Expansion of inflammatory monocytes in periphery and infiltrated into thyroid tissue in Graves’ disease

AbstractMonocytes are important mediators of immune system and are reported to be altered in autoimmune disorders. Little is known about the pathological role of monocytes in Graves’ disease (GD). Thus, we investigated monocytes in periphery and thyroid tissue in GD. Untreated GD patients were enrolled and followed up until remission. Monocytes were significantly increased and positively correlated with anti-thyrotropin receptor antibody (TRAb) in untreated GD (rcounts = 0.269, P < 0.001; rpercentage = 0.338, P < 0.001). Flow cytometry showed CD14++ CD16+ monocytes were increased and CD14++ CD16- monocytes were decreased in untreated GD (both P < 0.001). Skewed monocyte subsets were recovered in GD with remission. Serum B cell-activating factor (BAFF) was positively correlated with TRAb (r = 0.384 and P = 0.001). CD14++ CD16+ monocytes expressed higher level of BAFF in untreated GD (P < 0.05). The frequency of CD14+ monocytes and CD14+ CD16+ monocytes were significantly higher in GD thyroid tissue than in normal thyroid tissue (both P < 0.001). Our study suggested CD14++ CD16+ monocytes were significantly expanded and involved in the production of TRAb via secreting a higher level of BAFF in periphery. Besides, monocytes infiltrated into thyroid tissue and thus could serve as an important participant in GD pathogenesis.

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Intermediate microRNA expression profile in Graves’ disease falls between that of normal thyroid tissue and papillary thyroid carcinoma

Journal of Clinical Pathology ◽

10.1136/jclinpath-2016-203739 ◽

2016 ◽

Vol 70 (1) ◽

pp. 33-39 ◽

Cited By ~ 7

Author(s):

Matthias Pohl ◽

Florian Grabellus ◽

Karl Worm ◽

Georg Arnold ◽

Martin Walz ◽

...

Keyword(s):

Mirna Expression ◽

Expression Profiles ◽

Thyroid Tissue ◽

Fold Change ◽

Graves Disease ◽

Papillary Thyroid ◽

Normal Thyroid Tissue ◽

Normal Thyroid ◽

Significant Difference ◽

Benign Thyroid

AimsMany studies have previously reported a higher prevalence of papillary thyroid carcinomas (PTC) in patients with Graves' disease (GD). MicroRNAs (miRNAs) are small, non-coding RNAs that are upregulated in PTC compared with benign thyroid tissue. The objective of the study was to examine the miRNA expression of selected miRNAs that are known to be upregulated in PTC in patients with GD.MethodsParaffin embedded thyroid tissue from 159 patients with GD was screened for expression of the miRNAs 146b, 181b, 21, 221 and 222 by RT-PCR. The expression profiles of four normal thyroids, 50 PTCs without concomitant GD and 11 patients with untreated GD served as the controls.ResultsThe expression pattern of these miRNAs in patients with GD is intermediate between that of benign thyroid tissue (p<0.001) and PTC (in three out of five miRNAs, p<0.001). This corresponds to a 15-fold change for GD versus PTC, and a 31-fold change for GD versus normal thyroid tissue. The miRNA expression in 11 papillary microcarcinomas found in our study (a prevalence of 0.07) was not different from that in PTC samples from patients without GD for four of five miRNA types. Furthermore, we found a significant difference in the expression of miRNA 221/222 between treated and untreated GD tissue.ConclusionsIn conclusion, we found an intermediate expression of specific miRNAs in thyroid tissue from patients with GD that fell between the expression levels found in normal thyroid glands and PTC, which suggests a possible influence of certain miRNAs on developing PTC in patients with GD.

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Increased Expression of the Na+/I− Symporter in Cultured Human Thyroid Cells Exposed to Thyrotropin and in Graves’ Thyroid Tissue*

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.82.10.4269 ◽

1997 ◽

Vol 82 (10) ◽

pp. 3331-3336 ◽

Cited By ~ 1

Author(s):

Tsukasa Saito ◽

Toyoshi Endo ◽

Akio Kawaguchi ◽

Masato Ikeda ◽

Minoru Nakazato ◽

...

Keyword(s):

Thyroid Tissue ◽

Human Thyroid ◽

Thyroid Peroxidase ◽

Graves Disease ◽

Intracellular Camp ◽

Normal Thyroid Tissue ◽

Thyroid Cells ◽

Normal Thyroid ◽

Hormone Synthesis ◽

Messenger Ribonucleic Acid

Abstract The Na+/I− symporter (NIS) is important in hormone synthesis in the thyroid gland. NIS activity, as reflected by I− uptake, was increased by TSH (1 mU/mL) or forskolin (10μ mol/L) in primary cultured human thyroid cells. Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively. Immunoblot analysis revealed 2.7- and 2.4-fold increases, respectively, in the amount of NIS protein after 48 h, suggesting that elevated levels of intracellular cAMP induced the expression of NIS in human thyrocytes. We then studied the levels of NIS mRNA and protein in Graves’ thyroid tissue and found that the amount of NIS mRNA in thyroid tissue from individuals with Graves’ disease (n = 5) was 3.8 times that in normal thyroid tissue (n = 5). The abundance of NIS mRNA was significantly correlated with that of thyroid peroxidase or thyroglobulin mRNAs, but not with that of TSH receptor mRNA, in the Graves’ and normal thyroid tissue specimens. The amount of NIS protein was also increased 3.1-fold in Graves’ thyroid tissue compared with that in normal thyroid tissue. The increased expression of NIS may thus contribute to the development of Graves’ disease.

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MON-532 Characterization of the Angiogenic Factor SFRP2 in Papillary Thyroid Carcinoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.032 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Wyatt O Wofford ◽

Rupak Mukherjee ◽

Julie Siegel ◽

Denise Garcia ◽

Eleanor Hilliard ◽

...

Keyword(s):

Thyroid Cancer ◽

Cell Lines ◽

Thyroid Tissue ◽

Angiogenic Factor ◽

Papillary Thyroid ◽

Normal Thyroid Tissue ◽

Normal Thyroid ◽

Treatment Groups ◽

Vehicle Treatment

Abstract Over the last decade, there has been an average annual increase of 3.1% in thyroid cancer diagnosis in the U.S. Papillary thyroid carcinoma (PTC) accounts for 80% of all thyroid cancer diagnoses. However, few molecular markers exist to identify clinically aggressive phenotypes. The angiogenic factor, secreted frizzled-related protein 2 (SFRP2), is associated with a poor prognosis in several malignancies including breast cancer and melanoma. The role of SFRP2 in PTC has yet to be investigated. The aims of this study were to determine the differential expression of SFRP2 in PTC, benign thyroid adenomas, normal thyroid tissue (from patients without cancer), and normal adjacent tissue (NAT) (non-cancerous tissue from patients with PTC) and investigate the role of SFRP2 in tumor development in two PTC cell lines, PTC classical variant (PTC-CV) and PTC follicular variant (PTC-FV), upon treatment with a humanized anti-SFRP2 monoclonal antibody (hSFRP2 mAb). Immunohistochemistry (IHC) was performed using human tissue protein microarrays including 226 PTC, 79 benign adenomas, 112 NAT, and 30 normal thyroid tissue samples. In-vitro proliferation and apoptosis experiments were performed on MDA-T41 (PTC-CV) and MDA-T68 (PTC-FV) cell lines by treating with hSFRP2 mAb, Xolair IgG control, and a vehicle control. SFRP2 expression was significantly higher in PTC compared with benign adenomas and normal thyroid (mean expression scores 9, 6, and 1, respectively; p<0.05). SFRP2 expression was significantly higher in NAT than normal thyroid (mean expression score 4 and 0, respectively, p<0.05). Apoptotic rates were increased by 40% and 62% in the PTC-CV hSFRP2 mAb treatment group compared with the Xolair and vehicle treatment groups, respectively (p<0.05). Apoptotic rates were increased by 126% and 59% in the PTC-FV hSFRP2 mAb treatment group compared with the Xolair and vehicle treatment groups, respectively (p<0.05). Treatment with hSFRP2 mAb had no significant effect on proliferation in either cell line. In conclusion, SFRP2 expression is significantly higher in PTC than in benign adenomas and normal thyroid tissue. SFRP2 expression in NAT is significantly higher than in normal thyroid tissue and not significantly different from benign adenomas. SFRP2 expression in nonmalignant tissue adjacent to PTC could be due to expression in the tumor microenvironment. Treatment with a novel hSFPR2 mAb increases apoptotic rates in two different PTC cell lines. These data suggest that SFPR2 is involved in tumorigenesis of PTC.

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The CCK2-receptor is expressed in human medullary thyroid carcinomas as well as in normal thyroid tissue

Gastroenterology ◽

10.1016/s0016-5085(01)82515-4 ◽

2001 ◽

Vol 120 (5) ◽

pp. A507-A507

Author(s):

M BLAEKER ◽

A WEERTH ◽

L JONAS ◽

M TOMETTEN ◽

M SCHUTZ ◽

...

Keyword(s):

Thyroid Tissue ◽

Normal Thyroid Tissue ◽

Normal Thyroid ◽

Medullary Thyroid ◽

Thyroid Carcinomas ◽

Cck2 Receptor ◽

Medullary Thyroid Carcinomas

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Decreased Expression of GPER1 Gene and Protein in Goiter

International Journal of Endocrinology ◽

10.1155/2015/869431 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Raquel Weber ◽

Ana Paula Santin Bertoni ◽

Laura Walter Bessestil ◽

Ilma Simoni Brum ◽

Tania Weber Furlanetto

Keyword(s):

Estrogen Receptor ◽

Quantitative Polymerase Chain Reaction ◽

Thyroid Tissue ◽

Chain Reaction ◽

Normal Thyroid ◽

Protein Levels ◽

Protein Expressions ◽

Polymerase Chain ◽

G Protein Coupled

Goiter is more common in women, suggesting that estrogen could be involved in its physiopathology. The presence of classical estrogen receptors (ERαand ERβ) has been described in thyroid tissue, suggesting a direct effect of estrogen on the gland. A nonclassic estrogen receptor, the G-protein-coupled estrogen receptor (GPER1), has been described recently in several tissues. However, in goiter, the presence of this receptor has not been studied yet. We investigated GPER1 gene and protein expressions in normal thyroid and goiter using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. In normal thyroid (n=16) and goiter (n=19), GPER1 gene was expressed in all samples, while GPER1 protein was expressed in all samples of normal thyroid (n=15) but in only 72% of goiter samples (n=13). When comparing GPER1 gene and protein levels in both conditions, gene expression and protein levels were higher in normal thyroid than in goiter, suggesting a role of this receptor in this condition. Further studies are needed to elucidate the role of GPER1 in normal thyroid and goiter.

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Detection of parathyroid adenomas with 4DCT: Towards a true four-dimensional technique

10.21203/rs.3.rs-237831/v1 ◽

2021 ◽

Author(s):

Steven Raeymaeckers ◽

Yannick De Brucker ◽

Tim Vanderhasselt ◽

Nico Buls ◽

Johan De Mey

Keyword(s):

Primary Hyperparathyroidism ◽

Thyroid Tissue ◽

Motion Artifacts ◽

P Value ◽

Normal Thyroid Tissue ◽

Dose Length Product ◽

Normal Thyroid ◽

Parathyroid Adenomas ◽

Parathyroid Lesions ◽

Over Time

Abstract Background. 4DCT is a commonly performed examination in the management of primary hyperparathyroidism, combining three-dimensional imaging with enhancement over time as the fourth dimension. We propose a novel technique consisting of 16 different contrast phases, instead of three or four different phases. The main aim of this study was to see if this protocol allows for the detection of parathyroid adenomas within dose limits. Our secondary aim was examining the enhancement of parathyroid lesions over time.Methods. For this prospective study, we included 15 patients with primary hyperparathyroidism prior to surgery. We obtain a 4DCT with 16 different phases: an unenhanced phase followed by 11 consecutive arterial phases and 4 venous phases. Centered on the thyroid, continuous axial scanning is performed over a fixed 8cm or 16cm coverage volume after start of contrast administration.Results. In all patients an enlarged parathyroid can be demonstrated, mean lesion size is 13.6mm. Mean peak arterial peak enhancement for parathyroid lesions is 384 HU compared to 333 HU for the normal thyroid. No statistical difference could be found. Time to peak (TTP) is significantly earlier for parathyroid adenomas compared to normal thyroid tissue: 30.8s versus 32.3s (p value 0.008). Mean Slope of Increase (MSI) of the enhancement curve is significantly steeper compared to normal thyroid tissue: 29.8% versus 22.2% (p value 0.012). Mean dose length product was 890.7 mGy.cm with a calculated effective dose of 6.7 mSv.Conclusion. We propose a feasible 4DCT scanning-protocol for the detection of parathyroid adenomas. We manage to obtain a multitude of phases, allowing for a dynamic evaluation within an acceptable exposure range when compared to classic helical 4DCT. Our 4DCT protocol may allow for a better visualization of the pattern of enhancement of parathyroid lesions, as enhancement over time curves can be drawn. This way wash-in and wash-out of contrast in suspected lesions can be readily demonstrated. Motion artifacts are less problematic as multiple phases are available.

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Certain peculiarities of parenchymal-stromal correlations in the thyroid gland with nodular forms of goiter with its rucurrent and non-recurrent course

Clinical anatomy and operative surgery ◽

10.24061/1727-0847.19.1.2020.9 ◽

2020 ◽

Vol 19 (1) ◽

pp. 53-60

Author(s):

N. P. Tkachuk ◽

I. S. Davydenko

Keyword(s):

Thyroid Gland ◽

Slow Growth ◽

Thyroid Tissue ◽

Nodular Goiter ◽

Specific Weight ◽

Pathological Changes ◽

Normal Thyroid Tissue ◽

Normal Thyroid ◽

Stromal Component ◽

Correlation Parameters

In spite of a considerable efficacy of conservative treatment of goiter, surgery remains the main method of treatment of such patients. Though, on the one hand, total thyroidectomy inevitably results in the development of postsurgical hypothyroidism, on the other hand – in case organ-saving surgery is performed the risk of postsurgical relapse arises. Modern morphological methods are directed to detection of oncological risk of nodular formations, and recommendations concerning an adequate volume of surgery taking into account probability of relapse are practically lacking. Therefore, the objective of the study was finding criteria of a relapsing risk by means of investigation of morphological peculiarities of the parenchymal-stromal correlations in the thyroid gland with recurrent nodular and primary nodular (multinodular) goiter without signs of functional disorders. In the course of the research according to the examined correlation parameters of the parenchyma and stroma various forms of nodular goiter were found to differ from the thyroid tissue without pathological changes by a number of parameters. In particular, specific weight of the parenchyma on an average increases reliably in the tissue of nodular goiter with its various variants in comparison with the thyroid gland without pathological changes. Together with the increase of the parenchymal specific weight in nodular goiter the amount of colloid on an average decreases, and a specific dependence on the kind of goiter is observed – colloid volume decreases from goiter with slow growth to goiter with quick growth, and it is the smallest with goiter relapse. Quantitative analysis of the goiter tissue stromal component demonstrates a considerable increase of its specific volume in comparison with normal thyroid tissue. Evaluation of changes of the morphometric parameters in the thyroid follicles found that in case of nodular goiter with slow growth the percentage of follicles with colloid is close to 100%. On an average it does not differ from that of the normal thyroid tissue. At the same time, in case of nodular goiter with quick growth the percentage of follicles with colloid decreases sharply, and in case of relapse it appears to be still less than that in nodular goiter with quick growth. Besides, with nodular goiter the diameter of follicles on an average increases in comparison with the normal thyroid tissue. In a number of cases it can be estimated as macrofollicular goiter. At the same time, the diameter of follicles is smaller in nodular goiter with quick growth. It is still less in case of goiter relapse. The size of follicles becomes sharply diverse in case of nodular goiter with slow growth, but it decreases in case of nodular goiter with quick growth and relapse. Consequently, recurrent nodular goiter is mostly similar to that of primary nodular goiter with a quick growth, though certain differences between them exist. The peculiarities found enable to suggest that nodular goiter with a quick growth possesses more chances for relapse.

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A Pro-Tumorigenic Effect of Heparanase 2 (Hpa2) in Thyroid Carcinoma Involves Its Localization to the Nuclear Membrane

Frontiers in Oncology ◽

10.3389/fonc.2021.645524 ◽

2021 ◽

Vol 11 ◽

Author(s):

Itai Margulis ◽

Inna Naroditsky ◽

Miriam Gross-Cohen ◽

Neta Ilan ◽

Israel Vlodavsky ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Lymph Nodes ◽

Nuclear Membrane ◽

Tumor Metastasis ◽

Cellular Localization ◽

Thyroid Tissue ◽

Clinicopathological Parameters ◽

Regional Lymph Nodes ◽

Normal Thyroid

Activity of the endo-beta-glucuronidase heparanase, capable of cleaving heparan sulfate (HS), is most often elevated in many types of tumors, associating with increased tumor metastasis and decreased patients’ survival. Heparanase is therefore considered to be a valid drug target, and heparanase inhibitors are being evaluated clinically in cancer patients. Heparanase 2 (Hpa2) is a close homolog of heparanase that gained very little attention, likely because it lacks HS-degrading activity typical of heparanase. The role of Hpa2 in cancer was not examined in detail. In head and neck cancer, high levels of Hpa2 are associated with decreased tumor cell dissemination to regional lymph nodes and prolonged patients’ survival, suggesting that Hpa2 functions to attenuate tumor growth. Here, we examined the role of Hpa2 in normal thyroid tissue and in benign thyroid tumor, non-metastatic, and metastatic papillary thyroid carcinoma (PTC) utilizing immunostaining in correlation with clinicopathological parameters. Interestingly, we found that Hpa2 staining intensity does not significantly change in the transition from normal thyroid gland to benign, non-metastatic, or metastatic thyroid carcinoma. Remarkably, we observed that in some biopsies, Hpa2 is accumulating on the membrane (envelop) of the nucleus and termed this cellular localization NM (nuclear membrane). Notably, NM localization of Hpa2 occurred primarily in metastatic PTC and was associated with an increased number of positive (metastatic) lymph nodes collected at surgery. These results describe for the first time unrecognized localization of Hpa2 to the nuclear membrane, implying that in PTC, Hpa2 functions to promote tumor metastasis.

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