aniket R.; Chiamolera, Maria I.; Ortiga-Carvalho, Tania M.; Wondisford, Fredric E.

2009-01-01

Resistance to thyroid hormone (RTH) is most often due to point mutations in the β-isoform of the thyroid hormone (TH) receptor (TR-β). The majority of mutations involve the ligand-binding domain, where they block TH binding and receptor function on both stimulatory and inhibitory TH response elements. In contrast, a few mutations in the ligand-binding domain are reported to maintain TH binding and yet cause RTH in certain tissues. We introduced one such naturally occurring human RTH mutation (R429Q) into the germline of mice at the TR-β locus. R429Q knock-in (KI) mice demonstrated elevated serum TH and inappropriately normal thyroid-stimulating hormone (TSH) levels, consistent with hypothalamic–pituitary RTH. In contrast, 3 hepatic genes positively regulated by TH (Dio1, Gpd1, and Thrsp) were increased in R429Q KI animals. Mice were then rendered hypothyroid, followed by graded T3 replacement. Hypothyroid R429Q KI mice displayed elevated TSH subunit mRNA levels, and T3 treatment failed to normally suppress these levels. T3 treatment, however, stimulated pituitary Gh levels to a greater degree in R429Q KI than in control mice. Gsta, a hepatic gene negatively regulated by TH, was not suppressed in R429Q KI mice after T3 treatment, but hepatic Dio1 and Thrsp mRNA levels increased in response to TH. Cardiac myosin heavy chain isoform gene expression also showed a specific defect in TH inhibition. In summary, the R429Q mutation is associated with selective impairment of TH-mediated gene repression, suggesting that the affected domain, necessary for TR homodimerization and corepressor binding, has a critical role in negative gene regulation by TH. PMID:19439650

The Impact of Thyroid Autoimmunity on Thyroid Function in 12-year-old Children With Celiac Disease.

PubMed

Norström, Fredrik; van der Pals, Maria; Myléus, Anna; Hammarroth, Solveig; Högberg, Lotta; Isaksson, Anders; Ivarsson, Anneli; Carlsson, Annelie

2018-01-25

Celiac disease (CD) is associated with thyroid autoimmunity and other autoimmune diseases. However, data are lacking regarding the relationship between thyroid autoimmunity and thyroid function, especially in regard to CD. Our aim was to investigate the impact of thyroid autoimmunity on thyroid function in 12-year-old children with CD compared to their healthy peers. A case-referent study was conducted as part of a CD screening of 12-year-olds. Our study included 335 children with CD and 1,695 randomly selected referents. Thyroid autoimmunity was assessed with antibodies against thyroid peroxidase (TPOAb). Thyroid function was assessed with thyroid stimulating hormone and free thyroxine. TPOAb positivity significantly increased the risk of developing hypothyroidism in all children. The odds ratios (with 95% confidence intervals) were: 5.3 (2.7-11) in healthy 12-year-olds, 10 (3.2-32) in screening-detected CD cases, 19 (2.6-135) in previously diagnosed CD cases, and 12 (4.4-32) in all CD cases together. Among children with TPOAb positivity, hypothyroidism was significantly more common (odds ratio 3.1; 95% CI 1.03-9.6) in children with CD (10/19) than in children without CD (12/46). The risk of thyroid dysfunction due to thyroid autoimmunity is larger for those with CD than their healthy peers. Our study indicate that a gluten-free diet does not reduce the risk of thyroid dysfunction. Further studies are required for improved understanding of the role of the gluten-free diet for the risk of autoimmune diseases in children with CD.

Breaking Tolerance in Transgenic Mice Expressing the Human TSH Receptor A-Subunit: Thyroiditis, Epitope Spreading and Adjuvant as a ‘Double Edged Sword’

PubMed Central

McLachlan, Sandra M.; Aliesky, Holly A.; Chen, Chun-Rong; Chong, Gao; Rapoport, Basil

2012-01-01

Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a “double-edged sword”. On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the

Radiofrequency Ablation of Benign Thyroid Nodules and Recurrent Thyroid Cancers: Consensus Statement and Recommendations

PubMed Central

Na, Dong Gyu; Lee, Jeong Hyun; Jung, So Lyung; Kim, Ji-hoon; Sung, Jin Yong; Shin, Jung Hee; Kim, Eun-Kyung; Lee, Joon Hyung; Kim, Dong Wook; Park, Jeong Seon; Kim, Kyu Sun; Baek, Seon Mi; Lee, Younghen; Chong, Semin; Sim, Jung Suk; Huh, Jung Yin; Bae, Jae-Ik; Kim, Kyung Tae; Han, Song Yee; Bae, Min Young; Kim, Yoon Suk

2012-01-01

Thermal ablation using radiofrequency is a new, minimally invasive modality employed as an alternative to surgery in patients with benign thyroid nodules and recurrent thyroid cancers. The Task Force Committee of the Korean Society of Thyroid Radiology has developed recommendations for the optimal use of radiofrequency ablation for thyroid nodules. These recommendations are based on a comprehensive analysis of the current literature, the results of multicenter studies, and expert consensus. PMID:22438678

[Advances in postoperative thyroid-stimulating hormone suppression therapy in females with thyroid cancer].

PubMed

Song, F; Yi, H L

2018-05-07

Differentiated thyroid cancer is the most common malignant carcinoma in female population.Postoperative long-term thyroid-stimulating hormone(TSH) suppression therapy can reduce the risk of recurrence for differentiated thyroid cancer and control the progress of the disease, but it also induces simultaneously subclinical hypothyroidism and imposes negative effect on female. In addition to cardiovascular disease, TSH suppression therapy can lead to the alteration of sex hormone metabolism, menstrual disorder, poor influence on pregnancy and osteoporosis. This article reviews the recent studies on postoperative TSH suppression therapy in women with thyroid cancer.

Environmental Issues in Thyroid Diseases.

PubMed

Ferrari, Silvia Martina; Fallahi, Poupak; Antonelli, Alessandro; Benvenga, Salvatore

2017-01-01

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves' disease and Graves' ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction.

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horton, Megan K., E-mail: megan.horton@mssm.edu; Blount, Benjamin C.; Valentin-Blasini, Liza

Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New Yorkmore » City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal

Genetic and environmental influence on thyroid gland volume and thickness of thyroid isthmus: a twin study.

PubMed

Tarnoki, Adam Domonkos; Tarnoki, David Laszlo; Speer, Gabor; Littvay, Levente; Bata, Pal; Garami, Zsolt; Berczi, Viktor; Karlinger, Kinga

2015-12-01

Decreased thyroid volume has been related to increased prevalence of thyroid cancer. One hundred and fourteen Hungarian adult twin pairs (69 monozygotic, 45 dizygotic) with or without known thyroid disorders underwent thyroid ultrasound. Thickness of the thyroid isthmus was measured at the thickest portion of the gland in the midline using electronic calipers at the time of scanning. Volume of the thyroid lobe was computed according to the following formula: thyroid height*width*depth*correction factor (0.63). Age-, sex-, body mass index- and smoking-adjusted heritability of the thickness of thyroid isthmus was 50% (95% confidence interval [CI], 35 to 66%). Neither left nor right thyroid volume showed additive genetic effects, but shared environments were 68% (95% CI, 48 to 80%) and 79% (95% CI, 72 to 87%), respectively. Magnitudes of monozygotic and dizygotic co-twin correlations were not substantially impacted by the correction of covariates of body mass index and smoking. Unshared environmental effects showed a moderate influence on dependent parameters (24-50%). Our analysis support that familial factors are important for thyroid measures in a general twin population. A larger sample size is needed to show whether this is because of common environmental (e.g. intrauterine effects, regional nutrition habits, iodine supply) or genetic effects.

Thyroid abnormalities after therapeutic external radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hancock, S.L.; McDougall, I.R.; Constine, L.S.

1995-03-30

The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves` disease or euthyroid Graves` ophthalmopathy. Silent thyroiditis, cystic degeneration, benignmore » adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity. 39 refs.« less

Thyroid Ultrasonography in Differentiation between Graves' Disease and Hashimoto's Thyroiditis.

PubMed

Pishdad, P; Pishdad, G R; Tavanaa, S; Pishdad, R; Jalli, R

2017-03-01

Graves' disease and Hashimoto's thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves' disease from Hashimoto's thyroiditis. This study included 149 patients divided into three groups, patients with Graves' disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto's thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves' was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto's group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves' group with 100% and 17.6% specificity and sensitivity, respectively. Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves' disease or Hashimoto's thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed.

Thyroid cell lines in research on goitrogenesis.

PubMed

Gerber, H; Peter, H J; Asmis, L; Studer, H

1991-12-01

Thyroid cell lines have contributed a lot to the understanding of goitrogenesis. The cell lines mostly used in thyroid research are briefly discussed, namely the rat thyroid cell lines FRTL and FRTL-5, the porcine thyroid cell lines PORTHOS and ARTHOS, The sheep thyroid cell lines OVNIS 5H and 6H, the cat thyroid cell lines PETCAT 1 to 4 and ROMCAT, and the human thyroid cell lines FTC-133 and HTh 74. Chinese hamster ovary (CHO) cells and COS-7 cells, stably transfected with TSH receptor cDNA and expressing a functional TSH receptor, are discussed as examples for non-thyroidal cells, transfected with thyroid genes.

TSH (Thyroid-stimulating hormone) test

MedlinePlus

... your blood ( hyperthyroidism ), or too little thyroid hormone ( hypothyroidism ). Symptoms of hyperthyroidism, also known as overactive thyroid, ... Bulging of the eyes Difficulty sleeping Symptoms of hypothyroidism, also known as underactive thyroid, include: Weight gain ...

Clear cell variant of follicular thyroid carcinoma with normal thyroid-stimulating hormone value: a case report

PubMed Central

2014-01-01

Introduction Clear cell carcinomas of the thyroid gland with normal thyroid-stimulating hormone value are very rare, but clear cell changes are described in most reported cases of thyroidal lesions. Case presentation In this report, we describe the case of a 50-year-old Caucasian woman with a normal thyroid-stimulating hormone level who underwent surgery to treat a multi-nodular goiter. The pathology was a clear cell variant of follicular thyroid carcinoma. The tumor was 1cm in diameter and consisted of pure clear cells. Conclusion Clear cell variants of follicular thyroid carcinoma are rarely seen, especially it is misdiagnosed with metastatic renal cell carcinoma. In this report, we describe the case of a patient with a clear cell variant of follicular thyroid carcinoma with an interesting pathology. PMID:24884725

[Lymph node and distant metastases of thyroid gland cancer. Metastases in the thyroid glands].

PubMed

Schmid, K W

2015-11-01

The different biological features of the various major entities of thyroid cancer, e.g. papillary, follicular, poorly differentiated, anaplastic and medullary, depend to a large extent on their different metastatic spread. Papillary thyroid cancer (PTC) has a propensity for cervical lymphatic spread that occurs in 20-50 % of patients whereas distant metastasis occurs in < 5 % of cases. Cervical lymphadenopathy may be the first symptom particularly of (micro) PTC. In contrast follicular thyroid cancer (FTC) has a marked propensity for vascular but not lymphatic invasion and 10-20 % of FTC develop distant metastases. At the time of diagnosis approximately one third of medullary thyroid cancer (MTC) cases show lymph node metastases, in 10-15 % distant metastases and 25 % develop metastases during the course of the disease. Poorly differentiated (PDTC) and anaplastic thyroid cancer (ATC) spread via both lymphatic and vascular invasion. Thus distant metastases are relatively uncommon in DTC and when they occur, long-term stable disease is the typical clinical course. The major sites of distant metastases are the lungs and bone. Metastases to the brain, breasts, liver, kidneys, muscle and skin are relatively rare or even rare. The thyroid gland itself can be a site of metastases from a variety of other tumors. In autopsy series of patients with disseminated cancer disease, metastases to the thyroid gland were found in up to 10 % of cases. Metastases from other primary tumors to the thyroid gland have been reported in 1.4-3 % of patients who have surgery for suspected cancer of the thyroid gland. The most common primary cancers that metastasize to the thyroid gland are renal cell (48.1 %), colorectal (10.4 %), lung (8.3 %) and breast cancer (7.8 %) and surprisingly often sarcomas (4.0 %).

Triple ectopic thyroid: A rare entity

PubMed Central

Nilegaonkar, Sujit; Naik, Chetna; Sonar, Sameer; Hirawe, Deepti

2011-01-01

Ectopic thyroid tissue is an uncommon congenital aberration. It is extremely rare to have three ectopic foci at three different sites. The thyroid scan has been used successfully to diagnose ectopic thyroid tissue. We report a case of ectopic thyroid tissue at base of tongue, another at the level of hyoid and third one as aberrant tissue at suprahyoid location in a 16 year old female who presented with swelling in front of neck. This patient was clinically diagnosed as thyroglossal cyst and was being planned for surgery. Preoperative thyroid scan helped in establishing diagnosis of ectopic thyroid which was the only functioning thyroid tissue. Thus, it prevented unnecessary surgery. Therefore it is suggested that thyroid scan and USG/CT scan must be done as routine work up in neck swellings pre operatively to avoid unnecessary surgeries. PMID:23559716

Relational Stability of Thyroid Hormones in Euthyroid Subjects and Patients with Autoimmune Thyroid Disease

PubMed Central

Hoermann, Rudolf; Midgley, John E.M.; Larisch, Rolf; Dietrich, Johannes W.

2016-01-01

Background/Aim Operating far from its equilibrium resting point, the thyroid gland requires stimulation via feedback-controlled pituitary thyrotropin (TSH) secretion to maintain adequate hormone supply. We explored and defined variations in the expression of control mechanisms and physiological responses across the euthyroid reference range. Methods We analyzed the relational equilibria between thyroid parameters defining thyroid production and thyroid conversion in a group of 271 thyroid-healthy subjects and 86 untreated patients with thyroid autoimmune disease. Results In the euthyroid controls, the FT3-FT4 (free triiodothyronine-free thyroxine) ratio was strongly associated with the FT4-TSH ratio (tau = −0.22, p < 0.001, even after correcting for spurious correlation), linking T4 to T3 conversion with TSH-standardized T4 production. Using a homeostatic model, we estimated both global deiodinase activity and maximum thyroid capacity. Both parameters were nonlinearly and inversely associated, trending in opposite directions across the euthyroid reference range. Within the panel of controls, the subgroup with a relatively lower thyroid capacity (<2.5 pmol/s) displayed lower FT4 levels, but maintained FT3 at the same concentrations as patients with higher functional and anatomical capacity. The relationships were preserved when extended to the subclinical range in the diseased sample. Conclusion The euthyroid panel does not follow a homogeneous pattern to produce random variation among thyroid hormones and TSH, but forms a heterogeneous group that progressively displays distinctly different levels of homeostatic control across the euthyroid range. This suggests a concept of relational stability with implications for definition of euthyroidism and disease classification. PMID:27843807

Potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in papillary thyroid cancer.

PubMed

Zeng, Rui-Chao; Jin, Lang-Ping; Chen, En-Dong; Dong, Si-Yang; Cai, Ye-Feng; Huang, Guan-Li; Li, Quan; Jin, Chun; Zhang, Xiao-Hua; Wang, Ou-Chen

2016-04-01

The purpose of this study was to evaluate the potential relationship between Hashimoto's thyroiditis and BRAF(V600E) mutation status in patients with papillary thyroid carcinoma (PTC). A total of 619 patients with PTC who underwent total thyroidectomy with lymph node dissection were enrolled in this study. Univariable and multivariate analyses were used. Hashimoto's thyroiditis was present in 35.9% (222 of 619) of PTCs. Multivariate logistic regressions showed that BRAF(V600E) mutation, sex, extrathyroidal extension, and lymph node metastasis were independent factors for Hashimoto's thyroiditis. Female sex, more frequent extrathyroidal extension, and a higher incidence of lymph node metastasis were significantly associated with PTCs accompanied by BRAF(V600E) mutation without Hashimoto's thyroiditis compared with PTCs accompanied by BRAF(V600E) mutation with Hashimoto's thyroiditis. Hashimoto's thyroiditis was negatively associated with BRAF(V600E) mutation, extrathyroidal extension, and lymph node metastasis. In addition, Hashimoto's thyroiditis was related to less lymph node metastasis and extrathyroidal extension in PTCs with BRAF(V600E) mutation. Therefore, Hashimoto's thyroiditis is a potentially protective factor in PTC. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1019-E1025, 2016. © 2015 Wiley Periodicals, Inc.

Thyroid disorders in older adults.

PubMed

Visser, W Edward; Visser, Theo J; Peeters, Robin P

2013-06-01

This article summarizes the current literature about serum thyroid parameters and thyroid disease during aging. Changes in thyroid function tests may be part of the physiology of aging, after exclusion of confounding variables. Overt thyroid disease requires immediate treatment. Treatment of subclinical hyperthyroidism in the elderly can be advocated, while watchful waiting may be an appropriate approach for subclinical hypothyroidism. Copyright © 2013 Elsevier Inc. All rights reserved.

American Thyroid Association Statement on Remote-Access Thyroid Surgery.

PubMed

Berber, Eren; Bernet, Victor; Fahey, Thomas J; Kebebew, Electron; Shaha, Ashok; Stack, Brendan C; Stang, Michael; Steward, David L; Terris, David J

2016-03-01

Remote-access techniques have been described over the recent years as a method of removing the thyroid gland without an incision in the neck. However, there is confusion related to the number of techniques available and the ideal patient selection criteria for a given technique. The aims of this review were to develop a simple classification of these approaches, describe the optimal patient selection criteria, evaluate the outcomes objectively, and define the barriers to adoption. A review of the literature was performed to identify the described techniques. A simple classification was developed. Technical details, outcomes, and the learning curve were described. Expert opinion consensus was formulated regarding recommendations for patient selection and performance of remote-access thyroid surgery. Remote-access thyroid procedures can be categorized into endoscopic or robotic breast, bilateral axillo-breast, axillary, and facelift approaches. The experience in the United States involves the latter two techniques. The limited data in the literature suggest long operative times, a steep learning curve, and higher costs with remote-access thyroid surgery compared with conventional thyroidectomy. Nevertheless, a consensus was reached that, in appropriate hands, it can be a viable option for patients with unilateral small nodules who wish to avoid a neck incision. Remote-access thyroidectomy has a role in a small group of patients who fit strict selection criteria. These approaches require an additional level of expertise, and therefore should be done by surgeons performing a high volume of thyroid and robotic surgery.

HASHIMOTO THYROIDITIS AND VESTIBULAR DYSFUNCTION.

PubMed

Chiarella, Giuseppe; Russo, Diego; Monzani, Fabio; Petrolo, Claudio; Fattori, Bruno; Pasqualetti, Giuseppe; Cassandro, Ettore; Costante, Giuseppe

2017-07-01

The aim of this review was to analyze the existing literature concerning the relationship between Hashimoto thyroiditis (HT) and vestibular dysfunction. We used electronic databases (PubMed, EMBASE, Cochrane Library) to search and collect all published articles about the association between HT and vestibular disorders. Several observational and retrospective studies have postulated a relationship between thyroid autoimmunity and vestibular disorders. In most cases, an appropriate control group was lacking, and the impact of thyroid functional status could not precisely be established. In recent years, two well-designed prospective studies have provided convincing evidence that the association is not random. One article reported that patients with Ménière disease (MD) had a significantly higher prevalence of positive anti-thyroid autoantibody as compared to healthy controls. Moreover, more than half of MD patients had either positive anti-thyroid or non-organ-specific autoantibody titers, compared to less than 30% of both patients with unilateral vestibular paresis without cochlear involvement and healthy controls. Another study found that patients with benign paroxysmal positional vertigo (BPPV) had significantly higher serum thyroid-stimulating hormone and antithyroid autoantibody levels than healthy controls. Additionally, almost one-fifth of euthyroid patients with HT had signs of BPPV. The published results indicate that patients with MD or BPPV are potential candidates to also develop HT. Thus, in HT patients, the presence of even slight symptoms or signs potentially related to vestibular lesions should be carefully investigated. AITD = autoimmune thyroid disease; BPPV = benign paroxysmal positional vertigo; EH = endolymphatic hydrops; HT = Hashimoto thyroiditis; L-T 4 = L-thyroxine; MD = Ménière disease; PS = Pendred syndrome; Tg = thyroglobulin; TPO = thyroid peroxidase; TSH = thyroid-stimulating hormone.

Acute exacerbation of Hashimoto thyroiditis mimicking anaplastic carcinoma of the thyroid: A complicated case.

PubMed

Kanaya, Hiroaki; Konno, Wataru; Fukami, Satoru; Hirabayashi, Hideki; Haruna, Shin-ichi

2014-12-01

The fibrous variant of Hashimoto thyroiditis is uncommon, accounting for approximately 10% of all cases of Hashimoto thyroiditis. We report a case of this variant that behaved like a malignant neoplasm. The patient was a 69-year-old man who presented with a right-sided anterior neck mass that had been rapidly growing for 2 weeks. Fine-needle aspiration cytology revealed clusters of large multinucleated cells suggestive of an anaplastic carcinoma. A week after presentation, we ruled out that possibility when the mass had shrunk slightly. Instead, we diagnosed the patient with an acute exacerbation of Hashimoto thyroiditis on the basis of laboratory findings. We performed a right thyroid lobectomy, including removal of the isthmus, to clarify the pathology and alleviate pressure symptoms. The final diagnosis was the fibrous variant of Hashimoto thyroiditis, with no evidence of malignant changes. Physicians should keep in mind that on rare occasions, Hashimoto thyroiditis mimics a malignant neoplasm.

Multifocal hyperfunctioning thyroid carcinoma without metastases.

PubMed

Nishida, Akiko T; Hirano, Shigeru; Asato, Ryo; Tanaka, Shinzo; Kitani, Yoshiharu; Honda, Nobumitsu; Fujiki, Nobuya; Miyata, Kouji; Fukushima, Hideyuki; Ito, Juichi

2008-09-01

Hyperthyroidism due to thyroid carcinoma is rare, and most cases are caused by hyperfunctioning metastatic thyroid carcinoma rather than primary carcinoma. Among primary hyperfunctioning thyroid carcinoma, multifocal thyroid carcinoma is exceedingly rare, with the only one case being reported in the literature. Here, we describe the case of a 62-year-old woman with multifocal functioning thyroid carcinoma. Technetium-99m (99m Tc) scintigraphic imaging showed four hot areas in the thyroid gland. Histopathological examination of all four nodules revealed papillary carcinoma, corresponding to hot areas in the 99m Tc scintigram. DNA sequencing of the thyrotropin receptor (TSH-R) gene from all nodules revealed no mutation, indicating that activation of TSH-R was unlikely in the pathophysiogenesis of hyperfunctioning thyroid carcinoma in the present case.

Anaplastic thyroid cancer

MedlinePlus

... M, Ladenson P. Thyroid. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 226. Lai SY, Mandel SJ, Weber RS. Management of thyroid neoplasms. In: Flint PW, Haughey BH, Lund LJ, et ...

Stimulation of generation of inositol phosphates by carbamoylcholine and its inhibition by phorbol esters and iodide in dog thyroid cells.

PubMed Central

Laurent, E; Mockel, J; Takazawa, K; Erneux, C; Dumont, J E

1989-01-01

The action of carbamoylcholine (Cchol), NaF and other agonists on the generation of inositol phosphates (IPs) was studied in dog thyroid slices prelabelled with myo-[2-3H]inositol. The stimulation by Cchol (0.1 microM-0.1 mM) of IPs accumulation through activation of a muscarinic receptor [Graff, Mockel, Laurent, Erneux & Dumont (1987) FEBS Lett. 210, 204-210] was pertussis- and cholera-toxin insensitive. Ins(1,4,5)P3, Ins(1,3,4)P3 and InsP4 were generated. NaF (5-20 mM) also increased IPs generation (Graff et al., 1987); this effect was potentiated by AlCl3 (10 microM) and unaffected by pertussis toxin. Although phorbol dibutyrate (5 microM) abolished the cholinergic stimulation of IPs generation (Graff et al., 1987), it did not affect the fluoride-induced response. Cchol and NaF did not require extracellular Ca2+ to exert their effect, and neither KCl-induced membrane depolarization nor ionophore A23187 (10 microM) had any influence on basal IPs levels, or on cholinergic stimulation. However, more stringent Ca2+ depletion with EGTA (0.1 or 1 mM) decreased basal IPs levels as well as the amplitude of the stimulation by Cchol without abolishing it. Dibutyryl cyclic AMP, forskolin, cholera toxin and prostaglandin E1 had no effect on basal IPs levels and did not decrease the response to Cchol. Iodide (4 or 40 microM) also strongly decreased the cholinergic action on IPs, this inhibition being relieved by methimazole (1 mM). Our data suggest that Cchol activates a phospholipase C hydrolysing PtdIns(4,5)P2 in the dog thyroid cell in a cyclic AMP-independent manner. This activation requires no extracellular Ca2+ and depends on a GTP-binding protein insensitive to both cholera toxin and requires no extracellular Ca2+ and depends on a GTP-binding protein insensitive to both cholera toxin and pertussis toxin. The data are consistent with a rapid metabolism of Ins(1,4,5)P3 to Ins(1,3,4)P3 via the Ins(1,4,5)P3 3-kinase pathway, followed by dephosphorylation by a 5

Nitrate intake and the risk of thyroid cancer and thyroid disease.

PubMed

Ward, Mary H; Kilfoy, Briseis A; Weyer, Peter J; Anderson, Kristin E; Folsom, Aaron R; Cerhan, James R

2010-05-01

Nitrate is a contaminant of drinking water in agricultural areas and is found at high levels in some vegetables. Nitrate competes with uptake of iodide by the thyroid, thus potentially affecting thyroid function. We investigated the association of nitrate intake from public water supplies and diet with the risk of thyroid cancer and self-reported hypothyroidism and hyperthyroidism in a cohort of 21,977 older women in Iowa who were enrolled in 1986 and who had used the same water supply for >10 years. We estimated nitrate ingestion from drinking water using a public database of nitrate measurements (1955-1988). Dietary nitrate intake was estimated using a food frequency questionnaire and levels from the published literature. Cancer incidence was determined through 2004. We found an increased risk of thyroid cancer with higher average nitrate levels in public water supplies and with longer consumption of water exceeding 5 mg/L nitrate-N (for >or=5 years at >5 mg/L, relative risk [RR] = 2.6 [95% confidence interval (CI) = 1.1-6.2]). We observed no association with prevalence of hypothyroidism or hyperthyroidism. Increasing intake of dietary nitrate was associated with an increased risk of thyroid cancer (highest vs. lowest quartile, RR = 2.9 [1.0-8.1]; P for trend = 0.046) and with the prevalence of hypothyroidism (odds ratio = 1.2 [95% CI = 1.1-1.4]), but not hyperthyroidism. Nitrate may play a role in the etiology of thyroid cancer and warrants further study.

Effect of estrogen therapy for 1 year on thyroid volume and thyroid nodules in postmenopausal women.

PubMed

Ceresini, Graziano; Milli, Bruna; Morganti, Simonetta; Maggio, Marcello; Bacchi-Modena, Alberto; Sgarabotto, Maria Paola; Chirico, Carla; Di Donato, Pietro; Campanati, Paolo; Valcavi, Roberto; Ceda, Gian Paolo; Braverman, Lewis E; Valenti, Giorgio

2008-01-01

Estrogen receptors are present in thyroid follicular cells in normal and neoplastic tissue. We evaluated changes in total thyroid volume and volume of thyroid nodules in postmenopausal women given either hormone therapy (HT) or no treatment in a 1-year observational follow-up. We studied 33 women receiving HT and 76 women receiving no treatment, comparing total thyroid volume, thyroid nodule volume, and serum concentrations of thyroid-stimulating hormone and estradiol at baseline and 1 year of follow-up. Serum thyroid-stimulating hormone concentrations were not different between groups either at baseline or at 1 year. Estradiol rose significantly in the HT group. The final percent changes in total thyroid volume were comparable between groups (HT, 1.59 +/- 2.56%; no treatment, 1.20 +/- 2.28%). At baseline, nodules were detected in 17 (51.5%) and 33 (43.4%) of women in the HT and no treatment groups, respectively, with no statistically significant difference between groups. The final number of nodules was unchanged or reduced in 88.2% and 81.1% and increased in 11.8% and 18.9% of women in the HT and no treatment groups, respectively, with no differences between groups. Baseline volumes of thyroid nodules were 0.8 +/- 0.4 and 1.4 +/- 0.4 mL in women in the HT and no treatment groups, respectively (P = 0.4). After 1 year the volume of thyroid nodules was unchanged or reduced in 47.1% and 52.8% and increased in 52.9% and 47.2% of women in the HT and no treatment groups, respectively, with no differences between groups. Estrogen administration for 1 year did not affect thyroid volume or the number and volume of thyroid nodules in postmenopausal women.

Elaboration of antibiofilm surfaces functionalized with antifungal-cyclodextrin inclusion complexes.

PubMed

Gharbi, Aïcha; Humblot, Vincent; Turpin, Frédéric; Pradier, Claire-Marie; Imbert, Christine; Berjeaud, Jean-Marc

2012-07-01

To tackle the loss of activity of surfaces functionalized by coating and covalently bound molecules to materials, an intermediate system implying the noncovalent immobilization of active molecules in the inner cavity of grafted cyclodextrins (CDs) was investigated. The antifungal and antibiofilm activities of the most stable complexes of Anidulafungin (ANF; echinocandin) and thymol (THY; terpen) in various CDs were demonstrated to be almost the same as the free molecules. The selected CD was covalently bond to self-assembled monolayers on gold surfaces. The immobilized antifungal agents reduced the number of culturable Candida albicans ATCC 3153 attached to the surface by 64 ± 8% for ANF and 75 ± 15% for THY. The inhibitory activity was persistent for THY-loaded samples, whereas it was completely lost for ANF-loaded surfaces after one use. However, reloading of the echinocandin restored the activity. Using fluorescent dying and confocal microscopy, it was proposed that the ANF-loaded surfaces inhibited the adherence of the yeasts, whereas the activity of immobilized THY was found fungicidal. This kind of tailored approach for functionalizing surfaces that could allow a progressive release of ANF or THY gave promising results but still needs to be improved to display a full activity. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Synchronous thyroid metastasis from lung adenocarcinoma.

PubMed

Rossini, Matteo; Ruffini, Livia; Ampollini, Luca; Cozzani, Federico; Del Rio, Paolo

2015-01-01

Metastases from other primary malignancies to the thyroid gland are clinically uncommon, far less frequent than any malignant primary neoplasm, mostly affecting elderly patients. Recent autopsy studies have shown that metastases to the tyroid is relatively common, with a prevalence of of 1,9-24%. We present a case of a man (72 years old) with lung cancer and synchronous metastasis to thyroid gland. Typically the interval between the diagnosis of the primary tumor and the detection of thyroid metastasis is from one month to 26 years. Clinical manifestation of thyroid metastases are rare Thyroid cancer, Thyroid metastases, Thyroidectomy.

Thyroid hormone effects on mitochondrial energetics.

PubMed

Harper, Mary-Ellen; Seifert, Erin L

2008-02-01

Thyroid hormones are the major endocrine regulators of metabolic rate, and their hypermetabolic effects are widely recognized. The cellular mechanisms underlying these metabolic effects have been the subject of much research. Thyroid hormone status has a profound impact on mitochondria, the organelles responsible for the majority of cellular adenosine triphosphate (ATP) production. However, mechanisms are not well understood. We review the effects of thyroid hormones on mitochondrial energetics and principally oxidative phosphorylation. Genomic and nongenomic mechanisms have been studied. Through the former, thyroid hormones stimulate mitochondriogenesis and thereby augment cellular oxidative capacity. Thyroid hormones induce substantial modifications in mitochondrial inner membrane protein and lipid compositions. Results are consistent with the idea that thyroid hormones activate the uncoupling of oxidative phosphorylation through various mechanisms involving inner membrane proteins and lipids. Increased uncoupling appears to be responsible for some of the hypermetabolic effects of thyroid hormones. ATP synthesis and turnover reactions are also affected. There appear to be complex relationships between mitochondrial proton leak mechanisms, reactive oxygen species production, and thyroid status. As the majority of studies have focused on the effects of thyroid status on rat liver preparations, there is still a need to address fundamental questions regarding thyroid hormone effects in other tissues and species.

Functional insulin receptors are overexpressed in thyroid tumors: is this an early event in thyroid tumorigenesis?

PubMed

Frittitta, L; Sciacca, L; Catalfamo, R; Ippolito, A; Gangemi, P; Pezzino, V; Filetti, S; Vigneri, R

1999-01-15

Insulin receptor (IR), a member of the receptor tyrosine kinase family, is expressed in normal thyroid cells and affects thyroid cell proliferation and differentiation. The authors measured IR content in benign and malignant thyroid tumors by three independent methods: a specific radioimmunoassay, 125I-insulin binding studies, and immunohistochemistry. The results obtained were compared with the IR content in paired, adjacent, normal thyroid tissue. To assess IR function in thyroid carcinoma cells, glucose uptake responsiveness to insulin was also studied in a human transformed thyroid cell line (B-CPAP) and in follicular carcinoma cells in primary culture. In 9 toxic adenomas, the average IR content was similar to that observed in the 9 paired normal thyroid tissue specimens from the same patients (2.2+/-0.3 vs. 2.1+/-0.3). In 13 benign nonfunctioning, or "cold," adenomas, the average IR content was significantly higher (P < 0.001) than in paired normal tissue specimens (4.3+/-0.5 vs. 1.8+/-0.1). In 12 papillary and 10 follicular carcinomas, IR content was significantly higher (P < 0.001) than in the adjacent normal thyroid tissue (4.0+/-0.4 vs. 1.6+/-0.2 and 5.6+/-1.0 vs. 1.8+/-0.2, respectively). The finding of a higher IR content in benign "cold" adenomas and in thyroid carcinomas was confirmed by both binding and immunostaining studies. The current studies indicate that 1) IR content is elevated in most follicular and papillary differentiated thyroid carcinomas, and 2) IR content is also elevated in most benign follicular adenomas ("cold" nodules) but not in highly differentiated, hyperfunctioning follicular adenomas ("hot" nodules), which very rarely become malignant. This observation suggests that increased IR expression is not restricted to the thyroid malignant phenotype but is already present in the premalignant "cold" adenomas. It may contribute, therefore, to thyroid tumorigenesis and/or represent an early event that gives a selective growth advantage

The Influence of Thyroid-Stimulating Hormone and Thyroid-Stimulating Hormone Receptor Antibodies on Osteoclastogenesis

PubMed Central

Morshed, Syed; Latif, Rauf; Zaidi, Mone; Davies, Terry F.

2011-01-01

Background We have shown that thyroid-stimulating hormone (TSH) has a direct inhibitory effect on osteoclastic bone resorption and that TSH receptor (TSHR) null mice display osteoporosis. To determine the stage of osteoclast development at which TSH may exert its effect, we examined the influence of TSH and agonist TSHR antibodies (TSHR-Ab) on osteoclast differentiation from murine embryonic stem (ES) cells to gain insight into bone remodeling in hyperthyroid Graves' disease. Methods Osteoclast differentiation was initiated in murine ES cell cultures through exposure to macrophage colony stimulation factor, receptor activator of nuclear factor кB ligand, vitamin D, and dexamethasone. Results Tartrate resistant acid phosphatase (TRAP)-positive osteoclasts formed in ∼12 days. This coincided with the expected downregulation of known markers of self renewal and pluripotency (including Oct4, Sox2, and REX1). Both TSH and TSHR-Abs inhibited osteoclastogenesis as evidenced by decreased development of TRAP-positive cells (∼40%–50% reduction, p = 0.0047), and by decreased expression, in a concentration-dependent manner, of osteoclast differentiation markers (including the calcitonin receptor, TRAP, cathepsin K, matrix metallo-proteinase-9, and carbonic anhydrase II). Similar data were obtained using serum immunoglobulin-Gs (IgGs) from patients with hyperthyroid Graves' disease and known TSHR-Abs. TSHR stimulators inhibited tumor necrosis factor-alpha mRNA and protein expression, but increased the expression of osteoprotegerin (OPG), an antiosteoclastogenic human soluble receptor activator of nuclear factor кB ligand receptor. Neutralizing antibody to OPG reversed the inhibitory effect of TSH on osteoclast differentiation evidencing that the TSH effect was at least in part mediated by increased OPG. Conclusion These data establish ES-derived osteoclastogenesis as an effective model system to study the regulation of osteoclast differentiation in early development

Hypothalamic mTOR pathway mediates thyroid hormone-induced hyperphagia in hyperthyroidism.

PubMed

Varela, Luis; Martínez-Sánchez, Noelia; Gallego, Rosalía; Vázquez, María J; Roa, Juan; Gándara, Marina; Schoenmakers, Erik; Nogueiras, Rubén; Chatterjee, Krishna; Tena-Sempere, Manuel; Diéguez, Carlos; López, Miguel

2012-06-01

Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-α (TRα). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC-derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Thyroid consequences of the Chernobyl nuclear accident.

PubMed

Pacini, F; Vorontsova, T; Molinaro, E; Shavrova, E; Agate, L; Kuchinskaya, E; Elisei, R; Demidchik, E P; Pinchera, A

1999-12-01

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid

PREDICTION OF RELAPSE FROM HYPERTHYROIDISM FOLLOWING ANTITHYROID MEDICATION WITHDRAWAL USING TECHNETIUM THYROID UPTAKE SCANNING.

PubMed

Nakhjavani, Manouchehr; Abdollahi, Soraya; Farzanefar, Saeed; Abousaidi, Mohammadtagi; Esteghamati, Alireza; Naseri, Maryam; Eftekhari, Mohamad; Abbasi, Mehrshad

2017-04-02

Technetium thyroid uptake (TTU) is not inhibited by antithyroid drugs (ATD) and reflects the degree of thyroid stimulation. We intended to predict the relapse rate from hyperthyroidism based on TTU measurement. Out of 44 initially enrolled subjects, 38 patients aged 41.6 ± 14.6 with Graves disease (duration: 84 ± 78 months) completed the study. TTU was performed with 40-second imaging of the neck and mediastinum 20 minutes after injection of 1 mCi technetium-99m pertechnetate. TTU was measured as the percentage of the count of activity accumulated in the thyroidal region minus the mediastinal background uptake to the count of 1 mCi technetium-99m under the same acquisition conditions. Then methimazole was stopped and patients were followed. The optimal TTU cutoff value for Graves relapse prediction was calculated using Youden's J statistic. Hyperthyroidism relapsed in 11 (28.9%) patients 122 ± 96 (range: 15-290) days post-ATD withdrawal. The subjects in remission were followed for 209 ± 81 days (range: 88-390). TTU was significantly higher in patients with forthcoming relapse (12.0 ± 8.0 vs. 3.9 ± 2.0, P = .007). The difference was significant after adjustment for age, sex, history of previous relapse, disease duration, and thyroid-stimulating hormone (TSH) levels before withdrawal. The area under the receiver operative characteristic (ROC) curve was 0.87. The optimal TTU cutoff value for classification of subjects with relapse and remission was 8.7 with sensitivity, specificity, and positive and negative predictive value of 73%, 100%, 100%, and 90%, respectively (odds ratio [OR] = 10.0; 95% confidence interval [CI]: 3.4-29.3). TTU evaluation in hyperthyroid patients receiving antithyroid medication is an accurate and practical method for predicting relapse after ATD withdrawal. ATD = antithyroid drugs RIU = radio-iodine uptake TSH = thyroid-stimulating hormone TSI = thyroid-stimulating immunoglobulin TTU = technetium thyroid uptake.

Hypocalcaemia after thyroid surgery for differentiated thyroid carcinoma: preliminary study report.

PubMed

Radivojević, Renata Curić; Prgomet, Drago; Markesić, Josip; Ezgeta, Carmen

2012-11-01

Hypocalcaemia is one of the most common major complications after thyroid surgery with the wide range of incidence from 6.9 to 46%. Thyroidectomy is usually first choice treatment for differentiated thyroid carcinoma (DTC). The study comprised 46 adult patients operated at Zagreb University Hospital Centre. Intraoperative and postoperative ionized calcium and intact parathyroid hormone (iPTH) were studied. The object of this study is to investigate risk factors, incidence of hypocalcaemia after surgical treatment of differentiated thyroid carcinoma, and the role of iPTH in comparison to ionized calcium as a predictor for hypocalcaemia.

Thyroid hormones and fetal brain development.

PubMed

Pemberton, H N; Franklyn, J A; Kilby, M D

2005-08-01

Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

EVALUATION OF QUANTITATIVE THYROID SCINTIGRAPHY FOR DIAGNOSIS AND STAGING OF DISEASE SEVERITY IN CATS WITH HYPERTHYROIDISM: COMPARISON OF THE PERCENT THYROIDAL UPTAKE OF PERTECHNETATE TO THYROID-TO-SALIVARY RATIO AND THYROID-TO-BACKGROUND RATIOS.

PubMed

Peterson, Mark E; Guterl, Jade N; Rishniw, Mark; Broome, Michael R

2016-07-01

Thyroid scintigraphy is commonly used for evaluation of cats with hyperthyroidism, with the thyroid-to-salivary ratio (T/S) being the most common method to quantify the degree of thyroid activity and disease. Calculation of thyroid-to-background ratios (T/B) or percent thyroidal uptake of (99m) TcO(-) 4 (TcTU) has only been reported in a few studies. The purpose of this prospective, cross-sectional study was to evaluate a number of quantitative scintigraphic indices as diagnostic tests for hyperthyroidism, including the T/S, three different T/B, TcTU, and estimated thyroid volume. Of 524 cats referred to our clinic for evaluation of suspected hyperthyroidism, the diagnosis was confirmed (n = 504) or excluded (n = 20) based on results of a serum thyroid panel consisting of thyroxine (T4 ), triiodothyronine (T3 ), free T4 (fT4 ), and thyroid-stimulating hormone (TSH) concentrations. In the hyperthyroid cats, median values for TcTU, T/S, and three T/B ratios were all significantly higher (P < 0.001) than values in euthyroid suspect cats or clinically normal cats. All scintigraphic parameters were relatively sensitive and specific as diagnostic tests for hyperthyroidism, but the T/S ratio had the highest test accuracy. The T/S ratio correlated strongly with the TcTU (r = 0.85). However, the TcTU had a higher and more significant correlation (P < 0.01) with serum T4 (r = 0.76 vs. 0.64), T3 (r = 0.77 vs. 0.64), and estimated thyroid volume (r = 0.62 vs. 0.38). Overall, calculation of TcTU is an accurate diagnostic test, but also appears to be the best parameter to predict the functional volume and metabolic activity of the feline adenomatous thyroid gland. © 2016 American College of Veterinary Radiology.

Occupation and thyroid cancer.

PubMed

Aschebrook-Kilfoy, Briseis; Ward, Mary H; Della Valle, Curt T; Friesen, Melissa C

2014-05-01

Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text 'occupation' 'job' 'employment' or 'work' and 'thyroid cancer'. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarised the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design and exposure assessment approach. Where available, gender-stratified results are reported. The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and healthcare occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis.

The effect of thyroid antigens on the in vitro migration of leucocytes from patients with Hashimoto thyroiditis

PubMed Central

Calder, Elizabeth A.; McLeman, Dena; Barnes, E. W.; Irvine, W. J.

1972-01-01

A total of fifty-two patients with Hashimoto thyroiditis were tested for delayed hypersensitivity to thyroid antigens using the leucocyte migration test. The percentage of patients showing abnormal migration in the presence of crude thyroid extract, thyroglobulin, thyroid mitochondria and thyroid microsomes was 75, 44, 54 and 34% respectively. Fifty-three control patients were studied concurrently with the same antigens and the percentage showing abnormal migration was 4, 6, 6 and 6% respectively. The antigenic activity of the mitochondrial fraction was not organ specific; both liver and kidney mitochondria interfered with the migration of leucocytes from patients with Hashimoto thyroiditis. PMID:4568149

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mortensen, Mary E., E-mail: MMortensen@cdc.gov; Birch, Rebecca; Wong, Lee-Yang

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO{sub 3}) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnantmore » women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO{sub 3}, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO{sub 3} on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001–2012. The geometric mean (GM) for urinary perchlorate was 4.04 µg/L, for TSH 1.46 mIU/L, and the arithmetic mean for FT4 1.11 ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO{sub 3

Thyroid Autoantibodies Are Rare in Nonhuman Great Apes and Hypothyroidism Cannot Be Attributed to Thyroid Autoimmunity

PubMed Central

Aliesky, Holly; Courtney, Cynthia L.; Rapoport, Basil

2013-01-01

The great apes include, in addition to Homo, the genera Pongo (orangutans), Gorilla (gorillas), and Pan, the latter comprising two species, P. troglodytes (chimpanzees) and P. paniscus (bonobos). Adult-onset hypothyroidism was previously reported in 4 individual nonhuman great apes. However, there is scarce information on normal serum thyroid hormone levels and virtually no data for thyroid autoantibodies in these animals. Therefore, we examined thyroid hormone levels and TSH in all nonhuman great ape genera including adults, adolescents, and infants. Because hypothyroidism in humans is commonly the end result of thyroid autoimmunity, we also tested healthy and hypothyroid nonhuman great apes for antibodies to thyroglobulin (Tg), thyroid peroxidase (TPO), and the TSH receptor (TSHR). We established a thyroid hormone and TSH database in orangutans, gorillas, chimpanzees, and bonobos (447 individuals). The most striking differences are the greatly reduced free-T4 and free-T3 levels in orangutans and gorillas vs chimpanzees and bonobos, and conversely, elevated TSH levels in gorillas vs Pan species. Antibodies to Tg and TPO were detected in only 2.6% of adult animals vs approximately 10% in humans. No animals with Tg, TPO, or TSHR antibodies exhibited thyroid dysfunction. Conversely, hypothyroid nonhuman great apes lacked thyroid autoantibodies. Moreover, thyroid histology in necropsy tissues was similar in euthyroid and hypothyroid individuals, and lymphocytic infiltration was absent in 2 hypothyroid animals. In conclusion, free T4 and free T3 are lower in orangutans and gorillas vs chimpanzees and bonobos, the closest living human relatives. Moreover, thyroid autoantibodies are rare and hypothyroidism is unrelated to thyroid autoimmunity in nonhuman great apes. PMID:24092641

Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1.

PubMed

Meyer Zu Schwabedissen, Henriette E; Ferreira, Celio; Schaefer, Anima M; Oufir, Mouhssin; Seibert, Isabell; Hamburger, Matthias; Tirona, Rommel G

2018-07-01

Levothyroxine replacement therapy forms the cornerstone of hypothyroidism management. Variability in levothyroxine oral absorption may contribute to the well-recognized large interpatient differences in required dose. Moreover, levothyroxine-drug pharmacokinetic interactions are thought to be caused by altered oral bioavailability. Interestingly, little is known regarding the mechanisms contributing to levothyroxine absorption in the gastrointestinal tract. Here, we aimed to determine whether the intestinal drug uptake transporter organic anion transporting polypeptide 2B1 (OATP2B1) may be involved in facilitating intestinal absorption of thyroid hormones. We also explored whether thyroid hormones regulate OATP2B1 gene expression. In cultured Madin-Darby Canine Kidney II/OATP2B1 cells and in OATP2B1-transfected Caco-2 cells, thyroid hormones were found to inhibit OATP2B1-mediated uptake of estrone-3-sulfate. Competitive counter-flow experiments evaluating the influence on the cellular accumulation of estrone-3-sulfate in the steady state indicated that thyroid hormones were substrates of OATP2B1. Additional evidence that thyroid hormones were OATP2B1 substrates was provided by OATP2B1-dependent stimulation of thyroid hormone receptor activation in cell-based reporter assays. Bidirectional transport studies in intestinal Caco-2 cells showed net absorptive flux of thyroid hormones, which was attenuated by the presence of the OATP2B1 inhibitor, atorvastatin. In intestinal Caco-2 and LS180 cells, but not in liver Huh-7 or HepG2 cells, OATP2B1 expression was induced by treatment with thyroid hormones. Reporter gene assays revealed thyroid hormone receptor α -mediated transactivation of the SLCO2B1 1b and the SLCO2B1 1e promoters. We conclude that thyroid hormones are substrates and transcriptional regulators of OATP2B1. These insights provide a potential mechanistic basis for oral levothyroxine dose variability and drug interactions. Copyright © 2018 by The American

Acoustic Radiation Force Impulse Quantification in the Evaluation of Thyroid Elasticity in Pediatric Patients With Hashimoto Thyroiditis.

PubMed

Yucel, Serap; Ceyhan Bilgici, Meltem; Kara, Cengiz; Can Yilmaz, Gulay; Aydin, H Murat; Elmali, Muzaffer; Tomak, Leman; Saglam, Dilek

2018-05-01

To evaluate the parenchymal elasticity of the thyroid gland with acoustic radiation force impulse imaging in pediatric patients with Hashimoto thyroiditis and to compare it with healthy volunteers. Twenty-six patients with Hashimoto thyroiditis and 26 healthy volunteers between 6 and 17 years were included. The shear wave velocity (SWV) values of both thyroid lobes in both groups were evaluated. The age and sex characteristics of the controls and patients with Hashimoto thyroiditis were similar. The SWV of the thyroid gland in patients with Hashimoto thyroiditis (mean ± SD, 1.67 ± 0.63 m/s) was significantly higher than that in the control group (1.30 ± 0.13 m/s; P < .001). There was no significant difference between the thyroid lobes in both groups. A receiver operating characteristic curve analyses showed an optimal cutoff value of 1.41 m/s, with 73.1% sensitivity, 80.8% specificity, a 79.2 % positive predictive value, and a 75.0% negative predictive value (area under the curve, 0.806; P < .001). In patients with Hashimoto thyroiditis, there was a positive correlation between the SWV values versus anti-thyroperoxidase (Pearson r = 0.46; P = .038). There were no correlations between age, body mass index, thyroid function test results, and anti-thyroglobulin values and versus SWV values. Also, no significant differences were seen between the groups for gland size, gland vascularity, and l-thyroxine treatment. Acoustic radiation force impulse elastography showed a significant difference in the stiffness of the thyroid gland between children with Hashimoto thyroiditis and the healthy group. Using acoustic radiation force impulse elastography immediately after a standard ultrasound evaluation may predict chronic autoimmune thyroiditis. © 2017 by the American Institute of Ultrasound in Medicine.

Thyroid function during the spontaneous course of subacute thyroiditis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teixeira, V.L.; Romaldini, J.H.; Rodrigues, H.F.

1985-05-01

A study of changes in serum T/sub 4/, T/sub 3/, and Tg as well as of serum TSH response to TRH was done in ten patients with subacute thyroiditis, from the acute phase up to 56 mo. All patients had symptoms of thyrotoxicosis. The mean serum T/sub 4/, T/sub 3/, and Tg concentration were significantly higher than in normal subjects. The basal TSH concentrations failed to increase in response to TRH. Mean serum T/sub 3/ and serum Tg levels remained higher than in normal subjects until 4 to 5 mo after the acute phase. Thyroid autoantibodies were absent during themore » whole period of study. An exaggerated response of TSH to TRH in six out of seven patients was observed from a 2 to 3 mo period until the end of follow-up. All patients with T/sub 3/ to T/sub 4/ ratio above the normal range (7-24 ng/..mu..g) showed also an exaggerated response of TSH to TRH. These data suggest that the spontaneous course of subacute thyroiditis may lead to a low thyroid reserve detectable even 5 yr following the acute phase of the disease.« less

Induction of painless thyroiditis in patients receiving programmed death 1 receptor immunotherapy for metastatic malignancies.

PubMed

Orlov, Steven; Salari, Farnaz; Kashat, Lawrence; Walfish, Paul G

2015-05-01

Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described. We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months. Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.

PREVALENCE OF AUTOIMMUNE THYROIDITIS AND THYROID DYSFUNCTION IN HEALTHY ADULT MEXICANS WITH A SLIGHTLY EXCESSIVE IODINE INTAKE.

PubMed

Flores-Rebollar, Armando; Moreno-Castañeda, Lidia; Vega-Servín, Norman S; López-Carrasco, Guadalupe; Ruiz-Juvera, Aída

2015-08-01

the purpose of this study was to evaluate the prevalence of autoimmune thyroiditis and thyroid dysfunction in healthy individuals with no previously known thyroid disease, in an urban area of Mexico City. the study was conducted on volunteers with no known thyroid disease. We recruited 427 subjects among the hospital's medical and administration personnel. All underwent thyroid ultrasound (US) and TSH, free T4 (FT4), total T3 (TT3), thyroid anti-peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies were measured. Hypoechogenicity and thyroid volume were determined by US. Urinary iodine (UI) excretion was also measured. the frequency of autoimmune thyroiditis was 8.4% (36/427) and women were most commonly affected than men (11.6 vs. 4.3% respectively, P = 0.008); when including cases of atrophic thyroid, the frequency increased to 15.7% (67/427). Clinical hypothyroidism was detected in 1.2% (5/427) and it was sub-clinical in 5.6% of individuals. A goiter was present in 5.9% (25/427) of volunteers. Median UI was 267 μg/L, (IQR 161.3 - 482.5). in spite of our study's limitations, the frequency of autoimmune thyroiditis is clearly elevated in the studied population. Further studies are necessary in order to define the prevalence of autoimmune thyroid disease as well as the current iodine nutritional status in our country. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Occult thyroid carcinoma in our experience -- should we reconsider total thyroidectomy for benign thyroid pathology?

PubMed

Alecu, L; Bărbulescu, M; Ursuţ, B; Enciu, O; Slavu, I; Braga, V

2014-01-01

The reported incidence rate of occult thyroid carcinoma in patients operated for benign thyroid pathology has been much higher than expected in the last years,especially for multinodular goitre, which raises the question about which should the proper surgical management for these cases be. To assess the incidence rate of OTC in a single medium volume surgical center and to establish the correct indication for initial surgical management, as well as to identify the benign thyroid pathology most frequently associated with OTC. We also reviewed the relevant scientific literature on this topic. We conducted a retrospective study in the General Surgery Clinic of "Prof. dr. Agrippa Ionescu" Clinical Emergency Hospital, Bucharest, on a series of 145 patients who underwent surgical interventions for preoperatively diagnosed benign thyroid pathology over a ten year period, between 1st January 2002 - 31st December 2012. All cases of known thyroid cancer were excluded. Incidence rate of occult thyroid carcinoma in our series was 6.9 % (10 out of 145 patients), 80 % of them being diagnosed with multinodular goitre and two cases (20 %) with Hashimoto's lymphocytic thyroiditis. 6.8 % of all patients with multinodular goitre were found to present occult carcinoma,but this association was without statistical significance(p 0.05). Incidence rate of occult cancer among patients with Hashimoto thyroiditis was proved to be as high as 28.6%,statistically significant (p=0.020). The mean size of postoperatively diagnosed occult microcarcinoma was 7 mm, ranging between 3 mm and 14 mm, 90% of them being smaller than 1cm. Histologically, papillary microcarcinoma was found in all cases. The mean age of the patients diagnosed with occult microcarcinoma was 47.8 years with majority of the female gender. The most frequent operation performed was total thyroidectomy (70.8%). Overall morbidity in our series was 6.9% with a 0.7 % mortality rate (1 case). In our opinion, primary total thyroidectomy

American Thyroid Association Statement on Remote-Access Thyroid Surgery

PubMed Central

Bernet, Victor; Fahey, Thomas J.; Kebebew, Electron; Shaha, Ashok; Stack, Brendan C.; Stang, Michael; Steward, David L.; Terris, David J.

2016-01-01

Background: Remote-access techniques have been described over the recent years as a method of removing the thyroid gland without an incision in the neck. However, there is confusion related to the number of techniques available and the ideal patient selection criteria for a given technique. The aims of this review were to develop a simple classification of these approaches, describe the optimal patient selection criteria, evaluate the outcomes objectively, and define the barriers to adoption. Methods: A review of the literature was performed to identify the described techniques. A simple classification was developed. Technical details, outcomes, and the learning curve were described. Expert opinion consensus was formulated regarding recommendations for patient selection and performance of remote-access thyroid surgery. Results: Remote-access thyroid procedures can be categorized into endoscopic or robotic breast, bilateral axillo-breast, axillary, and facelift approaches. The experience in the United States involves the latter two techniques. The limited data in the literature suggest long operative times, a steep learning curve, and higher costs with remote-access thyroid surgery compared with conventional thyroidectomy. Nevertheless, a consensus was reached that, in appropriate hands, it can be a viable option for patients with unilateral small nodules who wish to avoid a neck incision. Conclusions: Remote-access thyroidectomy has a role in a small group of patients who fit strict selection criteria. These approaches require an additional level of expertise, and therefore should be done by surgeons performing a high volume of thyroid and robotic surgery. PMID:26858014

Effect of recombinant human thyroid stimulating hormone on serum thyroxin and thyroid scintigraphy in euthyroid cats.

PubMed

van Hoek, Ingrid M; Peremans, Kathelijne; Vandermeulen, Eva; Duchateau, Luc; Gommeren, Kris; Daminet, Sylvie

2009-04-01

This study investigated the thyroidal response to administration of recombinant human thyroid stimulating hormone (rhTSH) by means of serum total thyroxine (TT(4)) concentration and pertechnetate uptake by the thyroid gland in six healthy euthyroid spayed female cats. A pertechnetate scan was performed on day 1 to calculate thyroid/salivary gland (T/S) uptake ratio. On day 3, 25 microg rhTSH was injected intravenously. Six hours later the thyroid scan was repeated as on day 1. Blood was drawn for serum TT(4) measurement prior to injection of rhTSH and performance of the pertechnetate scan. Statistically significant differences in mean serum TT(4) concentration, T/S uptake ratio before and 6h after rhTSH administration and T/S uptake ratio between left and right lobes were noted. We can conclude that 25 microg rhTSH increases pertechnetate uptake in the thyroid glands of cats, this should be taken into account when thyroid scintigraphy after rhTSH administration is interpreted.

Hashimoto thyroiditis: a century later.

PubMed

Ahmed, Rania; Al-Shaikh, Safa; Akhtar, Mohammed

2012-05-01

More than a century has passed since the first description of Hashimoto thyroiditis (HT) as a clinicopathologic entity. HT is an autoimmune disease in which a breakdown of immune tolerance is caused by interplay of a variety of immunologic, genetic, and environmental factors. Thyrocyte injury resulting from environmental factors results in expression of new or hidden epitopes that leads to proliferation of autoreactive T and B cells. Infiltration of thyroid by these cells results in HT. In addition to the usual type of HT, several variants such as the fibrous type and Riedal thyroiditis are also recognized. The most recently recognized variant is immunoglobulin G4(+) HT, which may occur as isolated thyroid limited disease or as part of a generalized Ig4-related sclerosing disease. The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. HT is frequently associated with papillary thyroid carcinoma and may indeed be a risk factor for developing this type of cancer. The relationship between thyroid lymphoma and HT on the other hand appears well established.

Thyroid hormones and female reproduction.

PubMed

Silva, Juneo F; Ocarino, Natália M; Serakides, Rogéria

2018-05-14

Thyroid hormones are vital for the proper functioning of the female reproductive system, since they modulate the metabolism and development of ovarian, uterine and placental tissues. Therefore, hypo- and hyperthyroidism may result in subfertility or infertility in both women and animals. Other well-documented sequelae of maternal thyroid dysfunctions include menstrual/estral irregularity, anovulation, abortion, preterm delivery, preeclampsia, intrauterine growth restriction, postpartum thyroiditis, and mental retardation in children. Several studies have been carried out involving prospective and retrospective studies of women with thyroid dysfunction, as well as in vivo and in vitro assays of hypo- and hyperthyroidism using experimental animal models and/or ovarian, uterine and placental cell culture. These studies have sought to elucidate the mechanisms by which thyroid hormones influence reproduction to better understand the physiology of the reproductive system and to provide better therapeutic tools for reproductive dysfunctions that originate from thyroid dysfunctions. Therefore, this review aims to summarize and update the available information related to the role of thyroid hormones in the morphophysiology of the ovary, uterus and placenta in women and animals and the effects of hypo- and hyperthyroidism on the female reproductive system.

Long Noncoding RNA H19 Inhibits Cell Viability, Migration, and Invasion Via Downregulation of IRS-1 in Thyroid Cancer Cells

PubMed Central

Wang, Peng; Xu, Weimin; Liu, Haixia; Bu, Qingao; Sun, Diwen

2017-01-01

Thyroid cancer is a common endocrine gland malignancy which exhibited rapid increased incidence worldwide in recent decades. This study was aimed to investigate the role of long noncoding RNA H19 in thyroid cancer. Long noncoding RNA H19 was overexpressed or knockdown in thyroid cancer cells SW579 and TPC-1, and the expression of long noncoding RNA H19 was detected by real-time polymerase chain reaction. The cell viability, migration, and invasion were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide assay, Transwell assay, and wound healing assay, respectively. Furthermore, cell apoptosis was analyzed by flow cytometry, and expressions of some factors that were related to phosphatidyl inositide 3-kinases/protein kinase B and nuclear factor κB signal pathway were measured by Western blotting. This study revealed that cell viability and migration/invasion of SW579 and TPC-1 were significantly decreased by long noncoding RNA H19 overexpression compared with the control group (P < .05), whereas cell apoptosis was statistically increased (P < .001). Meanwhile, cell viability and migration/invasion were significantly increased after long noncoding RNA H19 knockdown (P < .05). Furthermore, long noncoding RNA H19 negatively regulated the expression of insulin receptor substrate 1 and thus effect on cell proliferation and apoptosis. Insulin receptor substrate 1 regulated the activation of phosphatidyl inositide 3-kinases/AKT and nuclear factor κB signal pathways. In conclusion, long noncoding RNA H19 could suppress cell viability, migration, and invasion via downregulation of insulin receptor substrate 1 in SW579 and TPC-1 cells. These results suggested the important role of long noncoding RNA H19 in thyroid cancer, and long noncoding RNA H19 might be a potential target of thyroid cancer treatment. PMID:29332545

Thyroid peroxidase autoantibody fingerprints. II. A longitudinal study in postpartum thyroiditis.

PubMed

Jaume, J C; Parkes, A B; Lazarus, J H; Hall, R; Costante, G; McLachlan, S M; Rapoport, B

1995-03-01

It is not known whether epitopes recognized by autoantibodies in an individual remain constant or change over time, especially during perturbations of the humoral immune response. To address this question, we studied the epitopic profile ("fingerprint") of autoantibodies to thyroid peroxidase (TPO) in the sera of 19 women during the postpartum period. Fingerprints were determined in competition studies using 4 recombinant F(ab). At delivery and at 3 time intervals over the subsequent 9-12 months, the pool of F(ab) inhibited autoantibody binding to TPO by 80-100%, consistent with the definition by these F(ab) of a TPO immunodominant region (A1, A2, B1, and B2 domains). Despite a wide spectrum among individuals, the TPO epitopic fingerprints for all 19 women were relatively unchanged throughout the postpartum period. Fingerprint constancy occurred regardless of fluctuations in serum TPO autoantibody levels. When assessed numerically as a ratio of inhibition by the A domain F(ab) to inhibition by the B domain F(ab), the A/B domain ratios in individual women ranged from 0.2 (predominantly B domain) to more than 3.0 (predominantly A domain). However, for each individual woman, the A/B epitopic ratio was conserved throughout the study interval. Our TPO autoantibody epitopic fingerprint data have potential implications for understanding the humoral autoimmune response in man. First, the present study indicates a remarkable lack of spreading of B cell epitopes during a state of perturbation of the immune system over a period of 1 yr. Second, and perhaps more important, despite marked variations in TPO epitopic profiles among different individuals, their constancy over time suggests that TPO autoantibody fingerprints may be inherited.

American Thyroid Association Guidelines on the Management of Thyroid Nodules and Differentiated Thyroid Cancer Task Force Review and Recommendation on the Proposed Renaming of Encapsulated Follicular Variant Papillary Thyroid Carcinoma Without Invasion to Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features.

PubMed

Haugen, Bryan R; Sawka, Anna M; Alexander, Erik K; Bible, Keith C; Caturegli, Patrizio; Doherty, Gerard M; Mandel, Susan J; Morris, John C; Nassar, Aziza; Pacini, Furio; Schlumberger, Martin; Schuff, Kathryn; Sherman, Steven I; Somerset, Hilary; Sosa, Julie Ann; Steward, David L; Wartofsky, Leonard; Williams, Michelle D

2017-04-01

American Thyroid Association (ATA) leadership asked the ATA Thyroid Nodules and Differentiated Thyroid Cancer Guidelines Task Force to review, comment on, and make recommendations related to the suggested new classification of encapsulated follicular variant papillary thyroid carcinoma (eFVPTC) without capsular or vascular invasion to noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The task force consists of members from the 2015 guidelines task force with the recusal of three members who were authors on the paper under review. Four pathologists and one endocrinologist were added for this specific review. The manuscript proposing the new classification and related literature were assessed. It is recommended that the histopathologic nomenclature for eFVPTC without invasion be reclassified as a NIFTP, given the excellent prognosis of this neoplastic variant. This is a weak recommendation based on moderate-quality evidence. It is also noted that prospective studies are needed to validate the observed patient outcomes (and test performance in predicting thyroid cancer outcomes), as well as implications on patients' psychosocial health and economics.

Thyroid Ultrasonography in Differentiation between Graves’ Disease and Hashimoto’s Thyroiditis

PubMed Central

Pishdad, P.; Pishdad, G.R.; Tavanaa, S.; Pishdad, R.; Jalli, R.

2017-01-01

Objective: Graves’ disease and Hashimoto’s thyroiditis are the most common causes of hyper and hypothyroidism, respectively. Differentiation of these 2 diseases, if the patient is euthyroid, may sometimes be extremely difficult on the basis of clinical and laboratory findings. The purpose of this study was to determine the sensitivity and specificity of gray scale sonography in differentiation of Graves’ disease from Hashimoto’s thyroiditis. Methods: This study included 149 patients divided into three groups, patients with Graves’ disease (34 patients, mean age = 36.8 ± 10.17 years), Patients with Hashimoto’s thyroiditis (62 patients, mean age = 33.4 ± 12.16 years) and control group (53 healthy people, mean age = 34.74 ± 16.87 years). Members of all groups were referred to a single radiologist for thyroid sonography for evaluation of thyroid echogenicity pattern. Results: A total of 117 women and 32 men were examined by sonography. The most common sonographic pattern in Hashimoto and Graves’ was homogenous hypo-echogenicity which was observed in 45.2% and 47.1% of cases, respectively. Peripheral hypo-echogenicity pattern was seen in 40.3% of Hashimoto’s group with 100% specificity and 40.3% sensitivity. Central-hypoechogenic pattern was observed in 17.6% of Graves’ group with 100% and 17.6% specificity and sensitivity, respectively. Conclusion: Our findings indicate that sonography has high specificity but low sensitivity in the diagnosis of either Graves’ disease or Hashimoto’s thyroiditis. It is therefore not possible to differentiate between these two diseases using sonography alone. Confirmation by laboratory data is also needed. PMID:28451576

Effect of iodine or iopanoic acid on thyroid Ca2+/NADPH-dependent H2O2-generating activity and thyroperoxidase in toxic diffuse goiters.

PubMed

Cardoso, Luciene C; Martins, Denise C L; Campos, Denise V B; Santos, Luciana M; Corrêa da Costa, Vânia M; Rosenthal, Doris; Vaisman, Mario; Violante, Alice H D; Carvalho, Denise P

2002-09-01

The aim of the present study was to compare the effects of iopanoic acid (IOP) or a saturated solution of potassium iodide (SSKI) administration to patients with toxic diffuse goiters (TDG). Patients with TDG are treated with thionamides and high doses of iodine preoperatively. In this study, two types of preoperative drug regimens were used: propylthiouracil or methimazole plus SSKI for 10-15 days (n=8) or IOP for 7 days (n=6). Serum thyroid hormones (total and free thyroxine (T(4)), total tri-iodothyronine (T(3)) and reverse T(3) (rT(3)), were evaluated after 7 days of either SSKI or IOP treatment, and after 10-15 days of SSKI administration. During thyroidectomy, samples of thyroid gland were obtained to evaluate thyroperoxidase and thyroid H(2)O(2)-generating activities. Serum total T(3) was significantly decreased after 7 days of either treatment, and serum rT(3) was significantly increased in IOP-treated patients. Serum total and free T(4) were unaffected by 7 days of IOP treatment, but decreased after 7 days of SSKI treatment, although significantly diminished levels were only reached after a further 3-8 days of SSKI administration. During both drug regimens, serum TSH remained low (SSKI: 0.159+/-0.122; IOP: 0.400+/-0.109 microU/ml). Thyroperoxidase activity was significantly lower in thyroid samples from patients treated with SSKI for 10-15 days than in the thyroid glands from IOP-treated patients. However, thyroid H(2)O(2) generation was inhibited in samples from patients treated with either IOP or SSKI. We show herein that IOP treatment can be effective in the management of hyperthyroidism and that this drug inhibits thyroid NADPH oxidase activity, just as previously described for SSKI, probably due to its iodine content.

Flow cytometry in the differential diagnostics of Hashimoto's thyroiditis and MALT lymphoma of the thyroid.

PubMed

Adamczewski, Zbigniew; Stasiołek, Mariusz; Dedecjus, Marek; Smolewski, Piotr; Lewiński, Andrzej

2015-01-01

A combination of traditional cytology methods with fluorescence activated cell sorting (FACS) analysis of fine-needle aspiration biopsy (FNAB) material is considered a powerful diagnostic tool in the differential diagnosis of thyroid lesions suspected of mucosa-associated lymphoid tissue lymphoma (MALT-L). The aim of this study was to demonstrate the FACS-based diagnostic process of thyroid lesions in a clinical situation where ultrasound and cytological examinations did not allow differentiation between Hashimoto's thyroiditis (HT) and MALT-L. The patients analysed in this study presented significantly different clinical courses of thyroid disease: quickly enlarging painless tumour of the thyroid right lobe in the first case, and chronic HT with palpable tumour in the thyroid isthmus in the second patient. Due to the suspicion of MALT-L resulting from indeterminate ultrasound and FNAB-cytology results, FNAB material was obtained from all the previously examined thyroid lesions and directly subjected to FACS assessment, encompassing κ/λ light chain restriction analysis, as well as measurements of B and T cell surface antigens. The FACS analysis of FNAB material obtained from our patients did not show any definite signs of light chain restriction. Although one of the samples showed a borderline value of κ/λ ratio (κ/λ = 0.31), further immunophenotyping confirmed clonal expansion in none of the examined thyroid regions. Histopathological findings documented the diagnosis of HT in both clinical cases. We believe that FACS represents a useful and reliable complementary diagnostic measure in FNAB-based differential diagnosis of lymphoproliferative thyroid disorders.

Evaluation of thyroid dysfunction and autoimmunity in gestational diabetes mellitus and its relationship with postpartum thyroiditis.

PubMed

Maleki, N; Tavosi, Z

2015-02-01

To evaluate thyroid dysfunction and autoimmunity in women with gestational diabetes and to investigate the frequency of postpartum thyroiditis in women with gestational diabetes. A total of 350 women with gestational diabetes and 350 healthy pregnant women were enrolled in the study. We studied the thyroid hormone profiles of the women in each group during pregnancy (at 24-28 weeks' gestation) and after delivery (at 6 weeks, 3, 6 and 9 months, and 1 year postpartum). A total of 342 women with gestational diabetes and 313 healthy pregnant women completed the follow-up during pregnancy and 1 year after delivery. Of the women with gestational diabetes, 16.6% had thyroid dysfunction, while of the healthy pregnant women, 6.1% had thyroid dysfunction. The prevalence of postpartum thyroiditis was higher in the women with a history of gestational diabetes (19.6%) than in the healthy pregnant women (10.2%), and this difference was statistically significant. According to the results of the present study, the prevalence of postpartum thyroiditis was higher in women with a history of gestational diabetes than in healthy women. We recommend that all women with gestational diabetes and women who have previous thyroid dysfunction should be screened for thyroid hormonal abnormalities during pregnancy and for 1 year after pregnancy. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Painful Hashimoto's thyroiditis: myth or reality?

PubMed

Rotondi, M; Capelli, V; Locantore, P; Pontecorvi, A; Chiovato, L

2017-08-01

Neck pain is a common complain, being in most cases due to non-thyroidal causes. However, a minority of patients suffer from painful thyroid diseases. Among them, sub-acute thyroiditis (SAT) is the most frequent one. Rare thyroid-related causes of neck pain include hemorrhage within a thyroid nodule as well as Riedel's thyroiditis and suppurative thyroiditis. In the last 30 years, a few cases of a painful variant of Hashimoto's thyroiditis (HT) have been described. Biochemical, ultrasound, and histologic features were clearly suggestive for HT in all of the published cases and definitely ruled out the diagnosis of SAT. While sound descriptions of painful HT are present in the literature, it is important to emphasize that only 20 cases were reported from the year 2000 until now. The condition, however, is clinically relevant because neck pain was reported to be refractory both to steroids and to other analgesic drugs, being thyroidectomy the only effective treatment for pain relief in these patients. This short review analyzes currently available data supporting a role for HT as a rare cause of neck pain.

Occupation and Thyroid Cancer

PubMed Central

Aschebrook-Kilfoy, Briseis; Ward, Mary H.; Valle, Curt T. Della; Friesen, Melissa C.

2014-01-01

Objectives Numerous occupational and environmental exposures have been shown to disrupt thyroid hormones, but much less is known about their relationships with thyroid cancer. Here we review the epidemiology studies of occupations and occupational exposures and thyroid cancer incidence to provide insight into preventable risk factors for thyroid cancer. Methods The published literature was searched using the Web of Knowledge database for all articles through August 2013 that had in their text “occupation” “job” ”employment” or “work” and “thyroid cancer”. After excluding 10 mortality studies and 4 studies with less than 5 exposed incident cases, we summarized the findings of 30 articles that examined thyroid cancer incidence in relation to occupations or occupational exposure. The studies were grouped by exposure/occupation category, study design, and exposure assessment approach. Where available, gender stratified results are reported. Results The most studied (19 of 30 studies) and the most consistent associations were observed for radiation-exposed workers and health care occupations. Suggestive, but inconsistent, associations were observed in studies of pesticide-exposed workers and agricultural occupations. Findings for other exposures and occupation groups were largely null. The majority of studies had few exposed cases and assessed exposure based on occupation or industry category, self-report, or generic (population-based) job exposure matrices. Conclusion The suggestive, but inconsistent findings for many of the occupational exposures reviewed here indicate that more studies with larger numbers of cases and better exposure assessment are necessary, particularly for exposures known to disrupt thyroid homeostasis. PMID:24604144

Histopathologic study of the so called 'palpation thyroiditis'.

PubMed Central

Hwang, T. S.; Park, S. H.

1988-01-01

We have reviewed 1066 thyroid lesions and compared the relative incidence of the so called 'palpation thyroiditis' between autoimmune thyroiditis and normal thyroid parenchyme surrounding the nodular thyroid lesion and also discussed the pathogenesis of palpation thyroiditis. The typical histopathologic features of 'palpation thyroiditis' were seen in 275 cases among 467 adenomatous goiters and in none of the autoimmune thyroiditis. We here in this paper suggest that the so called 'palpation thyroiditis' is not merely a secondary phenomenon to mechanical follicular damage by vigorous palpation, but this lesion more likely develops in conditions where certain types of physiologic alteration has occurred in follicular basement membrane, just like a pathogenesis of subacute granulomatous thyroiditis. PMID:3079564

Temporary ovarian failure in thyroid cancer patients after thyroid remnant ablation with radioactive iodine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Raymond, J.P.; Izembart, M.; Marliac, V.

We studied ovarian function retrospectively in 66 women who had regular menstrual cycles before undergoing complete thyroidectomy for differentiated thyroid cancer and subsequent thyroid remnant ablation with /sup 131/I. Eighteen women developed temporary amenorrhea accompanied by increased serum gonadotropin concentrations during the first year after /sup 131/I therapy. No correlation was found between the radioactive iodine dose absorbed, thyroid uptake before treatment, oral contraceptive use, or thyroid autoimmunity. Only age was a determining factor, with the older women being the most affected. We conclude that radioiodine ablation therapy is followed by transient ovarian failure, especially in older women.

[Poorly differentiated thyroid carcinomas: new therapeutic considerations].

PubMed

Graf, Hans

2005-10-01

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.

Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis.

PubMed

Asik, Mehmet; Binnetoglu, Emine; Sen, Hacer; Gunes, Fahri; Muratli, Asli; Kankaya, Duygu; Uysal, Fatma; Sahin, Mustafa; Ukinc, Kubilay

2015-01-01

Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). We reviewed reports of primary SCC of the thyroid gland published in the English literature. We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases.

Silent Thyroiditis

PubMed Central

Walker, Peter

1984-01-01

Silent or painless thyroiditis is a frequent cause of transient hyperthyroidism, which is characterized by recent onset of symptoms in a patient with a normal to modestly enlarged and firm thyroid gland. The hallmarks of the disease are the absence of thyroidal pain or tenderness and a markedly reduced radioiodine uptake. Histologically, the gland is characterized by an important lymphocytic infiltration, occasionally to the point of lymphoid follicle formation. However, other indices of an autoimmune cause are usually absent. The disease appears to have a predilection for the postpartum period. Relapses may occur with subsequent pregnancies. Otherwise, the course is usually benign and transient, requiring moderate doses of β-adrenergic blocking agents for symptomatic relief. No pathogenetic factors are known, but the disease may conceivably have an autoimmune basis, particularly in the postpartum patient. PMID:21278944

Thyroid neoplasia, autoimmune thyroiditis, and hypothyroidism in persons exposed to iodine 131 from the hanford nuclear site.

PubMed

Davis, Scott; Kopecky, Kenneth J; Hamilton, Thomas E; Onstad, Lynn

2004-12-01

Approximately 740,000 Ci (2.73 x 10(16) Bq) of iodine 131 (131I) were released to the atmosphere from the Hanford Nuclear Site in Washington State from 1944 through 1957. The risk of thyroid disease resulting from prolonged environmental 131I exposure is poorly understood. The Hanford Thyroid Disease Study (HTDS) was conducted to determine if thyroid disease is increased among persons exposed as children to atmospheric releases of 131I from Hanford. Retrospective cohort study. Exposure could have occurred from December 1944 through 1957. Follow-up occurred until the time of the HTDS examination (December 1992-September 1997). Participants' thyroid radiation doses from Hanford's 131I releases were estimated from interview data regarding residence and dietary histories. The cohort included a sample of all births from 1940 through 1946 to mothers with usual residence in 1 of 7 counties in eastern Washington State. Of 5199 individuals identified, 4350 were located alive and 3440 were evaluable; ie, had sufficient data for dose estimation and received an HTDS evaluation for thyroid disease, including a thyroid ultrasound, physical examination, and fine needle biopsy if required to evaluate thyroid nodularity. Thyroid cancer, benign thyroid nodules, total neoplasia, any thyroid nodules, autoimmune thyroiditis, and hypothyroidism. There was no evidence of a relationship between Hanford radiation dose and the cumulative incidence of any of the outcomes. These results remained unchanged after taking into account several factors that might confound the relationship between radiation dose and the outcomes of interest. These results do not support the hypothesis that exposure during infancy and childhood to 131I at the dose levels (median, 97 mGy; mean, 174 mGy) and exposure circumstances experienced by our study participants increases the risk of the forms of thyroid disease evaluated in this study.

Radiation-related thyroid autoimmunity and dysfunction

PubMed Central

Nagayama, Yuji

2018-01-01

Abstract The thyroid gland is vulnerable not only to external radiation but also to internal radiation, because the thyroid cells can incorporate radioactive iodine when synthesizing thyroid hormones. Since radiation-induction of thyroid neoplasia, including thyroid cancer, is well recognized, the data on radiation-related thyroid autoimmunity and dysfunction are summarized and reviewed. High-dose irradiation, irrespective of being external or internal, is strongly associated with a risk of hypothyroidism (with the prevalence ranging from 2.4% to 31%) and of Graves’ hyperthyroidism (with the prevalence being up to 5%). It is easy to understand that high-dose irradiation induces hypothyroidism with some frequency, because high-dose irradiation destroys the thyroid gland. On the other hand, the basis for development of hyperthyroidism is mechanistically unclear, and it is merely speculative that autoantigens may be released from damaged thyroid glands and recognized by the immune system, leading to the development of anti-thyrotropin receptor antibodies and Graves’ hyperthyroidism in subjects who are immunologically predisposed to this ailment. In contrast, the data on moderate to low-dose irradiation on thyroid autoimmunity and dysfunction are inconsistent. Although it is difficult to draw a definitive conclusion, some data may suggest a transient effect of moderate- to low-dose irradiation on hypothyroidism and autoimmune thyroiditis, implying that the effect, if it exists, is reversible. Finally, no report has shown a statistically significant increase in the prevalence of moderate- to low-dose irradiation–induced Graves’ hyperthyroidism. PMID:29069397

Lovastatin inhibits proliferation of anaplastic thyroid cancer cells through up-regulation of p27 by interfering with the Rho/ROCK-mediated pathway.

PubMed

Zhong, Wen-Bin; Hsu, Sung-Po; Ho, Pei-Yin; Liang, Yu-Chih; Chang, Tien-Chun; Lee, Wen-Sen

2011-12-01

Previously, we demonstrated that lovastatin, a HMG-CoA reductase inhibitor, induced apoptosis, differentiation, and inhibition of invasiveness of human anaplastic thyroid carcinoma cells (ATCs). Here, we further examined the effect of lovastatin on the growth of ARO cells. Lovastatin (0-20μM) concentration-dependently decreased cell number in cultured ATC and arrested the cell at the G0/G1 phase of the cell cycle. Western blot analysis revealed that lovastatin caused an increase of the protein level of p27 and cyclin-dependent kinase (CDK)4 and a decrease of the protein level of cyclin A2, cyclin D3, and phosphorylated Rb (pRb), but did not significantly change the protein levels of p21, cyclins D1 and E, and CDK2, in ARO cells. The formation of the CDK2-p27 complex was increased and the CDK2 activity was decreased in the lovastatin-treated ARO cells. Pretreatment of ARO cells with a p27, but not p21, antisense oligonucleotide prevented the lovastatin-induced G0/G1 arrest in ARO cells. The lovastatin-induced growth inhibition and translocation of RhoA and Rac1 in ARO cells were completely prevented by mevalonate and partially by geranylgeranyl pyrophosphate. Treatment of ARO cells with Y27632, an inhibitor of Rho-associated kinase, abolished the GGPP-mediated prevention of lovastatin-induced anti-proliferation and up-regulation and prolonged degradation of p27. Taken together, these data suggest that lovastatin treatment caused a reduction of Rho geranylgeranylation, which in turn increased the expression and stability of p27, and then inhibited ARO cell proliferation. These data suggest that lovastatin merits further investigation as multipotent therapy for treatment ATC. Copyright © 2011 Elsevier Inc. All rights reserved.

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review

PubMed Central

Xing, Wanjia; Liu, Xiaohong; He, Qingqing; Zhang, Zongjing; Jiang, Zhaoshun

2017-01-01

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAFV600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAFV600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm. PMID:28928829

BRAFV600E mutation contributes papillary thyroid carcinoma and Hashimoto thyroiditis with resistance to thyroid hormone: A case report and literature review.

PubMed

Xing, Wanjia; Liu, Xiaohong; He, Qingqing; Zhang, Zongjing; Jiang, Zhaoshun

2017-09-01

Resistance to thyroid hormone (RTH) is a rare autosomal hereditary disorder characterized by increased serum thyroid hormone (TH) levels with unsuppressed or increased thyrotropin concentration. It remains unknown whether the coexistence of RTH with papillary thyroid carcinoma (PTC) and Hashimoto thyroiditis (HT) is incidental or whether it possesses a genetic or pathophysiological association. In the present study, a case of RTH with PTC and HT in an 11-year-old Chinese patient was examined and the clinical presentation of RTH with PTC was discussed. In addition, the possible associations between RTH, PTC and HT were determined. HT was confirmed in the patient using an autoimmune assay and thyroid ultrasound. RTH was diagnosed on the basis of clinical manifestations, laboratory information and gene analysis, and PTC was diagnosed according to histological results. Results of BRAF V600E mutation analysis were positive. A literature review of 14 cases of RTH with PTC was included for comparison. The present case report indicates an association of RTH with PTC and HT coexistence in the patient. Close follow-up, histological evaluation and BRAF V600E mutation detection should be performed in each RTH case with HT, since a persistent increase in TSH may be a risk factor for the development of thyroid neoplasm.

Thyroid and adrenal relationships

PubMed Central

Parsons, Victor; Ramsay, Ian

1968-01-01

A brief review of the actions of adrenal medullary and thyroid hormones is presented and the ways in which they interact are examined. It is concluded that thyroid hormone produces the necessary intracellular environment without which the steady state and emergency actions of cathecholamines would be vitiated. In hyperthyroidism the increased concentration of thyroid hormones results in a lowering of the threshold for catecholamine action. For this reason it is possible to alleviate many of the symptoms of thyrotoxicosis by means of drugs which block β-adrenergic receptors. Attention is also drawn to the simultaneous occurrence of thyroid and adrenal disease, in the hope that this will encourage the search for further links in this field of endocrinology. PMID:5655216

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

ClinicalTrials.gov

2018-05-08

Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Thyroglobulin Antibody Negative; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

Association of vitamin D insufficiency/deficiency with thyroid artery Doppler ultrasonography in patients with Hashimoto thyroiditis.

PubMed

Nalbant, Ahmet; Aydin, Ayhan; Karacan, Alper; Onmez, Attila; Tamer, Ali; Cinemre, Hakan

2017-01-01

During the course of the autoimmune thyroid diseases, ultrasonography change parallel to histopathology. Vitamin D is associated with autoimmune diseases and thus can affect thyroid blood flow. Our aim was to investigate the relationship between vitamin D insufficiency/deficiency and thyroid hemodynamic indices in patients with Hashimoto thyroiditis. A total of 93 patients who presented to Sakarya University Endocrinology outpatient clinic from April to September 2016 and diagnosed with Hashimoto thyroiditis were included in this study. Clinical and serologic data, thyroid antibodies and 25(OH)D3 were evaluated. Mean peak systolic velocity(mPSV), mean end-diastolic velocity (EDV), mean resistive index (RI) flows of superior and inferior thyroid arteries were measured with B-mode Doppler ultrasonography. Vitamin D insufficiency/deficiency was detected in 59 (63.4%). TPO Ab and TgAb levels were found higher in patients with vitamin D insufficiency/deficiency. In the normal vitamin D group, superior thyroid artery mPSV (32.21±6.73cm/s) and EDV(13.27±2.80 cm/s) were higher than in the low vitamin D group [mPSV (28.32±8.99cm/s) and EDV(10.67±3.68 cm/s)] (P=0.034, P=0.001, respectively). Inferior thyroid artery EDV value was higher in the normal compared to the low vitamin D group (0.032). RI measured in all arteries were higher in the vitamin D insufficient/deficient group compared to the Vitamin D normal group (p=0.001). Vitamin-D insufficiency/deficiency has led to reduced parenchymal blood supply and increased micro-vascular resistance in Hashimoto thyroiditis patients.

Chronic lymphocytic thyroiditis is associated with invasive characteristics of differentiated thyroid carcinoma in children and adolescents.

PubMed

Iliadou, Paschalia K; Effraimidis, Grigoris; Konstantinos, Michalakis; Grigorios, Panagiotou; Mitsakis, Periklis; Patakiouta, Frideriki; Pazaitou-Panayiotou, Kalliopi

2015-12-01

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. 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. 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, P=0.024). Familial papillary thyroid carcinoma (PTC) was more frequent in patients with CLT compared to those without CLT (20.7% vs 2.8% respectively, P=0.009). There was no better outcome with respect to the presence of CLT or not. Children and adolescents with CLT present more frequently familial PTC as well as thyroid cancer with invasive characteristics. © 2015 European Society of Endocrinology.

Molecular pathobiology of thyroid neoplasms.

PubMed

Tallini, Giovanni

2002-01-01

Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.

Insulin resistance is associated with larger thyroid volume in adults with type 1 diabetes independently from presence of thyroid autoimmunity.

PubMed

Rogowicz-Frontczak, Anita; Pilacinski, Stanislaw; Chwialkowska, Anna Teresa; Naskret, Dariusz; Zozulinska-Ziolkiewicz, Dorota

2018-04-19

To investigate the effect of insulin resistance (IR) on thyroid function, thyroid autoimmunity (AIT) and thyroid volume in type 1 diabetes (T1DM). 100 consecutive patients with T1DM aged 29 (±6) years with diabetes duration 13 (±6) years were included. Exclusion criteria were: history of thyroid disease, current treatment with L-thyroxin or anti-thyroid drugs. Evaluation of thyroid stimulating hormone (TSH), free thyroid hormones and anti-thyroid antibodies was performed. Thyroid volume was measured by ultrasonography. IR was assessed using the estimated glucose disposal rate (eGDR) formula. In the study group 22% of subjects had insulin resistance defined as eGDR lower or equal to 7.5 mg/kg/min. The prevalence of thyroid autoimmunity (positivity for ATPO or ATg or TRAb) in the study group was 37%. There were no significant differences in the concentration of TSH, FT3, FT4, the prevalence of AIT and hypothyroidism between IR and insulin sensitive (IS) group. Mean (±SD) thyroid volume was 15.6 (±6.2) mL in patients with IR and 11.7 (±4.7) mL in IS subjects (p = .002). Thyroid volume correlated inversely with eGDR (r = -0.35, p < .001). In a multivariate linear regression model the association between thyroid volume and eGDR was independent of sex, age, duration of diabetes, daily insulin dose, BMI, cigarette smoking, TSH value and presence of thyroid autoimmunity (beta: -0.29, p = .012). Insulin resisance is associated with larger thyroid volume in patients with type 1 diabetes independently of sex, body mass index, TSH value and presence of autoimmune thyroid disease.

[Thyroid dysfunction during pregnancy].

PubMed

Díez, Juan J; Iglesias, Pedro; Donnay, Sergio

2015-10-21

Recent clinical practice guidelines on thyroid dysfunction and pregnancy have changed health care provided to pregnant women, although their recommendations are under constant revision. Trimester- and area-specific reference ranges for serum thyroid-stimulating hormone are required for proper diagnosis of hypothyroidism and hyperthyroidism. There is no doubt on the need of therapy for overt hypothyroidism, while therapy for subclinical hypothyroidism is controversial. Further research is needed to settle adverse effects of isolated hypothyroxinemia and thyroid autoimmunity. Differentiation between hyperthyroidism due to Graves' disease and the usually self-limited gestational transient thyrotoxicosis is critical. It is also important to recognize risk factors for postpartum thyroiditis. Supplementation with iodine is recommended to maintain adequate iodine nutrition during pregnancy and avoid serious consequences in offspring. Controversy remains about universal screening for thyroid disease during pregnancy or case-finding in high-risk women. Opinions of some scientific societies and recent cost-benefit studies favour universal screening. Randomized controlled studies currently under development should reduce the uncertainties that still remain in this area. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Oncogenesis of Thyroid Cancer

PubMed Central

Younis, Enas

2017-01-01

Thyroid neoplasms encompass a variety of lesions that range from benign adenomas to malignancies. These latter can be well-differentiated, poorly differentiated or undifferentiated (anaplastic) carcinomas. More than 95% of thyroid cancers are derived from thyroid follicular cells, while 2-3% (medullary thyroid cancers, MTC) originate from calcitonin producing C-cells. Over the last decade, investigators have developed a clearer understanding of genetic alterations underlying thyroid carcinogenesis. A number of point mutations and translocations are involved, not only in its tumorigenesis, but also as have potential use as diagnostic and prognostic indicators and therapeutic targets. Many occur in genes for several important signaling pathways, in particular the mitogen-activated protein kinase (MAPK) pathway. Sporadic (isolated) lesions account for 75% of MTC cases, while inherited MTC, often in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, constitute the remainder. However, non-MEN familial MTC may also occur. Advances in genetic testing have revolutionized the management of MTC, with prospects of genetic screening, testing and early prophylactic thyroidectomy. Ethical concerns of these advances are addressed. PMID:28610401

[Indications for surgery in thyroiditis].

PubMed

Diaconescu, M R; Glod, M; Costea, I; Grigorovici, M; Diaconescu, S

2012-01-01

Inflammatory processes of the thyroid represents a main proportion of the gland's pathology but the majority of them are treated by medical methods, surgery being indicated. In 14 cases (3%) from 464 operations for different thyroid conditions we have encountered authentic inflammatory lesions in 9 cases of Hashimoto's thyroiditis (two associated with papillary thyroid carcinoma and one with malignant lymphoma), two cases of Riedel's thyroiditis and respectively de Quervain thyoiditis, tuberculous thyroiditis and actynomicosis one case each. The common lymphoplasmacytic infiltration in Basedow's disease was not considered likewise as the inflammatory nespecific lesions encountered in benign and malignant pathology of the gland. The clinical and imagistic data, biological evaluation and titer of anticorps but particularly the paraffine examination together with intraoperative estimations are decisive for the diagnosis. Firm diagnosis of thyroiditis was rarely affirmed before operation, surgical indication being formulated on clinical criterions dominated by cancer suspicion. Among these are diffuse or (multi)nodular thyromegaly with a dominant nodule with recent appearance and rapid growing in temporal and geographic proximity of Chemobyl disaster, with hard consistence, celsian or compressive features and adenopathy. More added the imagistic signs but especially suspect aspects of the FNAB (follicular or with Hürthle cells smears) and also of the frozen sections. Certainty diagnosis was established by paraffine examination not always without hesitations or reexamination (Hashimoto's thyroiditis diagnosed in one case was finally a malignant lymphoma). Large removal decided after intraoperative findings induced for the most of patients a definitive hypothyroidism. All the diagnosis resources must be exhausted for the diagnosis of the inflammatory lesions of the thyroid to avoid unnecessary surgery. On the other side the chronic overstimulation by the TSH of the

Co-occurrence of papillary thyroid carcinoma and mucosa-associated lymphoid tissue lymphoma in a patient with long-standing hashimoto thyroiditis.

PubMed

Nam, Yoon Jeong; Kim, Bo Hyun; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-12-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies.

[Thyroid hormone metabolism and action].

PubMed

Köhrle, Josef

2004-05-01

Reductive deiodination of thyroid hormones at the phenolic and tyrosyl ring leads to the activation or inactivation of the thyromimetic activity inherent to thyroid hormones. Alterations in the activities of the three selenocysteine-containing enzymes, the iodothyronine deiodinases, have been reported during development and in specific cells and tissues of the adult organism. Furthermore, pathophysiological changes in the deiodinase expression lead to therapeutically relevant disturbances of the homeostasis of thyroid hormones. Metabolisation of thyroid hormones by conjugation of their phenolic 4'-OH group, their alanine side chain or cleavage of their diphenylether bridge also contributes to both local and systemic supply of thyromimetic activity or hormone degradation. Further components mediating the pleiotropic action of thyroid hormones in part include redundant T3 receptors, binding and transport proteins, metabolising enzymes and T3-regulated gene products. This is achieved in a finely tuned manner with multiple feedback control, malfunction or complete failure of individual components and networks involved in the iodothyronine metabolism and thyroid hormone action can thus be compensated or prevented.

Sonographic Features of Nodular Hashimoto Thyroiditis.

PubMed

Oppenheimer, Daniel Corey; Giampoli, Ellen; Montoya, Simone; Patel, Swapnil; Dogra, Vikram

2016-09-01

The aim of the study was to analyze the sonographic features of nodular Hashimoto thyroiditis (HT) in patients with diffuse background thyroiditis and normal background thyroid parenchyma. Eighty-six patients who had fine-needle aspiration biopsy of 100 thyroid nodules confirmed to be HT and a thyroid ultrasound within 1 year of the biopsy were included in the study. Retrospective analysis of several sonographic features of each nodule was then performed. The mean age of patients with nodular HT was 53 years, 84% of which were female. Nodular HT occurred in a background of diffuse thyroiditis in 85% and in a homogeneous normal background in 15%. Ninety-three percent of nodules were completely solid and 7% of nodules were cystic and solid. Although the sonographic appearance of nodular HT was variable, the most common appearance was a solid (93/100) and hypoechoic nodule (44/100) with a thin hypoechoic halo (42/100) without calcifications (96/100). On color Doppler, 17% of nodules showed peripheral hypervascularity, 14% of nodules were diffusely hypervascular, 34% were iso vascular, 32% were hypovascular, and 3% were avascular. The sonographic appearance of nodular HT was not significantly different in patients with diffuse background thyroiditis compared with those without background thyroiditis. The sonographic appearance of nodular HT is variable, but the most common appearance is a solid sharply circumscribed hypoechoic nodule with thin hypoechoic halo without calcification. There was no significant difference in the appearance of nodular HT in patients with diffuse background thyroiditis compared with patients with normal background thyroid parenchyma.

Struma Ovarii with Papillary Thyroid Carcinoma

PubMed Central

Alvarez, Daniel M.; Lee, Victor; Bhatt, Shweta; Dogra, Vikram S.

2011-01-01

Struma ovarii is an uncommon condition, in which thyroid tissue is the predominant or exclusive element in an ovarian teratoma. Thyroid tissue may demonstrate the same spectrum of pathological features as in the normal thyroid including benign and malignant changes. We present a case of papillary thyroid carcinoma arising in a struma ovarii of the left ovary in a 21-year-old female. PMID:22315711

Neurodevelopment and Thyroid Hormone Synthesis Inhibition in the Rat: Quantitative Understanding Within the Adverse Outcome Pathway Framework

EPA Science Inventory

Adequate levels of thyroid hormones (TH) are needed for proper brain development, deficiencies may lead to adverse neurological outcomes in humans and animal models. Environmental chemicals have been linked to TH disruption, yet the relationship between developmental exposures an...

Hashimoto's Thyroiditis Pathology and Risk for Thyroid Cancer

PubMed Central

Paparodis, Rodis; Imam, Shahnawaz; Todorova-Koteva, Kristina; Staii, Anca

2014-01-01

Background: Hashimoto's thyroiditis (HT) has been found to coexist with differentiated thyroid cancer (DTC) in surgical specimens, but an association between the two conditions has been discounted by the medical literature. Therefore, we performed this study to determine any potential relationship between HT and the risk of developing DTC. Methods: We collected data for thyrotropin (TSH), thyroxine (T4), thyroid peroxidase antibody (TPO-Ab) titers, surgical pathology, and weight-based levothyroxine (LT4) replacement dose for patients who were referred for thyroid surgery. Patients with HT at final pathology were studied further. To estimate thyroid function, patients with preoperative hypothyroid HT (Hypo-HT) were divided into three equal groups based on their LT4 replacement: LT4-Low (<0.90 μg/kg), LT4-Mid (0.90–1.43 μg/kg), and LT4-High (>1.43 μg/kg). A group of preoperatively euthyroid (Euth-HT) patients but with HT by pathology was also studied. All subjects were also grouped based on their TPO-Ab titer in TPO-high (titer >1:1000) or TPO-low/negative (titer <1:1000 or undetectable) groups. The relationship of HT and DTC was studied extensively. Results: Of 2811 subjects, 582 had HT on surgical pathology, 365 of whom were Euth-HT preoperatively. DTC was present in 47.9% of the Euth-HT, in 59.7% of LT4-Low, 29.8% of LT4-Mid, and 27.9% of LT4-High groups. The relative risk (RR) for DTC was significantly elevated for the Euth-HT and LT4-Low groups (p<0.001), but not for the LT4-Mid or LT4-High replacement dose groups. TPO-low/negative status conferred an increased RR in the Euth-HT and LT4-Low replacement dose groups (p<0.001 both), while TPO-high status decreased it in Euth-HT group (p<0.05) and made it nonsignificant in the LT4-Low group. Conclusions: HT pathology increases the risk for DTC only in euthyroid subjects and those with partially functional thyroid glands (LT4-Low) but not in fully hypothyroid HT (LT4-Mid and LT4-High). High TPO-Ab titers

[Isolated thyroid gland sarcoidosis and hyperthyroidism].

PubMed

Langsteger, W; Lind, P; Beham, A; Költringer, P; Eber, O

1989-04-29

A case of isolated sarcoidosis of the thyroid gland, associated with hyperthyroidism, is reported in a 28-year-old male patient whose thyroid was removed for hyperthyroid multinodular goitre. Histology revealed a regressive adenoma and sarcoidosis in non-adenomatous thyroid residue. Further diagnosis, therapeutic management and a 3-year follow-up did not disclose any specific changes or involvement of other tissues. Isolated thyroidal sarcoidosis with hyperthyroid alterations are extremely rare and mostly chance findings; simultaneous occurrence of thyroid sarcoidosis and hyperthyroidism may be a symptom of gland infiltration for which an adequate explanation is still lacking.

Thyroid Disease in the Older Patient

MedlinePlus

... or a history of extensive surgery and/or radiotherapy to the neck. A decision to treat the ... Weight Thyroiditis Pediatric Thyroid Information Childhood Head & Neck Irradiation Congenital Hypothyroidism FNA Biopsy of Thyroid Nodules in ...

Thyroid Disorders (For Kids)

MedlinePlus

... of thyroid disorder or thyroid disease. Hyperthyroidism (say: hi-per-THYE-roy-diz-em) happens when the ... Kids with the opposite problem have hypothyroidism (say: hi-po-THYE-roy-diz-em). In this case, ...

Thyroid Dysfunction from Antineoplastic Agents

PubMed Central

Larsen, P. Reed; Marqusee, Ellen

2011-01-01

Unlike cytotoxic agents that indiscriminately affect rapidly dividing cells, newer antineoplastic agents such as targeted therapies and immunotherapies are associated with thyroid dysfunction. These include tyrosine kinase inhibitors, bexarotene, radioiodine-based cancer therapies, denileukin diftitox, alemtuzumab, interferon-α, interleukin-2, ipilimumab, tremelimumab, thalidomide, and lenalidomide. Primary hypothyroidism is the most common side effect, although thyrotoxicosis and effects on thyroid-stimulating hormone secretion and thyroid hormone metabolism have also been described. Most agents cause thyroid dysfunction in 20%–50% of patients, although some have even higher rates. Despite this, physicians may overlook drug-induced thyroid dysfunction because of the complexity of the clinical picture in the cancer patient. Symptoms of hypothyroidism, such as fatigue, weakness, depression, memory loss, cold intolerance, and cardiovascular effects, may be incorrectly attributed to the primary disease or to the antineoplastic agent. Underdiagnosis of thyroid dysfunction can have important consequences for cancer patient management. At a minimum, the symptoms will adversely affect the patient’s quality of life. Alternatively, such symptoms can lead to dose reductions of potentially life-saving therapies. Hypothyroidism can also alter the kinetics and clearance of medications, which may lead to undesirable side effects. Thyrotoxicosis can be mistaken for sepsis or a nonendocrinologic drug side effect. In some patients, thyroid disease may indicate a higher likelihood of tumor response to the agent. Both hypothyroidism and thyrotoxicosis are easily diagnosed with inexpensive and specific tests. In many patients, particularly those with hypothyroidism, the treatment is straightforward. We therefore recommend routine testing for thyroid abnormalities in patients receiving these antineoplastic agents. PMID:22010182

Cytomorphological Spectrum of Thyroiditis: A Review of 110 Cases

PubMed Central

Nair, Rahul; Gambhir, Anushree; Kaur, Supreet; Pandey, Aditi; Shetty, Abhinav; Naragude, Piyusha

2018-01-01

Introduction Different types of thyroiditis may share some parallel clinical and biochemical features. Timely intervention can significantly reduce morbidity and mortality. Aim Aim of this study is to find the frequency of various thyroiditis, study the cytomorphological features and correlate with clinical findings including radiological findings, thyroid function test, and anti-thyroid peroxidase antibodies (Anti-TPO antibodies). Materials and Methods The study included consecutive 110 cases of thyroiditis. Detailed cytomorphological features were studied and correlated with ultrasonography findings, thyroid function test, anti-thyroid peroxidase antibodies (anti-TPO) and histopathological features where thyroidectomy specimens were received for histopathological examination. Results The majority were Hashimoto's thyroiditis (n = 100) and females (n = 103). Other forms of thyroiditis were Hashimoto's thyroiditis with colloid goiter (n = 5), De Quervain's thyroiditis (n = 3), and one case each of postpartum thyroiditis and Hashimoto's thyroiditis with associated malignancy. The majority of patients were in the age group of 21–40 (n = 70) and the majority (n = 73) had diffuse enlargement of thyroid. The majority of patients were hypothyroid (n = 52). The serum anti-TPO antibodies were elevated in 47 patients out of 71 patients. In the 48 patients who underwent ultrasonography, 38 were diagnosed as having thyroiditis. The most consistent cytomorphological features seen in fine-needle aspiration smears of Hashimoto's thyroiditis were increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. Conclusion The diagnostic cytological features in Hashimoto's thyroiditis are increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. FNAC remains the “Gold Standard” for diagnosing Hashimoto's thyroiditis. Clinical history, thyroid function, and biochemical

Co-Occurrence of Papillary Thyroid Carcinoma and Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Long-Standing Hashimoto Thyroiditis

PubMed Central

Nam, Yoon Jeong; Lee, Seong Keun; Jeon, Yun Kyung; Kim, Sang Soo; Jung, Woo Jin; Kahng, Dong Hwahn; Kim, In Ju

2013-01-01

Papillary thyroid carcinoma (PTC) is a common affliction of the thyroid gland, accounting for 70% to 80% of all thyroid cancers, whereas mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland is uncommon. The simultaneous occurrence of both malignancies is extremely rare. We report the case of a patient with both PTC and MALT lymphoma in the setting of Hashimoto thyroiditis. An 81-year-old female patient was first admitted with goiter and hoarseness, which was attributed to an ultrasonographic thyroid nodule. Subsequent fine-needle aspirate, interpreted as suspicious of papillary thyroid cancer, prompted total thyroidectomy. MALT lymphoma was an incidental postsurgical finding, coexisting with PTC in the setting of Hashimoto thyroiditis. Although the development of MALT lymphoma is very rare, patients with longstanding Hashimoto thyroiditis should undergo careful surveillance for both malignancies. PMID:24396701

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

PubMed

Wells, Samuel A; Asa, Sylvia L; Dralle, Henning; Elisei, Rossella; Evans, Douglas B; Gagel, Robert F; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G

2015-06-01

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.

Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

PubMed Central

Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

2015-01-01

Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

Metabolic Reprogramming in Thyroid Carcinoma

PubMed Central

Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

2018-01-01

Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

Thyroid Cancer Screening in South Korea Increases Detection of Papillary Cancers with No Impact on Other Subtypes or Thyroid Cancer Mortality.

PubMed

Ahn, Hyeong Sik; Kim, Hyun Jung; Kim, Kyoung Hoon; Lee, Young Sung; Han, Seung Jin; Kim, Yuri; Ko, Min Ji; Brito, Juan P

2016-11-01

The incidence of thyroid cancer has increased worldwide. The country where the incidence has increased most is South Korea. The goal of this study is to understand the magnitude of association between opportunistic thyroid cancer screening and thyroid cancer incidence, thyroid cancer subtype, and disease-specific mortality. We used the 2010 Korea Community Health Survey, which queried 226,873 individuals if they had been screened for thyroid cancer in the last two years. Thyroid cancer incidence data from 2008 to 2010 were obtained from the Korea Cancer registry data, and mortality data from 2007-2010 were obtained from the Statistics Korea database. The ecological association between thyroid screening and thyroid cancer incidence and mortality by age and sex were examined across Korea's 16 administrative regions by general linear regression models. Between 2008 and 2010, the incidence of thyroid cancer was 64.1 per 100,000 individuals: the incidence in females was 107.3 and in males was 21.1. There was a strong positive correlation between regional thyroid cancer screening and regional thyroid cancer incidence (r = 0.77, [95% confidence interval 0.70-0.82]). The magnitude of correlation was higher for females (r = 0.88 [CI 0.83-0.92]) than in males (r = 0.76 [CI 0.67-0.84]) in any age group. Thyroid screening was only associated with increased detection of papillary thyroid cancer (r = 0.74 [CI 0.59-0.88]); and not associated with mortality (r = -0.08 [CI -0.59-0.63]) due to thyroid cancer. The magnitude of association between thyroid cancer screening in South Korea and the incidence of thyroid cancer strongly suggests that screening is the most important driver of the epidemic of thyroid cancer, particularly among females. Thyroid cancer screening, however, was only associated with the increase of one tumor histology, papillary thyroid cancer, and it did not have any association with thyroid cancer mortality. The extent to which opportunistic

Thyroid cancer - papillary carcinoma

MedlinePlus

... this page: //medlineplus.gov/ency/article/000331.htm Thyroid cancer - papillary carcinoma To use the sharing features on ... the lower neck. Causes About 80% of all thyroid cancers diagnosed in the United States are the papillary ...

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

What Does the Thyroid Gland Do?

MedlinePlus

... it helps other cells do their job. hypothyroidism (hi-poh-THY-royd-izm): when your thyroid gland ... thyroid hormone (“hypo” means ‘under’ or ‘below’). hyperthyroidism (hi-purr-THY-royd-izm): when your thyroid gland ...

Thyroid-specific questions on work ability showed known-groups validity among Danes with thyroid diseases.

PubMed

Nexo, Mette Andersen; Watt, Torquil; Bonnema, Steen Joop; Hegedüs, Laszlo; Rasmussen, Åse Krogh; Feldt-Rasmussen, Ulla; Bjorner, Jakob Bue

2015-07-01

We aimed to identify the best approach to work ability assessment in patients with thyroid disease by evaluating the factor structure, measurement equivalence, known-groups validity, and predictive validity of a broad set of work ability items. Based on the literature and interviews with thyroid patients, 24 work ability items were selected from previous questionnaires, revised, or developed anew. Items were tested among 632 patients with thyroid disease (non-toxic goiter, toxic nodular goiter, Graves' disease (with or without orbitopathy), autoimmune hypothyroidism, and other thyroid diseases), 391 of which had participated in a study 5 years previously. Responses to select items were compared to general population data. We used confirmatory factor analyses for categorical data, logistic regression analyses and tests of differential item function, and head-to-head comparisons of relative validity in distinguishing known groups. Although all work ability items loaded on a common factor, the optimal factor solution included five factors: role physical, role emotional, thyroid-specific limitations, work limitations (without disease attribution), and work performance. The scale on thyroid-specific limitations showed the most power in distinguishing clinical groups and time since diagnosis. A global single item proved useful for comparisons with the general population, and a thyroid-specific item predicted labor market exclusion within the next 5 years (OR 5.0, 95 % CI 2.7-9.1). Items on work limitations with attribution to thyroid disease were most effective in detecting impact on work ability and showed good predictive validity. Generic work ability items remain useful for general population comparisons.

Inhibiting the phosphatidylinositide 3-kinase pathway blocks radiation-induced metastasis associated with Rho-GTPase and Hypoxia-inducible factor-1 activity.

PubMed

Burrows, Natalie; Telfer, Brian; Brabant, Georg; Williams, Kaye J

2013-09-01

Undifferentiated follicular and anaplastic thyroid tumours often respond poorly to radiotherapy and show increased metastatic potential. We evaluated radiation-induced effects on metastasis in thyroid carcinoma cells and tumours, mechanistically focusing on phosphatidylinositide 3-kinase (PI3K) and associated pathways. Migration was analysed in follicular (FTC133) and anaplastic (8505c) cells following radiotherapy (0-6 Gray) with concomitant pharmacological (GDC-0941) or genetic inhibition of PI3K. Hypoxia-inducible factor-1 (HIF-1)-activity was measured using luciferase reporter assays and was inhibited using a dominant-negative variant. Activation and subcellular localisation of target proteins were assessed via Western blot and immunofluorescence. In vivo studies used FTC133 xenografts with metastatic lung dissemination assessed ex vivo. Radiation induced migration in a HIF-dependent manner in FTC133 cells but decreased migration in 8505c's. Post-radiation HIF-activity correlated with migratory phenotype. PI3K-targeting inhibited migration under basal and irradiated conditions through inhibition of HIF-1α, Rho-GTPase expression/activity and localisation whilst having little effect on src/FAK. In vivo, radiation induced PI3K, HIF, Rho-GTPases and src but only PI3K, HIF and Rho-GTPases were inhibited by GDC-0941. Co-treatment with GDC-0941 and radiation significantly reduced metastatic dissemination versus radiotherapy alone. Radiation modifies metastatic characteristics of thyroid carcinoma cells, which can be successfully inhibited by targeting PI3K using GDC-0941 in vitro and in vivo. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Interphase ribosomal RNA cistron staining in thyroid epithelial cells in Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland

PubMed Central

Mamaev, N N; Grynyeva, E N; Blagosklonnaya, Y V

1996-01-01

Aim—To evaluate the expression of ribosomal cistrons in human thyroid epithelial cells (TECs) of patients with Grave's disease, Hashimoto's thyroiditis and benign and malignant tumours of the thyroid gland. Methods—TEC nucleoli were investigated in fine needle biopsy specimens from 10 controls, 39 patients with Grave's disease, 15 with Hashimoto's thyroiditis, 56 with benign, and 15 with malignant tumours of the thyroid. A one step silver staining method was applied. In most cases serum concentrations of thyroxine and triiodothyronine as well as goitre size were determined. In every case 100 TECs were evaluated for the mean numbers of nucleoli and for the average number of argyrophilic nucleolar organiser regions (AgNORs) per nucleus. Results—NORs were activated in all patients, but not in controls. The numbers of AgNORs in patients with Grave's disease were closely correlated with thyroxine or triiodothyronine, or both, concentrations and with the size of the thyroid. In patients with Hashimoto's thyroiditis about 30% of TECs nucleoli did not contain AgNORs, whereas others were heavily impregnated with silver. Compared with controls and benign tumours, the nucleoli of carcinomatous TECs were larger and irregular in shape. The mean number of AgNORs per nucleus in malignant cells was higher than that in their benign counterparts. Conclusions—The mechanism by which NORs are activated in TECs varies depending on the type of lesion. The higher AgNOR score in TECs from malignant tumours can be used to distinguish them from their benign counterparts. Images PMID:16696083

Thyroid cancer risk and dietary nitrate and nitrite intake in the Shanghai women's health study.

PubMed

Aschebrook-Kilfoy, Briseis; Shu, Xiao-Ou; Gao, Yu-Tang; Ji, Bu-Tian; Yang, Gong; Li, Hong Lan; Rothman, Nathaniel; Chow, Wong-Ho; Zheng, Wei; Ward, Mary H

2013-02-15

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds and nitrate can disrupt thyroid homeostasis by inhibiting iodide uptake. We evaluated nitrate and nitrite intake and risk of thyroid cancer in the Shanghai Women's Health Study that included 73,317 women, aged 40-70 years enrolled in 1996-2000. Dietary intake was assessed at baseline using a food frequency questionnaire. During approximately 11 years of follow-up, 164 incident thyroid cancer cases with complete dietary information were identified. We used Cox proportional hazards regression to estimate relative risks (RRs). We determined the nitrate and nitrite contents of foods using values from the published literature and focusing on regional values for Chinese foods. Nitrate intake was not associated with thyroid cancer risk [RR(Q4) = 0.93; 95% confidence interval (CI): 0.42-2.07; p for trend = 0.40]. Compared to the lowest quartile, women with the highest dietary nitrite intake had about a twofold risk of thyroid cancer (RR(Q4) = 2.05; 95%CI: 1.20-3.51), but there was not a monotonic trend with increasing intake (p for trend = 0.36). The trend with increasing nitrite intake from animal sources was significant (p for trend = 0.02) and was stronger for nitrite from processed meats (RR(Q4) = 1.96; 95%CI: 1.28-2.99; p for trend < 0.01). Although we did not observe an association for nitrate as hypothesized, our results suggest that women consuming higher levels of nitrite from animal sources, particularly from processed meat, may have an increased risk of thyroid cancer. Copyright © 2012 UICC.

Complications of acromegaly: thyroid and colon.

PubMed

Tirosh, Amit; Shimon, Ilan

2017-02-01

In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

Thyroid disrupting chemicals: Mechanisms and mixtures

EPA Science Inventory

Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones.

PubMed

Gholap, S; Kar, A

2003-06-01

The efficacy of Inula racemosa (root) and Gymnema sylvestre (leaf) extracts either alone or in combination was evaluated in the amelioration of corticosteroid-induced hyperglycaemia in mice. Simultaneously thyroid hormone levels were estimated by radio-immunoassay (RIA) in order to ascertain whether the effects are mediated through thyroid hormones or not. While the corticosteroid (dexamethasone) administration increased the serum glucose concentration, it decreased serum concentrations of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Administration of the two plant extracts either alone or in combination decreased the serum glucose concentration in dexamethasone induced hyperglycaemic animals. However, the administration of Inula racemosa and Gymnema sylvestre extracts in combination proved to be more effective than the individual extracts. These effects were comparable to a standard corticosteroid-inhibiting drug, ketoconazole. As no marked changes in thyroid hormone concentrations were observed by the administration of any of the plant extracts in dexamethasone treated animals, it is further suggested that these plant extracts may not prove to be effective in thyroid hormone mediated type II diabetes, but for steroid induced diabetes.

Pax8 modulates the expression of Wnt4 that is necessary for the maintenance of the epithelial phenotype of thyroid cells

PubMed Central

2014-01-01

Background The transcription factor Pax8 is expressed during thyroid development and is involved in the morphogenesis of the thyroid gland and maintenance of the differentiated phenotype. In particular, Pax8 has been shown to regulate genes that are considered markers of thyroid differentiation. Recently, the analysis of the gene expression profile of FRTL-5 differentiated thyroid cells after the silencing of Pax8 identified Wnt4 as a novel target. Like the other members of the Wnt family, Wnt4 has been implicated in several developmental processes including regulation of cell fate and patterning during embryogenesis. To date, the only evidence on Wnt4 in thyroid concerns its down-regulation necessary for the progression of thyroid epithelial tumors. Results Here we demonstrate that Pax8 is involved in the transcriptional modulation of Wnt4 gene expression directly binding to its 5’-flanking region, and that Wnt4 expression in FRTL-5 cells is TSH-dependent. Interestingly, we also show that in thyroid cells a reduced expression of Wnt4 correlates with the alteration of the epithelial phenotype and that the overexpression of Wnt4 in thyroid cancer cells is able to inhibit cellular migration. Conclusions We have identified and characterized a functional Pax8 binding site in the 5’-flanking region of the Wnt4 gene and we show that Pax8 modulates the expression of Wnt4 in thyroid cells. Taken together, our results suggest that in thyroid cells Wnt4 expression correlates with the integrity of the epithelial phenotype and is reduced when this integrity is perturbed. In the end, we would like to suggest that the overexpression of Wnt4 in thyroid cancer cells is able to revert the mesenchymal phenotype. PMID:25270402

[Thyroid gland in the gravidity].