The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

PubMed

Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

2014-09-01

Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

CHANGES IN TOOTH HARD TISSUE MINERALI-ZATION AND BLOOD RHEOLOGY IN HEALTHY ADOLESCENTS AND THOSE WITH THYROID DYSFUNCTION.

PubMed

Beriashvili, S; Nikolaishvili, M; Mantskava, M; Momtsemlidze, N; Franchuk, K

2016-11-01

Thyroid dysfunction causes spreading and development of caries in the teeth and changes in periodontal tissues. In addition, it causes changes in peripheral blood flow and mineralization, local transcapillary metabolism causes changes in blood rheology. There are only few works in this direction and, therefore, the purpose of our research was to find out how the mineralization and the rheological properties of blood are changed in lesion of periodontal tissue on a background of thyroid dysfunction. Accordingly, the stomatological study was conducted in 75 adolescents aged 12-18 years by the standard method, recommended by the World Health Organization. According to the study, 45 patients out of them suffered from thyroid dysfunction, in particular from hypothyroidism. The comparator group consisted of 30 children of the same age without endocrine abnormalities. By the gained results it is noted that in spite of different type lesions due to dental caries, the caries incidence and intensiveness is higher in children with hypothyroidism as compared to healthy children. Decrease in saliva excretion rate and increase in oral fluid viscosity was found in children with thyroid and endocrine diseases as compared to healthy children. In children with endocrine disorders concurrent increase in calcium content (1,43±0,08 mmol/l) and decrease in inorganic phosphate concentrations (4,54±0,15 mmol/l) is reliably established. In children with thyroid disfunction and while periodontal tissue pathology, rheological features are disordered more dramatically than in healthy children. Therefore, it can be said that the changes in the adolescents' thyroid function is one of the reasons for formation of periodontal tissue diseases.Therefore, at detecting even the first signs of the periodontal tissue diseases, it is desirable in adolescents to assess the thyroid functional condition, since it will be the precondition for effective treatment and management of dental disease, in particular, dental caries and lesions of periodontal tissue.

Marine-Lenhart syndrome with papillary thyroid carcinoma.

PubMed

Atmaca, Hulusi; Çolak, Ramis; Yazici, Zihni Acar; Kefeli, Mehmet; Tosun, Fevziye Canbaz

2015-04-01

Graves' disease with accompanying functioning nodules is known as Marine-Lenhart syndrome. Autonomously functioning thyroid nodules (AFTNs) also within Graves' thyroid tissue are almost always bening in nature. A 45-year-old man developed hyperthyroidism due to the coexistence of Graves' disease and AFTN. Total thyroidectomy was performed. The hyperfunctioning nodule with centrally hypoactive foci detected by technetium-99m thyroid scanning was histologically diagnosed as papillary thyroid carcinoma that was 2.5 cm in diameter. We report the presence of papillary thyroid carcinoma within AFTN in patients with Marine-Lenhart syndrome, which has not been reported so far.

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 equally capable as the thyroid extractives of palliating the acute cachexia in totally thyroidless dogs. (9) Neither of the above substances is an enzyme, nor does either contain iodine. (10) Neither the feeding of minced raw thyroid glands, nor the injection of aqueous thyroid extracts, decoctions, and concentrated solutions of the extracted palliative thyroid principles is capable of keeping totally thyroidless young dogs alive longer than a few weeks (possibly three weeks). Still less capable are the thyroid preparations containing decomposition products. (11) The presence of one, or usually several, small accessory thyroid bodies, which gradually hypertrophy and wholly or partially assume the functions of the excised thyroid lobes, accounts for the occasionally long survival of thyroidectomized, thyroid-fed, young dogs. (12) Totally thyroidless young dogs are so quickly overwhelmed by the cachexia, and the intervals between the thyroidectomy and the onset of the severe dyspnœic attacks and subsequent deaths differ so slightly, no matter which of the usual varieties of fresh food are employed, that kinds of fresh food cannot be unquestionably affirmed to influence the onset of the cachexia in any especially definite manner. Animal foods, in which constituents poisonous to rabbits have developed, probably slightly hasten the onset of the severer symptoms, and the vaunted remarkably modifying influence of a diet of ordinary milk, such as Breisacher observed, does not exist in the case of the totally thyroidless dog. (13) Monkeys whose general metabolism is disturbed in consequence of the removal of a greater portion of the thyroid gland, evidently become more susceptible to those constituents of meat that are poisonous to rabbits, and sufficient clinical evidence exists for concluding that probably a like susceptibility to animal foods containing such constituents also exists in men when the function of the thyroid gland is sufficiently disturbed. (14) And, finally, as regards the thyroid factor in the pathology of exophthalmic goitre, I agree with Gley that the majority of the symptoms in many patients with that disease can apparently, from an experimental standpoint, be as plausibly explained by the hypothesis of partially deficient thyroid activity as by the hypothesis of augmentation of thyroid function. PMID:19866869

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

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.

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.

Free Thyroid Transfer: A Novel Procedure to Prevent Radiation-induced Hypothyroidism

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

Harris, Jeffrey; Almarzouki, Hani; Department of Otolaryngology-Head and Neck Surgery, King Abdulaziz University, Jeddah

Purpose: The incidence of hypothyroidism after radiation therapy for head and neck cancer (HNC) has been found to be ≤53%. Medical treatment of hypothyroidism can be costly and difficult to titrate. The aim of the present study was to assess the feasibility of free thyroid transfer as a strategy for the prevention of radiation-induced damage to the thyroid gland during radiation therapy for HNC. Methods and Materials: A prospective feasibility study was performed involving 10 patients with a new diagnosis of advanced HNC undergoing ablative surgery, radial forearm free-tissue transfer reconstruction, and postoperative adjuvant radiation therapy. During the neck dissection,more » hemithyroid dissection was completed with preservation of the thyroid arterial and venous supply for implantation into the donor forearm site. All patients underwent a diagnostic thyroid technetium scan 6 weeks and 12 months postoperatively to examine the functional integrity of the transferred thyroid tissue. Results: Free thyroid transfer was executed in 9 of the 10 recruited patients with advanced HNC. The postoperative technetium scans demonstrated strong uptake of technetium at the forearm donor site at 6 weeks and 12 months for all 9 of the transplanted patients. Conclusions: The thyroid gland can be transferred as a microvascular free transfer with maintenance of function. This technique could represent a novel strategy for maintenance of thyroid function after head and neck irradiation.« less

DEVELOPMENT OF AN AMPHIBIAN METAMORPHOSIS MODEL FOR DETECTING THYROID AXIS DISRUPTION

EPA Science Inventory

Metamorphosis in Xenopus laevis represents an elaborate process of post-embryonic development which is thyroid hormone (TH) dependent. The development of a functional thyroid axis and the responses of tissues to different TH concentrations are well defined in this species, provid...

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 peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties.

PubMed

Godlewska, Marlena; Arczewska, Katarzyna D; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław; Czarnocka, Barbara

2017-01-01

Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

MicroRNAs in thyroid development, function and tumorigenesis.

PubMed

Fuziwara, Cesar Seigi; Kimura, Edna Teruko

2017-11-15

MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that modulate the vast majority of cellular processes. During development, the correct timing and expression of miRNAs in the tissue differentiation is essential for organogenesis and functionality. In thyroid gland, DICER and miRNAs are necessary for accurately establishing thyroid follicles and hormone synthesis. Moreover, DICER1 mutations and miRNA deregulation observed in human goiter influence thyroid tumorigenesis. The thyroid malignant transformation by MAPK oncogenes is accompanied by global miRNA changes, with a marked reduction of "tumor-suppressor" miRNAs and activation of oncogenic miRNAs. Loss of thyroid cell differentiation/function, and consequently iodine trapping impairment, is an important clinical characteristic of radioiodine-refractory thyroid cancer. However, few studies have addressed the direct role of miRNAs in thyroid gland physiology. Here, we focus on what we have learned in the thyroid follicular cell differentiation and function as revealed by cell and animal models and miRNA modulation in thyroid tumorigenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The immune system which adversely alter thyroid functions: a review on the concept of autoimmunity.

PubMed

Mansourian, Azad Reza

2010-08-15

The immune system protect individual from many pathogens exists within our environment and in human body, by destroying them through molecular and cellular mechanism of B and T cells of immune system. Autoimmunity is an adverse relation of immune system against non- foreign substances leaving behind either alters the normal function or destroying the tissue involved. Autoimmunity occur in genetically predispose persons with familial connections. The autoimmunity to the thyroid gland mainly consists of Hashimato thyroiditis and Grave's disease, the two end of spectrum in thyroid function of hypo and hyperactivity, respectively. The thyroid stimulating hormone receptor, thyroglobuline, enzymes of thyroid hormones synthesis are targeted by autoantibodies and cell- mediated reactions. The aim of this review is to explore the studies reported on the autoimmunity to the thyroid gland.

Development of a functional thyroid model based on an organoid culture system.

PubMed

Saito, Yoshiyuki; Onishi, Nobuyuki; Takami, Hiroshi; Seishima, Ryo; Inoue, Hiroyoshi; Hirata, Yuki; Kameyama, Kaori; Tsuchihashi, Kenji; Sugihara, Eiji; Uchino, Shinya; Ito, Koichi; Kawakubo, Hirofumi; Takeuchi, Hiroya; Kitagawa, Yuko; Saya, Hideyuki; Nagano, Osamu

2018-03-04

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid-like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRAS Q61R ) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

HPLC-ICP/MS Analysis of Thyroid Hormone and Related Iodinated Compounds in Tissues and Media

EPA Science Inventory

Quantifying thyroid hormone (TH) and the synthetic precursors and metabolic products of TH is important for developing models of the hypothalamic-pituitary-thyroid (HPT) axis as well as for understanding the effects of xenobiotics on HPT axis function. In this study, the developm...

New Insights into Thyroid Hormone Action

PubMed Central

Mendoza, Arturo; Hollenberg, Anthony N.

2017-01-01

Thyroid hormones (TH) are endocrine messengers essential for normal development and function of virtually every vertebrate. The hypothalamic-pituitary-thyroid axis is exquisitely modulated to maintain nearly constant TH (T4 and T3) concentrations in circulation. However peripheral tissues and the CNS control the intracellular availability of TH, suggesting that circulating concentrations of TH are not fully representative of what each cell type sees. Indeed, recent work in the field has identified that TH transporters, deiodinases and thyroid hormone receptor coregulators can strongly control tissue-specific sensitivity to a set amount of TH. Furthermore, the mechanism by which the thyroid hormone receptors regulate target gene expression can vary by gene, tissue and cellular context. This review will highlight novel insights into the machinery that controls the cellular response to TH, which include unique signaling cascades. These findings shed new light into the pathophysiology of human diseases caused by abnormal TH signaling. PMID:28174093

Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.

PubMed

Mahmoudi, Asma; Ghorbel, Hèla; Feki, Ines; Bouallagui, Zouhaier; Guermazi, Fadhel; Ayadi, Lobna; Sayadi, Sami

2018-04-27

Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Thyroid peroxidase (TPO) expressed in thyroid and breast tissues shows similar antigenic properties

PubMed Central

Godlewska, Marlena; Arczewska, Katarzyna D.; Rudzińska, Magdalena; Łyczkowska, Anna; Krasuska, Wanda; Hanusek, Karolina; Ruf, Jean; Kiedrowski, Mirosław

2017-01-01

Background Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed. Methods In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs. Results We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs. Conclusions Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism. PMID:28575127

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

Notch3 expression correlates with thyroid cancer differentiation, induces apoptosis, and predicts disease prognosis.

PubMed

Somnay, Yash R; Yu, Xiao-Min; Lloyd, Ricardo V; Leverson, Glen; Aburjania, Zviadi; Jang, Samuel; Jaskula-Sztul, Renata; Chen, Herbert

2017-03-01

Thyroid tumorigenesis is characterized by a progressive loss of differentiation exhibited by a range of disease variants. The Notch receptor family (1-4) regulates developmental progression in both normal and cancerous tissues. This study sought to characterize the third Notch isoform (Notch3) across the various differentiated states of thyroid cancer, and determine its clinical impact. Notch3 expression was analyzed in a tissue microarray of normal and pathologic thyroid biopsies from 155 patients. The functional role of Notch3 was then investigated by upregulating its expression in a follicular thyroid cancer (FTC) cell line. Notch3 expression regressed across decreasingly differentiated, increasingly malignant thyroid specimens, correlated with clinicopathological attributes reflecting poor prognosis, and independently predicted survival following univariate and multivariate analyses. Overexpression of the active Notch3 intracellular domain (NICD3) in a gain-of-function FTC line led to functional activation of centromere-binding protein 1, while increasing thyroid-specific gene transcription. NICD3 induction also reduced tumor burden in vivo and initiated the intrinsic apoptotic cascade, alongside suppressing cyclin and B-cell lymphoma 2 family expression. Loss of Notch3 expression may be fundamental to the process of dedifferentiation that accompanies thyroid oncogenesis. Conversely, activation of Notch3 in thyroid cancer exerts an antiproliferative effect and restores elements of a differentiated phenotype. These findings provide preclinical rationale for evaluating Notch3 as a disease prognosticator and therapeutic target in advanced thyroid cancer. Cancer 2017;123:769-82. © 2016 American Cancer Society. © 2016 American Cancer Society.

Functional expression of the thyrotropin receptor in C cells: new insights into their involvement in the hypothalamic-pituitary-thyroid axis

PubMed Central

Morillo-Bernal, Jesús; Fernández-Santos, José M; Utrilla, José C; de Miguel, Manuel; García-Marín, Rocío; Martín-Lacave, Inés

2009-01-01

Thyroid C cells, or parafollicular cells, are mainly known for producing calcitonin, a hormone involved in calcium homeostasis with hypocalcemic and hypophosphatemic effects. Classically, the main endocrine activity of this cell population has been believed to be restricted to its roles in serum calcium and bone metabolism. Nonetheless, in the last few years evidence has been accumulating in the literature with regard to local regulatory peptides secreted by C cells, such as somatostatin, ghrelin, thyrotropin releasing hormone or the recently described cocaine- and amphetamine-related transcript, which could modify thyroid function. As thyrotropin is the main hormone controlling the hypothalamic-pituitary-thyroid axis and, accordingly, thyroid function, we have examined the functional expression of the thyrotropin receptor in C-cell lines and in thyroid tissues. We have found that rat and human C-cell lines express the thyrotropin receptor at both mRNA and protein levels. Furthermore, incubation of C cells with thyrotropin resulted in a 10-fold inhibition of thyrotropin-receptor expression, and a concomitant decrease of the steady-state mRNA levels for calcitonin and calcitonin gene-related peptide determined by quantitative real-time PCR was found. Finally, thyrotropin receptor expression by C cells was confirmed at protein level in both normal and pathological thyroid tissues by immunohistochemistry and immunofluorescence. These results confirm that C cells, under regulation by thyrotropin, are involved in the hypothalamic-pituitary-thyroid axis and suggest a putative role in local fine-tuning of follicular cell activity. PMID:19493188

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 altered hormone synthesis and release genes. ► Rat thyroid was more sensitive to the drug effects than human tissue.« less

Evaluation of thyroid tissue by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Teixeira, C. S. B.; Bitar, R. A.; Santos, A. B. O.; Kulcsar, M. A. V.; Friguglietti, C. U. M.; Martinho, H. S.; da Costa, R. B.; Martin, A. A.

2010-02-01

Thyroid gland is a small gland in the neck consisting of two lobes connected by an isthmus. Thyroid's main function is to produce the hormones thyroxine (T4), triiodothyronine (T3) and calcitonin. Thyroid disorders can disturb the production of these hormones, which will affect numerous processes within the body such as: regulating metabolism and increasing utilization of cholesterol, fats, proteins, and carbohydrates. The gland itself can also be injured; for example, neoplasias, which have been considered the most important, causing damage of to the gland and are difficult to diagnose. There are several types of thyroid cancer: Papillary, Follicular, Medullary, and Anaplastic. The occurrence rate, in general is between 4 and 7%; which is on the increase (30%), probably due to new technology that is able to find small thyroid cancers that may not have been found previously. The most common method used for thyroid diagnoses are: anamnesis, ultrasonography, and laboratory exams (Fine Needle Aspiration Biopsy- FNAB). However, the sensitivity of those test are rather poor, with a high rate of false-negative results, therefore there is an urgent need to develop new diagnostic techniques. Raman spectroscopy has been presented as a valuable tool for cancer diagnosis in many different tissues. In this work, 27 fragments of the thyroid were collected from 18 patients, comprising the following histologic groups: goitre adjacent tissue, goitre nodular tissue, follicular adenoma, follicular carcinoma, and papillary carcinoma. Spectral collection was done with a commercial FTRaman Spectrometer (Bruker RFS100/S) using a 1064 nm laser excitation and Ge detector. Principal Component Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. Comparing the goitre adjacent tissue with the goitre nodular region, an index of 58.3% of correct classification was obtained. Between goitre (nodular region and adjacent tissue) and papillary carcinoma, the index of correct classification was 64.9%, and the classification between benign tissues (goitre and follicular adenoma) and malignant tissues (papillary and follicular carcinomas), the index was 72.5%.

Effective visualization of suppressed thyroid tissue by means of baseline 99mTc-methoxy isobutyl isonitrile in comparison with 99mTc-pertechnetate scintigraphy after TSH stimulation.

PubMed

Vattimo, A; Bertelli, P; Burroni, L

1992-01-01

Baseline 99mTc-MIBI thyroid scintigraphy was compared with 99mTc-pertechnetate scintigraphy after TSH stimulation in seven patients with suppressed thyroid tissue due to an autonomously functioning thyroid nodule (AFTN). In all patients the suppressed thyroid tissue was visualized by means of both baseline 99mTc-MIBI and post-TSH 99mTc-pertechnetate scintigraphy, and in some cases the former technique provided better visualization. In one patient presenting a "warm" nodule T3-suppression did not affect the nodular/extranodular uptake ratio of 99mTc-MIBI, whereas the 99mTc-pertechnetate uptake ratio increased significantly. This leads us to hypothesize that the thyroid uptake of 99mTc-MIBI is not related to TSH control, but rather to other mechanisms such as the blood flow. Since exogenous TSH is no longer available, 99mTc-MIBI scintigraphy can be successfully used in the place of repeated 99mTc-pertechnetate scintigraphy after TSH stimulation in the assessment of AFTN.

Thyroid hormone-induced oxidative stress.

PubMed

Venditti, P; Di Meo, S

2006-02-01

Hypermetabolic state in hyperthyroidism is associated with tissue oxidative injury. Available data indicate that hyperthyroid tissues exhibit an increased ROS and RNS production. The increased mitochondrial ROS generation is a side effect of the enhanced level of electron carriers, by which hyperthyroid tissues increase their metabolic capacity. Investigations of antioxidant defence system have returned controversial results. Moreover, other thyroid hormone-linked biochemical changes increase tissue susceptibility to oxidative challenge, which exacerbates the injury and dysfunction they suffer under stressful conditions. Mitochondria, as a primary target for oxidative stress, might account for hyperthyroidism linked tissue dysfunction. This is consistent with the inverse relationship found between functional recovery of ischemic hyperthyroid hearts and mitochondrial oxidative damage and respiration impairment. However, thyroid hormone-activated mitochondrial mechanisms provide protection against excessive tissue dysfunction, including increased expression of uncoupling proteins, proteolytic enzymes and transcriptional coactivator PGC-1, and stimulate opening of permeability transition pores.

Selenium and the control of thyroid hormone metabolism.

PubMed

Köhrle, Josef

2005-08-01

Thyroid hormone synthesis, metabolism and action require adequate availability of the essential trace elements iodine and selenium, which affect homeostasis of thyroid hormone-dependent metabolic pathways. The three selenocysteine-containing iodothyronine deiodinases constitute a novel gene family. Selenium is retained and deiodinase expression is maintained at almost normal levels in the thyroid gland, the brain and several other endocrine tissues during selenium deficiency, thus guaranteeing adequate local and systemic levels of the active thyroid hormone T(3). Due to their low tissue concentrations and their mRNA SECIS elements deiodinases rank high in the cellular and tissue-specific hierarchy of selenium distribution among various selenoproteins. While systemic selenium status and expression of abundant selenoproteins (glutathione peroxidase or selenoprotein P) is already impaired in patients with cancer, disturbed gastrointestinal resorption, unbalanced nutrition or patients requiring intensive care treatment, selenium-dependent deiodinase function might still be adequate. However, disease-associated alterations in proinflammatory cytokines, growth factors, hormones and pharmaceuticals modulate deiodinase isoenzyme expression independent from altered selenium status and might thus pretend causal relationships between systemic selenium status and altered thyroid hormone metabolism. Limited or inadequate supply of both trace elements, iodine and selenium, leads to complex rearrangements of thyroid hormone metabolism enabling adaptation to unfavorable conditions.

Thyroid hormone upregulates zinc-α2-glycoprotein production in the liver but not in adipose tissue.

PubMed

Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M

2014-01-01

Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight loss in hyperthyroidism.

Thyroid Hormone Upregulates Zinc-α2-glycoprotein Production in the Liver but Not in Adipose Tissue

PubMed Central

Simó, Rafael; Hernández, Cristina; Sáez-López, Cristina; Soldevila, Berta; Puig-Domingo, Manel; Selva, David M.

2014-01-01

Overproduction of zinc-α2-glycoprotein by adipose tissue is crucial in accounting for the lipolysis occurring in cancer cachexia of certain malignant tumors. The main aim of this study was to explore whether thyroid hormone could enhance zinc-α2-glycoprotein production in adipose tissue. In addition, the regulation of zinc-α2-glycoprotein by thyroid hormone in the liver was investigated. We performed in vitro (HepG2 cells and primary human adipocytes) and in vivo (C57BL6/mice) experiments addressed to examine the effect of thyroid hormone on zinc-α2-glycoprotein production (mRNA and protein levels) in liver and visceral adipose tissue. We also measured the zinc-α2-glycoprotein serum levels in a cohort of patients before and after controlling their hyperthyroidism. Our results showed that thyroid hormone up-regulates zinc-α2-glycoprotein production in HepG2 cells in a dose-dependent manner. In addition, the zinc-α2-glycoprotein proximal promoter contains functional thyroid hormone receptor binding sites that respond to thyroid hormone treatment in luciferase reporter gene assays in HepG2 cells. Furthermore, zinc-α2-glycoprotein induced lipolysis in HepG2 in a dose-dependent manner. Our in vivo experiments in mice confirmed the up-regulation of zinc-α2-glycoprotein induced by thyroid hormone in the liver, thus leading to a significant increase in zinc-α2-glycoprotein circulating levels. However, thyroid hormone did not regulate zinc-α2-glycoprotein production in either human or mouse adipocytes. Finally, in patients with hyperthyroidism a significant reduction of zinc-α2-glycoprotein serum levels was detected after treatment but was unrelated to body weight changes. We conclude that thyroid hormone up-regulates the production of zinc-α2-glycoprotein in the liver but not in the adipose tissue. The neutral effect of thyroid hormones on zinc-α2-glycoprotein expression in adipose tissue could be the reason why zinc-α2-glycoprotein is not related to weight loss in hyperthyroidism. PMID:24465683

Functional Toll-like Receptor 4 Overexpression in Papillary Thyroid Cancer by MAPK/ERK-Induced ETS1 Transcriptional Activity.

PubMed

Peyret, Victoria; Nazar, Magalí; Martín, Mariano; Quintar, Amado A; Fernandez, Elmer A; Geysels, Romina C; Fuziwara, Cesar S; Montesinos, María M; Maldonado, Cristina A; Santisteban, Pilar; Kimura, Edna T; Pellizas, Claudia G; Nicola, Juan P; Masini-Repiso, Ana M

2018-05-01

Emerging evidence suggests that unregulated Toll-like receptor (TLR) signaling promotes tumor survival signals, thus favoring tumor progression. Here, the mechanism underlying TLR4 overexpression in papillary thyroid carcinomas (PTC) mainly harboring the BRAF V600E mutation was studied. TLR4 was overexpressed in PTC compared with nonneoplastic thyroid tissue. Moreover, paired clinical specimens of primary PTC and its lymph node metastasis showed a significant upregulation of TLR4 levels in the metastatic tissues. In agreement, conditional BRAF V600E expression in normal rat thyroid cells and mouse thyroid tissue upregulated TLR4 expression levels. Furthermore, functional TLR4 expression was demonstrated in PTC cells by increased NF-κB transcriptional activity in response to the exogenous TLR4-agonist lipopolysaccharide. Of note, The Cancer Genome Atlas data analysis revealed that BRAF V600E -positive tumors with high TLR4 expression were associated with shorter disease-free survival. Transcriptomic data analysis indicated a positive correlation between TLR4 expression levels and MAPK/ERK signaling activation. Consistently, chemical blockade of MAPK/ERK signaling abrogated BRAF V600E -induced TLR4 expression. A detailed study of the TLR4 promoter revealed a critical MAPK/ERK-sensitive Ets-binding site involved in BRAF V600E responsiveness. Subsequent investigation revealed that the Ets-binding factor ETS1 is critical for BRAF V600E -induced MAPK/ERK signaling-dependent TLR4 gene expression. Together, these data indicate that functional TLR4 overexpression in PTCs is a consequence of thyroid tumor-oncogenic driver dysregulation of MAPK/ERK/ETS1 signaling. Implications: Considering the participation of aberrant NF-κB signaling activation in the promotion of thyroid tumor growth and the association of high TLR4 expression with more aggressive tumors, this study suggests a prooncogenic potential of TLR4 downstream signaling in thyroid tumorigenesis. Mol Cancer Res; 16(5); 833-45. ©2018 AACR . ©2018 American Association for Cancer Research.

Tissue-specific thyroid hormone regulation of gene transcripts encoding iodothyronine deiodinases and thyroid hormone receptors in striped parrotfish (Scarus iseri).

PubMed

Johnson, Kaitlin M; Lema, Sean C

2011-07-01

In fish as in other vertebrates, the diverse functions of thyroid hormones are mediated at the peripheral tissue level through iodothyronine deiodinase (dio) enzymes and thyroid hormone receptor (tr) proteins. In this study, we examined thyroid hormone regulation of mRNAs encoding the three deiodinases dio1, dio2 and dio3 - as well as three thyroid hormone receptors trαA, trαB and trβ - in initial phase striped parrotfish (Scarus iseri). Parrotfish were treated with dissolved phase T(3) (20 nM) or methimazole (3 mM) for 3 days. Treatment with exogenous T(3) elevated circulating T(3), while the methimazole treatment depressed plasma T(4). Experimentally-induced hyperthyroidism increased the relative abundance of transcripts encoding trαA and trβ in the liver and brain, but did not affect trαB mRNA levels in either tissue. In both sexes, methimazole-treated fish exhibited elevated dio2 transcripts in the liver and brain, suggesting enhanced outer-ring deiodination activity in these tissues. Accordingly, systemic hyperthyroidism elevated relative dio3 transcript levels in these same tissues. In the gonad, however, patterns of transcript regulation were distinctly different with elevated T(3) increasing mRNAs encoding dio2 in testicular and ovarian tissues and dio3, trαA and trαB in the testes only. Thyroid hormone status did not affect dio1 transcript abundance in the liver, brain or gonads. Taken as a whole, these results demonstrate that thyroidal status influences relative transcript abundance for dio2 and dio3 in the liver, provide new evidence for similar patterns of dio2 and dio3 mRNA regulation in the brain, and make evident that fish exhibit tr subtype-specific transcript abundance changes to altered thyroid status. Copyright © 2011 Elsevier Inc. All rights reserved.

[The expression and clinical significance of EphA2 and E-cadherin in papillary thyroid carcinoma].

PubMed

Liu, Yan; Miao, Yuhua; Li, Xiaoming

2015-06-01

To investigate the expression and clinical significance of EphA2 and E cadherin proteins in papillary thyroid carcinoma tissues, and to explore the relationship between them. Using immunohistochemical SP/PV method, we detected the expression of EphA2 and E cadherin in tumors of 43 papillary thyroid carcinomas, 11 thyroid adenoma and 10 normal thyroid tissues, then studied their relationships with clinic pathological factors. The total positive rates of EphA2 and E cadherin expression were 58. 14% and 32. 56% in papillary thyroid carcinoma tissues, 18. 18% and 81. 81% in thyroid adenoma.tissues and they were 10. 00% and 100. 00% in normal thyroid tissues respectively. The positive expression of EphA2 in carcinoma tissues was higher than in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05) and the positive expression of E cadherin in carcinoma tissues was lower than that in the thyroid adenoma tissues and normal thyroid tissues (P<0. 05). The positive expression of EphA2 and E cadherin was associated with lymph node metastasis and histological grade (P<0. 05), but it was not associated with all the clinic-pathological factors including age, sex and the tumor size (P>0. 05). In papillary thyroid carcinoma tissues, the expression of EphA2 was negatively correlated with the expression of E cadherin protein (r= -0. 416, P<0. 01). EphA2 and E cadherin may be involved in carcinogenesis and development of papillary thyroid carcinoma.

Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo- and hyperthyroid patients: an in vivo microdialysis study.

PubMed

Nedvidkova, Jara; Haluzik, Martin; Bartak, Vladimir; Dostalova, Ivana; Vlcek, Petr; Racek, Pavel; Taus, Michal; Behanova, Magdalena; Svacina, Stepan; Alesci, Salvatore; Pacak, Karel

2004-06-01

Thyroid function plays an important role in the regulation of overall metabolic rate and lipid metabolism. However, it is uncertain whether thyroid hormones directly affect lipolysis in adipose tissue and to what extent those changes contribute to overall metabolic phenotype. Our study was designed, using the microdialysis technique, to determine basal and isoprenaline-stimulated local lipolysis and to determine local concentrations of lipolysis-regulating catecholamines in abdominal subcutaneous adipose tissue in 12 patients with hypothyroidism, 6 patients with hyperthyroidism, and 12 healthy control subjects. Plasma norepinephrine (NE) concentrations in hypothyroid subjects were significantly higher than in the control and hyperthyroid groups. In contrast, systemic, adipose NE levels in hypothyroid patients were decreased relative to controls. Hyperthyroidism, on the other hand, resulted in four-fold higher adipose NE levels. Basal lipolysis measured by glycerol concentrations in adipose tissue was significantly attenuated in hypothyroid patients and markedly increased in hyperthyroid patients in comparison with the control group. In addition to differences in basal lipolysis, hypothyroidism resulted in attenuated, and hyperthyroidism in enhanced, lipolytic response to local stimulation with beta(1,2)-adrenergic agonist isoprenaline. These results demonstrate that lipolysis in abdominal subcutaneous adipose tissue is strongly modulated by thyroid function. We suggest that thyroid hormones regulate lipolysis primarily by affecting local NE concentration and/or adrenergic postreceptor signaling.

A Rapid CRISPR/Cas-based Mutagenesis Assay in Zebrafish for Identification of Genes Involved in Thyroid Morphogenesis and Function.

PubMed

Trubiroha, A; Gillotay, P; Giusti, N; Gacquer, D; Libert, F; Lefort, A; Haerlingen, B; De Deken, X; Opitz, R; Costagliola, S

2018-04-04

The foregut endoderm gives rise to several organs including liver, pancreas, lung and thyroid with important roles in human physiology. Understanding which genes and signalling pathways regulate their development is crucial for understanding developmental disorders as well as diseases in adulthood. We exploited unique advantages of the zebrafish model to develop a rapid and scalable CRISPR/Cas-based mutagenesis strategy aiming at the identification of genes involved in morphogenesis and function of the thyroid. Core elements of the mutagenesis assay comprise bi-allelic gene invalidation in somatic mutants, a non-invasive monitoring of thyroid development in live transgenic fish, complementary analyses of thyroid function in fixed specimens and quantitative analyses of mutagenesis efficiency by Illumina sequencing of individual fish. We successfully validated our mutagenesis-phenotyping strategy in experiments targeting genes with known functions in early thyroid morphogenesis (pax2a, nkx2.4b) and thyroid functional differentiation (duox, duoxa, tshr). We also demonstrate that duox and duoxa crispants phenocopy thyroid phenotypes previously observed in human patients with bi-allelic DUOX2 and DUOXA2 mutations. The proposed combination of efficient mutagenesis protocols, rapid non-invasive phenotyping and sensitive genotyping holds great potential to systematically characterize the function of larger candidate gene panels during thyroid development and is applicable to other organs and tissues.

Hypothyroidism after Hemithyroidectomy: The Incidence and Risk Factors.

PubMed

Chotigavanich, Chanticha; Sureepong, Paiboon; Ongard, Sunun; Eiamkulvorapong, Apaporn; Boonyaarunnate, Thiraphon; Chongkolwatana, Cheerasook; Metheetrairut, Choakchai

2016-01-01

To evaluate the incidence of post-hemithyroidectomy hypothyroidism and identify possible risk factors that indicates whether patients require thyroid function monitoring after surgery. A retrospective review of patients with benign non-toxic thyroid disease undergoing hemithyroidectomy between April 2004 and November 2008 in the Department of Otorhinolaryngology, Siriraj Hospital was conducted All patients were in euthyroid state preoperatively. Thyroid specimens were examined for pathological diagnosis and degree of lymphocytic infiltration in thyroid tissue, and thyroid function was evaluated again six weeks after surgery. One hundred patients who received hemithyroidectomy were recruited for the present study. All had normal preoperative thyroid function. Six weeks after surgery, 27% of the cases developed hypothyroidism (6% overt or symptomatic hypothyroidism and 21% subclinical hypothyroidism). The mean preoperative thyrotropin level was significantly higher in the hypothyroid group than in the euthyroid group (1.9±1.2 vs. 1.1±0.7 micro IU/ml). Fifty-eight point three percent of patients with preoperative thyroid stimulating hormone (TSH) level more than or equal 2 micro IU/ml developed hypothyroidism in comparison to only 17.1% of those with preoperative TSH <2 micro IU/ml (odds ratio 6.8). Fifteen patients had signifcant lymphocytic infiltration (grade 2-4); nine of those (60%) had post-operative hypothyroidism. In contrary, only 18 of 85 patients (21.2%) with minimal infiltrates (grade 0-1) developed hypothyroidism (odds ratio 5.6). Twenty-seven percent of the patients in the present study developed hypothyroidism after hemithyroidectomy. Preoperative TSH more than or equal 2 micro IU/ml and significant lymphocytic infiltration in thyroid tissue or thyroiditis warrant post-operative close TSH monitoring. The awareness of such risk factors for post-operative hypothyroidism would improve patients care.

Detection of survivin 2α gene expression in thyroid nodules.

PubMed

Kyani, Keyhaneh; Babaei, Esmaeil; Feizi, Mohammad Ali Hosseinpour; Vandghanooni, Somayeh; Montazeri, Vahid; Halimi, Monireh

2014-01-01

Functional studies of the survivin splice variants have been performed almost exclusively in various types of cancer and produced remarkable advances in our understanding of cancer biology and cancer genetics. To observation the expression of survivin 2α in thyroid nodules and estimate its potential as a new molecular marker in thyroid nodules screening and malignant thyroid, as well. We detected the expression of a splice variant of survivin, survivin 2α, in thyroid nodules. Expression of survivin 2α mRNA was evaluated with specific primers by Hemi-Nested RT-PCR in 77 thyroid nodules including malignant and benign tumors, non-tumoral (goiter and thyroiditis) as well as surgical margin, non-neoplastic normal tissues adjacent to the malignant lesions. Our data revealed for the first time the expression of survivin 2α in thyroid nodules. It was detected in 85.7% of non-neoplastic surgical margin tissues, 71.4% of non tumoral, 63.2% of tumoral samples. Also, the expression of survivin 2α in benign tumor samples (64.2%) is more than malignant groups (62.8%). Survivin 2α expression is the highest in non-neoplastic surgical margin rather than other samples and the lowest expression was that of malignancy. According to the results, it can be concluded that survivin 2α protein may be has a vital protective effect throw survivin quenching due to the high expression in normal tissue compared with lesions.

Developmental and cell-specific expression of thyroid hormone transporters in the mouse cochlea.

PubMed

Sharlin, David S; Visser, Theo J; Forrest, Douglas

2011-12-01

Thyroid hormone is essential for the development of the cochlea and auditory function. Cochlear response tissues, which express thyroid hormone receptor β (encoded by Thrb), include the greater epithelial ridge and sensory epithelium residing inside the bony labyrinth. However, these response tissues lack direct blood flow, implying that mechanisms exist to shuttle hormone from the circulation to target tissues. Therefore, we investigated expression of candidate thyroid hormone transporters L-type amino acid transporter 1 (Lat1), monocarboxylate transporter (Mct)8, Mct10, and organic anion transporting polypeptide 1c1 (Oatp1c1) in mouse cochlear development by in situ hybridization and immunofluorescence analysis. L-type amino acid transporter 1 localized to cochlear blood vessels and transiently to sensory hair cells. Mct8 localized to the greater epithelial ridge, tympanic border cells underlying the sensory epithelium, spiral ligament fibrocytes, and spiral ganglion neurons, partly overlapping with the Thrb expression pattern. Mct10 was detected in a highly restricted pattern in the outer sulcus epithelium and weakly in tympanic border cells and hair cells. Organic anion transporting polypeptide 1c1 localized primarily to fibrocytes in vascularized tissues of the spiral limbus and spiral ligament and to tympanic border cells. Investigation of hypothyroid Tshr(-/-) mice showed that transporter expression was delayed consistent with retardation of cochlear tissue maturation but not with compensatory responses to hypothyroidism. The results demonstrate specific expression of thyroid hormone transporters in the cochlea and suggest that a network of thyroid hormone transport underlies cochlear development.

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...

Hypothyroidism: etiology, diagnosis, and management.

PubMed

Almandoz, Jaime P; Gharib, Hossein

2012-03-01

Hypothyroidism is the result of inadequate production of thyroid hormone or inadequate action of thyroid hormone in target tissues. Primary hypothyroidism is the principal manifestation of hypothyroidism, but other causes include central deficiency of thyrotropin-releasing hormone or thyroid-stimulating hormone (TSH), or consumptive hypothyroidism from excessive inactivation of thyroid hormone. Subclinical hypothyroidism is present when there is elevated TSH but a normal free thyroxine level. Treatment involves oral administration of exogenous synthetic thyroid hormone. This review presents an update on the etiology and types of hypothyroidism, including subclinical disease; drugs and thyroid function; and diagnosis and treatment of hypothyroidism. Copyright © 2012 Elsevier Inc. All rights reserved.

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

Transcriptional response to 131I exposure of rat thyroid gland.

PubMed

Rudqvist, Nils; Spetz, Johan; Schüler, Emil; Parris, Toshima Z; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2017-01-01

Humans are exposed to 131I in medical diagnostics and treatment but also from nuclear accidents, and better knowledge of the molecular response in thyroid is needed. The aim of the study was to examine the transcriptional response in thyroid tissue 24 h after 131I administration in rats. The exposure levels were chosen to simulate both the clinical situation and the case of nuclear fallout. Thirty-six male rats were i.v. injected with 0-4700 kBq 131I, and killed at 24 h after injection (Dthyroid = 0.0058-3.0 Gy). Total RNA was extracted from individual thyroid tissue samples and mRNA levels were determined using oligonucleotide microarray technique. Differentially expressed transcripts were determined using Nexus Expression 3.0. Hierarchical clustering was performed in the R statistical computing environment. Pathway analysis was performed using the Ingenuity Pathway Analysis tool and the Gene Ontology database. T4 and TSH plasma concentrations were measured using ELISA. Totally, 429 differentially regulated transcripts were identified. Downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified in some groups, and an impact on thyroid function was supported by the pathway analysis. Recurring downregulation of Dbp and Slc47a2 was found. Dbp exhibited a pattern with monotonous reduction of downregulation with absorbed dose at 0.0058-0.22 Gy. T4 plasma levels were increased and decreased in rats whose thyroids were exposed to 0.057 and 0.22 Gy, respectively. Different amounts of injected 131I gave distinct transcriptional responses in the rat thyroid. Transcriptional response related to thyroid function and changes in T4 plasma levels were found already at very low absorbed doses to thyroid.

Role of Dicer1 in thyroid cell proliferation and differentiation.

PubMed

Penha, Ricardo Cortez Cardoso; Sepe, Romina; De Martino, Marco; Esposito, Francesco; Pellecchia, Simona; Raia, Maddalena; Del Vecchio, Luigi; Decaussin-Petrucci, Myriam; De Vita, Gabriella; Pinto, Luis Felipe Ribeiro; Fusco, Alfredo

2017-01-01

DICER1 plays a central role in the biogenesis of microRNAs and it is important for normal development. Altered microRNA expression and DICER1 dysregulation have been described in several types of tumors, including thyroid carcinomas. Recently, our group identified a new somatic mutation (c.5438A>G; E1813G) within DICER1 gene of an unknown function. Herein, we show that DICER1 is overexpressed, at mRNA level, in a significant-relative number of papillary (70%) and anaplastic (42%) thyroid carcinoma samples, whereas is drastically downregulated in all the analyzed human thyroid carcinoma cell lines (TPC-1, BCPAP, FRO and 8505c) in comparison with normal thyroid tissue samples. Conversely, DICER1 is downregulated, at protein level, in PTC in comparison with normal thyroid tissues. Our data also reveals that DICER1 overexpression positively regulates thyroid cell proliferation, whereas its silencing impairs thyroid cell differentiation. The expression of DICER1 gene mutation (c.5438A>G; E1813G) negatively affects the microRNA machinery and cell proliferation as well as upregulates DICER1 protein levels of thyroid cells but has no impact on thyroid differentiation. In conclusion, DICER1 protein is downregulated in papillary thyroid carcinomas and affects thyroid proliferation and differentiation, while DICER1 gene mutation (c.5438A>G; E1813G) compromises the DICER1 wild-type-mediated microRNA processing and cell proliferation.

Resistance to thyroid hormone due to defective thyroid receptor alpha.

PubMed

Moran, Carla; Chatterjee, Krishna

2015-08-01

Thyroid hormones act via nuclear receptors (TRα1, TRβ1, TRβ2) with differing tissue distribution; the role of α2 protein, derived from the same gene locus as TRα1, is unclear. Resistance to thyroid hormone alpha (RTHα) is characterised by tissue-specific hypothyroidism associated with near-normal thyroid function tests. Clinical features include dysmorphic facies, skeletal dysplasia (macrocephaly, epiphyseal dysgenesis), growth retardation, constipation, dyspraxia and intellectual deficit. Biochemical abnormalities include low/low-normal T4 and high/high-normal T3 concentrations, a subnormal T4/T3 ratio, variably reduced reverse T3, raised muscle creatine kinase and mild anaemia. The disorder is mediated by heterozygous, loss-of-function, mutations involving either TRα1 alone or both TRα1 and α2, with no discernible phenotype attributable to defective α2. Whole exome sequencing and diagnostic biomarkers may enable greater ascertainment of RTHα, which is important as thyroxine therapy reverses some metabolic abnormalities and improves growth, constipation, dyspraxia and wellbeing. The genetic and phenotypic heterogeneity of RTHα and its optimal management remain to be elucidated. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Lipid peroxidation and antioxidants status in human malignant and non-malignant thyroid tumours.

PubMed

Stanley, J A; Neelamohan, R; Suthagar, E; Vengatesh, G; Jayakumar, J; Chandrasekaran, M; Banu, S K; Aruldhas, M M

2016-06-01

Thyroid epithelial cells produce moderate amounts of reactive oxygen species that are physiologically required for thyroid hormone synthesis. Nevertheless, when they are produced in excessive amounts, they may become toxic. The present study is aimed to compare the lipid peroxidation (LPO), antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non-protein thiols (reduced glutathione (GSH)) in human thyroid tissues with malignant and non-malignant disorders. The study used human thyroid tissues and blood samples from 157 women (147 diseased and 10 normal). Thyroid hormones, oxidative stress markers and antioxidants were estimated by standard methods. LPO significantly increased in most of the papillary thyroid carcinoma (PTC: 82.9%) and follicular thyroid adenoma (FTA: 72.9%) tissues, whilst in a majority of nodular goitre (69.2%) and Hashimoto's thyroiditis (HT: 73.7%) thyroid tissues, it remained unaltered. GSH increased in PTC (55.3%), remained unaltered in FTA (97.3%) and all other goiter samples studied. SOD increased in PTC (51.1%) and all other malignant thyroid tissues studied. CAT remained unaltered in PTC (95.7%), FTA (97.3%) and all other non-malignant samples (HT, MNG, TMNG) studied. GPx increased in PTC (63.8%), all other malignant thyroid tissues and remained unaltered in many of the FTA (91.9%) tissues and all other non-malignant samples (HT, MNG, TMNG) studied. In the case of non-malignant thyroid tumours, the oxidant-antioxidant balance was undisturbed, whilst in malignant tumours the balance was altered, and the change in r value observed in the LPO and SOD pairs between normal and PTC tissues and also in many pairs with multi-nodular goitre (MNG)/toxic MNG tissues may be used as a marker to differentiate/detect different malignant/non-malignant thyroid tumours. © The Author(s) 2015.

Automated MicroSPECT/MicroCT Image Analysis of the Mouse Thyroid Gland.

PubMed

Cheng, Peng; Hollingsworth, Brynn; Scarberry, Daniel; Shen, Daniel H; Powell, Kimerly; Smart, Sean C; Beech, John; Sheng, Xiaochao; Kirschner, Lawrence S; Menq, Chia-Hsiang; Jhiang, Sissy M

2017-11-01

The ability of thyroid follicular cells to take up iodine enables the use of radioactive iodine (RAI) for imaging and targeted killing of RAI-avid thyroid cancer following thyroidectomy. To facilitate identifying novel strategies to improve 131 I therapeutic efficacy for patients with RAI refractory disease, it is desired to optimize image acquisition and analysis for preclinical mouse models of thyroid cancer. A customized mouse cradle was designed and used for microSPECT/CT image acquisition at 1 hour (t1) and 24 hours (t24) post injection of 123 I, which mainly reflect RAI influx/efflux equilibrium and RAI retention in the thyroid, respectively. FVB/N mice with normal thyroid glands and TgBRAF V600E mice with thyroid tumors were imaged. In-house CTViewer software was developed to streamline image analysis with new capabilities, along with display of 3D voxel-based 123 I gamma photon intensity in MATLAB. The customized mouse cradle facilitates consistent tissue configuration among image acquisitions such that rigid body registration can be applied to align serial images of the same mouse via the in-house CTViewer software. CTViewer is designed specifically to streamline SPECT/CT image analysis with functions tailored to quantify thyroid radioiodine uptake. Automatic segmentation of thyroid volumes of interest (VOI) from adjacent salivary glands in t1 images is enabled by superimposing the thyroid VOI from the t24 image onto the corresponding aligned t1 image. The extent of heterogeneity in 123 I accumulation within thyroid VOIs can be visualized by 3D display of voxel-based 123 I gamma photon intensity. MicroSPECT/CT image acquisition and analysis for thyroidal RAI uptake is greatly improved by the cradle and the CTViewer software, respectively. Furthermore, the approach of superimposing thyroid VOIs from t24 images to select thyroid VOIs on corresponding aligned t1 images can be applied to studies in which the target tissue has differential radiotracer retention from surrounding tissues.

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.

Developmental and Cell-Specific Expression of Thyroid Hormone Transporters in the Mouse Cochlea

PubMed Central

Sharlin, David S.; Visser, Theo J.

2011-01-01

Thyroid hormone is essential for the development of the cochlea and auditory function. Cochlear response tissues, which express thyroid hormone receptor β (encoded by Thrb), include the greater epithelial ridge and sensory epithelium residing inside the bony labyrinth. However, these response tissues lack direct blood flow, implying that mechanisms exist to shuttle hormone from the circulation to target tissues. Therefore, we investigated expression of candidate thyroid hormone transporters L-type amino acid transporter 1 (Lat1), monocarboxylate transporter (Mct)8, Mct10, and organic anion transporting polypeptide 1c1 (Oatp1c1) in mouse cochlear development by in situ hybridization and immunofluorescence analysis. L-type amino acid transporter 1 localized to cochlear blood vessels and transiently to sensory hair cells. Mct8 localized to the greater epithelial ridge, tympanic border cells underlying the sensory epithelium, spiral ligament fibrocytes, and spiral ganglion neurons, partly overlapping with the Thrb expression pattern. Mct10 was detected in a highly restricted pattern in the outer sulcus epithelium and weakly in tympanic border cells and hair cells. Organic anion transporting polypeptide 1c1 localized primarily to fibrocytes in vascularized tissues of the spiral limbus and spiral ligament and to tympanic border cells. Investigation of hypothyroid Tshr−/− mice showed that transporter expression was delayed consistent with retardation of cochlear tissue maturation but not with compensatory responses to hypothyroidism. The results demonstrate specific expression of thyroid hormone transporters in the cochlea and suggest that a network of thyroid hormone transport underlies cochlear development. PMID:21878515

Ras mutations are rare in solitary cold and toxic thyroid nodules.

PubMed

Krohn, K; Reske, A; Ackermann, F; Müller, A; Paschke, R

2001-08-01

Activation of ras proto-oncogenes as a result of point mutations is detectable in a significant percentage of most types of tumour. Similar to neoplasms of other organs, mutations of all three ras genes can be found in thyroid tumours. H-, K- and N-ras mutations have been detected in up to 20% of follicular adenomas and adenomatous nodules which were not functionally characterized. This raises the question as to whether ras mutations are specific for hypofunctional nodules and TSH receptor mutations for hyperfunctioning nodules. To investigate ras and TSH receptor mutations with respect to functional differentiation we studied 41 scintigraphically cold nodules and 47 toxic thyroid nodules. To address the likelihood of a somatic mutation we also studied the clonal origin of these tumours. Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 1 and 2 of the H- and K-ras gene were PCR amplified and sequenced using big dye terminator chemistry. Denaturing gradient gel electrophoresis (DGGE) was used to verify sequencing results for the H-ras gene and to analyse the N-ras gene because its greater sensitivity in detecting somatic mutations. Clonality of nodular thyroid tissue was evaluated using X-Chromosome inactivation based on PCR amplification of the human androgen receptor locus. Monoclonal origin was detectable in 14 of 23 informative samples from cold thyroid nodules. In toxic thyroid nodules the frequency of clonal tissue was 20 in 30 informative cases. Only one point mutation could be found in the N-ras gene codon 61 (Gly to Arg) in a cold adenomatous nodule which was monoclonal. In toxic thyroid nodules no ras mutation was detectable. Our study suggests that ras mutations are rare in solitary cold and toxic thyroid nodules and that the frequent monoclonal origin of these tumours implies somatic mutations in genes other than H-, K- and N-ras.

Hyperfunctioning solid/trabecular follicular carcinoma of the thyroid gland.

PubMed

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the (99m)Tc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules.

Neurotrophin Receptors TrkA, p75NTR, and Sortilin Are Increased and Targetable in Thyroid Cancer.

PubMed

Faulkner, Sam; Jobling, Philip; Rowe, Christopher W; Rodrigues Oliveira, S M; Roselli, Severine; Thorne, Rick F; Oldmeadow, Christopher; Attia, John; Jiang, Chen Chen; Zhang, Xu Dong; Walker, Marjorie M; Hondermarck, Hubert

2018-01-01

Neurotrophin receptors are emerging targets in oncology, but their clinicopathologic significance in thyroid cancer is unclear. In this study, the neurotrophin tyrosine receptor kinase TrkA (also called NTRK1), the common neurotrophin receptor p75 NTR , and the proneurotrophin receptor sortilin were analyzed with immunohistochemistry in a cohort of thyroid cancers (n = 128) and compared with adenomas and normal thyroid tissues (n = 62). TrkA was detected in 20% of thyroid cancers, compared with none of the benign samples (P = 0.0007). TrkA expression was independent of histologic subtypes but associated with lymph node metastasis (P = 0.0148), suggesting the involvement of TrkA in tumor invasiveness. Nerves in the tumor microenvironment were positive for TrkA. p75 NTR was overexpressed in anaplastic thyroid cancers compared with papillary and follicular subtypes (P < 0.0001). Sortilin was overexpressed in thyroid cancers compared with benign thyroid tissues (P < 0.0001). Neurotrophin receptor expression was confirmed in a panel of thyroid cancer cell lines at the mRNA and protein levels. Functional investigations using the anaplastic thyroid cancer cell line CAL-62 found that siRNA against TrkA, p75 NTR , and sortilin decreased cell survival and cell migration through decreased SRC and ERK activation. Together, these data reveal TrkA, p75 NTR , and sortilin as potential therapeutic targets in thyroid cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Radionuclide thyroid imaging in the newborn with suspected hypothyroidism

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

Yoosufani, Z.; Karimeddini, M.K.; Spencer, R.P.

1985-05-01

The authors reviewed their experience with thyroid imaging in newborns with suspected congenital hypothyroidism. The infants were selected through a hypothyroidism screening program. There were 19 infants (14 females, 5 males) from 2 to 8 weeks of age with a blood T4 <6 ..mu..g/dl. Thyroid imaging was performed with either IV or IM injection of 0.5 to 1 mCi of Tc 99m pertechnetate using a gamma camera with a pinhole collimator. Salivary glands and stomach were also imaged for assessing the presence of the transport system. In 6 infants (32%) no thyroid tissue was visualized (thyroid hypoplasia). Four infants (21%)more » showed ectopic thyroid tissue in the lingual or sublingual area. Two infants (10%) had evidence of goiter. The remaining 7 infants (37%) had normal appearing glands in size and position. TSH values were markedly elevated (> 100 ..mu mu../ml) in all 10 patients with hypoplastic or ectopic thyroid. Two patients were subsequently found to have normal thyroid function (one with TBG deficiency and one with transient hypothyroidism). Thyroidal as well as salivary gland trapping of the radiotracer in these two infants was clearly less than that of adults suggesting immaturity of the transport/trapping mechanism. All 4 patients with ectopic thyroid had markedly increased uptake of the radiotracer. All other patients with elevated TSH levels had increased uptake of the radiotracer as compared to the normals. They conclude that thyroid scanning is an important tool in delineating the etiology of congenital hypothyroidism.« less

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

Low Iodine in the Follicular Lumen Caused by Cytoplasm Mis-localization of Sodium Iodide Symporter may Induce Nodular Goiter.

PubMed

Huang, Huibin; Shi, Yaxiong; Liang, Bo; Cai, Huiyao; Cai, Qingyan

2017-10-01

Iodine is a key ingredient in the synthesis of thyroid hormones and also a major factor in the regulation of thyroid function. A local reduction of iodine content in follicular lumen leads to overexpression of local thyroid-stimulating hormone receptor (TSHr), which in turn excessively stimulates the regional thyroid tissue, and result in the formation of nodular goiter. In this study, we investigated the relationship between iodine content and sodium iodide symporter (NIS) expression by using the clinical specimens from patients with nodular goiter and explored the pathogenesis triggered by iodine deficiency in nodular goiter. In total, 28 patients were clinically histopathologically confirmed to have nodular goiter and the corresponding adjacent normal thyroid specimens were harvested simultaneously. Western blot and immunohistochemistry were performed to assay NIS expression and localization in thyrocytes of both nodular goiter and adjacent normal thyroid tissues. NIS expression mediated by iodine in follicular lumen was confirmed by follicular model in vitro. Meanwhile, radioscan with iodine-131were conducted on both nodular goiter and adjacent normal thyroid. Our data showed that NIS expression in nodular goiter was significantly higher than that in adjacent normal tissues, which was associated with low iodine in the follicular lumen. Abnormal localization of NIS and lower amount of radioactive iodine-131 were also found in nodular goiter. Our data implied that low iodine in the follicular lumen caused by cytoplasm mis-localization of NIS may induce nodular goiter.

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

PubMed

Zhang, Li; Liu, Lianyong; He, Xiaohua; Shen, Yunling; Liu, Xuerong; Wei, Jing; Yu, Fang; Tian, Jianqing

2016-08-26

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. Our findings collectively indicate that CHIP functions as an oncogene in thyroid cancer, and is therefore a potential therapeutic target for this disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Stimulation of S14 mRNA and lipogenesis in brown fat by hypothyroidism, cold exposure, and cafeteria feeding: evidence supporting a general role for S14 in lipogenesis and lipogenesis in the maintenance of thermogenesis

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

Freake, H.C.; Oppenheimer, J.H.

1987-05-01

In liver, thyroid hormone rapidly induces S14 mRNA, which encodes a small acidic protein. This sequence is abundantly expressed only in lipogenic tissues and is thought to have some function in fat metabolism. In the euthyroid rat, we measured 20-fold higher levels of S14 mRNA in interscapular brown adipose tissue than liver. Furthermore, whereas in liver or epididymal fat, hypothyroidism resulted in an 80% fall in S14 mRNA, in brown fat the level of this sequence increased a further 3-fold. In all three tissues, the expression of S14 mRNA correlated well with lipogenesis, as assessed by /sup 3/H/sub 2/O incorporation.more » Physiological activation of brown fat by chronic cold exposure or cafeteria feeding increased the concentration of S14 mRNA in this tissue and again this was accompanied by a greater rate of fatty acid synthesis. Overall, in liver and white and brown adipose tissue, S14 mRNA and lipogenesis were well correlated and strongly suggest a function of the S14 protein related to fat synthesis. These studies suggest that the S14 protein and lipogenesis may be important for thyroid hormone-induced and brown adipose tissue thermogenesis and that stimulation of these functions in hypothyroid brown fat is a consequence of decreased thyroid hormone-induced thermogenesis elsewhere.« less

Long-term follow-up in toxic solitary autonomous thyroid nodules treated with radioactive iodine

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

Huysmans, D.A.; Corstens, F.H.; Kloppenborg, P.W.

1991-01-01

The long-term effects of radioiodine treatment on thyroid function in patients with a toxic solitary autonomous thyroid nodule were evaluated. Fifty-two patients received a therapeutic dose of 20 mCi of iodine-131 ({sup 131}I). Duration of follow-up was 10 +/- 4 yr. Follow-up data included a biochemical evaluation of thyroid function. The failure rate (recurrent hyperthyroidism) was 2%. The incidence of hypothyroidism was 6% and was not related to the dose per gram of nodular tissue. Oral administration of 20 mCi of radioiodine is a simple and highly effective method for the treatment of patients with a toxic autonomous thyroid nodule.more » The risk of development of hypothyroidism is low if extranodular uptake of {sup 131}I is prevented. This can be achieved by not treating euthyroid patients, by no longer using injections of exogenous thyroid stimulating hormone in the diagnostic work-up of the patients and by always performing radioiodine imaging shortly before treatment.« less

Ontogenetic Profile of the Expression of Thyroid Hormone Receptors in Rat and Human Corpora Cavernosa of the Penis

PubMed Central

Carosa, Eleonora; Di Sante, Stefania; Rossi, Simona; Castri, Alessandra; D'Adamo, Fabio; Gravina, Giovanni Luca; Ronchi, Piero; Kostrouch, Zdenek; Dolci, Susanna; Lenzi, Andrea; Jannini, Emmanuele A

2010-01-01

Introduction In the last few years, various studies have underlined a correlation between thyroid function and male sexual function, hypothesizing a direct action of thyroid hormones on the penis. Aim To study the spatiotemporal distribution of mRNA for the thyroid hormone nuclear receptors (TR) α1, α2 and β in the penis and smooth muscle cells (SMCs) of the corpora cavernosa of rats and humans during development. Methods We used several molecular biology techniques to study the TR expression in whole tissues or primary cultures from human and rodent penile tissues of different ages. Main Outcome Measure We measured our data by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) amplification, Northern blot and immunohistochemistry. Results We found that TRα1 and TRα2 are both expressed in the penis and in SMCs during ontogenesis without development-dependent changes. However, in the rodent model, TRβ shows an increase from 3 to 6 days post natum (dpn) to 20 dpn, remaining high in adulthood. The same expression profile was observed in humans. While the expression of TRβ is strictly regulated by development, TRα1 is the principal isoform present in corpora cavernosa, suggesting its importance in SMC function. These results have been confirmed by immunohistochemistry localization in SMCs and endothelial cells of the corpora cavernosa. Conclusions The presence of TRs in the penis provides the biological basis for the direct action of thyroid hormones on this organ. Given this evidence, physicians would be advised to investigate sexual function in men with thyroid disorders. Carosa E, Di Sante S, Rossi S, Castri A, D'Adamo F, Gravina GL, Ronchi P, Kostrouch Z, Dolci S, Lenzi A, and Jannini EA. Ontogenetic profile of the expression of thyroid hormone receptors in rat and human corpora cavernosa of the penis. J Sex Med 2010;7:1381–1390. PMID:20141582

Nucleophosmin is overexpressed in thyroid tumors

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

Pianta, Annalisa; Puppin, Cinzia; Franzoni, Alessandra

2010-07-02

Nucleophosmin (NPM) is a protein that contributes to several cell functions. Depending on the context, it can act as an oncogene or tumor suppressor. No data are available on NPM expression in thyroid cells. In this work, we analyzed both NPM mRNA and protein levels in a series of human thyroid tumor tissues and cell lines. By using immunohistochemistry, NPM overexpression was detected in papillary, follicular, undifferentiated thyroid cancer, and also in follicular benign adenomas, indicating it as an early event during thyroid tumorigenesis. In contrast, various levels of NPM mRNA levels as detected by quantitative RT-PCR were observed inmore » tumor tissues, suggesting a dissociation between protein and transcript expression. The same behavior was observed in the normal thyroid FRTL5 cell lines. In these cells, a positive correlation between NPM protein levels, but not mRNA, and proliferation state was detected. By using thyroid tumor cell lines, we demonstrated that such a post-mRNA regulation may depend on NPM binding to p-Akt, whose levels were found to be increased in the tumor cells, in parallel with reduction of PTEN. In conclusion, our present data demonstrate for the first time that nucleophosmin is overexpressed in thyroid tumors, as an early event of thyroid tumorigenesis. It seems as a result of a dysregulation occurring at protein and not transcriptional level related to an increase of p-Akt levels of transformed thyrocytes.« less

Surface-enhanced Raman spectroscopy for differentiation between benign and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Zuanfang; Li, Chao; Lin, Duo; Huang, Zufang; Pan, Jianji; Chen, Guannan; Lin, Juqiang; Liu, Nenrong; Yu, Yun; Feng, Shangyuan; Chen, Rong

2014-04-01

The aim of this study was to evaluate the potential of applying silver nano-particle based surface-enhanced Raman scattering (SERS) to discriminate different types of human thyroid tissues. SERS measurements were performed on three groups of tissue samples including thyroid cancers (n = 32), nodular goiters (n = 20) and normal thyroid tissues (n = 25). Tentative assignments of the measured tissue SERS spectra suggest interesting cancer specific biomolecular differences. The principal component analysis (PCA) and linear discriminate analysis (LDA) together with the leave-one-out, cross-validated technique yielded diagnostic sensitivities of 92%, 75% and 87.5%; and specificities of 82.6%, 89.4% and 84.4%, respectively, for differentiation among normal, nodular and malignant thyroid tissue samples. This work demonstrates that tissue SERS spectroscopy associated with multivariate analysis diagnostic algorithms has great potential for detection of thyroid cancer at the molecular level.

Hürthle cell tumor dwelling in hot thyroid nodules: preoperative detection with technetium-99m-MIBI dual-phase scintigraphy.

PubMed

Vattimo, A; Bertelli, P; Cintorino, M; Burroni, L; Volterrani, D; Vella, A; Lazzi, S

1998-05-01

Single injection dual-phase scintigraphy (early and late acquisitions) with 99mTc-MIBI was used to differentiate benign and malignant hot thyroid nodules. Thirteen euthyroid and two hyperthyroid patients displaying a hot thyroid nodule on the 99mTc scan due to an autonomously functioning thyroid nodule (AFTN) underwent early (15-30 min) and late (3-4 hr) thyroid scintigraphy after the administration of 740-1000 MBq 99mTc-MIBI. Visual scoring was done to assess nodular tracer uptake and retention. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late image and the washout rates (WO) from the nodule and thyroidal tissue were measured. All patients underwent thyroid surgery. Histopathology revealed a Hürthle cell tumor in three nodules, a benign adenoma with oxyphilic metaplasia in two nodules and a benign adenoma without oxyphilic cells in the remaining 10 nodules. The Hürthle cell tumor nodules displayed intense and persistent uptake of 99mTc-MIBI (N/T was 2.81 +/- 0.52 and 5.53 +/- 1.06 in early and late images, respectively; WO from the nodule was 12.33 +/- 0.47, WO from the thyroidal tissue was 22.00 +/- 3.56). The benign nodules showed intense uptake in the early image and intense uptake to absent retention in the late image (N/T was 2.94 +/- 1.31 and 1.62 +/- 0.50 in the early and late images, respectively; WO from the nodule was 20.25 +/- 2.92, WO from the thyroidal tissue was 20.33 +/- 2.92). Single injection dual-phase 99mTc-MIBI scintigraphy of the thyroid with AFTN can identify nodules as a result of the activity of a Hürthle cell tumor, since these tumors cause intense and persistent tracer uptake in contrast with a benign AFTN.

Hyperfunctioning Solid/Trabecular Follicular Carcinoma of the Thyroid Gland

PubMed Central

Giovanella, Luca; Fasolini, Fabrizio; Suriano, Sergio; Mazzucchelli, Luca

2010-01-01

A 68-year-old woman with solid/trabecular follicular thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this paper. The patient was referred to our clinic for swelling of the neck and an increased pulse rate. Ultrasonography showed a slightly hypoechoic nodule in the right lobe of the thyroid. Despite suppressed TSH levels, the 99mTc-pertechnetate scan showed a hot area corresponding to the nodule with a suppressed uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed a solid/trabecular follicular thyroid carcinoma. To the best of our knowledge, this is the first case of hyperfunctioning follicular solid/trabecular carcinoma reported in the literature. Even if a hyperfunctioning thyroid carcinoma is an extremely rare malignancy, careful management is recommended so that a malignancy will not be overlooked in the hot thyroid nodules. PMID:20847957

The axolotl (Ambystoma mexicanum), a neotenic amphibian, expresses functional thyroid hormone receptors.

PubMed

Safi, Rachid; Bertrand, Stéphanie; Marchand, Oriane; Duffraisse, Marilyne; de Luze, Amaury; Vanacker, Jean-Marc; Maraninchi, Marie; Margotat, Alain; Demeneix, Barbara; Laudet, Vincent

2004-02-01

Neotenic amphibians such as the axolotl (Ambystoma mexicanum) are often unable to undergo metamorphosis under natural conditions. It is thought that neoteny represents a deviation from the standard course of amphibian ontogeny, affecting the thyroid axis at different levels from the central nervous system to peripheral organs. Thyroid hormone receptors (TRs) that bind the thyroid hormone (TH) T(3) have been described in axolotl. However, the full sequences of TR were needed to better characterize the TH response and to be able to assess their functional capacity at the molecular level. We report that each of the alpha and beta axolotl TRs bind both DNA and TH, and they activate transcription in response to TH in a mammalian cell-based transient transfection assay. Moreover, both TRs are expressed in axolotl tissues. Interestingly, each TR gene generates alternatively spliced isoforms, harboring partial or total deletions of the ligand-binding domain, which are expressed in vivo. Further, we found that in the axolotl, TH regulates the expression of stromelysin 3 and collagenase 3, which are TH target genes in Xenopus. Taken together, these results suggest that axolotl TRs are functional and that the molecular basis of neoteny in the axolotl is not linked to a major defect in TH response in peripheral tissues.

Cytoskeletal and functional changes in bioreactor assembled thyroid tissue organoids exposed to gamma radiation

NASA Technical Reports Server (NTRS)

Green, Lora M.; Patel, Zarana; Murray, Deborah K.; Rightnar, Steven; Burell, Cheryl G.; Gridley, Daila S.; Nelson, Gregory A.

2002-01-01

Fischer rat thyroid cells were grown under low-shear stress in a bioreactor to a stage of organization composed of integrated follicles resembling small thyroid glands prior to exposure to 3 Gray-gamma radiation. Bioreactor tissues and controls (both irradiated and non-irradiated) were harvested at 24, 48, 96 and 144 hours post-exposure. Tissue samples were fixed and fluorescently labeled for actin and microtubules. Tissues were assessed for changes in cytoskeletal components induced by radiation and quantified by laser scanning cytometry. ELISA's were used to quantify transforming growth factor-beta and thyroxin released from cells to the culture supernatant. Tissue architecture was disrupted by exposure to radiation with the structural organization of actin and loss of follicular content the most obviously affected. With time post-irradiation the actin appeared disordered and the levels of fluorescence associated with filamentous-actin and microtubules cycled in the tissue analogs, but not in the flask-grown cultures. Active transforming growth factor-beta was higher in supernatants from the irradiated bioreactor tissue. Thyroxin release paralleled cell survival in the bioreactors and control cultures. Thus, the engineered tissue responses to radiation differed from those of conventional tissue culture making it a potentially better mimic of the in vivo situation.

9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Disposition of thyroid glands and laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle...

9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Disposition of thyroid glands and laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle...

9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Disposition of thyroid glands and laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle...

9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Disposition of thyroid glands and laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle...

9 CFR 310.15 - Disposition of thyroid glands and laryngeal muscle tissue.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Disposition of thyroid glands and laryngeal muscle tissue. 310.15 Section 310.15 Animals and Animal Products FOOD SAFETY AND INSPECTION... of thyroid glands and laryngeal muscle tissue. (a) Livestock thyroid glands and laryngeal muscle...

IR Spectroscopic signs of malignant neoplasms in the thyroid gland

NASA Astrophysics Data System (ADS)

Tolstorozhev, G. B.; Skornyakov, I. V.; Butra, V. A.

2012-03-01

We use Fourier transform IR spectroscopy to study thyroid tumor tissues which were removed during surgery. The IR spectra of the tissues with pathological foci are compared with data from histologic examination. In the region of N-H, C-H, and C = O stretching vibrations, the IR spectra of the tissues for thyroid cancer are different from the IR spectra of tissues without malignant formations. We identify the spectral signs of thyroid cancer. We show that IR analysis is promising for identification of thyroid pathology at the molecular level.

[Lipid peroxidation in thyroid tissue of people with diffuse toxic goiter].

PubMed

Rom-Boguslavskaia, E S; Somova, E V; Ovsiannikova, T N; Diageleva, E A; Karachentsev, Iu I; Asaula, V A

1997-01-01

The processes of lipids free-radical oxidation in euthyroid and thyrotoxic tissue samples of human thyroid gland were studied. It was shown, that the content of TBA-active lipid peroxidation products was considerably increased in thyrotoxic tissue of the thyroid, and the activity of antioxidant enzymes (catalase, glutation peroxidase) was decreased in it. Possible mechanism of the tissue lipoperoxide alternation under conditions of the thyroid hyperfunction is discussed.

Submandibular Lateral Ectopic Thyroid Tissue: Ultrasonography, Computed Tomography, and Scintigraphic Findings

PubMed Central

Çeliker, Metin; Beyazal Çeliker, Fatma; Turan, Arzu; Beyazal, Mehmet; Beyazal Polat, Hatice

2015-01-01

Ectopic thyroid can be encountered anywhere between the base of tongue and pretracheal region. The most common form is euthyroid neck mass. Herein, we aimed to present the findings of a female case with ectopic thyroid tissue localized in the left submandibular region. A 44-year-old female patient, who underwent bilateral subtotal thyroidectomy four years ago with the diagnosis of multinodular goiter, was admitted to our hospital due to a mass localized in the left submandibular area that gradually increased in the last six months. Neck ultrasonography, contrast-enhanced computed tomography, and scintigraphic examination were performed on the patient. On thyroid scintigraphy with Tc-99m pertechnetate, thyroid tissue activity uptake showing massive radioactivity was observed in the normal localization of the thyroid gland and in the submandibular localization. The focus in the submandibular region was excised. Pathological examination of the specimen showed normal thyroid follicle cells with no signs of malignancy. The submandibular mass is a rarely encountered lateral ectopic thyroid tissue. Accordingly, ectopic thyroid tissue should also be considered in the differential diagnosis of masses in the submandibular region. PMID:26634164

Dose-specific transcriptional responses in thyroid tissue in mice after (131)I administration.

PubMed

Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

2015-03-01

In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid. Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid. During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread. Copyright © 2014 Elsevier Inc. All rights reserved.

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

The thyroid is one of the main endocrine glands of human body, which plays a crucial role in the body's metabolism. Thyroid cancer mortality ranks only second to ovarian cancer in endocrine cancer. Routine diagnostic methods of thyroid diseases in present clinic exist misdiagnosis and missed diagnosis to varying degrees. Those lead to miss the best period of cancer treatment--early. Photoacoustic spectroscopy technology is a new tool, which provides an effective and noninvasive way for biomedical materials research, being highly sensitive and without sample pretreatment. In this paper, we use photoacoustic spectroscopy technology (PAST) to detect the absorption spectrum between normal and malignant thyroid tissues. The result shows that the photoacoustic spectroscopy technology (PAST) could differentiate malignant thyroid tissue from normal thyroid tissue very well. This technique combined with routine diagnostic methods has the potential to increase the diagnostic accuracy in clinical thyroid cancer diagnosis.

Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.

PubMed

La Perle, K M; Jhiang, S M; Capen, C C

2000-08-01

Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53-/- mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53-/- mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53-/- mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/- mice

Association between thyroid hormones and TRAIL.

PubMed

Bernardi, Stella; Bossi, Fleur; Toffoli, Barbara; Giudici, Fabiola; Bramante, Alessandra; Furlanis, Giulia; Stenner, Elisabetta; Secchiero, Paola; Zauli, Giorgio; Carretta, Renzo; Fabris, Bruno

2017-11-01

Recent studies suggest that a circulating protein called TRAIL (TNF-related apoptosis-inducing ligand) might have a role in the regulation of body weight and metabolism. Interestingly, thyroid hormones seem to increase TRAIL tissue expression. This study aimed at evaluating whether overt thyroid disorders affected circulating TRAIL levels. TRAIL circulating levels were measured in euthyroid, hyperthyroid, and hypothyroid patients before and after thyroid function normalization. Univariate and multivariate analyses were performed to evaluate the correlation between thyroid hormones and TRAIL. Then, the stimulatory effect of both triiodothyronine (T3) and thyroxine (T4) on TRAIL was evaluated in vitro on peripheral blood mononuclear cells. Circulating levels of TRAIL significantly increased in hyperthyroid and decreased in hypothyroid patients as compared to controls. Once thyroid function was restored, TRAIL levels normalized. There was an independent association between TRAIL and both fT3 and fT4. Consistent with these findings, T3 and T4 stimulated TRAIL release in vitro. Here we show that thyroid hormones are associated with TRAIL expression in vivo and stimulate TRAIL expression in vitro. Given the overlap between the metabolic effects of thyroid hormones and TRAIL, this work sheds light on the possibility that TRAIL might be one of the molecules mediating thyroid hormones peripheral effects. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The bioartificial thyroid: a biotechnological perspective in endocrine organ engineering for transplantation replacement.

PubMed

Toni, Roberto; Casa, Claudia Della; Spaletta, Giulia; Marchetti, Giacomo; Mazzoni, Perseo; Bodria, Monica; Ravera, Simone; Dallatana, Davide; Castorina, Sergio; Riccioli, Vincenzo; Castorina, Emilio Giovanni; Antoci, Salvatore; Campanile, Enrico; Raise, Gabriella; Scalise, Gabriella; Rossi, Raffaella; Rossio, Raffaella; Ugolotti, Giorgio; Ugolottio, Giorgio; Martorella, Andrew; Roti, Elio; Rot, Elio; Sgallari, Fiorella; Pinchera, Aldo

2007-01-01

A new concept for ex situ endocrine organ bioengineering is presented, focused on the realization of a human bioartificial thyroid gland. It is based on the theoretical assumption and experimental evidence that symmetries in geometrical coordinates of the thyroid tissue remain invariant with respect to developmental, physiological or pathophysiological transformations occuring in the gland architecture. This topological arrangement is dependent upon physical connections established between cells, cell adhesion molecules and extracellular matrix, leading to the view that the thyroid parenchyma behaves like a deformable "putty", moulded onto an elastic stromal/vascular scaffold (SVS) dictating the final morphology of the gland. In particular, we have raised the idea that the geometry of the SVS per se provides pivotal epigenetic information to address the genetically-programmed, thyrocyte and endothelial/vascular proliferation and differentiation towards a functionally mature gland, making organ form a pre-requirementfor organ function. A number of experimental approaches are explored to obtain a reliable replica of a human thyroid SVS, and an informatic simulation is designed based on fractal growth of the thyroid intraparenchymal arterial tree. Various tissue-compatible and degradable synthetic or biomimetic polymers are discussed to act as a template of the thyroid SVS, onto which to co-seed autologous human thyrocyte (TPC) and endothelial/vascular (EVPC) progenitor cells. Harvest and expansion of both TPC and EVPC in primary culture are considered, with specific attention to the selection of normal thyrocytes growing at a satisfactory rate to colonize the synthetic matrix. In addition, both in vitro and in vivo techniques to authenticate TPC and EVPC lineage differentiation are reviewed, including immunocytochemistry, reverse trascriptase-polymerase chain reaction, flow cytomery and proteomics. Finally, analysis of viability of the thyroid construct following implantation in animal hosts is proposed, with the intent to obtain a bioartificial thyroid gland morphologically and functionally adequate for transplantation. We believe that the biotechnological scenario proposed herein may provide a template to construct other, more complex and clinically-relevant bioartificial endocrine organs ex situ, such as human pancreatic islets and the liver, and perhaps a new approach to brain bioengineering.

Microrna-199a-5p Functions as a Tumor Suppressor via Suppressing Connective Tissue Growth Factor (CTGF) in Follicular Thyroid Carcinoma.

PubMed

Sun, Dawei; Han, Shen; Liu, Chao; Zhou, Rui; Sun, Weihai; Zhang, Zhijun; Qu, Jianjun

2016-04-11

BACKGROUND The objective of this study was to explore the role of miR-199a-5p in the development of thyroid cancer, including its anti-proliferation effect and downstream signaling pathway. MATERIAL AND METHODS We conducted qRT-PCR analysis to detect the expressions of several microRNAs in 42 follicular thyroid carcinoma patients and 42 controls. We identified CTGF as target of miR-491, and viability and cell cycle status were determined in FTC-133 cells transfected with CTGF siRNA, miR-199a mimics, or inhibitors. RESULTS We identified an underexpression of miR-199a-5p in follicular thyroid carcinoma tissue samples compared with controls. Then we confirmed CTGF as a target of miR-199a-5p thyroid cells by using informatics analysis and luciferase reporter assay. Additionally, we found that mRNA and protein expression levels of CTGF were both clearly higher in malignant tissues than in benign tissues. miR-199a-5p mimics and CTGF siRNA similarly downregulated the expression of CTGF, and reduced the viability of FTC-133 cells by arresting the cell cycle in G0 phase. Transfection of miR-199a-5p inhibitors increased the expression of CTGF and promoted the viability of the cells by increasing the fraction of cells in G2/M and S phases. CONCLUSIONS Our study proves that the CTGF gene is a target of miR-199a-5p, demonstrating the negatively related association between CTGF and miR-199a. These findings suggest that miR-199a-5p might be a novel therapeutic target in the treatment of follicular thyroid carcinoma.

Corticotropin-releasing hormone: Mediator of vertebrate life stage transitions?

PubMed

Watanabe, Yugo; Grommen, Sylvia V H; De Groef, Bert

2016-03-01

Hormones, particularly thyroid hormones and corticosteroids, play critical roles in vertebrate life stage transitions such as amphibian metamorphosis, hatching in precocial birds, and smoltification in salmonids. Since they synergistically regulate several metabolic and developmental processes that accompany vertebrate life stage transitions, the existence of extensive cross-communication between the adrenal/interrenal and thyroidal axes is not surprising. Synergies of corticosteroids and thyroid hormones are based on effects at the level of tissue hormone sensitivity and gene regulation. In addition, in representative nonmammalian vertebrates, corticotropin-releasing hormone (CRH) stimulates hypophyseal thyrotropin secretion, and thus functions as a common regulator of both the adrenal/interrenal and thyroidal axes to release corticosteroids and thyroid hormones. The dual function of CRH has been speculated to control or affect the timing of vertebrate life history transitions across taxa. After a brief overview of recent insights in the molecular mechanisms behind the synergic actions of thyroid hormones and corticosteroids during life stage transitions, this review examines the evidence for a possible role of CRH in controlling vertebrate life stage transitions. Copyright © 2016 Elsevier Inc. All rights reserved.

Hashimoto's thyroiditis could be secondary to vitiligo: the possibility of antigen crossover and oxidative stress between the two diseases.

PubMed

Gong, Qingli; Li, Xue; Gong, Qixing; Zhu, Wenyuan; Song, Guoxin; Lu, Yan

2016-05-01

Autoimmune thyroid diseases (AITDs) are often accompanied by vitiligo, and the sera of patients with vitiligo often demonstrate increased frequencies of thyroid autoantibodies. In this study, we investigated the expression of melanocyte-associated antigens in tissues from patients with Hashimoto's thyroiditis (HT) without vitiligo using immunohistochemistry. Tissues of HT without vitiligo, as well as normal thyroid tissues, were both negative for the expression of NKI/beteb, gp100, tyrosinase-related protein 1 (TRP1), HMB-45 and S100, whereas they were positive for the expression of tyrosinase-related protein 2 (TRP2), lysosome-associated membrane protein 1 (LAMP1) and CD69. Tyrosinase (TYR) was only detected in tissues of HT, and levels of LAMP1 and CD69 were higher in tissues of HT than in normal thyroid tissues (p < 0.005). These results suggest the possibility of antigen crossover and oxidative stress between vitiligo and HT that might represent an immunological basis for secondary HT associated with vitiligo.

Application of SEC-ICP-MS for comparative analyses of metal-containing species in cancerous and healthy human thyroid samples.

PubMed

Boulyga, Sergei F; Loreti, Valeria; Bettmer, Jörg; Heumann, Klaus G

2004-09-01

Size exclusion chromatography (SEC) was coupled on-line to inductively coupled plasma mass spectrometry (ICP-MS) for speciation study of trace metals in cancerous thyroid tissues in comparison to healthy thyroids aimed to estimation of changes in metalloprotein speciation in pathological tissue. The study showed a presence of species binding Cu, Zn, Cd and Pb in healthy thyroid tissue with a good reproducibility of chromatographic results, whereas the same species could not be detected in cancerous tissues. Thus, remarkable differences with respect to metal-binding species were revealed between healthy and pathological thyroid samples, pointing out a completely different distribution of trace metals in cancerous tissues. The metal-binding species could not be identified in the frame of this work because of a lack of appropriate standards. Nevertheless, the results obtained confirm the suitability of SEC-ICP-MS for monitoring of changes in trace metal distribution in cancerous tissue and will help to better understand the role of metal-containing species in thyroid pathology.

Selenium glutathione peroxidase activities and thyroid functions in human individuals

NASA Astrophysics Data System (ADS)

Bellisola, G.; Calza Contin, M.; Ceccato, D.; Cinque, G.; Francia, G.; Galassini, S.; Liu, N. Q.; Lo Cascio, C.; Moschini, G.; Sussi, P. L.

1996-04-01

At least two enzymes are involved in metabolism of thyroid hormones. GSHPx protects thyrocyte from high H 2O 2 levels that are required for iodination of prohormones to form T4 in thyroid cell. Type I iodothyronine 5'-deiodinase (5'-D) catalyzes the deiodination of L-thyroxin (T4) to the biologically active thyroid hormone 3,3'-5-triiodothyronine (T 3) in liver, in kidney and in thyroid tissues. Circulating thyroid hormones, plasma Se levels, GSHPx activities in platelets and in plasma were investigated in 29 human individuals with increased thyroid mass. PIXE was applied to measure Se in 1 ml of plasma because we supposed patients were in a marginal carential status for Se. Plasma Se concentrations were compared with those of normal individuals. Correlation studies between plasma Se level and both GSHPx activities were carried out as well as between platelets and plasma GSHPx activities to verify the hypothesis of a marginal Se deficiency in patients. Significance of circulating thyroid hormones levels will be discussed.

[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.

CD40 expression in human thyroid tissue: evidence for involvement of multiple cell types in autoimmune and neoplastic diseases.

PubMed

Smith, T J; Sciaky, D; Phipps, R P; Jennings, T A

1999-08-01

CD40, a member of the tumor necrosis factor-alpha (TNF-alpha) receptor family of surface molecules, is expressed by a variety of cell types. It is a crucial activational molecule displayed by lymphocytes and other bone marrow-derived cells and recently has also been found on nonlymphoid cells such as fibroblasts, endothelia, and epithelial cells in culture. While its role in lymphocyte signaling and activation has been examined in great detail, the function of CD40 expression on nonlymphoid cells, especially in vivo, is not yet understood. Most of the studies thus far have been conducted in cell culture. In this article, we report that several cell types resident in thyroid tissue in vivo can display CD40 under pathological conditions. Sections from a total of 46 different cases were examined immunohistochemically and included nodular hyperplasia, chronic lymphocytic thyroiditis, diffuse hyperplasia, follicular neoplasia, papillary carcinoma, and medullary carcinoma. Thyroid epithelial cells, lymphocytes, macrophages, endothelial cells, and spindle-shape fibroblast-like cells were found to stain positively in the context of inflammation. The staining pattern observed in all cell types was entirely membranous. In general, epithelial staining was limited to that adjacent to lymphocytic infiltration except in 5 of 17 cases of neoplasia and in diffuse hyperplasia. Moreover, we were able to detect CD40 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) in human thyroid tissue. These results constitute convincing evidence for expression of CD40 in nonlymphocytic elements of the human thyroid gland. Our findings suggest a potentially important pathway that might be of relevance to the pathogenesis of thyroid diseases. They imply the potential participation of the CD40/CD40 ligand bridge in the cross-talk between resident thyroid cells and bone marrow-derived cells recruited to the thyroid.

The hypothalamic-pituitary-thyroid (HPT) axis in fish and its role in fish development and reproduction.

PubMed

Blanton, Michael L; Specker, Jennifer L

2007-01-01

Bony fishes represent the largest vertebrate class and are a very diverse animal group. This chapter provides a thorough review of the available scientific literature on the thyroid system in these important vertebrate animals. The molecular components of the hypothalamic-pituitary-thyroid (HPT) axis in this group correspond closely to those of mammals. The thyroid tissue in the fishes is organized as diffuse follicles, with a few exceptions, rather than as an encapsulated gland as is found in most other vertebrate species. The features of this diffuse tissue in fishes are reviewed with an emphasis on feedback relationships within the HPT axis, the molecular biology of the thyroid system in fishes, and comparisons versus the thyroid systems of other vertebrate taxa. A review of the role of thyroid hormone in fish development and reproduction is included. Available information about the HPT axis in fishes is quite detailed for some species and rather limited or absent in others. This review focuses on species that have been intensively studied for their value as laboratory models in assays to investigate disruption in normal function of the thyroid system. In addition, in vitro and in vivo assay methods for screening chemicals for their potential to interfere with the thyroid system are reviewed. It is concluded that there are currently no in vitro or in vivo assays in fish species that are sufficiently developed to warrant recommendation for use to efficiently screen chemicals for thyroid disruption. Methods are available that can be used to measure thyroid hormones, although our ability to interpret the causes and implications of potential alterations in T4 or T3 levels in fishes is nonetheless limited without further research.

Deiodinase activities in thyroids and tissues of iodine-deficient female rats.

PubMed

Lavado-Autric, Rosalia; Calvo, Rosa Maria; de Mena, Raquel Martinez; de Escobar, Gabriella Morreale; Obregon, Maria-Jesus

2013-01-01

Severe iodine deficiency is characterized by goiter, preferential synthesis, and secretion of T(3) in thyroids, hypothyroxinemia in plasma and tissues, normal or low plasma T(3), and slightly increased plasma TSH. We studied changes in deiodinase activities and mRNA in several tissues of rats maintained on low-iodine diets (LIDs) or LIDs supplemented with iodine (LID+I). T(4) and T(3) concentrations decreased in plasma, tissues, and thyroids of LID rats, and T(4) decreased more than T(3) (50%). The highest type 1 iodothyronine deiodinase (D1) activities were found in the thyroid, kidney, and the liver; pituitary, lung, and ovary had lower D1 activities; but the lowest levels were found in the heart and skeletal muscle. D1 activity decreased in all tissues of LID rats (10-40% of LID+I rats), except for ovary and thyroids, which D1 activity increased 2.5-fold. Maximal type 2 iodothyronine deiodinase (D2) activities were found in thyroid, brown adipose tissue, and pituitary, increasing 6.5-fold in thyroids of LID rats and about 20-fold in the whole gland. D2 always increased in response to LID, and maximal increases were found in the cerebral cortex (19-fold), thyroid, brown adipose tissue, and pituitary (6-fold). Lower D2 activities were found in the ovary, heart, and adrenal gland, which increased in LID. Type 3 iodothyronine deiodinase activity was undetectable. Thyroidal Dio1 and Dio2 mRNA increased in the LID rats, and Dio1 decreased in the lung, with no changes in mRNA expression in other tissues. Our data indicate that LID induces changes in deiodinase activities, especially in the thyroid, to counteract the low T(4) synthesis and secretion, contributing to maintain the local T(3) concentrations in the tissues with D2 activity.

Differential expression of glucose transporters in normal and pathologic thyroid tissue.

PubMed

Matsuzu, Kenichi; Segade, Fernando; Matsuzu, Utako; Carter, Aaron; Bowden, Donald W; Perrier, Nancy D

2004-10-01

Malignant cells demonstrate increased glucose uptake and utilization. Immunohistochemical studies have suggested that enhanced glucose uptake in cancer cells may be caused by the overexpression of glucose transporters (GLUTs), in most cases GLUT1 and/or GLUT3. The aim of this study was to examine in detail the expression pattern and levels of GLUT genes in normal and pathologic thyroid tissues and to evaluate the clinical significance of GLUT mRNA levels. One hundred fifty-two surgically resected thyroid tissue samples from 103 patients were evaluated. Samples included: normal thyroid tissue (n = 58), benign thyroid disease (n = 61), and thyroid carcinoma (n = 33). Expression of the GLUT1, GLUT2, GLUT3, GLUT4, and GLUT10 genes were examined by reverse transcription-polymerase chain reaction (RT-PCR) and mRNA levels were quantitated by real-time RT-PCR. All thyroid parenchymal cells expressed GLUT1, GLUT3, GLUT4, and GLUT10. GLUT1 showed increased expression in carcinoma cases (p < 0.0001) and also in comparison with paired normal tissue samples from the same patient (p < 0.0001). Other GLUTs were statistically unchanged in pathologic tissues. These results are consistent with the theory that GLUT1 is upregulated during carcinogenesis and may play a major role in enhanced glucose uptake in thyroid cancer cells.

Causes of appearance of scintigraphic hot areas on thyroid scintigraphy analyzed with clinical features and comparative ultrasonographic findings.

PubMed

Iwata, Masahiro; Kasagi, Kanji; Hatabu, Hiroto; Misaki, Takashi; Iida, Yasuhiro; Fujita, Toru; Konishi, Junji

2002-06-01

This study was done retrospectively to analyze the ultrasonographic (US) findings in thyroid scintigraphic hot areas (HA). Three-thousand, eight-hundred and thirty-nine consecutive patients who underwent 99mTc-pertechnetate (n = 3435) or 123I (n = 457) scintigraphy were analyzed. HA were regarded as present when the tracer concentration was greater than the remaining thyroid tissue, or when hemilobar uptake was observed. High-resolution US examinations were performed with a real-time electronic linear scanner with a 7.5 or 10 MHz transducer. One hundred and four (2.7%) were found to be scintigraphic HA (n = 120). US revealed a nodular lesion or well-demarcated thyroid tissue corresponding to the HA in 94 areas (78.4%, Category 1), an ill-defined region with different echogenicity in 13 areas (10.8%, Category 2), and no correlating lesion in 13 areas (10.8%, Category 3). These 104 patients included 43 with adenomatous goiter (59 areas), 33 with adenoma, 11 with Hashimoto's thyroiditis, 5 with primary thyroid cancer, 4 with euthyroid ophthalmic Graves' disease (EOG), 3 with hemilobar atrophy or hypogenesis, 2 with hemilobar agenesis, 2 with hypothyroidism with blocking-type TSH-receptor antibodies (TSHRAb), I with acute suppurative thyroiditis. Among the 59 adenomatous nodules and 33 adenomas, 51 (86.4%) and 32 (97.0%), respectively, belonged to Category 1. A solitary toxic nodule was significantly larger and occurs more often in older patients than in younger patients. On the other hand, all 17 patients with known autoimmune thyroid diseases including Hashimoto's thyroiditis, EOG and hypothyroidism with blocking TSHRAb belonged to Category 2 or 3. Possible underlying mechanisms are 1) hyperfunctioning tumors or nodules, 2) localized functioning thyroid tissue freed from autoimmune destruction, inflammation or tumor invasion, 3) congenital abnormality, 4) clusters of hyperactive follicular cells caused by long-term TSH and/or TSHRAb stimulation, 5) asymmetry, etc. Scintigraphic HA are observed in patients with various thyroid diseases and high-resolution US appears to be helpful clinically for the differential diagnosis of the above mentioned disorders.

[Selenium treatment in thyreopathies].

PubMed

Sotak, Štefan

Selenium (latin Selenium) is a micronutrient embedded in several proteins. In adults, the thyroid is the organ with the highest amount of selenium per gram of tissue. Selenium levels in the body depend on the characteristics of the population and its diet and geographic area. In the thyroid, selenium is required for the antioxidant function and for the metabolism of thyroid hormones. The literature suggests that selenium supplementation of patients with Hashimotos thyroiditis is associated with a reduction in antithyroperoxidase antibody levels. Selenium supplementation also in mild Graves orbitopathy is associated with delayed progression of ocular disorders. As a consequence of this observation The European Group on Graves Orbitopathy recommend six months selenium preparates supportive therapy for patients with mild form of Graves orbitopathy.Key words: Graves-Basedows disease - Hashimotos thyroiditis - selenium - supplementation.

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

Two novel mutations in the sixth transmembrane segment of the thyrotropin receptor gene causing hyperfunctioning thyroid nodules.

PubMed

Gozu, Hulya; Avsar, Melike; Bircan, Rifat; Claus, Maren; Sahin, Serap; Sezgin, Ozlem; Deyneli, Oguzhan; Paschke, Ralf; Cirakoglu, Beyazit; Akalin, Sema

2005-04-01

Autonomously functioning thyroid nodules (AFTNs) can present as hyperfunctioning adenomas or toxic multinodular goiters. In the last decade, a large number of activating mutations have been identified in the thyrotropin receptor (TSHR) gene in autonomously functioning thyroid nodules. Most have been situated close to, or within the sixth transmembrane segment and third intracellular loop of the TSHR where the receptor interacts with the Gs protein. In this study we describe two novel mutations in the sixth transmembrane segment of the TSHR causing hyperfunctioning thyroid nodules. Genomic DNAs were isolated from four hyperfunctioning thyroid nodules, normal tissues and peripheral leukocytes of two patients with toxic multinodular goiter. After amplifying the related regions, TSHR and G(s)alpha genes were analyzed by single-strand conformation polymorphism (SSCP) analysis. The precise localization of the mutations was identified by automatic DNA sequence analysis. Functional studies were done by site-directed mutagenesis and transfection of a mutant construct into COS-7 cells. We identified two novel TSHR mutations in two hyperfunctioning thyroid nodules: Phe631Val in the first patient and Iso630Met in the second patient. Both mutant receptors display an increase in constitutive stimulation of basal cyclic adenosine monophosphate (cAMP) levels compared to the wild-type receptor. This confirms that these mutant receptors cause hyperfunctioning thyroid nodules.

Scientific and Regulatory Policy Committee (SRPC) Points to Consider*: Histopathology Evaluation of the Pubertal Development and Thyroid Function Assay (OPPTS 890.1450, OPPTS 890.1500) in Rats to Screen for Endocrine Disruptors

PubMed Central

Keane, Kevin A.; Parker, George A.; Regan, Karen S.; Picut, Catherine; Dixon, Darlene; Creasy, Dianne; Giri, Dipak; Hukkanen, Renee R.

2015-01-01

The U.S. Environmental Protection Agency Endocrine Disruptor Screening Program (EDSP) is a multitiered approach to determine the potential for environmental chemicals to alter the endocrine system. The Pubertal Development and Thyroid Function in Intact Juvenile/Peripubertal Female and Male Rats (OPPTS 890.1450, 890.1500) are 2 of the 9 EDSP tier 1 test Guidelines, which assess upstream mechanistic pathways along with downstream morphological end points including histological evaluation of the kidneys, thyroid, and select male/female reproductive tissues (ovaries, uterus, testes, and epididymides). These assays are part of a battery of in vivo and in vitro screens used for initial detection of test article endocrine activity. In this Points to Consider article, we describe tissue processing, evaluation, and nomenclature to aid in standardization of assay results across laboratories. Pubertal assay end points addressed include organ weights, estrous cyclicity, clinical pathology, hormonal assays, and histological evaluation. Potential treatment-related findings that may indicate endocrine disruption are reviewed. Additional tissues that may be useful in assessment of endocrine disruption (vagina, mammary glands, and liver) are discussed. This Points to Consider article is intended to provide information for evaluating peripubertal tissues within the context of individual assay end points, the overall pubertal assay, and tier I assays of the EDSP program. PMID:25948506

Subclinical hyperthyroidism: possible danger of overzealous thyroxine replacement therapy.

PubMed

Ross, D S

1988-12-01

Many patients taking customary doses of levothyroxine have slightly elevated serum thyroxine (T4), apparently normal serum triiodothyronine, suppressed serum thyrotropin (thyroid-stimulating hormone; TSH) concentrations, and no clinical symptoms of hyperthyroidism. Recent reports suggest that these patients may have adverse effects from subclinical hyperthyroidism, including abnormally short systolic time intervals, elevations in liver enzymes, and reductions in bone density. Controversy exists about which thyroid function tests should be used to monitor patients taking levothyroxine. A review of currently available data suggests that replacement doses of levothyroxine given to hypothyroid patients should be adjusted so that serum TSH measured by the new sensitive assays is within the normal range. Patients requiring suppressive doses of levothyroxine to shrink goitrous thyroid tissue or to prevent growth of abnormal tissue should be given the minimal dose needed to accomplish the desired clinical or biochemical response.

Selenium nanoparticles prevents lead acetate-induced hypothyroidism and oxidative damage of thyroid tissues in male rats through modulation of selenoenzymes and suppression of miR-224.

PubMed

Atteia, Hebatallah Husseini; Arafa, Manar Hamed; Prabahar, Kousalya

2018-03-01

Selenium nanoparticles (Se-NPs) are customizable drug delivery vehicles that show good bioavailability, higher efficacy and lower toxicity than ordinary Se. Pre-treatment of male rats with these NPs has been recently shown to exert a protective effect against chromium-induced thyroid dysfunction. This study, therefore, aimed to investigate and characterize the potential protective mechanism of Se-NPs against lead (Pb) acetate-induced thyrotoxicity. We found that prophylactic and concurrent treatment of Pb acetate-exposed rats with Nano-Se (0.5 mg/kg, i.p) for 15 wk significantly alleviated the decrease in free triiodothyronine (fT3) and free thyroxine (fT4) levels as well as fT3/fT4 ratio% and the increase in thyroid stimulating hormone (TSH) levels to approach control values. This was accompanied by a reduction in the accumulation of Pb in serum and thyroid tissues as well as maintenance of thyroidal pro-oxidant/antioxidant balance and iodothyronine deiodinase type 1 (ID1), an essential enzyme for metabolizing of T4 into active T3, gene expression. Surprisingly, miR-224, a direct complementary target of ID1 mRNA, expression in the thyroid tissues was significantly down-regulated in Nano-Se-pre- and co-treated Pb acetate intoxicated animals. Such changes in miR-224 expression were negatively correlated with the changes in ID1 gene expression and serum fT3 level. These results suggest that Se-NPs can rescue from Pb-induced impairment of thyroid function through the maintenance of selenoproteins and down-regulation of miR-224. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Comparative study of the primary cilia in thyrocytes of adult mammals

PubMed Central

Utrilla, J C; Gordillo-Martínez, F; Gómez-Pascual, A; Fernández-Santos, J M; Garnacho, C; Vázquez-Román, V; Morillo-Bernal, J; García-Marín, R; Jiménez-García, A; Martín-Lacave, I

2015-01-01

Since their discovery in different human tissues by Zimmermann in 1898, primary cilia have been found in the vast majority of cell types in vertebrates. Primary cilia are considered to be cellular antennae that occupy an ideal cellular location for the interpretation of information both from the environment and from other cells. To date, in mammalian thyroid gland, primary cilia have been found in the thyrocytes of humans and dogs (fetuses and adults) and in rat embryos. The present study investigated whether the existence of this organelle in follicular cells is a general event in the postnatal thyroid gland of different mammals, using both immunolabeling by immunofluorescence and electron microscopy. Furthermore, we aimed to analyse the presence of primary cilia in various thyroid cell lines. According to our results, primary cilia are present in the adult thyroid gland of most mammal species we studied (human, pig, guinea pig and rabbit), usually as a single copy per follicular cell. Strikingly, they were not found in rat or mouse thyroid tissues. Similarly, cilia were also observed in all human thyroid cell lines tested, both normal and neoplastic follicular cells, but not in cultured thyrocytes of rat origin. We hypothesize that primary cilia could be involved in the regulation of normal thyroid function through specific signaling pathways. Nevertheless, further studies are needed to shed light on the permanence of these organelles in the thyroid gland of most species during postnatal life. PMID:26228270

Primary hyperthyroidism--diagnosis and treatment. Indications and contraindications for radioiodine therapy.

PubMed

Gurgul, Edyta; Sowinski, Jerzy

2011-01-01

Isotope therapy is one of the methods used in primary hyperthyroidism. The therapy is based on short-range beta radiation emitted from radioactive iodine. Radioiodine administration must always be preceded by pharmacological normalization of thyroid function. Otherwise, post-radiation thyrocyte destruction and thyroid hormones release may lead to hyperthyroidism exacerbation. Indications for radioiodine therapy in Graves-Basedow disease include recurrent hyperthyroidism after thyrostatic treatment or thyroidectomy and side-effects observed during thyrostatic treatment. In toxic nodule, isotope therapy is the first choice therapy. Radioiodine is absorbed only in autonomous nodule. Therefore, it destroys only this area and does not damage the remaining thyroid tissue. In toxic goitre, radioiodine is used mostly in recurrent nodules. Absolute contraindications for radioiodine treatment are pregnancy and lactation. Relative contraindications are thyroid nodules suspected of malignancy and age under 15 years. In patients with thyroid nodules suspected of malignancy, radioiodine treatment may be applied as a preparation for surgery, if thyrostatic drugs are ineffective or contraindicated. In children, radioiodine therapy should be considered in recurrent toxic goitre and when thyrostatic drugs are ineffective. In patients with Graves-Basedow disease and thyroid-associated orbitopathy, radioiodine treatment may increase the inflammatory process and exacerbate the ophthalmological symptoms. However, thyroid-associated orbitopathy cannot be considered as a contraindication for isotope therapy. The potential carcinogenic properties of radioiodine, especially associated with tissues with high iodine uptake (thyroid, salivary glands, stomach, intestine, urinary tract, breast), have not been confirmed.

Loss of p53 Promotes Anaplasia and Local Invasion in ret/PTC1-Induced Thyroid Carcinomas

PubMed Central

La Perle, Krista M. D.; Jhiang, Sissy M.; Capen, Charles C.

2000-01-01

Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53−/− mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53−/− mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53−/− mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/− mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/− mice ≤28 weeks of age or p53−/− mice ≤ 17 weeks of age; however, an older (170-day-old) male p53−/− mouse used to maintain the colony developed anaplastic thyroid carcinoma with liver metastases. These findings demonstrate that the lack of functional p53 in ret/PTC1 mice promotes anaplasia and invasiveness of thyroid carcinomas. PMID:10934169

Increased sensitivity of thyroid hormone-mediated signaling despite prolonged fasting.

PubMed

Martinez, Bridget; Scheibner, Michael; Soñanez-Organis, José G; Jaques, John T; Crocker, Daniel E; Ortiz, Rudy M

2017-10-01

Thyroid hormones (TH) can increase cellular metabolism. Food deprivation in mammals is typically associated with reduced thyroid gland responsiveness, in an effort to suppress cellular metabolism and abate starvation. However, in prolonged-fasted, elephant seal pups, cellular TH-mediated proteins are up-regulated and TH levels are maintained with fasting duration. The function and contribution of the thyroid gland to this apparent paradox is unknown and physiologically perplexing. Here we show that the thyroid gland remains responsive during prolonged food deprivation, and that its function and production of TH increase with fasting duration in elephant seals. We discovered that our modeled plasma TH data in response to exogenous thyroid stimulating hormone predicted cellular signaling, which was corroborated independently by the enzyme expression data. The data suggest that the regulation and function of the thyroid gland in the northern elephant seal is atypical for a fasted animal, and can be better described as, "adaptive fasting". Furthermore, the modeling data help substantiate the in vivo responses measured, providing unique insight on hormone clearance, production rates, and thyroid gland responsiveness. Because these unique endocrine responses occur simultaneously with a nearly strict reliance on the oxidation of lipid, these findings provide an intriguing model to better understand the TH-mediated reliance on lipid metabolism that is not otherwise present in morbidly obese humans. When coupled with cellular, tissue-specific responses, these data provide a more integrated assessment of thyroidal status that can be extrapolated for many fasting/food deprived mammals. Copyright © 2017 Elsevier Inc. All rights reserved.

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

PubMed Central

Johnson, Jennifer M; Lai, Stephen Y.; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A.; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Outschoorn, Ubaldo Martinez; Curry, Joseph

2015-01-01

Aims Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically Monocarboxylate Transporter 1 (MCT1) and Translocase of the Outer Mitochondrial Membrane Member 20 (TOMM20). Methods Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer (PTC), and 8 non-cancerous thyroid) and 9 ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. Results MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (p<0.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (p<0.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (p<0.001). These xenograft tumors have high 13C- pyruvate uptake. Conclusions Anaplastic thyroid cancer has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. PMID:26615136

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 aquacultured species could occur. It is therefore imperative that the effects of such pollutants on the thyroid system of Australian native fish be investigated. Copyright © 2016 Elsevier Inc. All rights reserved.

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior

PubMed Central

Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Pereira Gimba, Etel Rodrigues; Soares, Paula

2016-01-01

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches. PMID:27409830

Osteopontin-a splice variant is overexpressed in papillary thyroid carcinoma and modulates invasive behavior.

PubMed

Ferreira, Luciana Bueno; Tavares, Catarina; Pestana, Ana; Pereira, Catarina Leite; Eloy, Catarina; Pinto, Marta Teixeira; Castro, Patricia; Batista, Rui; Rios, Elisabete; Sobrinho-Simões, Manuel; Gimba, Etel Rodrigues Pereira; Soares, Paula

2016-08-09

Osteopontin (OPN) is a matricellular protein overexpressed in cancer cells and modulates tumorigenesis and metastasis, including in thyroid cancer (TC). The contribution of each OPN splice variant (OPN-SV), named OPNa, OPNb and OPNc, in TC is currently unknown. This study evaluates the expression of total OPN (tOPN) and OPN-SV in TC tissues and cell lines, their correlation with clinicopathological, molecular features and their functional roles. We showed that tOPN and OPNa are overexpressed in classic papillary thyroid carcinoma (cPTC) in relation to adjacent thyroid, adenoma and follicular variant of papillary thyroid carcinoma (fvPTC) tissues. In cPTC, OPNa overexpression is associated with larger tumor size, vascular invasion, extrathyroid extension and BRAFV600E mutation. We found that TC cell lines overexpressing OPNa exhibited increased proliferation, migration, motility and in vivo invasion. Conditioned medium secreted from cells overexpressing OPNa induce MMP2 and MMP9 metalloproteinases activity. In summary, we described the expression pattern of OPN-SV in cPTC samples and the key role of OPNa expression on activating TC tumor progression features. Our findings highlight OPNa variant as TC biomarker, besides being a putative target for cPTC therapeutic approaches.

Papillary Carcinoma in Median Aberrant Thyroid (Ectopic) - Case Report

PubMed Central

K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-01-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed. PMID:25121039

Papillary carcinoma in median aberrant thyroid (ectopic) - case report.

PubMed

Hebbar K, Ashwin; K, Shashidhar; Deshmane, Vijaya Laxmi; Kumar, Veerendra; Arjunan, Ravi

2014-06-01

Median ectopic thyroid may be encountered anywhere from the foramen caecum to the diaphragm. Non lingual median aberrant thyroid (incomplete descent) usually found in the infrahyoid region and malignant transformation in this ectopic thyroid tissue is very rare. We report an extremely rare case of papillary carcinoma in non lingual median aberrant thyroid in a 25-year-old female. The differentiation between a carcinoma arising in the median ectopic thyroid tissue and a metastatic papillary carcinoma from an occult primary in the main thyroid gland is also discussed.

RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease

PubMed Central

Su, Xuan; He, Caiyun; Ma, Jiangjun; Tang, Tao; Zhang, Xiao; Ye, Zulu; Long, Yakang; Shao, Qiong

2016-01-01

RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39–22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto's thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer. PMID:27802347

Goitrous hypothyroidism associated with treatment with trimethoprim-sulfamethoxazole in a young dog.

PubMed

Seelig, Davis M; Whittemore, Jacqueline C; Lappin, Michael R; Myers, Alan M; Avery, Paul R

2008-04-15

A 16-week-old female Boxer that had been treated for 5 weeks with trimethoprim-sulfamethoxazole and chloramphenicol because of aspiration pneumonia was evaluated for bilaterally symmetric masses in the subcutaneous tissues of the ventral neck, in the region of the larynx. Fine-needle aspirates were obtained from the neck masses; cytologic examination revealed well-differentiated thyroid epithelial tissue. A blood sample was collected for serum biochemical and thyroid function analyses. Mild hyperphosphatemia, severe hypercholesterolemia, mild hyperkalemia, and a mild increase in creatine kinase activity were identified. Serum concentration of total thyroxine was less than the lower reference limit, and that of thyroid-stimulating hormone was greater than the upper reference limit. Findings were consistent with a diagnosis of clinical hypothyroidism in a skeletally immature dog. Treatment with trimethoprim-sulfamethoxazole was discontinued. The dog was reevaluated 3 weeks later, at which time the neck masses were markedly decreased in size. Serum concentrations of cholesterol and potassium were lower; serum concentrations of total thyroxine and thyroid-stimulating hormone were near or within respective reference ranges. Age-appropriate increases in serum phosphorus concentration and serum alkaline phosphatase activity were also detected. To the authors' knowledge, this is the first report of antimicrobial-induced goiter in a dog. Cytologic examination of fine-needle aspirates and interpretation of data from serum biochemical and thyroid function analyses were needed to obtain a definitive diagnosis. Practitioners should include goiter among the differential diagnoses for ventral neck swellings in young dogs receiving potentiated sulfonamide antimicrobials.

[Method of detection of residual tissues in recurrent operations on the thyroid gland].

PubMed

Gostimskiĭ, A V; Romanchishen, A F; Zaĭtseva, I V; Kuznetsova, Iu V

2014-01-01

A search of residual tissues is complicated in recurrent operations on the thyroid gland. The Saint-Petersburg Centre of Surgery of the Endocrine System and Oncology developed the method of detection of residual tissues of the thyroid gland with the aim of preoperative chromothyroidolymphography under control of ultrasound. The method consisted of US performance during 15-20 minutes before the operation and an introduction of 1% sterile water solution of methylene blue in revealed residual tissues of the thyroid gland. The volume of injected coloring agent was 0.5-2 ml in the residual tissue volume smaller than 9 cm3 and 2-3 ml injected in case of more than 9 cm3. The residual tissues of the thyroid gland accurately visualized during the following operation. Described method gives the possibility to detect all regions of residual tissues which should be removed and at the same time it shortens a revision and surgery trauma.

[Changes in active cysteine cathepsins in lysosomes from tissues thyroid papillary carcinomas with various biological characteristics].

PubMed

Kalinichenko, O V; Myshunina, T M; Tron'ko, M D

2013-01-01

To clarify possible role of cysteine cathepsin H, B and L in the proteolytic processes that contribute to the progression of tumor growth in the thyroid, we studied their activity in lysosomes isolated from the tissue of papillary carcinomas. It was shown that for these enzymes there is a dependence of the changes in their activity on a number of biological characteristics of the tumors. Thus, the sharp increase in the activity ofcathepsin H observed in lysosomes of tissue carcinomas category T2 and T3, with intra-and ekstrathyroid and lymphatic invasion of tumor cells. An increase in the activity of cathepsin B is set in the lysosomes of tissue heterogeneous follicular structure, especially in the presence of solid areas, in comparison with typical papillary tumors and in the lysosomes of tissue carcinomas in intrathyroid and cathepsin L-at extrathyroid invasion. A common feature of the enzymes is to increase the activity of cathepsins in lysosomes of tissue nonencapsulated papillary carcinomas. These enzymes probably do not take part in the invasion of tumor cells into blood vessels and in the mechanisms of tumor metastasis to regional lymph nodes. The latter shows no changes in the activity of cathepsins in lysosomes of tissue carcinomas category N1. The results indicate the different role of cathepsin H, B and L in thyroid carcinogenesis, where each enzyme has its specific function.

Cold thyroid nodules show a marked increase in proliferation markers.

PubMed

Krohn, Knut; Stricker, Ingo; Emmrich, Peter; Paschke, Ralf

2003-06-01

Thyroid follicular adenomas and adenomatous thyroid nodules are a frequent finding in geographical areas with iodine deficiency. They occur as hypofunctioning (scintigraphically cold) or hyperfunctioning (scintigraphically hot) nodules. Their predominant clonal origin suggests that they result from clonal expansion of a single cell, which is very likely the result of a prolonged increase in proliferation compared with non-affected surrounding cells. To test whether increased cell proliferation is detectable in cold thyroid nodules, we studied paraffin-embedded tissue from 40 cold thyroid nodules and their surrounding normal thyroid tissue for the occurrence of the proliferating cell nuclear antigen (PCNA) and Ki-67 (MIB-1 antibody) epitopes as markers for cell proliferation. All 40 thyroid nodules were histologically well characterized and have been studied for molecular characteristics before. The labeling index (number of labeled cells versus total cell number) for nodular and surrounding tissue was calculated. In 33 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for PCNA was detectable. In 19 cold thyroid nodules a significant (p < or = 0.05) increase in the labeling index for Ki-67 was detectable. Moreover, surrounding tissues with lymphocyte infiltration showed a significantly higher labeling index for both PCNA and Ki-67 compared with normal surrounding tissue. These findings are first evidence that an increased thyroid epithelial cell proliferation is a uniform feature common to most cold nodules. However, the increase of proliferation markers shows a heterogeneity that is not correlated with histopathologic, molecular, or clinical characteristics.

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

PubMed

Johnson, Jennifer M; Lai, Stephen Y; Cotzia, Paolo; Cognetti, David; Luginbuhl, Adam; Pribitkin, Edmund A; Zhan, Tingting; Mollaee, Mehri; Domingo-Vidal, Marina; Chen, Yunyun; Campling, Barbara; Bar-Ad, Voichita; Birbe, Ruth; Tuluc, Madalina; Martinez Outschoorn, Ubaldo; Curry, Joseph

2015-12-01

Anaplastic thyroid cancer (ATC) is one of the most aggressive human cancers. Key signal transduction pathways that regulate mitochondrial metabolism are frequently altered in ATC. Our goal was to determine the mitochondrial metabolic phenotype of ATC by studying markers of mitochondrial metabolism, specifically monocarboxylate transporter 1 (MCT1) and translocase of the outer mitochondrial membrane member 20 (TOMM20). Staining patterns of MCT1 and TOMM20 in 35 human thyroid samples (15 ATC, 12 papillary thyroid cancer [PTC], and eight non-cancerous thyroid) and nine ATC mouse orthotopic xenografts were assessed by visual and Aperio digital scoring. Staining patterns of areas involved with cancer versus areas with no evidence of cancer were evaluated independently where available. MCT1 is highly expressed in human anaplastic thyroid cancer when compared to both non-cancerous thyroid tissues and papillary thyroid cancers (P<.001 for both). TOMM20 is also highly expressed in both ATC and PTC compared to non-cancerous thyroid tissue (P<.01 for both). High MCT1 and TOMM20 expression is also found in ATC mouse xenograft tumors compared to non-cancerous thyroid tissue (P<.001). These xenograft tumors have high (13)C- pyruvate uptake. ATC has metabolic features that distinguish it from PTC and non-cancerous thyroid tissue, including high expression of MCT1 and TOMM20. PTC has low expression of MCT1 and non-cancerous thyroid tissue has low expression of both MCT1 and TOMM20. This work suggests that MCT1 blockade may specifically target ATC cells presenting an opportunity for a new drug target. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Thyroid in pregnancy: From physiology to screening.

PubMed

Springer, Drahomira; Jiskra, Jan; Limanova, Zdenka; Zima, Tomas; Potlukova, Eliska

2017-03-01

Thyroid hormones are crucial for the growth and maturation of many target tissues, especially the brain and skeleton. During critical periods in the first trimester of pregnancy, maternal thyroxine is essential for fetal development as it supplies thyroid hormone-dependent tissues. The ontogeny of mature thyroid function involves organogenesis, and maturation of the hypothalamus, pituitary and the thyroid gland; and it is almost complete by the 12th-14th gestational week. In case of maternal hypothyroidism, substitution with levothyroxine must be started in early pregnancy. After the 14th gestational week, fetal brain development may already be irreversibly affected by lack of thyroid hormones. The prevalence of manifest hypothyroidism in pregnancy is about 0.3-0.5%. The prevalence of subclinical hypothyroidism varies between 4 and 17%, strongly depending on the definition of the upper TSH cutoff limit. Hyperthyroidism occurs in 0.1-1% of all pregnancies. Positivity for antibodies against thyroid peroxidase (TPOAb) is common in women of childbearing age with an incidence rate of 5.1-12.4%. TPOAb-positivity may be regarded as a manifestation of a general autoimmune state which may alter the fertilization and implantation processes or cause early missed abortions. Women positive for TPOAb are at a significant risk of developing hypothyroidism during pregnancy and postpartum. Laboratory diagnosis of thyroid dysfunction during pregnancy is based upon serum TSH concentration. TSH in pregnancy is physiologically lower than the non-pregnant population. Results of multiple international studies point toward creation of trimester-specific reference intervals for TSH in pregnancy. Screening for hypothyroidism in pregnancy is controversial and its implementation varies from country to country. Currently, the case-finding approach of screening high-risk women is preferred in most countries to universal screening. However, numerous studies have shown that one-third to one-half of women with thyroid disorders escape the case-finding approach. Moreover, the universal screening has been shown to be more cost-effective. Screening for thyroid disorders in pregnancy should include assessment of both TSH and TPOAb, regardless of the screening approach. This review summarizes the current knowledge on physiology of thyroid hormones in pregnancy, causes of maternal thyroid dysfunction and its effects on pregnancy course and fetal development. We discuss the question of case-finding versus universal screening strategies and we display an overview of the analytical methods and their reference intervals in the assessment of thyroid function and thyroid autoimmunity in pregnancy. Finally, we present our results supporting the implementation of universal screening.

Evaluation of the safety and efficacy of radiofrequency ablation for treating benign thyroid nodules

PubMed Central

Tang, Xiaoyin; Cui, Dan; Chi, Jiachang; Wang, Zhi; Wang, Tao; Zhai, Bo; Li, Ping

2017-01-01

Background: Radiofrequency ablation (RFA) is a relatively new procedure for treating benign thyroid nodules. The purpose of this study was to evaluate the safety and efficacy of RFA for treating benign thyroid nodules so as to serve as a reference for future clinical practice. Methods: This study retrospectively analyzed the clinical data of patients receiving percutaneous RFA for treating thyroid nodules from November 2014 to July 2015 in our medical center. One hundred and eight patients with a total of 380 nodules received ultrasound-guided RFA for treating thyroid nodules. Comparisons of the volume change of thyroid nodules before and after RFA treatment, post-treatment complication, and change of thyroid function, were carried out afterwards. Results: Before treatments, all patients received fine needle aspiration biopsy (FNA) which supported the diagnosis of benign tumor. There were 13 males and 95 females included in the study. Twenty-six cases (24.07%) had single nodule, and 82 cases (75.93%) had multiple nodules. Before treatments, the thyroid functions (FT3, FT4, and TSH) were normal originally or adjusted to normal range by endocrinology treatment. The preoperative nodules had minimum volume of 0.01mL, maximum volume of 70.89 mL, and mean volume of 1.02 ± 4.24mL. The volume of nodules one month and three months after RFA were 0.29 ± 0.72mL and 0.15 ± 0.87mL, respectively. In addition, volume reduction ratio (VRR) of nodules one month and three months after RFA were 64.12% and 85.54%, respectively. Both volume of nodules and VRR had statistically significant differences for pre-operative and post-operative comparison (P<0.05). Thyroid functions were in normal range after treatments, and there was no serious complications. Conclusions: Ultrasound-guided RFA treating benign thyroid nodules had the advantages of definite efficacy, safety, strong in control ability, no incision, less damage to surrounding normal tissues and no effect on thyroid function. It can be used as one of the main treatment methods for treating benign thyroid nodules. PMID:28382137

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.

The Genetics of the Thyroid Stimulating Hormone Receptor: History and Relevance

PubMed Central

Yin, Xiaoming; Latif, Rauf

2010-01-01

Background The thyroid stimulating hormone receptor (TSHR) is the key regulator of thyrocyte function. The gene for the TSHR on chromosome 14q31 has been implicated as coding for the major autoantigen in the autoimmune hyperthyroidism of Graves' disease (GD) to which T cells and autoantibodies are directed. Summary The TSHR is a seven-transmembrane domain receptor that undergoes complex posttranslational processing. In this brief review, we look at the genetics of this important autoantigen and its influence on a variety of tissue functions in addition to its role in the induction of GD. Conclusions There is convincing evidence that the TSH receptor gene confers increased susceptibility for GD, but not Hashimoto's thyroiditis. GD is associated with polymorphisms in the intron 1 gene region. How such noncoding nucleotide changes influence disease susceptibility remains uncertain, but is likely to involve TSHR splicing variants and/or microRNAs arising from this gene region. Whether such influences are confined to the thyroid gland or whether they influence cell function in the many extrathyroidal sites of TSHR expression remains unknown. PMID:20578897

Stuffy Nose

MedlinePlus

... release histamine, a chemical which dramatically increases blood flow to the nose and causes nasal tissue to swell. This inflames ... psychological stress, inadequate thyroid function, pregnancy, certain ... of decongesting nasal sprays, and exposure to irritants such as perfumes ...

Low-Dose Radioactive Iodine Destroys Thyroid Tissue Left after Surgery

Cancer.gov

A low dose of radioactive iodine given after surgery for thyroid cancer destroyed (ablated) residual thyroid tissue as effectively as a higher dose, with fewer side effects and less exposure to radiation, according to two randomized controlled trials.

Effects of varying dietary iodine supplementation levels as iodide or iodate on thyroid status as well as mRNA expression and enzyme activity of antioxidative enzymes in tissues of grower/finisher pigs.

PubMed

Li, Qimeng; Mair, Christiane; Schedle, Karl; Hellmayr, Isabella; Windisch, Wilhelm

2013-02-01

The objective of this study was to investigate the influence of high dietary iodine supply and different iodine sources on thyroid status and oxidative stress in target tissues of the thyroid hormones in fattening pigs. Eighty castrates (body weight: 33.3 ± 0.4 kg) were randomly allotted into five different treatments: The control diet contained 150 μg I/kg as KI, the other feeding groups were supplemented with 4,000 μg I/kg (as KI and KIO(3)) and 10,000 μg I/kg (as KI and KIO(3)), respectively. The mRNA expression levels of sodium/iodide symporter (NIS) and key antioxidant enzymes (Cu/Zn SOD, CAT, GPx) were analyzed in thyroid gland, liver, kidney, muscle, and adipose tissue sampled during slaughter. Furthermore, antioxidant enzyme activities and the effect on lipid peroxidation (MDA) were determined in liver and muscle. In thyroid gland, a significant downregulation of NIS and Cu/Zn SOD mRNA expression was observed in high-iodine groups. In liver, a source effect on the mRNA expression of Cu/Zn SOD between KI and KIO(3) at 4,000 μg I/kg was shown. In contrast, not SOD but GPx activity was affected by iodine source with strongest downregulation in high KIO(3) group. In muscle, GPx activity was affected by both iodine source and dose, showing stronger downregulation in KI groups. In kidney and adipose tissue, oxidative stress parameters showed no or only unsystematic changes. However, variation in iodine supply had no effect on MDA concentrations. NIS expression was significantly decreased with increased iodine supplementation, which is to ensure the thyroid gland function. However, the alleviating effect of iodine supplementation observed in antioxidant enzyme mRNA expression and activity did not reflect on the lipid peroxide level.

Cathepsin D in normal and neoplastic thyroid tissues.

PubMed

Kraimps, J L; Métayé, T; Millet, C; Margerit, D; Ingrand, P; Goujon, J M; Levillain, P; Babin, P; Begon, F; Barbier, J

1995-12-01

Cathepsin D is a widely distributed lysosomal acidic endopeptidase. It is an estrogen-regulated protein that is a prognostic factor in breast cancer. The aim of this study was to measure cathepsin D concentrations in thyroid tissues and to correlate these concentrations with clinical and pathologic parameters. Cathepsin D and thyroglobulin concentrations were measured in the cytosol of normal thyroid tissues (n = 14), benign nodules (n = 6), and thyroid carcinomas (n = 32) with an immunoradiometric assay. Statistical analysis was based on the Kruskal-Wallis and Wilcoxon tests and on the Spearman rank correlation coefficient. The mean level of cathepsin D, expressed as picomoles per milligram protein minus thyroglobulin, was higher in the 32 carcinomas, 29.1 +/- 15.5, than in the 14 normal thyroid tissues, 8.4 +/- 2.5 (p < 0.001) or in the 6 benign nodules, 11.2 +/- 7.3 (p = 0.003). Cathepsin D concentrations correlated with tumor size; Spearman rank correlation coefficient was rs = 0.44 (p = 0.012). No significant difference was found regarding histologic type. Cathepsin D concentrations were inversely correlated with the thyroglobulin level in the tumor; Spearman rank correlation coefficient was rs = -0.60 (p < 0.001). Cathepsin D concentration is higher in thyroid carcinoma than in normal thyroid tissue. Increased cathepsin D concentrations correlate with thyroid tumor size but not with histologic type. Further studies should be done to confirm the potential prognostic value of cathepsin D in patients with thyroid carcinomas.

Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto's thyroiditis and hypothyroidism.

PubMed

Nourbakhsh, Mitra; Ahmadpour, Fatemeh; Chahardoli, Behnam; Malekpour-Dehkordi, Zahra; Nourbakhsh, Mona; Hosseini-Fard, Seyed Reza; Doustimotlagh, Amirhossein; Golestani, Abolfazl; Razzaghy-Azar, Maryam

2016-03-01

The essential trace element selenium (Se) is required for thyroid hormone synthesis and metabolism. Selenoproteins contain selenocysteine and are responsible for biological functions of selenium. Glutathione peroxidase (GPx) is one of the major selenoproteins which protects the thyroid cells from oxidative damage. Selenoprotein P (SePP) is considered as the plasma selenium transporter to tissues. The aim of this study was to evaluate serum Se and SePP levels, and GPx activity in erythrocytes of children and adolescents with treated Hashimoto's thyroiditis, hypothyroidism, and normal subjects. Blood samples were collected from 32 patients with Hashimoto's thyroiditis, 20 with hypothyroidism, and 25 matched normal subjects. All the patients were under treatment with levothyroxine and at the time of analysis all of the thyroid function tests were normal. GPx enzyme activity was measured by spectrophotometry at 340 nm. Serum selenium levels were measured by high-resolution continuum source graphite furnace atomic absorption. SePP, TPOAb (anti-thyroid peroxidase antibody), and TgAb (anti-thyroglobulin antibody) were determined by ELISA kits. T4, T3, T3 uptake and TSH were also measured. Neither GPx activity nor SePP levels were significantly different in patients with Hashimoto's thyroiditis or hypothyroidism compared to normal subjects. Although GPx and SePP were both lower in patients with hypothyroidism compared to those with Hashimoto's thyroiditis and normal subjects but the difference was not significant. Serum Se levels also did not differ significantly in patients and normal subjects. We did not find any correlation between GPx or SePP with TPOAb or TgAb but SePP was significantly correlated with Se. Results show that in patients with Hashimoto's thyroiditis or hypothyroidism who have been under treatment with levothyroxine and have normal thyroid function tests, the GPx, SePP and Se levels are not significantly different. Copyright © 2015 Elsevier GmbH. All rights reserved.

Transoral videolaryngoscopic surgery for papillary carcinoma arising in lingual thyroid.

PubMed

Mogi, Chisato; Shinomiya, Hirotaka; Fujii, Natsumi; Tsuruta, Tomoyuki; Morita, Naruhiko; Furukawa, Tatsuya; Teshima, Masanori; Kanzawa, Maki; Hirokawa, Mitsuyoshi; Otsuki, Naoki; Nibu, Ken-Ichi

2018-05-15

Carcinoma arising in lingual thyroid is an extremely rare entity accounting for only 1% of all reported ectopic thyroids. Here, we report a case of carcinoma arising in lingual thyroid, which has been successfully managed by transoral resection and bilateral neck dissections. A lingual mass 4-cm in diameter with calcification was incidentally detected by computed tomography at medical check-up. No thyroid tissue was observed in normal position. Ultrasound examination showed bilateral multiple lymphadenopathies. Fine needle aspiration biopsy from lymph node in his right neck was diagnosed as Class III and thyroglobulin level of the specimen was 459ng/ml. Due to the difficulty in performing FNA of the lingual masses, right neck dissection was performed in advance for diagnostic purpose. Pathological examination showed existence of large and small follicular thyroid tissues in several lymph nodes, suggesting lymph node metastasis from thyroid carcinoma. Two months after the initial surgery, video-assisted transoral resection of lingual thyroid with simultaneous left neck dissection was performed. Postoperative course was uneventful. Papillary carcinoma was found in the lingual thyroid and thyroid tissues were also found in left cervical lymph nodes. Video-assisted transoral resection was useful for the treatment of thyroid cancer arising in lingual thyroid. Copyright © 2018 Elsevier B.V. All rights reserved.

Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves’ Disease

PubMed Central

Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

2014-01-01

Abstract Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves’ disease. She was diagnosed with Graves’ disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves’ disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves’ disease, few reports about thyroid cancer accompanied by Graves’ disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves’ disease. PMID:24790388

Thyroid Follicular Carcinoma in a Fourteen-year-old Girl with Graves' Disease.

PubMed

Kojima-Ishii, Kanako; Ihara, Kenji; Ohkubo, Kazuhiro; Matsuo, Terumichi; Toda, Naoko; Yamashita, Hiroyuki; Kono, Shinji; Hara, Toshiro

2014-04-01

Here we present the case of a 14-yr-old girl who developed thyroid follicular carcinoma accompanied by Graves' disease. She was diagnosed with Graves' disease at 10 yr of age and soon achieved a euthyroid state after starting treatment. When she was 13 yr of age, her hyperthyroidism and goiter worsened despite medical therapy. Multiple nodules were found in her enlarged thyroid gland by ultrasonography. Her serum Tg level seemed within the normal range. She underwent near-total thyroidectomy for control of thyroid function. Histopathological study demonstrated that multiple oxyphilic follicular neoplasms were surrounded by the thyroid tissue compatible with Graves' disease. Capsular invasion was identified in one of the nodules, and thus the histological diagnosis was minimally invasive follicular carcinoma. She did not have signs suggesting metastasis, and has had no relapse for 18 mo after the operation. Although some previous studies showed a high prevalence of thyroid cancer with an aggressive nature in adult patients with Graves' disease, few reports about thyroid cancer accompanied by Graves' disease are available in children. The present case, however, suggests that careful investigation is needed when we detect thyroid nodules or progressive thyroid enlargement, especially in children with Graves' disease.

Decreased expression of thyroid receptor-associated protein 220 in temporal lobe tissue of patients with refractory epilepsy

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

Li Jinmei; Wang Xuefeng; Xi Zhiqin

2006-10-06

Purpose: TRAP220 (thyroid hormone receptor-associated protein) functions as a coactivator for nuclear receptors and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. Thus, TRAP220 enhances the function of thyroid/steroid hormone receptors such as thyroid hormone and oestrogen receptors. This study investigated the expression of TRAP220 mRNA and protein level in epileptic brains comparing with human control. Methods: We examined the expression of TRAP220 mRNA and protein levels in temporal lobes from patients with chronic pharmacoresistant epilepsy who have undergone surgery. Results: Expression of TRAP220 mRNA and protein was shown to be decreased significantly in themore » temporal cortex of the patients with epilepsy. Conclusions: Our work showed that a decrease in TRAP220 mRNA and protein levels may be involved in the pathophysiology of epilepsy and may be associated with impairment of the brain caused by frequent seizures.« less

Sorting Nexin 2 (SNX2): a potential marker of active thyrocytes in normal and hyperfunctioning thyroid disorders.

PubMed

Kanzawa, Maki; Hara, Shigeo; Semba, Shuho; Yokozaki, Hiroshi; Hirokawa, Mitsuyoshi; Itoh, Tomoo

2014-04-01

Sorting nexins (SNXs) are a large, diverse group of cytoplasmic and membrane-associated proteins that function in a variety of cellular processes, including endocytosis, protein trafficking, and the retrieval of transmembrane proteins. In this study, we demonstrated that SNX2 is expressed in columnar and active thyroid follicular cells but not in flattened inactive thyrocytes. Morphometric analysis revealed a significant correlation between SNX2 positivity and columnar cell morphology. Immunohistochemical staining of serial sections of the thyroid tissue indicated that SNX2 localization was similar to sortilin, a protein expressed by active thyrocytes. Expression of SNX2 in thyrocytes is particularly marked and extensive in most hyperstimulated thyroid disorders, including Graves disease (diffusely SNX2 positive in 73.3% patients) and functioning nodules (93.8% patients). SNX2 immunolocalization in hyperstimulated follicular epithelial cells was specific among the SNXs family members examined. These results support the utility of SNX2 as a novel marker of active thyrocytes and reflect the endosomal trafficking activity in these cells.

The radiation biology of the thyroid.

PubMed

Malone, J F

1975-10-01

The structure and function of the thyroid gland are described. A detailed analysis of population kinetics in the gland suggests a method of measuring cell survival after irradiation that has many features in common with methods used in other mammalian cell systems. This method is used to obtain survival curves for thyroid cells afer irradiation. The effects on survival of splitting the radiation dose into two or multiple fractions, radiation type, and radioprotective agents are also examined. In the light of these data the tolerance of thyroid tissue to radiation exposure under various conditions is discussed. The dosimetry and biological effects of 125I and 131I are described in detail, and compared with X-rays. Radioiodine treatment of thyrotoxicosis is presented in relation to the known biological effects of the isotopes on the gland. Carcinogenic action of ionizing radiations in the thyroid are reviewed with particular reference to the clinical consequences of observations in this field.

Culture Models for Studying Thyroid Biology and Disorders

PubMed Central

Toda, Shuji; Aoki, Shigehisa; Uchihashi, Kazuyoshi; Matsunobu, Aki; Yamamoto, Mihoko; Ootani, Akifumi; Yamasaki, Fumio; Koike, Eisuke; Sugihara, Hajime

2011-01-01

The thyroid is composed of thyroid follicles supported by extracellular matrix, capillary network, and stromal cell types such as fibroblasts. The follicles consist of thyrocytes and C cells. In this microenvironment, thyrocytes are highly integrated in their specific structural and functional polarization, but monolayer and floating cultures cannot allow thyrocytes to organize the follicles with such polarity. In contrast, three-dimensional (3-D) collagen gel culture enables thyrocytes to form 3-D follicles with normal polarity. However, these systems never reconstruct the follicles consisting of both thyrocytes and C cells. Thyroid tissue-organotypic culture retains 3-D follicles with both thyrocytes and C cells. To create more appropriate experimental models, we here characterize four culture systems above and then introduce the models for studying thyroid biology and disorders. Finally, we propose a new approach to the cell type-specific culture systems on the basis of in vivo microenvironments of various cell types. PMID:22363871

Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging.

PubMed

Chaker, Layal; Cremers, Lotte G M; Korevaar, Tim I M; de Groot, Marius; Dehghan, Abbas; Franco, Oscar H; Niessen, Wiro J; Ikram, M Arfan; Peeters, Robin P; Vernooij, Meike W

2018-01-01

Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (β = 6.73 mL, 95% confidence interval = 2.94-9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

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

Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies

PubMed Central

Lindner, Claus; Johansson, Johannes; Weigel, Udo M.; Halperin, Irene; Hanzu, Felicia A.; Durduran, Turgut

2016-01-01

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs′) at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25–44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening. PMID:26815533

Oxidative Stress and Heart Failure in Altered Thyroid States

PubMed Central

Mishra, Pallavi; Samanta, Luna

2012-01-01

Increased or reduced action of thyroid hormone on certain molecular pathways in the heart and vasculature causes relevant cardiovascular derangements. It is well established that hyperthyroidism induces a hyperdynamic cardiovascular state, which is associated with a faster heart rate, enhanced left ventricular systolic and diastolic function whereas hypothyroidism is characterized by the opposite changes. Hyperthyroidism and hypothyroidism represent opposite clinical conditions, albeit not mirror images. Recent experimental and clinical studies have suggested the involvement of ROS tissue damage under altered thyroid status. Altered-thyroid state-linked changes in heart modify their susceptibility to oxidants and the extent of the oxidative damage they suffer following oxidative challenge. Chronic increase in the cellular levels of ROS can lead to a catastrophic cycle of DNA damage, mitochondrial dysfunction, further ROS generation and cellular injury. Thus, these cellular events might play an important role in the development and progression of myocardial remodeling and heart failure in altered thyroid states (hypo- and hyper-thyroidism). The present review aims at elucidating the various signaling pathways mediated via ROS and their modulation under altered thyroid state and the possibility of antioxidant therapy. PMID:22649319

[Computer simulation of thyroid regulatory mechanisms in health and malignancy].

PubMed

Abduvaliev, A A; Gil'dieva, M S; Khidirov, B N; Saĭdalieva, M; Saatov, T S

2010-07-01

The paper describes a computer model for regulation of the number of thyroid follicular cells in health and malignancy. The authors'computer program for mathematical simulation of the regulatory mechanisms of a thyroid follicular cellular community cannot be now referred to as good commercial products. For commercialization of this product, it is necessary to draw up a direct relation of the introduced corrected values from the actually existing normal values, such as the peripheral blood concentrations of thyroid hormones or the mean values of endocrine tissue mitotic activity. However, the described computer program has been also used in researches by our scientific group in the study of thyroid cancer. The available biological experimental data and theoretical provisions on thyroid structural and functional organization at the cellular level allow one to construct mathematical models for quantitative analysis of the regulation of the size of a cellular community of a thyroid follicle in health and abnormalities, by using the method for simulation of the regulatory mechanisms of living systems and the equations of cellular community regulatory communities.

Role of color Doppler in differentiation of Graves' disease and thyroiditis in thyrotoxicosis

PubMed Central

Donkol, Ragab Hani; Nada, Aml Mohamed; Boughattas, Sami

2013-01-01

AIM: To evaluate the role of thyroid blood flow assessment by color-flow Doppler ultrasonography in the differential diagnosis of thyrotoxicosis and compare it to technetium pertechnetate thyroid scanning. METHODS: Twenty-six patients with thyrotoxicosis were included in the study. Clinical history was taken and physical examination and thyroid function tests were performed for all patients. Thyroid autoantibodies were measured. The thyroid glands of all patients were evaluated by gray scale ultrasonography for size, shape and echotexture. Color-flow Doppler ultrasonography of the thyroid tissue was performed and spectral flow analysis of both inferior thyroid arteries was assessed. Technetium99 pertechnetate scanning of the thyroid gland was done for all patients. According to thyroid scintigraphy, the patients were divided into two groups: 18 cases with Graves’ disease and 8 cases with Hashimoto’s thyroiditis. All patients had suppressed thyrotropin. The diagnosis of Graves’ disease and Hashimoto’s thyroiditis was supported by the clinical picture and follow up of patients. RESULTS: Peak systolic velocities of the inferior thyroid arteries were significantly higher in patients with Graves’ disease than in patients with thyroiditis (P = 0.004 in the right inferior thyroid artery and P = 0.001 in left inferior thyroid artery). Color-flow Doppler ultrasonography parameters demonstrated a sensitivity of 88.9% and a specificity of 87.5% in the differential diagnosis of thyrotoxicosis. CONCLUSION: Color Doppler flow of the inferior thyroid artery can be used in the differential diagnosis of thyrotoxicosis, especially when there is a contraindication of thyroid scintigraphy by radioactive material in some patients. PMID:23671754

A putative OTU domain-containing protein 1 deubiquitinating enzyme is differentially expressed in thyroid cancer and identifies less-aggressive tumours

PubMed Central

Carneiro, A P; Reis, C F; Morari, E C; Maia, Y C P; Nascimento, R; Bonatto, J M C; de Souza, M A; Goulart, L R; Ward, L S

2014-01-01

Background: This study aimed to identify novel biomarkers for thyroid carcinoma diagnosis and prognosis. Methods: We have constructed a human single-chain variable fragment (scFv) antibody library that was selected against tumour thyroid cells using the BRASIL method (biopanning and rapid analysis of selective interactive ligands) and phage display technology. Results: One highly reactive clone, scFv-C1, with specific binding to papillary thyroid tumour proteins was confirmed by ELISA, which was further tested against a tissue microarray that comprised of 229 thyroid tissues, including: 110 carcinomas (38 papillary thyroid carcinomas (PTCs), 42 follicular carcinomas, 30 follicular variants of PTC), 18 normal thyroid tissues, 49 nodular goitres (NG) and 52 follicular adenomas. The scFv-C1 was able to distinguish carcinomas from benign lesions (P=0.0001) and reacted preferentially against T1 and T2 tumour stages (P=0.0108). We have further identified an OTU domain-containing protein 1, DUBA-7 deubiquitinating enzyme as the scFv-binding antigen using two-dimensional polyacrylamide gel electrophoresis and mass spectrometry. Conclusions: The strategy of screening and identifying a cell-surface-binding antibody against thyroid tissues was highly effective and resulted in a useful biomarker that recognises malignancy among thyroid nodules and may help identify lower-risk cases that can benefit from less-aggressive management. PMID:24937664

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.

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

Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.

PubMed Central

Xu, X. C.; el-Naggar, A. K.; Lotan, R.

1995-01-01

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7677193

Ectopic Multinodular Goiter: Multidetector Computed Tomography Findings

PubMed Central

Karakaya, Afak Durur; Kantarci, Mecit; Yalcin, Ahmet; Demir, Berrin

2008-01-01

The thyroid is the first endocrine gland to form during embryogenesis. At this stage, incomplete or anomalous migration of thyroid tissue causes ectopic localization of the gland. In our case, a 55-year-old woman who was evaluated via ultrasonography (USG) and multi-detector computed tomography (MDCT) had no thyroid gland at the normal location, but did have ectopic thyroid tissue in the left submandibular and submental regions. PMID:25610021

Demonstration of Iodide Transport Defect but Normal Iodide Organification in Nonfunctioning Nodules of Human Thyroid Glands

PubMed Central

Field, James B.; Larsen, P. Reed; Yamashita, Kamejiro; Mashiter, Keith; Dekker, Andrew

1973-01-01

Benign and malignant nodules in human thyroid glands, which did not concentrate iodide in vivo, were also unable to accumulate iodide in vitro. The mean thyroid-to-medium ratio (T/M) in seven benign nodules was 0.8±0.2 compared with 7±2 in adjacent normal thyroid tissue. In four malignant thyroid nodules, the mean T/M was 0.5±0.1 compared with 11±4 in adjacent normal thyroid. Despite the inability of such nodules to concentrate iodide, iodide organification was present but was only one-half to one-third as active as in surrounding normal thyroid. Thyroid-stimulating hormone (TSH) increased iodide organification equally in both benign nodules and normal thyroid although it had no effect in three of the four malignant lesions. The reduction in organification is probably related to the absence of iodide transport, since incubation of normal thyroid slices with perchlorate caused similar diminution in iodide incorporation but no change in the response to TSH. Monoiodotyrosine (MIT) and di-iodotyrosine (DIT) accounted for most of the organic iodide in both the nodules and normal tissue. The MIT/DIT ratio was similar in normal and nodule tissue. The normal tissue contained much more inorganic iodide than the nodules, consistent with the absence of the iodide trap in the latter tissue. The thyroxine content of normal thyroid was 149±17 μg/g wet wt and 18±4 μg/g wet wt in the nodules. The transport defect in the nodules was not associated with any reduction in total, Na+-K+- or Mg++-activated ATPase activities or the concentration of ATP. Basal adenylate cyclase was higher in nodules than normal tissue. Although there was no difference between benign and malignant nodules, the response of adenylate cyclase to TSH was greater in the benign lesions. These studies demonstrate that nonfunctioning thyroid nodules, both benign and malignant, have a specific defect in iodide transport that accounts for their failure to accumulate radioactive iodide in vivo. In benign nodules, iodide organification was increased by TSH while no such effect was found in three of four malignant lesions, suggesting additional biochemical defects in thyroid carcinomas. PMID:4353998

Graves' disease: diagnostic and therapeutic challenges (multimedia activity).

PubMed

Kahaly, George J; Grebe, Stefan K G; Lupo, Mark A; McDonald, Nicole; Sipos, Jennifer A

2011-06-01

Graves' disease is the most common cause of hyperthyroidism in the United States. Graves' disease occurs more often in women with a female:male ratio of 5:1 and a population prevalence of 1% to 2%. A genetic determinant to the susceptibility to Graves' disease is suspected because of familial clustering of the disease, a high sibling recurrence risk, the familial occurrence of thyroid autoantibodies, and the 30% concordance in disease status between identical twins. Graves' disease is an autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid antigen-specific T cells into the thyroid and thyroid-stimulating hormone receptor expressing tissues, with the production of autoantibodies to well-defined thyroidal antigens, such as thyroid peroxidase, thyroglobulin, and the thyroid-stimulating hormone receptor. The thyroid-stimulating hormone receptor is central to the regulation of thyroid growth and function. Stimulatory autoantibodies in Graves' disease activate the thyroid-stimulating hormone receptor leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Below-normal levels of baseline serum thyroid-stimulating hormone receptor, normal to elevated serum levels of T4, elevated serum levels of T3 and thyroid-stimulating hormone receptor autoantibodies, and a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow) thyroid gland confirm diagnosis of Graves' disease (available at: http://supplements.amjmed.com/2010/hyperthyroid/faculty.php). This Resource Center is also available through the website of The American Journal of Medicine (www.amjmed.com). Click on the “Thyroid/Graves' Disease” link in the “Resource Centers” section, found on the right side of the Journal homepage. Copyright © 2011 Elsevier Inc. All rights reserved.

Label-free Imaging of Thyroid and Parathyroid Glands Using Coherent Anti-Stokes Raman Scattering (CARS) Microscopy

NASA Astrophysics Data System (ADS)

Weng, Sheng

Thyroid and parathyroid glands play a vital role in regulating the body's metabolism and calcium levels. Surgical removal of the glands is the main treatment for both thyroid cancer and parathyroid adenoma. In thyroidectomy and parathyroidectomy, it's very important to differentiate thyroid, parathyroid, and the other tissues around the neck. Traditionally, physicians use ultrasound guided fine needle aspiration (FNA) to evaluate thyroid nodules, but up to 30% of FNA results are "inconclusive". The sestamibi scan can localize parathyroid adenoma, but currently it only has 50% accuracy. Here we applied the emerging CARS technique to image both thyroid and parathyroid tissues, which has potential to be used in real-time in vivo examination of different structures. We also developed algorithms to differentiate different cellular structures based on CARS images. When incorporated with a fiber optic endoscope in the future, CARS imaging technique can help surgeons identify cancerous thyroid tissue intraoperatively, preserve good parathyroid glands during thyroidectomy and find parathyroid adenoma during parathyroidectomy.

The thyroid and environmental stress in mammals

NASA Technical Reports Server (NTRS)

Galton, V. A.

1977-01-01

The effects of hyperoxia at ambient pressure on thyroid function and thyroid hormone metabolism have been assessed. Thyroidal activity was depressed in mice and rats by exposure to hyperoxia, due at least in part to a decrease in the rate of secretion of pituitary thyrotropin. The effects of hyperoxia on the peripheral deiodination of thyroxine were dependent on the concentration of oxygen employed and/or the duration of exposure. When significant changes were observed a reduction in the rate of deiodination and in the deiodinative clearance of T sub 4 occurred. Hyperoxia also resulted in a marked fall in circulating T sub 4 concentration and a decrease in T sub 4-binding activity in serum. Many of these effects of hyperoxia were prevented by the concomitant administration of large amounts of Vitamin E. These decreases in thyroid function and T sub 4 metabolism were associated with a decrease in the rate of whole body oxygen consumption. It was concluded that the deleterious effects of oxygen in the rat were not due to an oxygen induced hyperthyroid state in the peripheral tissues. Thyroxine was shown to be essential for survival during acute cold stress.

Increased thyrotropin binding in hyperfunctioning thyroid nodules.

PubMed

Müller-Gärtner, H W; Schneider, C; Bay, V; Tadt, A; Rehpenning, W; de Heer, K; Jessel, M

1987-08-01

The object of this study was to investigate TSH receptors in hyperfunctioning thyroid nodules (HFN). In HFN, obtained from seven patients, 125-I-TSH binding as determined by equilibrium binding analysis on particulate membrane preparations, was found to be significantly increased as compared with normal thyroid tissues (five patients; P less than 0.001). Scatchard analysis of TSH-binding revealed two kinds of binding sites for both normal thyroid tissue and HFN, and displayed significantly increased association constants of high- and low-affinity binding sites in HFN (Ka = 11.75 +/- 6.8 10(9) M-1, P less than 0.001 and Ka = 2.1 +/- 1.0 10(7) M-1, P less than 0.025; x +/- SEM) as compared with normal thyroid tissue (Ka = 0.25 +/- 0.06 10(9) M-1, Ka = 0.14 +/- 0.03 10(7) M-1; x +/- SEM). The capacity of the high-affinity binding sites in HFN was found to be decreased (1.8 +/- 1.1 pmol/mg protein, x +/- SEM) in comparison with normal thyroid tissue (4.26 +/- 1.27 pmol/mg protein; x +/- SEM). TSH-receptor autoradiography applied to cryostatic tissue sections confirmed increased TSH binding of the follicular epithelium in HFN. These data suggest that an increased affinity of TSH-receptor sites in HFN in iodine deficient areas may be an important event in thyroid autonomy.

Restoration of Cardiac Tissue Thyroid Hormone Status in Experimental Hypothyroidism: A Dose-Response Study in Female Rats

PubMed Central

Weltman, Nathan Y.; Ojamaa, Kaie; Savinova, Olga V.; Chen, Yue-Feng; Schlenker, Evelyn H.; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Pol, Christine J.

2013-01-01

Thyroid hormones (THs) play a pivotal role in regulating cardiovascular homeostasis. To provide a better understanding of the coordinated processes that govern cardiac TH bioavailability, this study investigated the influence of serum and cardiac TH status on the expression of TH transporters and cytosolic binding proteins in the myocardium. In addition, we sought to determine whether the administration of T3 (instead of T4) improves the relationship between THs in serum and cardiac tissue and cardiac function over a short-term treatment period. Adult female Sprague Dawley rats were made hypothyroid by 7 weeks treatment with the antithyroid drug 6-n-propyl-2-thiouracil (PTU). After establishing hypothyroidism, rats were assigned to 1 of 5 graded T3 dosages plus PTU for a 2-week dose-response experiment. Untreated, age-matched rats served as euthyroid controls. PTU was associated with depressed serum and cardiac tissue T3 and T4 levels, arteriolar atrophy, altered TH transporter and cytosolic TH binding protein expression, fetal gene reexpression, and cardiac dysfunction. Short-term administration of T3 led to a mismatch between serum and cardiac tissue TH levels. Normalization of serum T3 levels was not associated with restoration of cardiac tissue T3 levels or cardiac function. In fact, a 3-fold higher T3 dosage was necessary to normalize cardiac tissue T3 levels and cardiac function. Importantly, this study provides the first comprehensive data on the relationship between altered TH status (serum and cardiac tissue), cardiac function, and the coordinated in vivo changes in cardiac TH membrane transporters and cytosolic TH binding proteins in altered TH states. PMID:23594789

[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.

Expression of PACAP and PAC1 Receptor in Normal Human Thyroid Gland and in Thyroid Papillary Carcinoma.

PubMed

Bardosi, Sebastian; Bardosi, Attila; Nagy, Zsuzsanna; Reglodi, Dora

2016-10-01

Pituitary adenylate cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal peptide-secretin-glucagon peptide family, isolated first from ovine hypothalamus. The diverse physiological effects of PACAP are known mainly from animal experiments, including several actions in endocrine glands. Alteration of PACAP expression has been shown in several tumors, but changes in expression of PACAP and its specific PAC1 receptor in human thyroid gland pathologies have not yet been investigated. Therefore, the aim of the present study was to investigate expression of PACAP and its PAC1 receptor in human thyroid papillary carcinoma, the most common endocrine malignant tumor. PACAP and PAC1 receptor expressions were investigated from thyroid gland samples of patients with papillary carcinomas. The staining intensity of follicular epithelial cells and thyroid colloid of tumor tissue was compared to that of tumor-free tissue in the same thyroid glands in a semi-quantitative way. Our results reveal that both PACAP(-like) and PAC1 receptor(-like) immunoreactivities are altered in papillary carcinoma. Stronger PACAP immunoreactivity was observed in active follicles. Colloidal PACAP immunostaining was either lacking or very weak, and more tumorous cells displayed strong apical immunoreactivity. Regarding PAC1 receptor, cells of the normal thyroid tissue showed strong granular expression, which was lacking in the tumor cells. The cytoplasm of tumor cells displayed weak, minimal staining, while in a few tumor cells we observed strong PAC1 receptor expression. This pattern was similar to that observed in the PACAP expression, but fewer in number. In summary, we showed alteration of PACAP and PAC1 receptor expression in human thyroid papillary carcinoma, indicating that PACAP regulation is disturbed in tumorous tissue of the thyroid gland. The exact role of PACAP in thyroid tumor growth should be further explored.

Oxidative muscular injury and its relevance to hyperthyroidism.

PubMed

Asayama, K; Kato, K

1990-01-01

In experimental hyperthyroidism, acceleration of lipid peroxidation occurs in heart and slow-oxidative muscles, suggesting the contribution of reactive oxygen species to the muscular injury caused by thyroid hormones. This article reviews various models of oxidative muscular injury and considers the relevance of the accompanying metabolic derangements to thyrotoxic myopathy and cardiomyopathy, which are the major complications of hyperthyroidism. The muscular injury models in which reactive oxygen species are supposed to play a role are ischemia/reperfusion syndrome, exercise-induced myopathy, heart and skeletal muscle diseases related to the nutritional deficiency of selenium and vitamin E and related disorders, and genetic muscular dystrophies. These models provide evidence that mitochondrial function and the glutathione-dependent antioxidant system are important for the maintenance of the structural and functional integrity of muscular tissues. Thyroid hormones have a profound effect on mitochondrial oxidative activity, synthesis and degradation of proteins and vitamin E, the sensitivity of the tissues to catecholamine, the differentiation of muscle fibers, and the levels of antioxidant enzymes. The large volume of circumstantial evidence presented here indicates that hyperthyroid muscular tissues undergo several biochemical changes that predispose them to free radical-mediated injury.

Elevated interleukin-1β in peripheral blood mononuclear cells contributes to the pathogenesis of autoimmune thyroid diseases, especially of Hashimoto thyroiditis.

PubMed

Sun, Li; Zhang, Xiaoxu; Dai, Fang; Shen, Jijia; Ren, Cuiping; Zuo, Chunlin; Zhang, Qiu

2016-08-01

To explore the relationship between IL-1β expression and two common autoimmune thyroid diseases: Hashimoto thyroiditis (HT) and Graves' disease (GD). qRT-PCR, Quantiglo ELISA, and flow cytometry were used to evaluate the expression levels of IL-1β in serum, peripheral blood mononuclear cells (PBMCs), and thyroid tissue samples from patients with HT or GD. Local infiltration of monocytes was assessed by immunohistochemical study of patients' thyroid tissue samples. Although no significant differences in IL-1β levels were found between samples of serum from patients with HT or GD and normal controls, we found that IL-1β mRNA and protein levels in PBMCs of HT patients were significantly higher than those of patients with GD, which were in turn higher than the level in normal controls. In addition, IL-1β mRNA was also increased in thyroid gland tissue from patients with HT compared to those with GD, and this was accompanied by increased local infiltration of monocytes into thyroid tissues. Correlation analysis of the clinical samples validated the association of high IL-1β levels with the pathogenesis of HT. Our study suggests that IL-1β may be an active etiologic factor in the pathogenesis of HT and thus present a new target for novel diagnostics and treatment.

Altered thyroid status in lake trout (Salvelinus namaycush) exposed to co-planar 3,3',4,4',5-pentachlorobiphenyl.

PubMed

Brown, Scott B; Evans, Robert E; Vandenbyllardt, Lenore; Finnson, Ken W; Palace, Vince P; Kane, Andrew S; Yarechewski, Alvin Y; Muir, Derek C G

2004-03-30

Recent studies indicate that co-planar 3,3',4,4',5-pentachlorobiphenyl (PCB) congeners or their metabolites may disrupt thyroid function in fishes. Although co-planar PCB have been detected at microgram per kilogram levels in fish from contaminated areas, few studies have examined mechanisms whereby, co-planar PCBs may alter thyroid function in fish. We treated immature lake trout by intraperitoneal (i.p.)-injection or dietary gavage with vehicle containing 0, 0.7, 1.2, 25 or 40 microg 3,3',4,4',5-pentachlorobiphenyl (PCB 126) per kgBW. Blood and tissue samples were collected at various times up to 61 weeks following exposure. The treatments produced sustained dose-dependent elevations of tissue (PCB 126) concentrations. Thyroid epithelial cell height (TECH), plasma thyroxine (T4) and 3,3',5-triiodo-l-thyronine (T3) concentrations, hepatic 5'-monodeiodinase, hepatic glucuronidation of T4 and T3, as well as plasma T4 kinetics and fish growth were analyzed. Exposure to the highest doses of PCB 126 caused increased TECH, plasma T4 dynamics and T4-glucuronidation (T4-G). PCB 126 did not affect 5'-monodeiodinase and T3-glucuronidation (T3-G) and there were no effects on fish growth or condition. Because T3 status and growth were unaffected, the thyroid system was able to compensate for the alterations caused by the PCB 126 exposure. It is clear that concentrations of co-planar PCBs similar to those found in predatory fish from contaminated areas in the Great Lakes are capable of enhancing metabolism of T4. These changes may be of significance when T4 requirements are high for other reasons (e.g. periods of rapid growth, warm temperatures, metamorphosis, and parr-smolt transformation).

ΤND: a thyroid nodule detection system for analysis of ultrasound images and videos.

PubMed

Keramidas, Eystratios G; Maroulis, Dimitris; Iakovidis, Dimitris K

2012-06-01

In this paper, we present a computer-aided-diagnosis (CAD) system prototype, named TND (Thyroid Nodule Detector), for the detection of nodular tissue in ultrasound (US) thyroid images and videos acquired during thyroid US examinations. The proposed system incorporates an original methodology that involves a novel algorithm for automatic definition of the boundaries of the thyroid gland, and a novel approach for the extraction of noise resilient image features effectively representing the textural and the echogenic properties of the thyroid tissue. Through extensive experimental evaluation on real thyroid US data, its accuracy in thyroid nodule detection has been estimated to exceed 95%. These results attest to the feasibility of the clinical application of TND, for the provision of a second more objective opinion to the radiologists by exploiting image evidences.

Estrogen receptors and cathepsin D in human thyroid tissue.

PubMed

Métayé, T; Millet, C; Kraimps, J L; Aubouin, B; Barbier, J; Bégon, F

1993-09-15

To investigate the significance of estrogen receptors (ER) in the pathogenesis of thyroid dysplasia, the authors analyzed, by analogy with breast cancers, ER and three estrogen-regulated proteins: progesterone receptor (PR), cathepsin D, and pS2 protein, in cytosols of 42 human thyroid tissues. ER and PR were measured by an immunoenzymatic assay and cathepsin D and pS2 by an immunoradiometric assay. Tissue specimens included 7 normal tissues, 6 benign nodules, 8 toxic adenomas, 7 from patients with Graves disease, and 14 carcinomas. ER was present at very low concentrations, with no statistical difference between neoplastic and nonneoplastic tissues. The mean levels of cathepsin D, expressed as pmol/mg protein minus thyroglobulin, were higher in the 14 carcinomas (P = 0.0003), the 7 specimens from patients with Graves disease (P = 0.006), and the 8 toxic adenomas (P = 0.04) than in the 7 normal thyroid tissues. A significant difference also was observed between the carcinomas (P = 0.003) and six benign nodules. Compared to TNM parameters, cathepsin D concentrations correlated with tumor size: higher cathepsin D levels were found in pT4 than in pT2 and pT3 carcinomas. All the tissues tested were negative for PR and pS2 protein. The results clearly indicate a significant difference between neoplastic and normal thyroid tissue in terms of the amount of cathepsin D, but not that of ER. This suggests that cathepsin D probably is not regulated by estrogen but simply is a marker of protease activity during invasion by thyroid carcinomas.

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

Short communication: quantitative comparison of iodothyronine deiodinase I and II mRNA expression in ovine tissues.

PubMed

Foroughi, Mohammad Ali; Dehghani, Hesam

2013-12-01

Iodothyronine deiodinases I and II (DIO1 and DIO2) remove iodine from T4 to convert it to a more biologically active T3. The relative contribution of different tissue deiodinases to the establishment of a euthyroid state in sheep is not known. The objective of this study was to quantitate the amounts of transcription of DIO1 and DIO2 deiodinases in different ovine tissues. Using RT-qPCR, we found that DIO1 deiodinase is transcribed in skeletal muscle, kidney, and heart, more than thyroid, in diaphragm in quantities very similar to thyroid, and in liver, spleen, lung, and mammary gland lower than thyroid. We also found that the level of DIO2 transcription in all other tissues was lower than that in thyroid. In clinical settings, measurement of DIO1 and DIO2 expression in a given tissue may provide important clues on the intensity of selenium deficiency and its effects on the metabolism of thyroid hormones. Copyright © 2013 Elsevier Ltd. All rights reserved.

Activating thyrotropin receptor mutations in histologically heterogeneous hyperfunctioning nodules of multinodular goiter.

PubMed

Tonacchera, M; Vitti, P; Agretti, P; Giulianetti, B; Mazzi, B; Cavaliere, R; Ceccarini, G; Fiore, E; Viacava, P; Naccarato, A; Pinchera, A; Chiovato, L

1998-07-01

Activating thyrotropin (TSH) receptor mutations have been found in toxic adenomas and in hot nodules contained in toxic multinodular goiter. The typical feature of multinodular goiter is the heterogeneity in morphology and function of different follicles within the same enlarged gland. In this report we describe a patient with a huge multinodular goiter, normal free triiodothyronine (FT3) and free thyroxine (FT4) serum values, and subnormal TSH serum concentration. Thyroid scintiscan showed two hot areas corresponding to the basal and apical nodules of the left lobe. The right lobe was poorly visualized by the radioisotope. The patient underwent thyroidectomy, and histological examination of the tissue was performed. Genomic DNA was extracted from the tissue specimen and direct sequencing of the TSH receptor and Gs alpha genes was done. At histology, one hyperfunctioning nodule had the typical microscopic structure of thyroid adenomas, and the other contained multiple macrofollicular areas not confined by a capsule. In spite of this histological difference, both hyperfunctioning nodules harbored a mutation of the thyrotropin receptor (TSHr) gene: an isoleucine instead of a threonine in position 632 (T632I) in the first nodule and a methionine instead of an isoleucine in position 486 (I486M) in the second nodule. In conclusion, our findings show for the first time that gain-of-function TSHr mutations are not only present in hyperfunctioning thyroid nodules with the histological features of the true thyroid adenomas, but also in hyperfunctioning hyperplastic nodules contained in the same multinodular goiter.

Urinary metabolomics reveals glycemic and coffee associated signatures of thyroid function in two population-based cohorts

PubMed Central

Friedrich, Nele; Pietzner, Maik; Cannet, Claire; Thuesen, Betina H.; Hansen, Torben; Wallaschofski, Henri; Grarup, Niels; Skaaby, Tea; Budde, Kathrin; Pedersen, Oluf; Nauck, Matthias; Linneberg, Allan

2017-01-01

Background Triiodothyronine (T3) and thyroxine (T4) as the main secretion products of the thyroid affect nearly every human tissue and are involved in a broad range of processes ranging from energy expenditure and lipid metabolism to glucose homeostasis. Metabolomics studies outside the focus of clinical manifest thyroid diseases are rare. The aim of the present investigation was to analyze the cross-sectional and longitudinal associations of urinary metabolites with serum free T4 (FT4) and thyroid-stimulating hormone (TSH). Methods Urine Metabolites of participants of the population-based studies Inter99 (n = 5620) and Health2006/Health2008 (n = 3788) were analyzed by 1H-NMR spectroscopy. Linear or mixed linear models were used to detect associations between urine metabolites and thyroid function. Results Cross-sectional analyses revealed positive relations of alanine, trigonelline and lactic acid with FT4 and negative relations of dimethylamine, glucose, glycine and lactic acid with log(TSH). In longitudinal analyses, lower levels of alanine, dimethylamine, glycine, lactic acid and N,N-dimethylglycine were linked to a higher decline in FT4 levels over time, whereas higher trigonelline levels were related to a higher FT4 decline. Moreover, the risk of hypothyroidism was higher in subjects with high baseline trigonelline or low lactic acid, alanine or glycine values. Conclusion The detected associations mainly emphasize the important role of thyroid hormones in glucose homeostasis. In addition, the predictive character of these metabolites might argue for a potential feedback of the metabolic state on thyroid function. Besides known metabolic consequences of TH, the link to the urine excretion of trigonelline, a marker of coffee consumption, represents a novel finding of this study and given the ubiquitous consumption of coffee requires further research. PMID:28253303

Altered peptidase activities in thyroid neoplasia and hyperplasia.

PubMed

Larrinaga, Gorka; Blanco, Lorena; Errarte, Peio; Beitia, Maider; Sanz, Begoña; Perez, Itxaro; Irazusta, Amaia; Sánchez, Clara E; Santaolalla, Francisco; Andrés, Leire; López, José I

2013-01-01

Papillary thyroid carcinoma (PTC), follicular thyroid adenoma (FTA), and thyroid nodular hyperplasia (TNH) are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26) in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP), alanyl aminopeptidase (AlaAP), prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.

Characterization of Thyroid Hormone Transporter Protein Expression during Tissue-specific Metamorphic Events in Xenopus tropicalis

EPA Science Inventory

Thyroid hormone (TH) induces the dramatic morphological and physiological changes that together comprise amphibian metamorphosis. TH-responsive tissues vary widely with developmental timing of TH-induced changes. How larval tadpole tissues are able to employ distinct metamorphi...

Histopathologic and immunohistochemical features of Hashimoto thyroiditis.

PubMed

Amani, H Kazem

2011-01-01

Intrathyroid lymphoid tissue is accrued in Hashimoto thyroiditis (HT). Histologically, this acquired lymphoid tissue bears a close resemblance to mucosa-associated lymphoid tissue (MALT) and can evolve to lymphoma. To demonstrate the morphological, and immunohistochemical profiles of Hashimoto thyroiditis and to ascertain the importance of light chain restriction in distinguishing HT with extensive lymphoplasmacytoid infiltrate from MALT lymphoma. We studied histopathologically and immunohistochemically (CD20, CD3, Igk, Igl and cytokeratin) 30 cases of HT for evaluation of the lymphoid infiltrate and the presence of lymphoepithelial lesions (LELs). Distinguishing between early thyroid lymphoma and HT was evaluated by light chain restriction. These findings were compared with two cases of primary thyroid lymphoma. The histopathological findings were characteristic of HT. Immunohistochemistry confirmed inconspicuous, rare B-cell LELs as well as a prominent T-lymphocyte population. Testing for light chain restriction showed polyclonal population of plasma cells. The cases of MALT lymphoma had distinct destructive lymphoepithelial lesions, B-cell immunophenotyping and showed kappa light chain restriction in the plasmacytoid population. Hashimoto thyroiditis differs both histopathologically and immunohistochemically from thyroid lymphoma. In suspicious cases, immunohistochemistry could be helpful in reaching a definitive diagnosis.

Improved method for analysis of RNA present in long-term preserved thyroid cancer tissue of atomic bomb survivors.

PubMed

Hamatani, Kiyohiro; Eguchi, Hidetaka; Mukai, Mayumi; Koyama, Kazuaki; Taga, Masataka; Ito, Reiko; Hayashi, Yuzo; Nakachi, Kei

2010-01-01

Since many thyroid cancer tissue samples from atomic bomb (A-bomb) survivors have been preserved for several decades as unbuffered formalin-fixed, paraffin-embedded specimens, molecular oncological analysis of such archival specimens is indispensable for clarifying the mechanisms of thyroid carcinogenesis in A-bomb survivors. Although RET gene rearrangements are the most important targets, it is a difficult task to examine all of the 13 known types of RET gene rearrangements with the use of the limited quantity of RNA that has been extracted from invaluable paraffin-embedded tissue specimens of A-bomb survivors. In this study, we established an improved 5' rapid amplification of cDNA ends (RACE) method using a small amount of RNA extracted from archival thyroid cancer tissue specimens. Three archival thyroid cancer tissue specimens from three different patients were used as in-house controls to determine the conditions for an improved switching mechanism at 5' end of RNA transcript (SMART) RACE method; one tissue specimen with RET/PTC1 rearrangement and one with RET/PTC3 rearrangement were used as positive samples. One other specimen, used as a negative sample, revealed no detectable expression of the RET gene tyrosine kinase domain. We established a 5' RACE method using an amount of RNA as small as 10 ng extracted from long-term preserved, unbuffered formalin-fixed, paraffin-embedded thyroid cancer tissue by application of SMART technology. This improved SMART RACE method not only identified common RET gene rearrangements, but also isolated a clone containing a 93-bp insert of rare RTE/PTC8 in RNA extracted from formalin-fixed, paraffin-embedded thyroid cancer specimens from one A-bomb survivor who had been exposed to a high radiation dose. In addition, in the papillary thyroid cancer of another high-dose A-bomb survivor, this method detected one novel type of RET gene rearrangement whose partner gene is acyl coenzyme A binding domain 5, located on chromosome 10p. We conclude that our improved SMART RACE method is expected to prove useful in molecular analyses using archival formalin-fixed, paraffin-embedded tissue samples of limited quantity.

Functional morphology of pituitary -thyroid and -adrenocortical axes in middle-aged male rats treated with Vitex agnus castus essential oil.

PubMed

Šošić-Jurjević, Branka; Ajdžanović, Vladimir; Filipović, Branko; Trifunović, Svetlana; Jarić, Ivana; Ristić, Nataša; Milošević, Verica

2016-09-01

We previously reported that Vitex agnus-castus L. essential oil (VACEO), when administered to middle-aged males, exerts a bone-protective effect, induces silencing of locomotor activities and decreases pituitary prolactin immunopositivity. To further assess the putative endocrine effects of VACEO, we examined the pituitary-thyroid and -adrenocortical axes in our model. Sixteen-month-old Wistar rats were subcutaneously administered 60mg/kg of VACEO dissolved in sterile olive oil, while the control group received the same amount of vehicle alone for three weeks. Pituitaries, thyroids and adrenals were analyzed by qualitative and quantitative histological approaches. Concentration of thyroid stimulating hormone (TSH), total thyroxine and triiodothyronine (TH), adrenocorticotrophic hormone (ACTH), corticosterone in serum and in adrenal tissue were measured. In VACEO-treated rats, the relative volume density of pituitary thyrotrophs increased (p<0.001), while intensity of cytoplasmic TSHβ immunostaining decreased (p<0.001), consistent with elevated TSH in serum (p<0.01). The thyroid tissue was characterized by a micro-follicular structure, increased relative volume of follicular epithelium (p<0.05), decreased volume of luminal colloid (p<0.001) and increased basolateral expression of sodium-iodide symporter-immunopositivity (p<0.05). Serum TH also increased (p<0.01). The relative volume density of pituitary corticotrophs decreased (p<0.05), compatible with decline in circulating ACTH (p<0.05). Neither tissue nor serum corticosterone levels were affected by VACEO treatment. In conclusion, the observed changes in TSH and ACTH strongly indicate central endocrine effects of prolonged VACEO treatment. In this respect, production of ACTH decreased without impact on corticosterone production. Increase in serum concentration of both TH and TSH are not compatible with a negative feedback loop and suggest a major change in set-point regulation of the hypothalamic-pituitary-thyroid axis. Copyright © 2016 Elsevier GmbH. All rights reserved.

Semiquantitative immunohistochemical marker staining and localization in canine thyroid carcinoma and normal thyroid gland.

PubMed

Pessina, P; Castillo, V; Sartore, I; Borrego, J; Meikle, A

2016-09-01

Immunoreactive proteins in follicular cells, fibroblasts and endothelial cells were assessed in canine thyroid carcinomas and healthy thyroid glands. No differences were detected in thyrotropin receptor and thyroglobulin staining between cancer and normal tissues, but expression was higher in follicular cells than in fibroblasts. Fibroblast growth factor-2 staining was more intense in healthy follicular cells than in those of carcinomas. Follicular cells in carcinomas presented two- to three-fold greater staining intensity of thyroid transcription factor-1 and proliferating cell nuclear antigen, respectively, than healthy cells, and a similar trend was found for the latter antigen in fibroblasts. Vascular endothelial growth factor staining was more intense in the endothelial cells of tumours than in those of normal tissues. In conclusion, greater expression of factors related to proliferation and angiogenesis was demonstrated in several cell types within thyroid carcinomas compared to healthy tissues, which may represent mechanisms of tumour progression in this disease. © 2014 John Wiley & Sons Ltd.

Thyroid function appears to be significantly reduced in Space-borne MDS mice

NASA Astrophysics Data System (ADS)

Saverio Ambesi-Impiombato, Francesco; Curcio, Francesco; Fontanini, Elisabetta; Perrella, Giuseppina; Spelat, Renza; Zambito, Anna Maria; Damaskopoulou, Eleni; Peverini, Manola; Albi, Elisabetta

It is known that prolonged space flights induced changes in human cardiovascular, muscu-loskeletal and nervous systems whose function is regulated by the thyroid gland but, until now, no data were reported about thyroid damage during space missions. We have demonstrated in vitro that, during space missions (Italian Soyuz Mission "ENEIDE" in 2005, Shuttle STS-120 "ESPERIA" in 2007), thyroid in vitro cultured cells did not respond to thyroid stimulating hor-mone (TSH) treatment; they appeared healthy and alive, despite their being in a pro-apopotic state characterised by a variation of sphingomyelin metabolism and consequent increase in ce-ramide content. The insensitivity to TSH was largely due to a rearrangement of specific cell membrane microdomains, acting as platforms for TSH-receptor (TEXUS-44 mission in 2008). To study if these effects were present also in vivo, as part of the Mouse Drawer System (MDS) Tissue Sharing Program, we performed experiments in mice maintained onboard the Interna-tional Space Station during the long-duration (90 days) exploration mission STS-129. After return to earth, the thyroids isolated from the 3 animals were in part immediately frozen to study the morphological modification in space and in part immediately used to study the effect of TSH treatment. For this purpose small fragments of tissue were treated with 10-7 or 10-8 M TSH for 1 hour by using untreated fragments as controls. Then the fragments were fixed with absolute ethanol for 10 min at room temperature and centrifuged for 20 min. at 3000 x g. The supernatants were used for cAMP analysis whereas the pellet were used for protein amount determination and for immunoblotting analysis of TSH-receptor, sphingomyelinase and sphingomyelin-synthase. The results showed a modification of the thyroid structure and also the values of cAMP production after treatment with 10-7 M TSH for 1 hour were significantly lower than those obtained in Earth's gravity. The treatment with TSH induced relevant quanti-tative variations of TSH-receptor, sphingomyelinase and sphingomyelin-synthase, probably due to membrane microdomain structure modifications which in turn, as it occurs in vitro, influence the cellular response to TSH treatment.

Bioinorganic Activity of Technetium Radiopharmaceuticals.

ERIC Educational Resources Information Center

Pinkerton, Thomas C.; And Others

1985-01-01

Technetium radiopharmaceuticals are diagnostic imaging agents used in the field of nuclear medicine to visualize tissues, anatomical structures, and metabolic disorders. Bioavailability of technetium complexes, thyroid imaging, brain imaging, kidney imaging, imaging liver function, bone imaging, and heart imaging are the major areas discussed. (JN)

Iodine neutron capture therapy

NASA Astrophysics Data System (ADS)

Ahmed, Kazi Fariduddin

A new technique, Iodine Neutron Capture Therapy (INCT) is proposed to treat hyperthyroidism in people. Present thyroid therapies, surgical removal and 131I treatment, result in hypothyroidism and, for 131I, involve protracted treatment times and excessive whole-body radiation doses. The new technique involves using a low energy neutron beam to convert a fraction of the natural iodine stored in the thyroid to radioactive 128I, which has a 24-minute half-life and decays by emitting 2.12-MeV beta particles. The beta particles are absorbed in and damage some thyroid tissue cells and consequently reduce the production and release of thyroid hormones to the blood stream. Treatment times and whole-body radiation doses are thus reduced substantially. This dissertation addresses the first of the several steps needed to obtain medical profession acceptance and regulatory approval to implement this therapy. As with other such programs, initial feasibility is established by performing experiments on suitable small mammals. Laboratory rats were used and their thyroids were exposed to the beta particles coming from small encapsulated amounts of 128I. Masses of 89.0 mg reagent-grade elemental iodine crystals have been activated in the ISU AGN-201 reactor to provide 0.033 mBq of 128I. This activity delivers 0.2 Gy to the thyroid gland of 300-g male rats having fresh thyroid tissue masses of ˜20 mg. Larger iodine masses are used to provide greater doses. The activated iodine is encapsulated to form a thin (0.16 cm 2/mg) patch that is then applied directly to the surgically exposed thyroid of an anesthetized rat. Direct neutron irradiation of a rat's thyroid was not possible due to its small size. Direct in-vivo exposure of the thyroid of the rat to the emitted radiation from 128I is allowed to continue for 2.5 hours (6 half-lives). Pre- and post-exposure blood samples are taken to quantify thyroid hormone levels. The serum T4 concentration is measured by radioimmunoassay at different times after exposure as an indicator of thyroid function. Cell damage is assessed by postmortem histopathologic examination. The intent of this endeavor is to relate radiation dose, T4 concentration in the blood stream and cellular damage. This information will help better understand the dose response relationship of thyroid cells exposed to ionizing radiation.

Role of Virtual Touch Tissue Quantification in Hashimoto's Thyroiditis.

PubMed

Lin, Zi-Mei; Wang, Yao; Liu, Chun-Mei; Yan, Cao-Xin; Huang, Pin-Tong

2018-06-01

We investigated the role of the virtual touch tissue quantification (VTQ) technique in diagnosing Hashimoto's thyroiditis (HT) and in distinguishing various HT-related thyroid dysfunctions. Two hundred HT patients and 100 healthy volunteers (the control group) were enrolled. The diagnostic performance of VTQ in predicting HT was calculated as the area under the receiver operating characteristic curve (A Z ). The HT patients were further classified into three subgroups on the basis of serologic tests of thyroid function: hyperthyroidism, euthyroidism and hypothyroidism. Comparisons of shear wave velocity (SWV) between three subgroups were evaluated by analysis of variance. The mean SWV of the control group was significantly lower than that of the HT group (1.93 ± 0.33 m/s vs. 2.32 ± 0.49 m/s, p <0.001). A z was 0.734 with a cut-off value of 1.86 m/s for performance of SWV in distinguishing between HT and a healthy thyroid; the sensitivity and specificity were 82.5% and 50.0%, respectively. Mean SWV values in the three HT subgroups (hyperthyroidism [2.07 ± 0.37 cm/s] vs. euthyroidism [2.20 ± 0.40 cm/s] vs. hypothyroidism [2.49 ± 0.46 cm/s]) were significantly different (p <0.05). Our results suggest that VTQ is a promising technique for assessing HT and HT-related thyroid dysfunction. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

I-131 Radiation-Induced Myelosuppression in Differentiated Thyroid Cancer Therapy.

PubMed

Probst, Stephan; Abikhzer, Gad; Chaussé, Guillaume; Tamilia, Michael

2018-06-07

Radioactive iodine (RAI) treatment of differentiated thyroid cancer has been used in clinical practice for almost 60 years and is generally accepted to be a safe and efficacious treatment. Severe toxicity in the form of radiation pneumonitis, sometimes progressing to fibrosis, and bone marrow suppression are reported but remain rare. We present a case of severe myelosuppression requiring hospitalization and transfusion support in an otherwise well, young female patient who had received 175 mCi I-131 for low-volume micronodular lung disease one month prior, with a cumulative lifetime administered activity of 575 mCi. The most important risk factors for myelosuppression following RAI are the activity received, the amount of functioning thyroid tissue present, and the lifetime cumulative activity received.

[Presence of islands of fatty tissue in struma].

PubMed

Lax, S; Beham, A; Langsteger, W; Schmid, C

1988-04-01

We examined 929 surgically obtained thyroid glands derived from 791 female and 138 male patients and found intrathyroidal adipose tissue in 18 cases (1.94%). Only the thyroid glands of middle aged and older women (mean age 51 years) were affected, as well as in the case of follicular adenomas and nodular and diffuse hyperplasia. With respect to localization in the interstitial connective tissue, as well as between thyroid follicles, interstitial, parenchymatous and mixed types are proposed. In addition to sex and age there is a high correlation with obesity, which is suggestive of hormonal influences. Knowledge of the presence of intrathyroidal fat tissue is of interest to the pathologist since it may lead to erroneous interpretations of histological and cytological specimens of the thyroid gland. In conclusion, not one case of hypothyroidism was detected amongst the 18 cases investigated in this study.

Towards automated spectroscopic tissue classification in thyroid and parathyroid surgery.

PubMed

Schols, Rutger M; Alic, Lejla; Wieringa, Fokko P; Bouvy, Nicole D; Stassen, Laurents P S

2017-03-01

In (para-)thyroid surgery iatrogenic parathyroid injury should be prevented. To aid the surgeons' eye, a camera system enabling parathyroid-specific image enhancement would be useful. Hyperspectral camera technology might work, provided that the spectral signature of parathyroid tissue offers enough specific features to be reliably and automatically distinguished from surrounding tissues. As a first step to investigate this, we examined the feasibility of wide band diffuse reflectance spectroscopy (DRS) for automated spectroscopic tissue classification, using silicon (Si) and indium-gallium-arsenide (InGaAs) sensors. DRS (350-1830 nm) was performed during (para-)thyroid resections. From the acquired spectra 36 features at predefined wavelengths were extracted. The best features for classification of parathyroid from adipose or thyroid were assessed by binary logistic regression for Si- and InGaAs-sensor ranges. Classification performance was evaluated by leave-one-out cross-validation. In 19 patients 299 spectra were recorded (62 tissue sites: thyroid = 23, parathyroid = 21, adipose = 18). Classification accuracy of parathyroid-adipose was, respectively, 79% (Si), 82% (InGaAs) and 97% (Si/InGaAs combined). Parathyroid-thyroid classification accuracies were 80% (Si), 75% (InGaAs), 82% (Si/InGaAs combined). Si and InGaAs sensors are fairly accurate for automated spectroscopic classification of parathyroid, adipose and thyroid tissues. Combination of both sensor technologies improves accuracy. Follow-up research, aimed towards hyperspectral imaging seems justified. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

In Vivo Regulation of Human Skeletal Muscle Gene Expression by Thyroid Hormone

PubMed Central

Clément, Karine; Viguerie, Nathalie; Diehn, Maximilian; Alizadeh, Ash; Barbe, Pierre; Thalamas, Claire; Storey, John D.; Brown, Patrick O.; Barsh, Greg S.; Langin, Dominique

2002-01-01

Thyroid hormones are key regulators of metabolism that modulate transcription via nuclear receptors. Hyperthyroidism is associated with increased metabolic rate, protein breakdown, and weight loss. Although the molecular actions of thyroid hormones have been studied thoroughly, their pleiotropic effects are mediated by complex changes in expression of an unknown number of target genes. Here, we measured patterns of skeletal muscle gene expression in five healthy men treated for 14 days with 75 μg of triiodothyronine, using 24,000 cDNA element microarrays. To analyze the data, we used a new statistical method that identifies significant changes in expression and estimates the false discovery rate. The 381 up-regulated genes were involved in a wide range of cellular functions including transcriptional control, mRNA maturation, protein turnover, signal transduction, cellular trafficking, and energy metabolism. Only two genes were down-regulated. Most of the genes are novel targets of thyroid hormone. Cluster analysis of triiodothyronine-regulated gene expression among 19 different human tissues or cell lines revealed sets of coregulated genes that serve similar biologic functions. These results define molecular signatures that help to understand the physiology and pathophysiology of thyroid hormone action. [The list of transcripts corresponding to up-regulated and down-regulated genes is available as a web supplement at http://www.genome.org.] PMID:11827947

Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors.

PubMed

Arnaldi, L A T; Borra, R C; Maciel, R M B; Cerutti, J M

2005-03-01

To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tumors, we compared the gene expression profiles of three thyroid carcinoma cell lines, which represent major tumor subtypes of thyroid cancer and normal thyroid tissue. Using cDNA array methodology, we investigated the expression of 1807 open reading frame expressed sequence tags (ORESTES), selected from head and neck tumor libraries generated through the Brazilian Human Cancer Project-LICR/FAPESP. We found that 505 transcripts were differentially expressed in the thyroid carcinoma cell lines. Using a more stringent criterion, transcripts underexpressed or overexpressed more than fivefold in 1 of 3 or 3 of 3 carcinoma cell lines, a list of 55 ESTs were detected. Five candidate genes were further validated by quantitative polymerase chain reaction (qPCR) in an independent set of 52 thyroid tumors and 22 matched normal thyroid tissues. DCN was found underexpressed in a high percentage of the follicular thyroid adenomas, follicular thyroid carcinomas, and follicular variant of papillary thyroid carcinomas. DIO1 and DIO2 were underexpressed in nearly all papillary thyroid carcinomas. These genes not only could help to better define a tumor signature for thyroid tumors, but may, in part, also become useful as potential targets for thyroid tumor treatment.

mRNA-Seq Reveals Novel Molecular Mechanisms and a Robust Fingerprint in Graves' Disease

PubMed Central

Sachidanandam, Ravi; Morshed, Syed; Latif, Rauf; Shi, Ruijin; Davies, Terry F.

2014-01-01

Context: The immune response in autoimmune thyroid disease has been shown to occur primarily within the thyroid gland in which the most abundant antigens can be found. A variety of capture molecules are known to be expressed by thyroid epithelial cells and serve to attract and help retain an intrathyroidal immune infiltrate. Objective: To explore the entire repertoire of expressed genes in human thyroid tissue, we have deep sequenced the transcriptome (referred to as mRNA-Seq). Design and Patients: We applied mRNA-Seq to thyroid tissue from nine patients with Graves' disease subjected to total thyroidectomy and compared the data with 12 samples of normal thyroid tissue obtained from patients having a thyroid nodule removed. The expression for each gene was calculated from the sequencing data by taking the median of the coverage across the length of the gene. The expression levels were quantile normalized and a gene signature was derived from these. Results: On comparison of expression levels in tissues derived from Graves' patients and controls, there was clear evidence for overexpression of the antigen presentation pathway consisting of HLA and associated genes. We also found a robust disease signature and discovered active innate and adaptive immune signaling networks. Conclusions: These data reveal an active immune defense system in Graves' disease, which involves novel molecular mechanisms in its pathogenesis and development. PMID:24971664

Detection and a possible link between parvovirus B19 and thyroid cancer.

PubMed

Etemadi, Ashkan; Mostafaei, Shayan; Yari, Kheirollah; Ghasemi, Amir; Minaei Chenar, Hamzeh; Moghoofei, Mohsen

2017-06-01

Human parvovirus B19 (B19) is a small, non-enveloped virus and belongs to Parvoviridae family. B19 persists in many tissues such as thyroid tissue and even thyroid cancer. The main aim of this study was to determine the presence of B19, its association with increased inflammation in thyroid tissue, and thus its possible role in thyroid cancer progression. Studies have shown that virus replication in non-permissive tissue leads to overexpression of non-structural protein and results in upregulation of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha. A total of 36 paraffin-embedded thyroid specimens and serum were collected from patients and 12 samples were used as control. Various methods were employed, including polymerase chain reaction, real-time polymerase chain reaction, and enzyme-linked immunosorbent assay. The results have shown the presence of B19 DNA in 31 of 36 samples (86.11%). Almost in all samples, the levels of non-structural protein 1, nuclear factor kappa B, tumor necrosis factor alpha, and interleukin 6 were simultaneously high. The presence of parvovirus B19 has a significant positive correlation with nuclear factor kappa B, tumor necrosis factor alpha, and interleukin 6 levels. This study suggests that B19 infection may play an important role in tumorigenesis and thyroid cancer development via the inflammatory mechanisms.

DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

EPA Science Inventory

Criteria for distinguishing hyperplastic thyroid lesions from thyroid neoplasia in bony fishes have long been debated by scientists. Confusion exists because the thyroid tissue in most teleosts is unencapsulated, is occasionally found in ectopic sites, and is frequently predispos...

Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

PubMed Central

Gier, Belinda; Butler, Peter C.; Lai, Chi K.; Kirakossian, David; DeNicola, Matthew M.

2012-01-01

Background: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Methods: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Results: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. Conclusions: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted. PMID:22031513

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.

Orchestrating change: The thyroid hormones and GI-tract development in flatfish metamorphosis.

PubMed

Gomes, A S; Alves, R N; Rønnestad, I; Power, D M

2015-09-01

Metamorphosis in flatfish (Pleuronectiformes) is a late post-embryonic developmental event that prepares the organism for the larval-to-juvenile transition. Thyroid hormones (THs) play a central role in flatfish metamorphosis and the basic elements that constitute the thyroid axis in vertebrates are all present at this stage. The advantage of using flatfish to study the larval-to-juvenile transition is the profound change in external morphology that accompanies metamorphosis making it easy to track progression to climax. This important lifecycle transition is underpinned by molecular, cellular, structural and functional modifications of organs and tissues that prepare larvae for a successful transition to the adult habitat and lifestyle. Understanding the role of THs in the maturation of organs and tissues with diverse functions during metamorphosis is a major challenge. The change in diet that accompanies the transition from a pelagic larvae to a benthic juvenile in flatfish is associated with structural and functional modifications in the gastrointestinal tract (GI-tract). The present review will focus on the maturation of the GI-tract during metamorphosis giving particular attention to organogenesis of the stomach a TH triggered event. Gene transcripts and biological processes that are associated with GI-tract maturation during Atlantic halibut metamorphosis are identified. Gene ontology analysis reveals core biological functions and putative TH-responsive genes that underpin TH-driven metamorphosis of the GI-tract in Atlantic halibut. Deciphering the specific role remains a challenge. Recent advances in characterizing the molecular, structural and functional modifications that accompany the appearance of a functional stomach in Atlantic halibut are considered and future research challenges identified. Copyright © 2014 Elsevier Inc. All rights reserved.

Radioiodide induces apoptosis in human thyroid tissue in culture.

PubMed

Russo, Eleonora; Guerra, Anna; Marotta, Vincenzo; Faggiano, Antongiulio; Colao, Annamaria; Del Vecchio, Silvana; Tonacchera, Massimo; Vitale, Mario

2013-12-01

Radioiodide ((131)I) is routinely used for the treatment of toxic adenoma, Graves' disease, and for ablation of thyroid remnant after thyroidectomy in patients with thyroid cancer. The toxic effects of ionizing radiations on living cells can be mediated by a necrotic and/or apoptotic process. The involvement of apoptosis in radiation-induced cell death in the thyrocytes has been questioned. The knowledge of the mechanisms that underlie the thyrocyte death in response to radiations can help to achieve a successful treatment with the lowest (131)I dose. We developed a method to study the effects of (131)I in human thyroid tissue in culture, by which we demonstrated that (131)I induces thyroid cell apoptosis. Human thyroid tissues of about 1 mm(3) were cultured in vitro and cell viability was determined up to 3 weeks by the MTT assay. Radioiodide added to the culture medium was actively taken up by the tissues. The occurrence of apoptosis in the thyrocytes was assessed by measuring the production of a caspase-cleavage fragment of cytokeratin 18 (M30) by an enzyme-linked immunoassay. Neither variation of cell number nor spontaneous apoptosis was revealed after 1 week of culture. (131)I added to the culture medium induced a dose-dependent and a time-dependent generation of M30 fragment. The apoptotic process was confirmed by the generation of caspase-3 and PARP cleavage products. These results demonstrate that (131)I induces apoptosis in human thyrocytes. Human thyroid tissue cultures may be useful to investigate the cell death pathways induced by (131)I.

Analysis of orbital T cells in thyroid-associated ophthalmopathy

PubMed Central

Förster, G; Otto, E; Hansen, C; Ochs, K; Kahaly, G

1998-01-01

Thyroid-associated ophthalmopathy (TAO) has a major effect on the two compartments of the retro-orbital (RO) space, leading to enlargement of the extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue is a characteristic feature of TAO and there is current interest in whether these T cells are specifically and selectively reactive to RO tissue itself. We recently established 18 T cell lines (TCL) from RO adipose/connective tissue of six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T cells reactive to autologous RO tissue protein fractions. Here we report on the phenotype characteristics and cytokine gene expression profiles of these orbital TCL and on their immunoreactivity to the organ-specific thyroid antigens thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG). Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL), interferon-gamma (IFN-γ) (n = 10), tumour necrosis factor-beta (TNF-β) (n = 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-α (n = 12) and IL-10 (n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other 16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were predominantly CD4+ there were no significant relationships between TCL phenotype, cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare) occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine gene expression in all RO tissue-reactive TCL support the concept that TAO is a tissue-specific autoimmune disease, distinct immunologically from the thyroid, and involving both T cell and B cell autoimmune mechanisms in disease pathogenesis. PMID:9649211

Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice.

PubMed

Weiner, Juliane; Kranz, Mathias; Klöting, Nora; Kunath, Anne; Steinhoff, Karen; Rijntjes, Eddy; Köhrle, Josef; Zeisig, Vilia; Hankir, Mohammed; Gebhardt, Claudia; Deuther-Conrad, Winnie; Heiker, John T; Kralisch, Susan; Stumvoll, Michael; Blüher, Matthias; Sabri, Osama; Hesse, Swen; Brust, Peter; Tönjes, Anke; Krause, Kerstin

2016-12-12

The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white adipose tissue browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal 18 F-FDG PET/MRI was performed to determine the effects of hypo- and hyperthyroidism on BAT mass and BAT activity. Ex-vivo 14 C-acetate loading assay and assessment of thermogenic gene and protein expression permitted analysis of oxidative and thermogenic capacities of WAT and BAT of eu-, hyper and hypothyroid mice. 18 F-FDG PET/MRI revealed a lack of brown adipose tissue activity in hypothyroid mice, whereas hyperthyroid mice displayed increased BAT mass alongside enhanced 18 F-FDG uptake. In white adipose tissue of both, hyper- and hypothyroid mice, we found a significant induction of thermogenic genes together with multilocular adipocytes expressing UCP1. Taken together, these results suggest that both the hyperthyroid and hypothyroid state stimulate WAT thermogenesis most likely as a consequence of enhanced adrenergic signaling or compensation for impaired BAT function, respectively.

Flavonoid Rutin Increases Thyroid Iodide Uptake in Rats

PubMed Central

Lima Gonçalves, Carlos Frederico; de Souza dos Santos, Maria Carolina; Ginabreda, Maria Gloria; Soares Fortunato, Rodrigo; Pires de Carvalho, Denise; Freitas Ferreira, Andrea Claudia

2013-01-01

Thyroid iodide uptake through the sodium-iodide symporter (NIS) is not only an essential step for thyroid hormones biosynthesis, but also fundamental for the diagnosis and treatment of different thyroid diseases. However, part of patients with thyroid cancer is refractory to radioiodine therapy, due to reduced ability to uptake iodide, which greatly reduces the chances of survival. Therefore, compounds able to increase thyroid iodide uptake are of great interest. It has been shown that some flavonoids are able to increase iodide uptake and NIS expression in vitro, however, data in vivo are lacking. Flavonoids are polyhydroxyphenolic compounds, found in vegetables present in human diet, and have been shown not only to modulate NIS, but also thyroperoxidase (TPO), the key enzyme in thyroid hormones biosynthesis, besides having antiproliferative effect in thyroid cancer cell lines. Therefore, we aimed to evaluate the effect of some flavonoids on thyroid iodide uptake in Wistar rats in vivo. Among the flavonoids tested, rutin was the only one able to increase thyroid iodide uptake, so we decided to evaluate the effect of this flavonoid on some aspects of thyroid hormones synthesis and metabolism. Rutin led to a slight reduction of serum T4 and T3 without changes in serum thyrotropin (TSH), and significantly increased hypothalamic, pituitary and brown adipose tissue type 2 deiodinase and decreased liver type 1 deiodinase activities. Moreover, rutin treatment increased thyroid iodide uptake probably due to the increment of NIS expression, which might be secondary to increased response to TSH, since TSH receptor expression was increased. Thus, rutin might be useful as an adjuvant in radioiodine therapy, since this flavonoid increased thyroid iodide uptake without greatly affecting thyroid function. PMID:24023911

Expression of the membrane mucins MUC4 and MUC15, potential markers of malignancy and prognosis, in papillary thyroid carcinoma.

PubMed

Nam, Kee-Hyun; Noh, Tae-Woong; Chung, So-Hyang; Lee, So Hee; Lee, Mi Kyung; Hong, Soon Won; Chung, Woong Youn; Lee, Eun Jig; Park, Cheong Soo

2011-07-01

Papillary thyroid carcinoma (PTC) is the most frequent carcinoma of the thyroid gland and has a relatively good prognosis. However, it is important to identify PTC characteristics that indicate high risk for recurrence and metastasis. To date, overexpression of the membrane mucin, MUC1, has been investigated as a key molecular event in the pathogenesis of aggressive PTC. However, other membrane-associated mucins, matrix metalloproteinase-13 (MMP-13) and tissue inhibitor of metalloproteinase-13 (TIMP-3), have not been studied yet. The aim of this study was to evaluate the expression levels of MUC4, MUC15, MMP-13, and TIMP-3 and their prognostic significance in PTC. We analyzed MUC4, MUC15, MMP-13, and TIMP-3 expression in 10 PTC and 10 normal thyroid tissue samples using real-time reverse transcription-polymerase chain reaction. Tissue array blocks were obtained from 98 PTC cases. Tumor regions and nontumor regions were analyzed in tissue array blocks and immunohistochemistry studies were conducted using sectioned slides. Semiquantitative scores were correlated with clinicopathological factors of 98 PTC patients. MUC4- and MUC15-specific mRNA was increased by 78-fold and 4.75-fold, respectively, in PTC samples compared with normal thyroid tissues. MMP-13 and TIMP-3 gene expression levels were decreased by approximately 0.39-fold and 0.53-fold, respectively. By immunohistochemistry, MUC4 and MUC15 expression levels were increased in PTC samples compared with normal thyroid tissues (p < 0.001). MMP-13 and TIMP-3 expression levels were decreased in PTC samples compared with normal thyroid tissues (p < 0.001). High MUC4 scores were significantly correlated with small tumor size and papillary thyroid microcarcinoma subtype. High MUC15 scores were significantly correlated with age (≥45 years), distant metastasis, and multifocality. MUC4 and MUC15 were overexpressed in PTC, and high MUC15 expression was associated with high malignant potential. MUC15 may serve as a prognostic marker and potential novel therapeutic target in PTC.

Transcriptional activity of TGFβ1 and its receptors genes in thyroid gland.

PubMed

Kajdaniuk, Dariusz; Marek, Anna; Marek, Bogdan; Mazurek, Urszula; Fila-Daniłow, Anna; Foltyn, Wanda; Morawiec-Szymonik, Elżbieta; Siemińśka, Lucyna; Nowak, Mariusz; Głogowska-Szeląg, Joanna; Niedziołka-Zielonka, Danuta; Seemann, Michał; Kos-Kudła, Beata

2016-01-01

Determination of gene-candidates' profile expression responsible for fibrosis, immunosuppression, angiogenesis, and neoplasia processes in the pathogenesis of thyroid gland disease. Sixty-three patients underwent thyroidectomy: 27 with non-toxic nodular goitre (NG), 22 with toxic nodular goitre (TNG), six with papillary cancer (PTC), and eight with Graves' disease (GD). In thyroid tissues, transcriptional activity of TGFbeta1 and its receptors TGFbetaRI, TGFbetaRII, and TGFbetaRIII genes were assessed using RT-qPCR (Reverse Transcriptase Quantitative Polymerase Chain Reaction). Molecular analysis was performed in tissues derived from GD and from the tumour centre (PTC, NG, TNG) and from peripheral parts of the removed lobe without histopathological lesions (tissue control). Control tissue for analysis performed in GD was an unchanged tissue derived from peripheral parts of the removed lobe of patients surgically treated for a single benign tumour. Strict regulation observed among transcriptional activity of TGFb1 and their receptor TGFbetaRI-III genes in control tissues is disturbed in all pathological tissues - it is completely disturbed in PTC and GD, and partially in NG and TNG. Additionally, higher transcriptional activity of TGFb1 gene in PTC in comparison with benign tissues (NG, GD) and lower expression of mRNA TGFbRII (than in TNG, GD) and mRNA TGFbetaRIII than in all studied benign tissues (NG, TNG, GD) suggests a pathogenetic importance of this cytokine and its receptors in PTC development. In GD tissue, higher transcriptional activity of TGFbetaRII and TGFbetaRIII genes as compared to other pathological tissues was observed, indicating a participation of the receptors in the pathomechanism of autoimmune thyroid disease (AITD). TGFbeta1 blood concentrations do not reflect pathological processes taking place in thyroid gland. (Endokrynol Pol 2016; 67 (4): 375-382).

The significance of folic acid, tissue iron stores, and tissue viability in determining iron uptake from serum by thyroid tissue slices

PubMed Central

Buchanan, W. M.

1971-01-01

This paper describes an attempt to measure in vitro iron uptake from serum by human thyroid slices and to relate the uptake to tissue iron stores, folic acid status, and tissue viability. It is an extension of work previously reported (Buchanan, 1969). Thyroids were obtained from patients undergoing partial thyroidectomy for colloid goitre and serum from clinically normal healthy adults. The haemoglobin, serum iron, and folic acid levels of both thyroid and serum donors were measured and thyroids examined histologically for the presence of stainable iron. Viable and non-viable tissue slices were incubated in sera treated with radioactive iron so as to produce high and normal levels of transferrin saturation. Iron was taken up both from sera with normal and high transferrin saturation but the amount was, in almost all cases, greater from the more highly saturated. The uptake by non-viable tissue was appreciable but did not vary to any great extent from one serum to the next, and was attributed to simple diffusion of ionic iron into the tissue. There was, however, marked variation in uptake from different sera by viable tissue. It was concluded therefore that viability is a factor affecting the uptake. As the variation in uptake by viable tissue incubated in a single serum was significantly less than tissue incubated in a number of different sera it was further concluded that there was also a factor in the serum itself affecting iron uptake. The nature of the factor was not elucidated but neither folic acid nor levels of iron stores appeared to influence uptake because no correlation was found between iron uptake and iron stores or folic acid. Images PMID:5556118

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus.

PubMed

Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

2015-12-01

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients.

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus

PubMed Central

Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

2015-01-01

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. Objectives: The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. Patients and Methods: This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. Results: The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Conclusions: Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients. PMID:26756002

Mature cystic teratoma with high proportion of solid thyroid tissue: a controversial case with unusual imaging findings.

PubMed

Gil, Rui; Cunha, Teresa Margarida; Rolim, Ines

2017-07-01

We describe a case of a mature cystic teratoma of the ovary with high proportion of solid thyroid tissue (< 50% of the entire tumor) in a childbearing woman. The patient presented with non-specific abdominal bloating. Pelvic ultrasound and magnetic resonance imaging revealed a complex cystic-solid tumor confined to the left ovary with an anterior fat-containing locus compatible with mature cystic teratoma and a posterior predominantly solid component with low signal intensity on T2-weighted images that was histopatologically diagnosed as benign thyroid tissue. Thyroglobulin levels were in normal range. Although thyroid tissue is present in up to 20% of mature cystic teratomas, with exception of struma ovarii, it is not usually macroscopically nor radiologically identified. The differential diagnosis should include T2-hypointense adnexal lesions associated with mature cystic teratoma, malignant transformation of mature teratoma, and immature teratoma.

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

Cystinyl and pyroglutamyl-beta-naphthylamide hydrolyzing activities are modified coordinately between hypothalamus, liver and plasma depending on the thyroid status of adult male rats.

PubMed

Segarra, A B; Prieto, I; Martinez-Canamero, M; Vargas, F; De Gasparo, M; Vanderheyden, P; Zorad, S; Ramirez-Sanchez, M

2018-04-01

The hypothalamus determinates metabolic processes in liver through endocrine and autonomic control. Hypothalamic neuropeptides, such as thyrotropin releasing hormone or vasopressin, have been involved in liver metabolism. The thyroid status influences metabolic processes including liver metabolism in modulating those hypothalamic peptides whose functional status is regulated in part by aminopeptidase activities. In order to obtain data for a possible coordinated interaction between hypothalamus, plasma and liver, of some aminopeptidase activities that may partially reflect the hydrolysis of those peptides, pyroglutamyl- (pGluAP) and cystinyl- (CysAP) beta-naphthylamide hydrolyzing activities were determined fluorimetrically, both in their soluble and membrane-bound forms, in eu- hypo- and hyperthyroid adult male rats. Hyperthyroidism and hypothyroidism were induced with daily subcutaneous injections of tetraiodothyronine (300 μg/kg/day) or with 0.03% methimazole in drinking water for 6 weeks. Results demonstrated significant changes depending on the type of enzyme and the thyroid status. The most striking changes were observed for CysAP in liver where it was reduced in hypothyroidism and increased in hyperthyroidism. Significant intra- and inter-tissue correlations were observed. While there were positive inter-tissue correlations between liver, plasma and hypothalamus in eu-and hypothyroid rats, a negative correlation between hypothalamus and liver was observed in hyperthyroidism. These results suggest the influence of thyroid hormones and an interactive role for these activities in the control of liver metabolism. The present data also suggest a role for CysAP and pGluAP activities in liver function linked to their activities in hypothalamus.

Subclinical hypothyroidism in patients with non-alcoholic fatty liver disease at the background of carbohydrate metabolism disorders.

PubMed

Feisa, Snizhana V; Chopei, Ivan V

2018-01-01

Introduction: The prevalence of non-alcoholic fatty liver disease (NAFLD) is 25-30% in the general population and more than 75% among patients with carbohydrate metabolism disorders. One in six patients with NAFLD has concomitant subclinical hypothyroidism. The aim is to compare lipid and carbohydrate metabolism states in patients with NAFLD depending on the functional state of the thyroid gland. Materials and methods:215 patients with NAFLD and type 2 diabetes mellitus (T2-DM) or pre-diabetes (PD) were involved in study and devided into 6 groups according to the functional state of the thyroid gland. Results: In cases of adding subclinical hypothyroidism systolic and diastolic blood pressure are rising. In patients with overt hypothyroidism average HOMA-IR index is 29,98±1,05, which exceeds the corresponding figure in patients with concomitant subclinical hypothyroidism. In patients whose hypothyroidism has been compensated by levothyroxine, HOMA-IR index was reduced to 18,56±1,58, indicating a tendency to restore the sensitivity of peripheral tissues to insulin, on the assumption under the medicatedcorrection of thyroid functional status. Levels of common cholesterol and triglycerides were higher in cases of NAFLD with subclinical or overt hypothyroidism than in patients with NAFLD and normal thyroid function. Replacement therapy by levothyroxine leads to improving of lipid changes in patients with NAFLD and concomitant overt hypothyroidism: the levels of common cholesterol and triglycerides were reducing from 6,04±1,18 mmol/l and 3,96±1,34 mmol/l to 5,97±1,1 mmol/l and 3,45±1,13 mmol/l in accordance. Conclusions: Concomitant subclinical hypothyroidism in patients with NAFLD at the background of carbohydrate metabolism disorders leads to atherogenic dyslipidemia, increasing of blood atherogenicity. The index of lipid accumulated product (LAP) and the resistance of peripheral tissues to insulin also increases.

Iodine-131 dose-dependent gene expression: alterations in both normal and tumour thyroid tissues of post-Chernobyl thyroid cancers.

PubMed

Abend, M; Pfeiffer, R M; Ruf, C; Hatch, M; Bogdanova, T I; Tronko, M D; Hartmann, J; Meineke, V; Mabuchi, K; Brenner, A V

2013-10-15

A strong, consistent association between childhood irradiation and subsequent thyroid cancer provides an excellent model for studying radiation carcinogenesis. We evaluated gene expression in 63 paired RNA specimens from frozen normal and tumour thyroid tissues with individual iodine-131 (I-131) doses (0.008-8.6 Gy, no unirradiated controls) received from Chernobyl fallout during childhood (Ukrainian-American cohort). Approximately half of these randomly selected samples (32 tumour/normal tissue RNA specimens) were hybridised on 64 whole-genome microarrays (Agilent, 4 × 44 K). Associations between I-131 dose and gene expression were assessed separately in normal and tumour tissues using Kruskal-Wallis and linear trend tests. Of 155 genes significantly associated with I-131 after Bonferroni correction and with ≥2-fold increase per dose category, we selected 95 genes. On the remaining 31 RNA samples these genes were used for validation purposes using qRT-PCR. Expression of eight genes (ABCC3, C1orf9, C6orf62, FGFR1OP2, HEY2, NDOR1, STAT3, and UCP3) in normal tissue and six genes (ANKRD46, CD47, HNRNPH1, NDOR1, SCEL, and SERPINA1) in tumour tissue was significantly associated with I-131. PANTHER/DAVID pathway analyses demonstrated significant over-representation of genes coding for nucleic acid binding in normal and tumour tissues, and for p53, EGF, and FGF signalling pathways in tumour tissue. The multistep process of radiation carcinogenesis begins in histologically normal thyroid tissue and may involve dose-dependent gene expression changes.

Fluorescence lifetime of normal, benign, and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Brandao, Mariana; Iwakura, Ricardo; Basilio, Fagne; Haleplian, Kaique; Ito, Amando; de Freitas, Luiz Carlos Conti; Bachmann, Luciano

2015-06-01

Fine-needle aspiration cytology is the standard technique to diagnose thyroid pathologies. However, this method results in a high percentage of inconclusive and false negatives. The use of time-resolved fluorescence techniques to detect biochemical composition and tissue structure alterations could help to develop a portable, minimally invasive, and nondestructive method to assist during surgical procedures. This study aimed to use fluorescence lifetimes to differentiate healthy and benign tissues from malignant thyroid tissue. The thyroid tissue was excited at 298-300 nm and the fluorescence decay registered at 340 and 450 nm. We observed fluorescence lifetimes at 340 nm emission of 0.80±0.26 and 3.94±0.47 ns for healthy tissue; 0.90±0.24 and 4.05±0.46 ns for benign lesions; and 1.21±0.14 and 4.63±0.25 ns for malignant lesions. For 450 nm emissions, we obtain lifetimes of 0.25±0.18 and 3.99±0.39 ns for healthy tissue, 0.24±0.17 and 4.20±0.48 ns for benign lesions, 0.33±0.32 and 4.55±0.55 ns for malignant lesions. Employing analysis of variance, we differentiate malignant lesions from benign and healthy tissues. In addition, we use quadratic discriminant analysis to distinguish malignant from benign and healthy tissues with an accuracy of 76.1%, sensitivity of 74.7%, and specificity of 83.3%. These results indicate that time-resolved fluorescence can assist medical evaluation of thyroid pathologies during surgeries.

Influence of presence/absence of thyroid gland on the cutoff value for thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid carcinoma.

PubMed

Zhao, Huan; Wang, Yong; Wang, Min-Jie; Zhang, Zhi-Hui; Wang, Hai-Rui; Zhang, Bing; Guo, Hui-Qin

2017-04-28

Thyroglobulin measurement with fine-needle aspiration (Tg-FNA) is a sensitive method for detecting metastatic papillary thyroid carcinoma (PTC). However, the diagnostic threshold is not well established and the influence of the thyroid gland on the cutoff value is also controversial. In this study, patients were classified into two groups according to the presence or absence of thyroid tissue, to determine an appropriate cutoff value for clinical practice. Patients with a history of thyroid nodules or surgery for PTC and with enlarged cervical lymph nodes on an FNA examination were enrolled for Tg-FNA detection. One hundred ninety-six lymph nodes (189 patients) were included: 100 from preoperative patients, 49 from patients treated with partial thyroid ablation, and 47 from patients with total thyroid ablation. In 149 lymph nodes from patient with thyroids, the cutoff value for Tg-FNA was 55.99 ng/mL (sensitivity, 95.1%; specificity, 100%), whereas in 47 lymph nodes from patients without a thyroid, it was 9.71 ng/mL (sensitivity, 96.7%; specificity, 100%). Thus, the cutoff value for Tg-FNA was higher in patients with thyroids than in patients without thyroids. The cutoff value for Tg-FNA is influenced by residual thyroid tissue, and a higher cutoff value is recommended for patients with thyroids than for patients without thyroids.

Impairment and restoration of response to TSH in dog thyroid slices after treatment with phospholipase A and lubrol PX.

PubMed

Yamashita, K; Oka, H; Kaneko, T; Ogata, E

1976-01-01

Incubation of dog thyroid slices with phospholipase A (10-40 U/Ml) or Lubrol PX (0.08-0.4%) caused a diminution in the subsequent TSH effect on the tissue cyclic AMP level and glucose oxidation. The same treatment had no effect on the basal level of these parameters. When the phospholipase A or Lubrol PX-treated slices were rinsed intensively with a Krebs-Ringer bicarbonate buffer and then incubated at 37degreesC in the same buffer for a further 1 to 3 hours, responsiveness to TSH recovered progressively reaching almost completely that of the control slices. Again, these procedures were without any significant effect on the responsiveness of the control slices. The above results together with those reported previously suggest strongly that phospholipids are an essential component of the plasma membrane system by which TSH stimulates adenylate cyclase activity. In addition, these essential lipids in the membrane appear to be renewed rather efficiently in this tissue, thus securing the functional integrity of the thyroid in the face of various deleterious situations.

Tissue-specific regulation of malic enzyme by thyroid hormone in the neonatal rat.

PubMed

Sood, A; Schwartz, H L; Oppenheimer, J H

1996-05-15

Two recent studies have claimed that thyroid hormone administration accelerates malic enzyme gene expression in the neonatal brain in contrast to the well-documented lack of effect of triiodothyronine on malic enzyme gene expression in the adult brain. Since these observations conflict with earlier observations in our laboratory, we reinvestigated the effect of thyroid hormone status on the ontogeny of malic enzyme gene expression in the neonatal rat. Neither hypothyroidism nor hyperthyroidism influenced the ontogenesis of malic enzyme activity in neonatal brain whereas the patterns of gene expression and enzyme activity in liver were markedly affected. Our results suggest that tissue-specific factors in brain block thyroid hormone-induced gene expression by thyroid hormone.

Development of radiometric assays for quantification of enzyme activities of the key enzymes of thyroid hormones metabolism.

PubMed

Pavelka, S

2014-01-01

We newly elaborated and adapted several radiometric enzyme assays for the determination of activities of the key enzymes engaged in the biosynthesis (thyroid peroxidase, TPO) and metabolic transformations (conjugating enzymes and iodothyronine deiodinases, IDs) of thyroid hormones (THs) in the thyroid gland and in peripheral tissues, especially in white adipose tissue (WAT). We also elaborated novel, reliable radiometric methods for extremely sensitive determination of enzyme activities of IDs of types 1, 2 and 3 in microsomal fractions of different rat and human tissues, as well as in homogenates of cultured mammalian cells. The use of optimized TLC separation of radioactive products from the unconsumed substrates and film-less autoradiography of radiochromatograms, taking advantage of storage phosphor screens, enabled us to determine IDs enzyme activities as low as 10(-18) katals. In studies of the interaction of fluoxetine (Fluox) with the metabolism of THs, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT). Fluox is the most frequently used representative of a new group of non-tricyclic antidepressant drugs--selective serotonin re-uptake inhibitors. We used the elaborated assays for quantification the effects of Fluox and for the assessment of the degree of potential induction of rat liver ST and/or UDP-GT enzyme activities by Fluox alone or in combination with T(3). Furthermore, we studied possible changes in IDs activities in murine adipose tissue under the conditions that promoted either tissue hypertrophy (obesogenic treatment) or involution (caloric restriction), and in response to leptin, using our newly developed radiometric enzyme assays for IDs. Our results suggest that deiodinase D1 has a functional role in WAT, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue. Significant positive correlation between specific enzyme activity of D1 in WAT and plasma leptin levels was found. The newly developed and adapted radiometric enzyme assays proved to be very useful tools for studies of factors modulating THs metabolism, not only in model animals but also in clinical studies of human obesity.

Evaluation of the presence of Epstein-Barr virus (EBV) in Iranian patients with thyroid papillary carcinoma.

PubMed

Homayouni, Maryam; Mohammad Arabzadeh, Seyed Ali; Nili, Fatemeh; Razi, Farideh; Amoli, Mahsa Mohammad

2017-07-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. EBV is one of the most important viruses related to different types of malignancies. This study investigated the relationship between EBV and papillary thyroid carcinoma. In this study the presence of Epstein-Barr Nuclear Antigen 1 (EBNA1) gene in papillary thyroid carcinoma tissues were examined by nested-PCR method. Paraffin-embedded tissues (N=41) blocks of thyroid cancer were used. DNA was extracted from all samples and then samples were evaluated for the presence of EBV gene. In 41 samples, EBNA1 was detected in 65.8% of patients with papillary thyroid carcinoma which was significantly higher in younger ages. The significant presence of EBV genome in papillary thyroid carcinoma suggests that this virus may play a role in this cancer especially in younger ages. As a result, monitoring of patients with EBV latent infection for PTC can be very important. Copyright © 2017 Elsevier GmbH. All rights reserved.

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice.

PubMed

Rakov, Helena; Engels, Kathrin; Hönes, Georg Sebastian; Strucksberg, Karl-Heinz; Moeller, Lars Christian; Köhrle, Josef; Zwanziger, Denise; Führer, Dagmar

2016-01-01

Thyroid dysfunction is more common in the female population, however, the impact of sex on disease characteristics has rarely been addressed. Using a murine model, we asked whether sex has an influence on phenotypes, thyroid hormone status, and thyroid hormone tissue response in hyper- and hypothyroidism. Hypo- and hyperthyroidism were induced in 5-month-old female and male wildtype C57BL/6N mice, by LoI/MMI/ClO4 (-) or T4 i.p. treatment over 7 weeks, and control animals underwent sham treatment (N = 8 animals/sex/treatment). Animals were investigated for impact of sex on body weight, food and water intake, body temperature, heart rate, behaviour (locomotor activity, motor coordination, and strength), liver function, serum thyroid hormone status, and cellular TH effects on gene expression in brown adipose tissue, heart, and liver. Male and female mice showed significant differences in behavioural, functional, metabolic, biochemical, and molecular traits of hyper- and hypothyroidism. Hyperthyroidism resulted in increased locomotor activity in female mice but decreased muscle strength and motor coordination preferably in male animals. Hypothyroidism led to increased water intake in male but not female mice and significantly higher serum cholesterol in male mice. Natural sex differences in body temperature, body weight gain, food and water intake were preserved under hyperthyroid conditions. In contrast, natural sex differences in heart rate disappeared with TH excess and deprivation. The variations of hyper- or hypothyroid traits of male and female mice were not explained by classical T3/T4 serum state. TH serum concentrations were significantly increased in female mice under hyperthyroidism, but no sex differences were found under eu- or hypothyroid conditions. Interestingly, analysis of expression of TH target genes and TH transporters revealed little sex dependency in heart, while sex differences in target genes were present in liver and brown adipose tissue in line with altered functional and metabolic traits of hyper- and hypothyroidism. These data demonstrate that the phenotypes of hypo- and hyperthyroidism differ between male and female mice and indicate that sex is an important modifier of phenotypic manifestations.

Relative intranuclear magnesium and phosphorus contents in normal and tumor cells of the human thyroid gland as revealed by energy-dispersive X-ray microanalysis.

PubMed

Lukács, G L; Zs-Nagy, I; Steiber, J; Györi, F; Balázs, G

1996-01-01

Energy dispersive X-ray microanalysis was performed on altogether 42 surgically removed tissue specimens of 32 patients, which were taken either from intact thyroid parts or various histopathologically verified tumors of the thyroid gland. The tissue specimens were processed with the freeze-fracture-freeze-drying technique and then analyzed in the so-called bulk specimen form. The studies were carried out during the years 1980-81, when intranuclear monovalent ionic composition was studied in detail. From the retained total elemental peak list, it was possible to calculate retrospectively the relative intranuclear Mg and P contents. The data processed by nested (hierarchical) analysis of variance show that the intranuclear Mg content of the 5 diagnostic groups (normal thyroid tissue, thyroiditis, benign adenomas, differentiated carcinomas and undifferentiated thyroid tumors) increases significantly, in parallel with the increasing malignancy, but the P content remains unchanged. One can conclude that the elevated intranuclear Mg content in the tumors of high malignancy may be of diagnostic importance, and a warning signal for the therapeutic approaches based on Mg-supplementations.

THE CARDIOVASCULAR SYSTEM IN TYPE 2 DIABETES MELLITUS AND THYROID DISORDERS IN THE ABSENCE OF THYROID GLAND DYSFUNCTION.

PubMed

Ballyizek, M F; Ignat'eva Pa

The state of the cardiovascular system was studied in patients with type 2 diabetes mellitus and thyroid disorders in the absence of thyroid gland dysfunction. 76.9% of the 302 patients with DM2 had thyroid pathology; in 23,8% it was not previously diagnosed. We compared euthyroid patients with DM2 without thy'ropathies and with diffuse-nodular changes largely in the form of difuse- multinodular non-toxic goiter and autoinnnune thyroiditis (AIT). It was demonstrated that enhanced frequency of thyroid disorders is related to DM2 duration and vascular complications. The predominant thyroid pathology in DM2 was diffuse-multinodular non-toxic goiter followed by autoimnune thvroiditis. Nodular forms in AIT without DM2 are rare whereas multinodularformns in the patients with DM2 and AIT occur much more fequently. Node formation is related to such DM2 complications as diabetic nephropathy, angiopathy, and retinopathy. The study showed that the frequency of both non-specific clinical changes characteristic of thyroid dysfunction and of specific cardiological manifestations in euthyroid patients with DM2 and thyroid pathology signficantly increases especially in the presence of AIT and anti-thyreoperoxidase antibodies, regardless the form of thyropathy. It may be due to imimuno-inflammatory cross talk between thyroid and myocardial tissues. Patients with DM2 and diffuse-nodular changes in the thyroid gland more frequently presented with dif ferent forms of atrial fibrillation and high-grade ventricular extrasystole than patients with AIT or DM2 without thyropathies. It is concluded that euthyroid patients with DM2 need their thyroid function to be regularly monitored. The development of examination algorithm is an object of further studies.

Primary culture of human thyrocytes in Transwell bicameral chamber: thyrotropin promotes polarization and epithelial barrier function.

PubMed

Nilsson, M; Husmark, J; Nilsson, B; Tisell, L E; Ericson, L E

1996-10-01

Epithelial properties of thyrocytes are difficult to maintain in conventional cell culture systems. We used bicameral chambers (Transwell) in attempts to establish a functional epithelium of thyrocytes of human origin. Thyroid follicle segments were isolated by collagenase digestion of paradenomatous tissue obtained at surgery for follicular adenoma and of tissue from glands with Graves' disease. After careful separation from connective tissue and single cells by centrifugation, the follicles were plated at high density on the collagen-coated filter of the chambers and cultured in Eagle's essential medium (EMEM) containing 10% fetal calf serum (FCS) or Coon's modified Hams medium enriched with five or six factors (5H, 6H); the latter media contained 5% FCS without (5H) or with (6H) thyrotropin (TSH). The follicles were converted into a confluent cell layer, which had similar DNA content irrespective of type of medium, after 4-6 days. Cells grown in EMEM or 5H established a transepithelial electrical resistance (R) of 200-500 omega.cm2 and was impermeable to [3H]inulin, indicating the formation of epithelial junctions. Addition of 6H to confluent cells initially cultured in EMEM or 5H caused a further increase of R, maximally to 1500 omega.cm2, along with a rise of the transepithelial potential difference; 6H promoted the monolayer formation of cells, increased the number of apical microvilli and reinforced the junctional distribution of actin, cadherin and ZO-1; 6H also enhanced the polarized secretion of [3H]leucine-labeled thyroglobulin into the apical medium. Cells from Graves' thyroid tissue established an epithelium on the filter with similar characteristics to that of normal thyrocytes; some platings contained in addition large numbers of HLA-DR positive cells with a dendritic shape. HLA-DR expression was generally absent in EMEM-or 5H-grown thyrocytes, but appeared in limited areas of the cell layer after 6H and was expressed by all epithelial cells after interferon-gamma stimulation for 48 h. We conclude that human thyrocytes form a tight and polarized epithelium when cultured on permeable filters. The polarized structure and function of the cells are positively regulated by TSH. The culture system may be useful in studies addressing the role of the epithelial phenotype (cell polarity and tight barrier) in normal thyroid function as well as in pathological processes in the thyroid, such as autoimmunity, cell transformation and tumor progression.

Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti

PubMed Central

2013-01-01

Background Thyroid hormones regulate growth and development. However, the molecular mechanisms by which thyroid hormone regulates cell structural development are not fully understood. The mammalian cochlea is an intriguing system to examine these mechanisms, as cellular structure plays a key role in tissue development, and thyroid hormone is required for the maturation of the cochlea in the first postnatal week. Results In hypothyroid conditions, we found disruptions in sensory outer hair cell morphology and fewer microtubules in non-sensory supporting pillar cells. To test the functional consequences of these cytoskeletal defects on cell mechanics, we combined atomic force microscopy with live cell imaging. Hypothyroidism stiffened outer hair cells and supporting pillar cells, but pillar cells ultimately showed reduced cell stiffness, in part from a lack of microtubules. Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin. Conclusions These findings demonstrate that thyroid hormones may be involved in coordinating the processes that regulate cytoskeletal dynamics and suggest that manipulating thyroid hormone sensitivity might provide insight into the relationship between cytoskeletal formation and developing cell mechanical properties. PMID:23394545

Neuro-Modulation of Immuno-Endocrine Response Induced by Kaliotoxin of Androctonus Scorpion Venom.

PubMed

Ladjel-Mendil, Amina; Martin-Eauclaire, Marie-France; Laraba-Djebari, Fatima

2016-12-01

Kaliotoxin (KTX), a specific blocker of potassium channels, exerts various toxic effects due to its action on the central nervous system. Its use in experimental model could help the understanding of the cellular and molecular mechanisms involved in the neuropathological processes related to potassium channel dysfunctions. In this study, the ability of KTX to stimulate neuro-immuno-endocrine axis was investigated. As results, the intracerebroventricular injection of KTX leads to severe structural-functional alterations of both hypothalamus and thyroid. These alterations were characterized by a massive release of hormones' markers of thyroid function associated with damaged tissue which was infiltrated by inflammatory cell and an imbalanced redox status. Taken together, these data highlight that KTX is able to modulate the neuro-endocrine response after binding to its targets leading to the hypothalamus and the thyroid stimulation, probably by inflammatory response activation and the installation of oxidative stress in these organs. © 2016 Wiley Periodicals, Inc.

Early Hypoparathyroidism Reversibility with Treatment of Riedel's Thyroiditis.

PubMed

Stan, Marius N; Haglind, Elizabeth G; Drake, Matthew T

2015-09-01

Riedel's thyroiditis (RT) is a rare, fibroinflammatory condition which induces gradual thyroid gland destruction and adjacent soft-tissue fibrous infiltration. About one- seventh of RT cases are associated with hypoparathyroidism, necessitating long-term therapy for symptomatic hypocalcemia. The reversibility of the parathyroid hormone deficit has not been fully described. A 40-year-old woman with no prior history of thyroid disease presented with a six month history of progressive thyroid enlargement complicated by worsening dysphagia and positional dyspnea. Her past medical history was remarkable only for retroperitoneal fibrosis. Physical examination revealed a large, hard, non-mobile goiter. Thyroid indices while maintained on levothyroxine were normal, but marked asymptomatic hypocalcemia with an inappropriately normal parathyroid hormone level was noted. Thyroid imaging and fine needle aspiration were consistent with RT. Isthmectomy and subsequent serial corticosteroid and tamoxifen treatment led to rapid symptom improvement. Serum calcium and parathyroid hormone levels returned to the reference range within three months. We describe a case of RT in which hypoparathyroidism resolved after treatment targeted the mechanical compression and the fibroinflammatory milieu of the patient's thyroidal disease. RT can be associated with hypoparathyroidism that is clinically silent at presentation. Mechanical decompression of the goiter and immunomodulatory therapy can reverse the fibrosclerotic process and lead to rapid recovery of parathyroid gland function, as in this patient. However, in most cases hypoparathyroidism is persistent and requires continued treatment to prevent symptomatic hypocalcemia.

Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary-derived cell lines

PubMed Central

Godlewska, Marlena; Krasuska, Wanda

2018-01-01

Thyroid peroxidase (TPO) is an enzyme and autoantigen expressed in thyroid and breast tissues. Thyroid TPO undergoes a complex maturation process however, nothing is known about post-translational modifications of breast-expressed TPO. In this study, we have investigated the biochemical properties of TPO expressed in normal and cancerous human breast tissues, and the maturation process and antigenicity of TPO present in a panel of human breast tissue-derived cell lines. We found that the molecular weight of breast TPO was slightly lower than that of thyroid TPO due to decreased glycosylation and as suggest results of Western blot also shorter amino acid chain. Breast TPO exhibit enzymatic activity and isoelectric point comparable to that of thyroid TPO. The biochemical properties of TPO expressed in mammary cell lines and normal thyrocytes are similar regarding glycan content, molecular weight and isoelectric point. However, no peroxidase activity and dimer formation was detected in any of these cell lines since the majority of TPO protein was localized in the cytoplasmic compartment, and the TPO expression at the cell surface was too low to detect its enzymatic activity. Lactoperoxidase, a protein highly homologous to TPO expressed also in breast tissues, does not influence the obtained data. TPO expressed in the cell lines was recognized by a broad panel of TPO-specific antibodies. Although some differences in biochemical properties between thyroid and breast TPO were observed, they do not seem to be critical for the overall three-dimensional structure. This conclusion is supported by the fact that TPO expressed in breast tissues and cell lines reacts well with conformation-sensitive antibodies. Taking into account a close resemblance between both proteins, especially high antigenicity, future studies should investigate the potential immunotherapies directed against breast-expressed TPO and its specific epitopes. PMID:29513734

Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary-derived cell lines.

PubMed

Godlewska, Marlena; Krasuska, Wanda; Czarnocka, Barbara

2018-01-01

Thyroid peroxidase (TPO) is an enzyme and autoantigen expressed in thyroid and breast tissues. Thyroid TPO undergoes a complex maturation process however, nothing is known about post-translational modifications of breast-expressed TPO. In this study, we have investigated the biochemical properties of TPO expressed in normal and cancerous human breast tissues, and the maturation process and antigenicity of TPO present in a panel of human breast tissue-derived cell lines. We found that the molecular weight of breast TPO was slightly lower than that of thyroid TPO due to decreased glycosylation and as suggest results of Western blot also shorter amino acid chain. Breast TPO exhibit enzymatic activity and isoelectric point comparable to that of thyroid TPO. The biochemical properties of TPO expressed in mammary cell lines and normal thyrocytes are similar regarding glycan content, molecular weight and isoelectric point. However, no peroxidase activity and dimer formation was detected in any of these cell lines since the majority of TPO protein was localized in the cytoplasmic compartment, and the TPO expression at the cell surface was too low to detect its enzymatic activity. Lactoperoxidase, a protein highly homologous to TPO expressed also in breast tissues, does not influence the obtained data. TPO expressed in the cell lines was recognized by a broad panel of TPO-specific antibodies. Although some differences in biochemical properties between thyroid and breast TPO were observed, they do not seem to be critical for the overall three-dimensional structure. This conclusion is supported by the fact that TPO expressed in breast tissues and cell lines reacts well with conformation-sensitive antibodies. Taking into account a close resemblance between both proteins, especially high antigenicity, future studies should investigate the potential immunotherapies directed against breast-expressed TPO and its specific epitopes.

RAMAN spectroscopy imaging improves the diagnosis of papillary thyroid carcinoma

NASA Astrophysics Data System (ADS)

Rau, Julietta V.; Graziani, Valerio; Fosca, Marco; Taffon, Chiara; Rocchia, Massimiliano; Crucitti, Pierfilippo; Pozzilli, Paolo; Onetti Muda, Andrea; Caricato, Marco; Crescenzi, Anna

2016-10-01

Recent investigations strongly suggest that Raman spectroscopy (RS) can be used as a clinical tool in cancer diagnosis to improve diagnostic accuracy. In this study, we evaluated the efficiency of Raman imaging microscopy to discriminate between healthy and neoplastic thyroid tissue, by analyzing main variants of Papillary Thyroid Carcinoma (PTC), the most common type of thyroid cancer. We performed Raman imaging of large tissue areas (from 100 × 100 μm2 up to 1 × 1 mm2), collecting 38 maps containing about 9000 Raman spectra. Multivariate statistical methods, including Linear Discriminant Analysis (LDA), were applied to translate Raman spectra differences between healthy and PTC tissues into diagnostically useful information for a reliable tissue classification. Our study is the first demonstration of specific biochemical features of the PTC profile, characterized by significant presence of carotenoids with respect to the healthy tissue. Moreover, this is the first evidence of Raman spectra differentiation between classical and follicular variant of PTC, discriminated by LDA with high efficiency. The combined histological and Raman microscopy analyses allow clear-cut integration of morphological and biochemical observations, with dramatic improvement of efficiency and reliability in the differential diagnosis of neoplastic thyroid nodules, paving the way to integrative findings for tumorigenesis and novel therapeutic strategies.

Thyroid hormones and their effects: a new perspective.

PubMed

Hulbert, A J

2000-11-01

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3',5',3,5-L-tetraiodothyronine (T4), 3',5,3-L-triiodothyronine (T3), 3',5',3-L-triiodothyronine (rT3) and 3,5',-L-diiothyronine (3,5-T2). At physiological pH, dissociation of the phenolic -OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distrubtion throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones. (1) the nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroid-hormone-induced membrane rigidificataion. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellulara matrix. The effects of thyroid hormones are reviewed and appear to b combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re-examination of data from th early 1960s supports a membrane action. Findings from receptor 'knockout' mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as 'vitamone'-like molecules than traditional hormonal messengers.

BRAIN, LIVER AND THYROID BIOMARKERS REFLECT ENHANCED SENSITIVITY OF THE DEVELOPING RAT TO THYROID HORMONE DEPLETION.

EPA Science Inventory

Many developmental events are regulated at least in part by thyroid hormones. It was hypothesized that tissue biomarkers of thyroid status would be more accurate predictors of neurotoxicity than serum biomarkers in rats treated with the goitrogen propylthiouracil (PTU). Over seve...

An Adult Mouse Thyroid Side Population Cell Line that Exhibits Enriched Epithelial–Mesenchymal Transition

PubMed Central

Murata, Tsubasa; Iwadate, Manabu; Takizawa, Yoshinori; Miyakoshi, Masaaki; Hayase, Suguru; Yang, Wenjing; Cai, Yan; Yokoyama, Shigetoshi; Nagashima, Kunio; Wakabayashi, Yoshiyuki; Zhu, Jun

2017-01-01

Background: Studies of thyroid stem/progenitor cells have been hampered due to the small organ size and lack of tissue, which limits the yield of these cells. A continuous source that allows the study and characterization of thyroid stem/progenitor cells is desired to push the field forward. Method: A cell line was established from Hoechst-resistant side population cells derived from mouse thyroid that were previously shown to contain stem/progenitor-like cells. Characterization of these cells were carried out by using in vitro two- and three-dimensional cultures and in vivo reconstitution of mice after orthotopic or intravenous injection, in conjunction with quantitative reverse transcription polymerase chain reaction, Western blotting, immunohisto(cyto)chemistry/immunofluorescence, and RNA seq analysis. Results: These cells were named SPTL (side population cell-derived thyroid cell line). Under low serum culturing conditions, SPTL cells expressed the thyroid differentiation marker NKX2-1, a transcription factor critical for thyroid differentiation and function, while no expression of other thyroid differentiation marker genes were observed. SPTL cells formed follicle-like structures in Matrigel® cultures, which did not express thyroid differentiation marker genes. In mouse models of orthotopic and intravenous injection, the latter following partial thyroidectomy, a few SPTL cells were found in part of the follicles, most of which expressed NKX2-1. SPTL cells highly express genes involved in epithelial–mesenchymal transition, as demonstrated by RNA seq analysis, and exhibit a gene-expression pattern similar to anaplastic thyroid carcinoma. Conclusion: These results demonstrate that SPTL cells have the capacity to differentiate into thyroid to a limited degree. SPTL cells may provide an excellent tool to study stem cells, including cancer stem cells of the thyroid. PMID:28125936

The continuing importance of thyroid scintigraphy in the era of high-resolution ultrasound.

PubMed

Meller, J; Becker, W

2002-08-01

At the molecular level, the uptake of radioiodine and pertechnetate is proportional to the expression of the thyroidal sodium/iodine symporter (NIS). Qualitative and quantitative scintigraphic evaluation of the thyroid is performed with a gamma camera fitted with an on-line computer system and enables determination of the iodine uptake or the technetium uptake (TCTU) as an iodine clearance equivalent. Despite new molecular genetic insights into congenital hypothyroidism, the iodine-123 or pertechnetate scan remains the most accurate test for the detection of ectopic thyroid tissue. Following the identification of specific mutations of the genes coding for the NIS, thyroid peroxidase and pendrin, the discharge test has lost its role in establishing the diagnosis of inherited dyshormonogenesis, but it is still of value in the assessment of defect severity. In PDS mutations the test can be used to establish the diagnosis of syndromic disease. Quantitative pertechnetate scintigraphy is the most sensitive and specific technique for the diagnosis and quantification of thyroid autonomy. The method has proved to be valuable in risk stratification of spontaneous or iodine-induced hyperthyroidism, in the estimation of the target volume prior to radioiodine therapy and in the evaluation of therapeutic success after definitive treatment. In iodine deficiency areas the thyroid scan remains indispensable for the functional characterisation of a thyroid nodule and is still a first-line diagnostic procedure in cases of suspected thyroid malignancy. This is especially of importance in patients with Graves' disease, among whom a relatively high prevalence of cancer has been found in cold thyroid nodules. While determination of the TCTU is without any value in the differentiation between autoimmune thyroiditis and Graves' disease in most cases, it is of substantial importance in the differentiation between hyperthyroid autoimmune thyroiditis and Graves' disease.

Accounting for tissue heterogeneity in infrared spectroscopic imaging for accurate diagnosis of thyroid carcinoma subtypes.

PubMed

Martinez-Marin, David; Sreedhar, Hari; Varma, Vishal K; Eloy, Catarina; Sobrinho-Simões, Manuel; Kajdacsy-Balla, André; Walsh, Michael J

2017-07-01

Fourier transform infrared (FT-IR) microscopy was used to image tissue samples from twenty patients diagnosed with thyroid carcinoma. The spectral data were then used to differentiate between follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma using principle component analysis coupled with linear discriminant analysis and a Naïve Bayesian classifier operating on a set of computed spectral metrics. Classification of patients' disease type was accomplished by using average spectra from a wide region containing follicular cells, colloid, and fibrosis; however, classification of disease state at the pixel level was only possible when the extracted spectra were limited to follicular epithelial cells in the samples, excluding the relatively uninformative areas of fibrosis. The results demonstrate the potential of FT-IR microscopy as a tool to assist in the difficult diagnosis of these subtypes of thyroid cancer, and also highlights the importance of selectively and separately analyzing spectral information from different features of a tissue of interest.

NFE2-Related Transcription Factor 2 Coordinates Antioxidant Defense with Thyroglobulin Production and Iodination in the Thyroid Gland.

PubMed

Ziros, Panos G; Habeos, Ioannis G; Chartoumpekis, Dionysios V; Ntalampyra, Eleni; Somm, Emmanuel; Renaud, Cédric O; Bongiovanni, Massimo; Trougakos, Ioannis P; Yamamoto, Masayuki; Kensler, Thomas W; Santisteban, Pilar; Carrasco, Nancy; Ris-Stalpers, Carrie; Amendola, Elena; Liao, Xiao-Hui; Rossich, Luciano; Thomasz, Lisa; Juvenal, Guillermo J; Refetoff, Samuel; Sykiotis, Gerasimos P

2018-06-01

The thyroid gland has a special relationship with oxidative stress. While generation of oxidative substances is part of normal iodide metabolism during thyroid hormone synthesis, the gland must also defend itself against excessive oxidation in order to maintain normal function. Antioxidant and detoxification enzymes aid thyroid cells to maintain homeostasis by ameliorating oxidative insults, including during exposure to excess iodide, but the factors that coordinate their expression with the cellular redox status are not known. The antioxidant response system comprising the ubiquitously expressed NFE2-related transcription factor 2 (Nrf2) and its redox-sensitive cytoplasmic inhibitor Kelch-like ECH-associated protein 1 (Keap1) defends tissues against oxidative stress, thereby protecting against pathologies that relate to DNA, protein, and/or lipid oxidative damage. Thus, it was hypothesized that Nrf2 should also have important roles in maintaining thyroid homeostasis. Ubiquitous and thyroid-specific male C57BL6J Nrf2 knockout (Nrf2-KO) mice were studied. Plasma and thyroids were harvested for evaluation of thyroid function tests by radioimmunoassays and of gene and protein expression by real-time polymerase chain reaction and immunoblotting, respectively. Nrf2-KO and Keap1-KO clones of the PCCL3 rat thyroid follicular cell line were generated using CRISPR/Cas9 technology and were used for gene and protein expression studies. Software-predicted Nrf2 binding sites on the thyroglobulin enhancer were validated by site-directed in vitro mutagenesis and chromatin immunoprecipitation. The study shows that Nrf2 mediates antioxidant transcriptional responses in thyroid cells and protects the thyroid from oxidation induced by iodide overload. Surprisingly, it was also found that Nrf2 has a dramatic impact on both the basal abundance and the thyrotropin-inducible intrathyroidal abundance of thyroglobulin (Tg), the precursor protein of thyroid hormones. This effect is mediated by cell-autonomous regulation of Tg gene expression by Nrf2 via its direct binding to two evolutionarily conserved antioxidant response elements in an upstream enhancer. Yet, despite upregulating Tg levels, Nrf2 limits Tg iodination both under basal conditions and in response to excess iodide. Nrf2 exerts pleiotropic roles in the thyroid gland to couple cell stress defense mechanisms to iodide metabolism and the thyroid hormone synthesis machinery, both under basal conditions and in response to excess iodide.

Optical biopsy of head and neck cancer using hyperspectral imaging and convolutional neural networks

NASA Astrophysics Data System (ADS)

Halicek, Martin; Little, James V.; Wang, Xu; Patel, Mihir; Griffith, Christopher C.; El-Deiry, Mark W.; Chen, Amy Y.; Fei, Baowei

2018-02-01

Successful outcomes of surgical cancer resection necessitate negative, cancer-free surgical margins. Currently, tissue samples are sent to pathology for diagnostic confirmation. Hyperspectral imaging (HSI) is an emerging, non-contact optical imaging technique. A reliable optical method could serve to diagnose and biopsy specimens in real-time. Using convolutional neural networks (CNNs) as a tissue classifier, we developed a method to use HSI to perform an optical biopsy of ex-vivo surgical specimens, collected from 21 patients undergoing surgical cancer resection. Training and testing on samples from different patients, the CNN can distinguish squamous cell carcinoma (SCCa) from normal aerodigestive tract tissues with an area under the curve (AUC) of 0.82, 81% accuracy, 81% sensitivity, and 80% specificity. Additionally, normal oral tissues can be sub-classified into epithelium, muscle, and glandular mucosa using a decision tree method, with an average AUC of 0.94, 90% accuracy, 93% sensitivity, and 89% specificity. After separately training on thyroid tissue, the CNN differentiates between thyroid carcinoma and normal thyroid with an AUC of 0.95, 92% accuracy, 92% sensitivity, and 92% specificity. Moreover, the CNN can discriminate medullary thyroid carcinoma from benign multi-nodular goiter (MNG) with an AUC of 0.93, 87% accuracy, 88% sensitivity, and 85% specificity. Classical-type papillary thyroid carcinoma is differentiated from benign MNG with an AUC of 0.91, 86% accuracy, 86% sensitivity, and 86% specificity. Our preliminary results demonstrate that an HSI-based optical biopsy method using CNNs can provide multi-category diagnostic information for normal head-and-neck tissue, SCCa, and thyroid carcinomas. More patient data are needed in order to fully investigate the proposed technique to establish reliability and generalizability of the work.

Imaging of the thyroid in benign and malignant disease.

PubMed

Intenzo, Charles M; Dam, Hung Q; Manzone, Timothy A; Kim, Sung M

2012-01-01

The thyroid gland was one of the first organs imaged in nuclear medicine, beginning in the 1940s. Thyroid scintigraphy is based on a specific phase or prelude to thyroid hormone synthesis, namely trapping of iodide or iodide analogues (ie, Tc99m pertechnetate), and in the case of radioactive iodine, eventual incorporation into thyroid hormone synthesis within the thyroid follicle. Moreover, thyroid scintigraphy is a reflection of the functional state of the gland, as well as the physiological state of any structure (ie, nodule) within the gland. Scintigraphy, therefore, provides information that anatomical imaging (ie, ultrasound, computed tomography [CT], magnetic resonance imaging) lacks. Thyroid scintigraphy plays an essential role in the management of patients with benign or malignant thyroid disease. In the former, the structure or architecture of the gland is best demonstrated by anatomical or cross-sectional imaging, such as ultrasound, CT, or even magnetic resonance imaging. The role of scintigraphy, however, is to display the functional state of the thyroid gland or that of a clinically palpable nodule within the gland. Such information is most useful in (1) patients with thyrotoxicosis, and (2) those patients whose thyroid nodules would not require tissue sampling if their nodules are hyperfunctioning. In neoplastic thyroid disease, thyroid scintigraphy is often standard of care for postthyroidectomy remnant evaluation and in subsequent thyroid cancer surveillance. Planar radioiodine imaging, in the form of the whole-body scan (WBS) and posttherapy scan (PTS), is a fundamental tool in differentiated thyroid cancer management. Continued controversy remains over the utility of WBS in a variety of patient risk groups and clinical scenarios. Proponents on both sides of the arguments compare WBS with PTS, thyroglobulin, and other imaging modalities with differing results. The paucity of large, randomized, prospective studies results in dependence on consensus expert opinion and retrospective analysis with inherent bias. With a growing trend not to ablate low-risk patients, so that a PTS cannot be performed, some thyroid carcinoma patients may never have radioiodine imaging. In routine clinical practice, however, imaging plays a critical role in patient management both before and after treatment. Moreover, as evidenced by the robust flow of publications concerning WBS and PTS, planar imaging of thyroid carcinoma remains a topic of great interest in this modern age of rapidly advancing cross sectional and hybrid imaging with single-photon emission computed tomography, single-photon emission computed tomography/CT, and positron emission tomography/CT. Copyright © 2012. Published by Elsevier Inc.

The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications

PubMed Central

Ravera, Silvia; Reyna-Neyra, Andrea; Ferrandino, Giuseppe; Amzel, L. Mario; Carrasco, Nancy

2017-01-01

Active iodide (I−) transport in both the thyroid and some extrathyroidal tissues is mediated by the N a+/I− symporter (NIS). In the thyroid, NIS-mediated I− uptake plays a pivotal role in thyroid hormone (TH) biosynthesis. THs are key during embryonic and postembryonic development and critical for cell metabolism at all stages of life. The molecular characterization of NIS in 1996 and the use of radioactive I− isotopes have led to significan advances in the diagnosis and treatment of thyroid cancer and provide the molecular basis for studies aimed at extending the use of radioiodide treatment in extrathyroidal malignancies. This review focuses on the most recent finding on I− homeostasis and I− transport deficiency-causin NIS mutations, as well as current knowledge of the structure/function properties of NIS and NIS regulatory mechanisms. We also discuss employing NIS as a reporter gene using viral vectors and stem cells in imaging, diagnostic, and therapeutic procedures. PMID:28192058

Functional cystic thyroid adenoma in a cat.

PubMed

Hofmeister, E; Kippenes, H; Mealey, K L; Cantor, G H; Löhr, C V

2001-07-15

A 9-year-old cat with hyperthyroidism was referred for radioactive iodine treatment. The cat also had a ventral cervical mass that the owners reported had been present for several years and had increased in size during the past few weeks. On physical examination, the mass was found to have caused lateral displacement of the trachea, esophagus, jugular vein, and common carotid artery. The mass was aspirated and was determined to be cystic in nature. Concentrations of thyroid hormones in the cystic fluid were similar to serum concentrations, and nuclear scintigraphy revealed thyroactive tissue lining the cyst wall. Magnetic resonance imaging suggested that the cyst originated from the right lobe of the thyroid gland. The cat was treated with sodium iodide I 131 but died 4 days later, presumably as a result of aspiration of gastric or esophageal contents. A necropsy was not performed, but histologic examination of a biopsy specimen of the mass indicated that it was a cystic thyroid adenoma.

Recurrent High-Flow Arterio-Venous Malformation of the Thyroid Gland.

PubMed

Borchert, D H; Massmann, A; Kim, Y J; Bader, C A; Wolf, G; Eisele, R; Minko, P; Bücker, A; Glanemann, M

2015-09-01

Vascular malformations and hemangiomas of the thyroid gland are rare disorders. The first case of a patient with recurrent high-flow arterio-venous malformation of the right thyroid gland involving the right endolarynx is presented. In June 2013, a 42-year-old female patient presented to the surgical department with recurrent hoarseness and a soft, vibrating mass on the right side of her neck. In 1993, she underwent right subtotal hemithyroidectomy with embolization on the day before surgery for a high-flow arterio-venous malformation of the thyroid gland. Diagnostic work-up in 2013 demonstrated a complex recurrent high-flow arterio-venous malformation on the right side of her neck involving the endolarynx. Full function of the right vocal fold could not be ascertained. The lesion was embolized again and excised the following day. Intraoperative gross bleeding and scar tissue prevented visualization and monitoring of the recurrent laryngeal nerve. Gross bleeding was also noted on hemithyroidectomy after embolization in 1993. No therapy was needed for the endolaryngeal part of the lesion. Histology showed large arterio-venous malformations with thyroid tissue. She remains well without signs of recurrence 18 month later but with a definitive voice handicap. This is the first report of a recurrent high-flow arterio-venous malformation originally developing from the right thyroid gland involving the right endolarynx. Counseling, diagnostic, and therapeutic work-up of the patient was possible only with an interdisciplinary team. The endolaryngeal part of the hemangioma dried out after embolization and completion hemithyroidectomy. Her hoarseness has greatly improved but a definitive voice handicap remains. High-flow arterio-venous malformations of the thyroid gland are a rare disease, and recurrent lesions have not been reported. Interdisciplinary management of these patients is mandatory due to the complex nature of the underlying pathology. Recurrence might develop after long free intervals.

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.

Partial thyrocyte-specific Gαs deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.

PubMed

Patyra, Konrad; Jaeschke, Holger; Löf, Christoffer; Jännäri, Meeri; Ruohonen, Suvi T; Undeutsch, Henriette; Khalil, Moosa; Kero, Andreina; Poutanen, Matti; Toppari, Jorma; Chen, Min; Weinstein, Lee S; Paschke, Ralf; Kero, Jukka

2018-05-25

Thyroid function is controlled by thyroid-stimulating hormone (TSH), which binds to its G protein-coupled receptor [thyroid-stimulating hormone receptor (TSHR)] on thyrocytes. TSHR can potentially couple to all G protein families, but it mainly activates the G s - and G q/11 -mediated signaling cascades. To date, there is a knowledge gap concerning the role of the individual G protein cascades in thyroid pathophysiology. Here, we demonstrate that the thyrocyte-specific deletion of G s -protein α subunit (Gα s ) in adult mice [tamoxifen-inducible G s protein α subunit deficient (iTGα s KO) mice] rapidly impairs thyrocyte function and leads to hypothyroidism. Consequently, iTGα s KO mice show reduced food intake and activity. However, body weight and the amount of white adipose tissue were decreased only in male iTGα s KO mice. Unexpectedly, hyperplastic follicles and papillary thyroid cancer-like tumor lesions with increased proliferation and slightly increased phospho-ERK1/2 staining were found in iTGα s KO mice at an older age. These tumors developed from nonrecombined thyrocytes still expressing Gα s in the presence of highly elevated serum TSH. In summary, we report that partial thyrocyte-specific Gα s deletion leads to hypothyroidism but also to tumor development in thyrocytes with remaining Gα s expression. Thus, these mice are a novel model to elucidate the pathophysiological consequences of hypothyroidism and TSHR/G s /cAMP-mediated tumorigenesis.-Patyra, K., Jaeschke, H., Löf, C., Jännäri, M., Ruohonen, S. T., Undeutsch, H., Khalil, M., Kero, A., Poutanen, M., Toppari, J., Chen, M., Weinstein, L. S., Paschke, R., Kero, J. Partial thyrocyte-specific Gα s deficiency leads to rapid-onset hypothyroidism, hyperplasia, and papillary thyroid carcinoma-like lesions in mice.

The role of thyroid hormone signaling in the prevention of digestive system cancers.

PubMed

Brown, Adam R; Simmen, Rosalia C M; Simmen, Frank A

2013-08-06

Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVβ3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVβ3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals.

The Role of Thyroid Hormone Signaling in the Prevention of Digestive System Cancers

PubMed Central

Brown, Adam R.; Simmen, Rosalia C. M.; Simmen, Frank A.

2013-01-01

Thyroid hormones play a critical role in the growth and development of the alimentary tract in vertebrates. Their effects are mediated by nuclear receptors as well as the cell surface receptor integrin αVβ3. Systemic thyroid hormone levels are controlled via activation and deactivation by iodothyronine deiodinases in the liver and other tissues. Given that thyroid hormone signaling has been characterized as a major effector of digestive system growth and homeostasis, numerous investigations have examined its role in the occurrence and progression of cancers in various tissues of this organ system. The present review summarizes current findings regarding the effects of thyroid hormone signaling on cancers of the esophagus, stomach, liver, pancreas, and colon. Particular attention is given to the roles of different thyroid hormone receptor isoforms, the novel integrin αVβ3 receptor, and thyroid hormone-related nutrients as possible protective agents and therapeutic targets. Future investigations geared towards a better understanding of thyroid hormone signaling in digestive system cancers may provide preventive or therapeutic strategies to diminish risk, improve outcome and avert recurrence in afflicted individuals. PMID:23924944

Transoral robotic thyroid surgery

PubMed Central

Clark, James H.; Kim, Hoon Yub

2015-01-01

There is currently significant demand for minimally invasive thyroid surgery; however the majority of proposed surgical approaches necessitate a compromise between minimal tissue dissection with a visible cervical scar or extensive tissue dissection with a remote, hidden scar. The development of transoral endoscopic thyroid surgery however provides an approach which is truly minimally invasive, as it conceals the incision within the oral cavity without significantly increasing the amount of required dissection. The transoral endoscopic approach however presents multiple technical challenges, which could be overcome with the incorporation of a robotic operating system. This manuscript summarizes the literature on the feasibility and current clinical experience with transoral robotic thyroid surgery. PMID:26425456

[Thyroid proteins in endemic goitre and their relationship to the intrathyroidal thyroid hormone concentration].

PubMed

Platzer, S; Groebner, P; Hausen, A; Obendorf, L; Riccabona, G

1980-02-01

According to several reports we suspected that the pathogenesis of endemic goitre cannot be explained by iodine deficiency only, but that other--partially endogenous--goitrogenic factors must be present. We therefore studied 16 cases of "euthyroid" endemic goitre from the endemic goitre area of the province of Bolzano in Italy. After fractionation of tissue homogenates, T 4 and T 3 were measured by RIA and the I concentration was also termined. Thyroglobulin and its fractions were measured by ultracentrifuge procedures after assessment of the total protein concentration. Evaluation of the present results suggests that an insufficient synthesis of thyroglobulin in the examined goitres induces an inadequate adaptation of the organism to iodine deficiency, which, in turn, decreases the thyroid hormone concentration in thyroid tissue and enhances goitrogenesis. Considering the normal iodine content of the examined tissues, there obviously seems to be two intrathyroidal iodine pools, one of which supplies the body with thyroid hormones under pituitary stimulation even though its thyroglobulin pool is reduced, while a significant amount of the thyroidal iodine pool is bound in metabolically inert protein molecules and therefore increases the goitrogenic effect of iodine deficiency.

Effects of chlorpyrifos on in vitro sex steroid production and thyroid follicular development in adult and larval Lake Sturgeon, Acipenser fulvescens.

PubMed

Brandt, Catherine; Burnett, Duncan C; Arcinas, Liane; Palace, Vince; Gary Anderson, W

2015-08-01

Chlorpyrifos is a widely used organophosphate pesticide that has previously been shown to enter waterways in biologically relevant concentrations and has the potential to disrupt both thyroid hormone and sex steroid biosynthesis in vertebrates. Because gonadal maturation and larval development in Lake Sturgeon, Acipenser fulvescens, potentially coincide with the application of chlorpyrifos we examined the effects of chlorpyrifos on both thyroid follicular development in larval Lake Sturgeon, and sex hormone synthesis in adult Lake Sturgeon. For the first time, the present study reports steroidogenesis from testicular and ovarian tissue in Lake Sturgeon using an established in vitro bioassay. Furthermore, incubating gonad tissue with 5, 500 or 2000ngmL(-1) chlorpyrifos revealed an inhibitory effect on testosterone synthesis in both testicular (control, 40.29pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 21.84pgmg(-1) tissue wet weight(-1)h(-1)) and ovarian (control, 33.83pgmg(-1) tissue wet weight(-1)h(-1) compared to experimental, 15.19pgmg(-1) tissue wet weight(-1)h(-1)) tissue. In a second series of experiments, larval Lake Sturgeon were exposed to equivalent concentrations of chlorpyrifos as above for 10days (d) between hatch and the onset of exogenous feeding. Larvae from each treatment group were raised until 67days post hatch (dph) and growth rates were compared alongside key indicators of thyroid follicle growth. Chlorpyrifos treatment had no effect on the measured indicators of thyroid follicular development. Copyright © 2015 Elsevier Ltd. All rights reserved.

PRESENCE AND BIOSYNTHESIS OF THYROID HORMONES IN A TUNICATE, CIONA INTESTINALIS (in French)

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

Roche, L.J.; Salvatore, G.; Rametta, G.

1962-09-10

A tunicate, Ciona intestinalis L., binds very actively I/sup 131/-ions. The labeled iodine is preferentially located (75%) in the external layer of the tunic. The iodine metabolism is there chiefly oriented toward the biosynthesis of iodothyronines (thyroid hormones). The presence of free thyroxine and 3,5,3'- triiodothyronine in the tissues of Ciona has been established. Biogenesis of 3,5,3'-triiodothyronine and thyroxine proceeds chiefly in the tunic, in which three fractions of iodoproteins were characterized. Two of these, one soluble in various media, the other bound to insoluble structure, contain 3,5,3'- triiodothyronine, thyroxine and their precursors, 3-monoiodo- and 3,5- diiodotyrosine. The four iodinatedmore » amino acids are freed from these proteins by action of pancreatic proteinases and papain. An insoluble residue of iodinated scleroprotein, not hydrolyzed by proteinases, does not take part to endocrine activity; 3-monoiodotyrosine and 3,5-diiodotyrosine only are found in the products of its alkaline hydrolysis. The mechanism of hormonogenesis seems identical in all chordata (urochordata, cephalochordata, and vertebrates). As thyroid hormones are found in these and not in invertebrates lower than urochordata, their appearance in this subphylum can be considered as a fundamental step of biochemical evolution of the thyroid function. Biosynthesis of iodothyronines is characteristic of chordata. It proceeds in all of these, including protochordata, by the same mechanism, but under conditions submitted to the evolution of the secretory tissue through a series of steps, the last of which is the thyroid follicle of vertebrates. (auth)« less

What is the underestimation of radiation dose to the pediatric thyroid gland from contrast enhanced CT, if contrast medium uptake is not taken into account?

PubMed

Perisinakis, Kostas; Pouli, Styliani; Tzedakis, Antonis; Spanakis, Kostas; Hatzidakis, Adam; Raissaki, Maria; Damilakis, John

2018-05-01

To assess the underestimation of radiation dose to the thyroid of children undergoing contrast enhanced CT if contrast medium uptake is not taken into account. 161 pediatric head, head & neck and chest CT examinations were retrospectively studied to identify those involving pre- and post-contrast imaging and thyroid inclusion in imaged volume. CT density of thyroid tissue in HU was measured in non-enhanced (NECT) and corresponding contrast-enhanced CT (CECT) images. Resulting CT number increase (ΔHU) was recorded for each patient and corresponded to a % w/w iodine concentration. The relation of %w/w iodine concentration to %dose increase induced by iodinated contrast uptake was derived by Monte Carlo simulation experiments. The thyroid gland was visible in 11 chest and 3 neck CT examinations involving both pre- and post-contrast imaging. The %w/w concentration of iodine in the thyroid tissue at the time of CECT acquisition was found to be 0.13%-0.58% w/w (mean = 0.26%). The %increase of dose to thyroid tissue was found to be linearly correlated to%w/w iodine uptake. The increase in radiation dose to thyroid due to contrast uptake ranged from 12% to 44%, with a mean value of 23%. The radiation dose to the pediatric thyroid from CECT exposure may be underestimated by up to 44% if contrast medium uptake is not taken into account. Meticulous demarcation of imaged volume in pediatric chest CT examinations is imperative to avoid unnecessary direct exposure of thyroid, especially in CT examinations following intravenous administration of contrast medium. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Evaluation of proliferation potential in thyroid normo-/hypofunctioning and hyperfunctioning nodules.

PubMed

Cornianu, Marioara; Stan, V; Lazăr, Elena; Dema, Alis; Golu, Ioana; Tăban, Sorina; Vlad, Mihaela; Faur, Alexandra; Vărcuş, F; Babău, F

2011-01-01

Thyroid follicular adenomas (FA) and adenomatous thyroid nodules (AN) - lesions that are frequently found in areas with iodine deficiency, can be normo-/hypofunctioning (scintigraphically cold - SCN) or hyperfunctioning (scintigraphically hot - SHN) nodules. Evaluation of proliferation potential in thyroid nodules on tissue samples obtained at surgery from euthyroid patients clinically diagnosed with SCN and from patients with thyroid hyperfunction and SHN. We investigated the proliferation activity estimated by assessing PCNA and Ki-67 proliferation markers in 20 SCN (eight FA and 12 AN) and 16 toxic nodules (six hyperfunctioning FA and 10 toxic multinodular goiters), on formalin-fixed and paraffin-embedded tissue samples, 4-5 μm thick; we used the immunohistochemical technique in LSAB system (DAB visualization) with anti-PCNA (PC10) and anti-Ki-67 (MIB-1) monoclonal antibodies. For each case, we calculated the proliferation index PI-PCNA and PI-Ki-67. The dates were statistically evaluated using the t-unpaired test. We observed a higher PI-PCNA in thyroid nodules than in the normal surrounding thyroid tissue, with statistically significant values for FA (14.3% vs. 3.8%; p<0.029) and also for AN (8.36% vs. 1.24%; p<0.001). The mean PI-Ki-67 in nodules vs. surrounding thyroid tissue was 1.64% vs. 1.10% in FA (p<0.35) and 1.07% vs. 0.51% in AN (p>0.05). We also noted: (1) significantly higher PI-PCNA values (p < 0.01) in FA (14.03%) than in AN (8.36%), as compared to statistically insignificant values for Ki-67 (1.64% vs. 1.07%; p>0.05); (2) increased proliferation rate (p<0.01) in thyroid nodules with aspects of lymphocytic thyroiditis (LT) (PI-Ki-67 was 1.21%) as compared to nodules without LT (PI-Ki-67 was 0.12%); (3) a mean PI-PCNA of 8.5% and PI-Ki-67 of 4.61% in toxic thyroid nodules (TTN) vs. 3.01% and 1.5% in normal surrounding thyroid, respectively. The clinical expression of SCN is the consequence of increased thyrocyte proliferation in the nodules; the increased proliferative potential of TTN thyrocytes is a common feature of nodules, independent of their histopathological characteristics.

Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

NASA Astrophysics Data System (ADS)

Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

2017-06-01

Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed. [Figure not available: see fulltext.

L-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats.

PubMed

Rodríguez-Gómez, Isabel; Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

2016-03-01

This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. © 2015 by the Society for Experimental Biology and Medicine.

l-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats

PubMed Central

Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

2015-01-01

This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might contribute to the changes in cardiac and renal mass observed in thyroid disorders. PMID:26674221

Dedifferentiation of Human Primary Thyrocytes into Multilineage Progenitor Cells without Gene Introduction

PubMed Central

Saenko, Vladimir; Suzuki, Masatoshi; Matsuse, Michiko; Ohtsuru, Akira; Kumagai, Atsushi; Uga, Tatsuya; Yano, Hiroshi; Nagayama, Yuji; Yamashita, Shunichi

2011-01-01

While identification and isolation of adult stem cells have potentially important implications, recent reports regarding dedifferentiation/reprogramming from differentiated cells have provided another clue to gain insight into source of tissue stem/progenitor cells. In this study, we developed a novel culture system to obtain dedifferentiated progenitor cells from normal human thyroid tissues. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin, vimentin and cytokeratin-18, were cultured in a serum-free medium called SAGM. Although the vast majority of cells died, a small proportion (∼0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined in the proliferating cells. Moreover, sorted cells expressing thyroid peroxidase gave rise to proliferating clones in SAGM. These data suggest that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions. In summary, we have developed a novel system to generate multilineage progenitor cells from normal human thyroid tissues. This seems to be achieved by dedifferentiation of thyroid follicular cells. The presently described culture system may be useful for regenerative medicine, but the primary importance will be as a tool to elucidate the mechanisms of thyroid diseases. PMID:21556376

P38/TRHr-Dependent Regulation of TPO in Thyroid Cells Contributes to the Hypothyroidism of Triclosan-Treated Rats.

PubMed

Zhang, Pei; Yang, Min; Zeng, Li; Liu, Changjiang

2018-01-01

Triclosan, as an antimicrobial agent and a potential endocrine disruptor, has been used extensively in diverse products, resulting in widespread human exposure. In recent years, studies suggest that triclosan could disturb thyroid functions and decline thyroid hormones (THs). To verify our hypothesis that the MAPK pathway may function significantly in triclosan-induced hypothyroidism, Sprague-Dawley rats were gavaged with triclosan for 31 consecutive days; Nthy-ori 3-1 cells were treated with triclosan in the presence/absence of NAC, inhibitors (SB203580 and SB202474), or TRHr siRNA. Tissues and/or cells were analyzed by several techniques including transmission electron microscopy, confocal laser scanning microscopy, gene silencing, western blot, and real-time PCR. Triclosan led to histopathologic changes in the thyroid and decreases in triiodothyronine (T3) and thyroxine (T4). Triclosan stimulated ROS production and oxidative stress occurrence, thereby activating the p38 pathway in vivo and in vitro. Thyrotropin releasing hormone receptor (TRHr) was induced when the p38 pathway was activated, and was suppressed when that pathway was inhibited. Moreover, thyroid peroxidase (TPO) was restrained and modulated by the p38/TRHr pathway after triclosan treatment. Furthermore, deiodinase 3 (D3) and hepatic enzymes (Ugt2b1, CYP1a1, CYP1a2, CYP2b1, CYP3a1, and Sult1e1) were also induced by triclosan. Taken together, p38/TRHr-dependent regulation of TPO in thyroid cells contributes to the hypothyroidism of triclosan-treated rats. © 2018 The Author(s). Published by S. Karger AG, Basel.

Defects in iodide metabolism in thyroid cancer and implications for the follow-up and treatment of patients.

PubMed

Schlumberger, Martin; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Bidart, Jean-Michel

2007-03-01

The two major steps of iodine metabolism--uptake and organification--are altered in thyroid cancer tissues. Organification defects result in a rapid discharge of radioiodine from thyroid cells, a short effective half-life of iodine, and a low rate of thyroid hormone synthesis. These defects are mainly due to decreased expression of functional genes encoding the sodium-iodide symporter and thyroid peroxidase and could result in a low radiation dose to thyroid cancer cells. TSH stimulation that is achieved with injections of recombinant human TSH, or long-term withdrawal of thyroid hormone treatment increases iodine-131 uptake in two-thirds of patients with metastatic disease and increases thyroglobulin production in all patients with metastases, even in the absence of detectable uptake. Serum thyroglobulin determination obtained following TSH stimulation and neck ultrasonography is the most sensitive combination for the detection of small tumor foci. Radioiodine treatment is effective when a high radiation dose can be delivered (in patients with high uptake and retention of radioiodine) and when tumor foci are sensitive to the effects of radiation therapy (younger patients, with a well-differentiated tumor and/or with small metastases). The other patients rarely respond to radioiodine treatment, and when progression occurs, other treatment modalities should be considered. Novel strategies are currently being explored to restore iodine uptake in cancer cells that are unable to concentrate radioiodine.

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.

Is visual assessment of thyroid attenuation on unenhanced CT of the chest useful for detecting hypothyroidism?

PubMed

Maldjian, P D; Chen, T

2016-11-01

To determine if visual assessment of the attenuation of morphologically normal appearing thyroid glands on unenhanced computed tomography (CT) of the chest is useful for identifying patients with decreased thyroid function. This was a retrospective study of 765 patients who underwent both unenhanced CT of the chest and thyroid function tests performed within 1 year of the CT examination. Attenuation of the thyroid gland was visually assessed in each patient relative to the attenuation of the surrounding muscles to categorise the gland as "low attenuation" (attenuation similar to surrounding muscles) or "high attenuation" (attenuation greater than surrounding muscles). Thyroid attenuation was quantitatively measured in each case to determine the validity of the visual assessment. Results of thyroid function tests were used to classify thyroid function as hypothyroid, euthyroid, or hyperthyroid. Data were analysed to determine the relationship between visual assessment of thyroid attenuation and status of thyroid function. Thyroid glands of low attenuation were present in 4.2% (32/765) of the patients. Nearly half (47%) of the patients with low-attenuation thyroids had hypofunctioning thyroid glands. Compared to patients with high-attenuation thyroids, patients with low-attenuation thyroids were significantly more likely to have decreased thyroid function (clinical and subclinical hypothyroidism) and significantly less likely to be euthyroid (p<0.0001). Quantitative measurement of thyroid attenuation confirmed the validity of the visual assessment. Low attenuation of an otherwise normal-appearing thyroid gland on unenhanced CT of the chest is strongly associated with decreased thyroid function. Copyright © 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Evaluation of 3D printing materials for fabrication of a novel multi-functional 3D thyroid phantom for medical dosimetry and image quality

NASA Astrophysics Data System (ADS)

Alssabbagh, Moayyad; Tajuddin, Abd Aziz; Abdulmanap, Mahayuddin; Zainon, Rafidah

2017-06-01

Recently, the three-dimensional printer has started to be utilized strongly in medical industries. In the human body, many parts or organs can be printed from 3D images to meet accurate organ geometries. In this study, five common 3D printing materials were evaluated in terms of their elementary composition and the mass attenuation coefficients. The online version of XCOM photon cross-section database was used to obtain the attenuation values of each material. The results were compared with the attenuation values of the thyroid listed in the International Commission on Radiation Units and Measurements - ICRU 44. Two original thyroid models (hollow-inside and solid-inside) were designed from scratch to be used in nuclear medicine, diagnostic radiology and radiotherapy for dosimetry and image quality purposes. Both designs have three holes for installation of radiation dosimeters. The hollow-inside model has more two holes in the top for injection the radioactive materials. The attenuation properties of the Polylactic Acid (PLA) material showed a very good match with the thyroid tissue, which it was selected to 3D print the phantom using open source RepRap, Prusa i3 3D printer. The scintigraphy images show that the phantom simulates a real healthy thyroid gland and thus it can be used for image quality purposes. The measured CT numbers of the PA material after the 3D printing show a close match with the human thyroid CT numbers. Furthermore, the phantom shows a good accommodation of the TLD dosimeters inside the holes. The 3D fabricated thyroid phantom simulates the real shape of the human thyroid gland with a changeable geometrical shape-size feature to fit different age groups. By using 3D printing technology, the time required to fabricate the 3D phantom was considerably shortened compared to the longer conventional methods, where it took only 30 min to print out the model. The 3D printing material used in this study is commercially available and cost-effective compared to current commercial tissue-equivalent materials.

Selenoprotein Gene Expression in Thyroid and Pituitary of Young Pigs Is Not Affected by Dietary Selenium Deficiency or Excess1–3

PubMed Central

Zhou, Ji-Chang; Zhao, Hua; Li, Jun-Gang; Xia, Xin-Jie; Wang, Kang-Ning; Zhang, Ya-Jun; Liu, Yan; Zhao, Ying; Lei, Xin Gen

2009-01-01

Expression and function of selenoproteins in endocrine tissues remain unclear, largely due to limited sample availability. Pigs have a greater metabolic similarity and tissue size than rodents as a model of humans for that purpose. We conducted 2 experiments: 1) we cloned 5 novel porcine selenoprotein genes; and 2) we compared the effects of dietary selenium (Se) on mRNA levels of 12 selenoproteins, activities of 4 antioxidant enzymes, and Se concentrations in testis, thyroid, and pituitary with those in liver of pigs. In Experiment 1, porcine Gpx2, Sephs2, Sep15, Sepn1, and Sepp1 were cloned and demonstrated 84–94% of coding sequence homology to human genes. In Experiment 2, weanling male pigs (n = 30) were fed a Se-deficient (0.02 mg Se/kg) diet added with 0, 0.3, or 3.0 mg Se/kg as Se-enriched yeast for 8 wk. Although dietary Se resulted in dose-dependent increases (P < 0.05) in Se concentrations and GPX activities in all 4 tissues, it did not affect the mRNA levels of any selenoprotein gene in thyroid or pituitary. Testis mRNA levels of Txnrd1 and Sep15 were decreased (P < 0.05) by increasing dietary Se from 0.3 to 3.0 mg/kg. Comparatively, expressions of Gpx2, Gpx4, Dio3, and Sep15 were high in pituitary and Dio1, Sepp1, Sephs2, and Gpx1 were high in liver. In conclusion, the mRNA abundances of the 12 selenoprotein genes in thyroid and pituitary of young pigs were resistant to dietary Se deficiency or excess. PMID:19357213

Effects of thyroid status on cold-adaptive thermogenesis in Brandt's vole, Microtus brandti.

PubMed

Liu, X T; LI, Q F; Huang, C X; Sun, R Y

1997-01-01

Hyper- and hypothyroidism were induced by subcutaneous injection of thyroxine and by oral administration of methimazol in Brandt's voles. The effects of the two treatments on metabolic thermogenesis at 25 degrees C and 4 degrees C were investigated. The level of resting metabolic rate was closely related to thyroid status: high in the hyperthyroid case and low in the hypothyroid case. However, no increase in resting metabolic rate occurred in either case during further cold acclimation. Hyperthyroidism resulted in an increased nonshivering thermogenesis, which was much enhanced by lower temperature, but hypothyroidism led to a suppressed nonshivering thermogenesis in the cold. The state-4 and state-3 respirations and the activities of cytochrome-c oxidase of liver mitochondria were elevated in hyperthyroid animals but attenuated in hypothyroid ones. However, these levels were scarcely changed after further cold acclimation. Both hyperthyroidism and cold acclimation induced the recruitment of brown adipose tissue, but brown adipose tissue was different biochemically in the two cases: in hyperthyroidism, the total protein was reduced, while fat content increased; in cold acclimation, the total and mitochondrial proteins were increased. However, in hypothyroid voles, the normal adaptive changes in brown adipose tissue were impaired in further cold acclimation. The activity of cytochromec oxidase in brown adipose tissue was increased by hyperthyroidism and enhanced in further cold. In contrast, its activity was inhibited in hypothyroid animals, though activated to some extent in cold. These results demonstrate that normal thyroid function is essential for the cold-induced increase of resting metabolic rate and nonshivering thermogenesis and that there is a synergism between thyroid hormone and cold acclimation in the regulation of nonshivering thermogenesis in Brandt's vole. In addition, the blunted response of brown adipocytes to the cold may be the cytological mechanism for the suppressed nonshivering thermogenesis found with hypothyroidism.

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.

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

Experimental models of developmental hypothyroidism.

PubMed

Argumedo, G S; Sanz, C R; Olguín, H J

2012-02-01

Hypothyroidism is a systemic disease resulting from either thyroid gland's anatomical and functional absence or lack of hypophyseal stimulation, both of which can lead to deficiency in thyroid hormone (TH) production. TH is essential for human and animal development, growth, and function of multiple organs. Children with deficient TH can develop alterations in central nervous system (CNS), striated muscle, bone tissue, liver, bone marrow, and cardiorespiratory system. Among the clinical outlook are signs like breathing difficulty, cardiac insufficiency, dysphagia, and repeated bronchial aspiration, constipation, muscle weakness, cognitive alterations, cochlear dysfunction, reduced height, defects in temperature regulation, anaemia, jaundice, susceptibility to infection, and others. Experimental and clinical studies have shown that TH is very essential for normal brain development. Other research work based on mice pointed out that a reduced level of TH in pregnant mother leads to congenital hypothyroidism in animal models and it is associated with mental retardation, deep neurologic deficiency that impacts on cognitive, learning, and memory functions. The principal experimental model studies that have focused on hypothyroidism are reviewed in this study. This is important on considering the fact that almost all animal species require thyroid hormones for their metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

PubMed

Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

2015-08-06

Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

Cosmos 1887 mission overview - Effects of microgravity on rat body and adrenal weights and plasma constituents

NASA Technical Reports Server (NTRS)

Grindeland, R. E.; Vasques, M.; Arnaud, S. B.; Popova, I. A.

1990-01-01

Tissues of male, specific pathogen-free Wistar rats flown on the Cosmos 1887 biosatellite are studied. First the mission is described, and then analytical methods are outlined. It is noted that flight rats grew more slowly and had larger adrenal glands than earth gravity controls. Analysis of plasma reveals increased concentrations of hepatic alkaline phosphatase, glucose, urea nitrogen, and creatinine in flight rats. In contrast, electrolytes, total protein, albumin, corticosteron, prolactin, and immunoreactive growth hormone levels are unchanged. However, testosterone concentration is marginally decreased after flight and thyroid hormone levels are suggestive of reduced thyroid function.

Iodide Protects Heart Tissue from Reperfusion Injury

PubMed Central

Iwata, Akiko; Morrison, Michael L.; Roth, Mark B.

2014-01-01

Iodine is an elemental nutrient that is essential for mammals. Here we provide evidence for an acute therapeutic role for iodine in ischemia reperfusion injury. Infusion of the reduced form, iodide, but not the oxidized form iodate, reduces heart damage by as much as 75% when delivered intravenously following temporary loss of blood flow but prior to reperfusion of the heart in a mouse model of acute myocardial infarction. Normal thyroid function may be required because loss of thyroid activity abrogates the iodide benefit. Given the high degree of protection and the high degree of safety, iodide should be explored further as a therapy for reperfusion injury. PMID:25379708

Localized Ablation of Thyroid Tissue by High-Intensity Focused Ultrasound: an Alternative to Surgery?

NASA Astrophysics Data System (ADS)

Esnault, Olivier; Franc, Brigitte; Chapelon, Jean-Yves; Lacoste, Francois

2006-05-01

PURPOSE: The aim of this study was to evaluate the feasibility of using a High-intensity focused ultrasound (HIFU) device to obtain a localised destruction of the thyroid with no damage to adjacent tissues. MATERIALS AND METHODS: The ewe model was used because its thyroid gland is easily accessible with ultrasound. The animals were anaesthetised with 10 mg / kg IV injection of Penthothal. The HIFU pulses were generated by a 3-MHz spherical transducer under ultrasound guidance. Macroscopic and microscopic tissue lesions were identified after formalin fixation of the anterior part of the ewe's neck. RESULTS: After determining the optimal instrument settings to obtain localized thyroid ablation, the repeatability of the method was evaluated using a HIFU prototype designed specifically for human use: in 13 ewes (26 treated lobes), an average of 20 (range: 14-27) ultrasound pulses (pulse duration: 3 s) per lobe covering a mean volume of 0.5 cm3 (range: 0.3-0.7 cm3) were delivered. The ewes were sacrificed 2-5 weeks after treatment delivery. No damage to the nerves, trachea, esophagus or muscle was observed. Only 3 ewes suffered superficial skin burns. The desired thyroid lesions were obtained in 25/26 treated lobes, as demonstrated by fibrotic tissues, which replaced necrotic areas. CONCLUSION: These results obtained in the ewe model show that thyroid lesions of defined volume can be induced safely and suggest that the HIFU device is now ready for human trials.

Liver X receptor β controls thyroid hormone feedback in the brain and regulates browning of subcutaneous white adipose tissue.

PubMed

Miao, Yifei; Wu, Wanfu; Dai, Yubing; Maneix, Laure; Huang, Bo; Warner, Margaret; Gustafsson, Jan-Åke

2015-11-10

The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type 2 diabetes. Browning is the result of the induction in WAT of a newly discovered type of adipocyte, the beige cell. When mice are exposed to cold or several kinds of hormones or treatments with chemicals, specific depots of WAT undergo a browning process, characterized by highly activated mitochondria and increased heat production and energy expenditure. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride, and glucose metabolism. Following our previous finding that LXRs serve as repressors of uncoupling protein-1 (UCP1) in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyroid-stimulating hormone (TSH)-releasing hormone (TRH)-positive neurons in the paraventricular nucleus area of the hypothalamus and thus stimulated secretion of TSH from the pituitary. Consequently, production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knockout mice and provided support for targeting LXRs in treatment of obesity.

Intraoperative Identification of the Parathyroid Gland with a Fluorescence Detection System.

PubMed

Shinden, Yoshiaki; Nakajo, Akihiro; Arima, Hideo; Tanoue, Kiyonori; Hirata, Munetsugu; Kijima, Yuko; Maemura, Kosei; Natsugoe, Shoji

2017-06-01

Intraoperative identification of the difficult-to-spot parathyroid gland is critical during surgery for thyroid and parathyroid disease. Recently, intrinsic fluorescence of the parathyroid gland was identified, and a new method was developed for intraoperative detection of the parathyroid with an original fluorescent detection apparatus. Here, we describe a method for intraoperative detection of the parathyroid using a ready-made photodynamic eye (PDE) system without any fluorescent dye or contrast agents. Seventeen patients who underwent surgical treatment for thyroid or parathyroid disease at Kagoshima University Hospital were enrolled in this study. Intrinsic fluorescence of various tissues was detected with the PDE system. Intraoperative in vivo and ex vivo intrinsic fluorescence of the parathyroid, thyroid, lymph nodes and fat tissues was measured and analyzed. The parathyroid gland had a significantly higher fluorescence intensity than the other tissues, including the thyroid glands, lymph nodes and fat tissues, and we could identify them during surgery using the fluorescence-guided method. Our method could be applicable for two intraoperative clinical procedures: ex vivo tissue identification of parathyroid tissue and in vivo identification of the location of the parathyroid gland, including ectopic glands. The PDE system may be an easy and highly feasible method to identify the parathyroid gland during surgery.

Evidence of iodine storage within thyroid stroma after iodine treatment: imaging by secondary ion mass spectometry (SIMS) microscopy in goitrous tissue.

PubMed

el May, M; Jeusset, J; el May, A; Mtimet, S; Fragu, P

1996-06-01

We measured the 127I distribution within tyroid tissue to find out where intrathyroid iodine was deposited during iodine treatment in eight Tunisian female patients (aged 33-58 yr) with endemic euthyroid goiter. Before surgery, five patients were treated during 6 months either by Lugol's solution (group 1: three patients) or by Lugol's and L-thyroxine (group 2: two patients). All patients remained euthyroid during the course of the treatment, which supplied 3.8 mg/day iodine. Three other patients did not receive Lugol's solution (control group). Secondary ion mass spectrometry microscopy was used to map 127-I quantitatively on thyroid sections. Specimens obtained at thyroid surgery were divided macroscopically into nodular and extranodular tissue and chemically fixed to preserve organified iodine. The iodine profile of patients in group 1 did not differ from that in group 2: large amounts of iodine were localized in thyroid follicles and stroma of both nodular and extranodular tissues. In the control group, iodine within stroma was found only in the extranodular tissue. Despite the limited number of patients studied, these data suggest that stromal iodine might represent a storage compartment in times of large iodine supply.

False-positive iodine-131 whole-body scan findings in patients with differentiated thyroid carcinoma: report of 11 cases and review of the literature.

PubMed

Buton, Leckzinscka; Morel, Olivier; Gault, Patricia; Illouz, Frédéric; Rodien, Patrice; Rohmer, Vincent

2013-07-01

Iodine-131 (I-131) whole-body scan (WBS) plays an important role in the management of patients with differentiated thyroid carcinoma (DTC), to detect normal thyroid remnants and recurrent or metastatic disease. A focus of I-131 accumulation outside the thyroid bed and the areas of physiological uptake is strongly suggestive of a distant functioning metastasis. However, many false-positive I-131 WBS findings have been reported in the literature. We describe a series of 11 personal cases of patients with DTC, collected from 1992 to 2011, in whom diagnostic or post-treatment WBS showed false-positive retention of I-131 in various locations. False-positive accumulations of I-131 on WBS may be classified according to the underlying pathophysiological mechanisms: external and internal contaminations by body secretions, ectopic normal thyroid and gastric tissues, inflammatory and infectious diseases, benign and malignant tumors, cysts and effusions of serous cavities, thymic uptake, and other non classified causes. Clinicians must be aware of possible false-positive findings to avoid misinterpretations of the I-131 WBS, which could lead to inappropriate treatments. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Features of morfological changes in primary thyroid gland CTLL cultures of rats descendants prenatally exposed by radioisotopes of iodine-131.

PubMed

Boiko, O A; Lavrenchuk, H Yo; Lypska, A I; Talko, V V; Asmolkov, V S

2017-12-01

to investigate morphological changes in the primary thyroid cell culture of rat infants whose parents were prenatally exposed by radioisotope iodine 131. obtaining and culturing of thyroid tissue primary cell cultures of newborn rats, cytological (receipt and analysis of cell cultures agents for optical microscopy), biophysical (flow cytometry), statistics. It was shown that cells in thyroid primary culture of offspring rats prenatally exposed by radioisotopes of iodine 131 signs of destructive degenerative changes were observed mostly when animals of both sexes were irra diated. Increased number of two and three nuclear cells and induction of ring like cells is an evidence of signifi cant genotoxic violation and points to the genome instability in offspring of animals exposed by radioisotope iodine 131. Analysis and quantitative morphological parameters of cells in thyroid primary culture of newborn rats whose parents were exposed prenatally by radioisotopes of iodine 131 showed that upon exposure to radiation thy roid undergoes destructive changes at the cellular level and, even in the second generation of offspring, leads to disruption of its functions. O. A. Boiko, H. Yo. Lavrenchuk, A. I. Lypska, V. V. Talko, V. S. Asmolkov.

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

Opitz, Robert; Maquet, Emilie; Zoenen, Maxime; Dadhich, Rajesh

2011-01-01

TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. PMID:21737742

Biochemical and molecular characterization of thyroid tissue by micro-Raman spectroscopy and gene expression analysis

NASA Astrophysics Data System (ADS)

Neto, Lázaro P. M.; Martin, Aírton A.; Soto, Claudio A. T.; Santos, André B. O.; Mello, Evandro S.; Pereira, Marina A.; Cernea, Cláudio R.; Brandão, Lenine G.; Canevari, Renata A.

2016-02-01

Thyroid carcinomas represent the main endocrine malignancy and their diagnosis may produce inconclusive results. Raman spectroscopy and gene expression analysis have shown excellent results on the differentiation of carcinomas. This study aimed to improve the discrimination between different thyroid pathologies combining of both analyses. A total of 35 thyroid tissues samples including normal tissue (n=10), goiter (n=10), papillary (n=10) and follicular carcinomas (n=5) were analyzed. Confocal Raman spectra was obtain by using a Rivers Diagnostic System, 785 nm laser excitation and CCD detector. The data was processed by the software Labspec5 and Origin 8.5 and analyzed by Minitab® program. The gene expression analysis was performed by qRT-PCR technique for TG, TPO, PDGFB, SERPINA1, LGALS3 and TFF3 genes and statistically analyzed by Mann-Whitney test. The confocal Raman spectroscopy allowed a maximum discrimination of 91.1% between normal and tumor tissues, 84.8% between benign and malignant pathologies and 84.6% among carcinomas analyzed. Significant differences was observed for TG, LGALS3, SERPINA1 and TFF3 genes between benign lesions and carcinomas, and SERPINA1 and TFF3 genes between papillary and follicular carcinomas. Principal component analysis was performed using PC1 and PC2 in the papillary carcinoma samples that showed over gene expression when compared with normal sample, where 90% of discrimination was observed at the Amide 1 (1655 cm-1), and at the tyrosine spectra region (856 cm-1). The discrimination of tissues thyroid carried out by confocal Raman spectroscopy and gene expression analysis indicate that these techniques are promising tools to be used in the diagnosis of thyroid lesions.

Evaluation of the dose received in the tissues of the neck during quantification of iodine in the thyroid by X-ray fluorescence spectrometry

NASA Astrophysics Data System (ADS)

Portararo, Antonio; Licour, Caroline; Gerardy, Isabelle; Pozuelo Navarro, Fausto

2018-04-01

The determination of the iodine content in the thyroid is of great interest for many investigations of this gland. The conventional scintigraphic method, using radionuclides, is efficient but delivers a significant dose to the patient. The X-ray fluorescence spectrometry could give information about the iodine content in the thyroid. The measured signal is obtained after stimulation of the stable iodine contained in the gland by X-rays. The advantage of this technique is the complete absence of radioactive isotope injected into the patient body. By applying this, a decrease in effective dose to the patient should be obtained. In this work, the study of the dose received by a thyroid phantom (surrounded by the different tissues of the neck) was performed. The phantom is made of PLA. The dose is measured in optimised conditions defined for the analytical technique. A total head-neck phantom was also used in order to consider the absorbed dose in each different tissues and organs as spinal cord or eyes. Thermo-luminescence dosimeters were chosen for their small size, their sensitivity and the easy positioning on the surface of the phantom but also inside of it to evaluate dose to internal organs. Those LiF 100 dosimeters have been calibrated within the X-ray beam also used for the analysis of iodine. The repeatability and reproducibility of the method has been evaluated. The influence of parameters as concentration of iodine in the thyroid, distance between the X-ray generator and the neck, thickness of the tissues surrounding the thyroid, has been investigated in terms of modifying parameters of the dose received by different tissues situated in the neck and the head.

Physiologically-Based Pharmacokinetic (PBPK) Model for the Thyroid Hormones in the Pregnant Rat and Fetus.

EPA Science Inventory

A developmental PBPK model is constructed to quantitatively describe the tissue economy of the thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), in the rat. The model is also used to link maternal (THs) to rat fetal tissues via placental transfer. THs are importan...

Do unliganded thyroid hormone receptors have physiological functions?

PubMed

Chassande, O

2003-08-01

Thyroid hormone (TH) is required for the development of vertebrates and exerts numerous homeostatic functions in adults. TH acts through nuclear receptors which control the transcription of target genes. Unliganded and liganded thyroid hormone receptors (TRs) have been shown to exert opposite effects on the transcription of target genes in vitro. However, the occurance of an aporeceptor activity in vivo and its potential physiological significance has not been clearly addressed. Several data generated using experimental hypothyroidism and thyrotoxicosis in wild type and TR knockout mice support the notion that apoTRs have an intrinsic activity in several tIssues. ApoTRs, and in particular TRalpha1, are predominant during the early stages of vertebrate development and must be turned into holoTRs for post-natal development to proceed normally. However, the absence of striking alterations of embryonic and fetal development in mice devoid of TRs indicates that apoTRs do not play a fundamental role. During development, as well as in adults, apoTRs rather appears as a system which increases the range of transcriptional responses to moderate variations of T3.

Elastographic techniques of thyroid gland: current status.

PubMed

Andrioli, Massimiliano; Persani, Luca

2014-08-01

Thyroid nodules are very common with malignancies accounting for about 5 %. Fine-needle biopsy is the most accurate test for thyroid cancer diagnosis. Elastography, a new technology directly evaluating the elastic property of the tissue, has been recently added to the diagnostic armamentarium of the endocrinologists as noninvasive predictor of thyroid malignancy. In this paper, we critically reviewed characteristics and applications of elastographic methods in thyroid gland. Elastographic techniques can be classified on the basis of the following: source-of-tissue compression (free-hand, carotid vibration, ultrasound pulses), processing time (real-time, off-line), stiffness expression (qualitative, semi-quantitative, or quantitative). Acoustic radiation force impulse and aixplorer shear wave are the newest and most promising quantitative elastographic methods. Primary application of elastography is the detection of nodular lesions suspicious for malignancy. Published data show a high sensitivity and negative predictive value of the technique. Insufficient data are available on the possible application of elastography in the differential diagnosis of indeterminate lesions and in thyroiditis. Elastography represents a noninvasive tool able to increase the performance of ultrasound in the selection of thyroid nodules at higher risk of malignancy. Some technical improvements and definition of more robust quantitative diagnostic criteria are required for assigning a definite role in the management of thyroid nodules and thyroiditis to elastography.

[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 hormone regulation of adult intestinal stem cells: Implications on intestinal development and homeostasis.

PubMed

Sun, Guihong; Roediger, Julia; Shi, Yun-Bo

2016-12-01

Organ-specific adult stem cells are essential for organ homeostasis, tissue repair and regeneration. The formation of such stem cells often takes place during postembryonic development, a period around birth in mammals when plasma thyroid hormone concentration is high. The life-long self-renewal of the intestinal epithelium has made mammalian intestine a valuable model to study the function and regulation and adult stem cells. On the other hand, much less is known about how the adult intestinal stem cells are formed during vertebrate development. Here, we will review some recent progresses on this subject, focusing mainly on the formation of the adult intestine during Xenopus metamorphosis. We will discuss the role of thyroid hormone signaling pathway in the process and potential molecular conservations between amphibians and mammals as well as the implications in organ homeostasis and human diseases.

Recent Insights into the Cell Biology of Thyroid Angiofollicular Units

PubMed Central

Denef, Jean-François; Lengelé, Benoit; Many, Marie-Christine; Gérard, Anne-Catherine

2013-01-01

In thyrocytes, cell polarity is of crucial importance for proper thyroid function. Many intrinsic mechanisms of self-regulation control how the key players involved in thyroid hormone (TH) biosynthesis interact in apical microvilli, so that hazardous biochemical processes may occur without detriment to the cell. In some pathological conditions, this enzymatic complex is disrupted, with some components abnormally activated into the cytoplasm, which can lead to further morphological and functional breakdown. When iodine intake is altered, autoregulatory mechanisms outside the thyrocytes are activated. They involve adjacent capillaries that, together with thyrocytes, form the angiofollicular units (AFUs) that can be considered as the functional and morphological units of the thyroid. In response to iodine shortage, a rapid expansion of the microvasculature occurs, which, in addition to nutrients and oxygen, optimizes iodide supply. These changes are triggered by angiogenic signals released from thyrocytes via a reactive oxygen species/hypoxia-inducible factor/vascular endothelial growth factor pathway. When intra- and extrathyrocyte autoregulation fails, other forms of adaptation arise, such as euthyroid goiters. From onset, goiters are morphologically and functionally heterogeneous due to the polyclonal nature of the cells, with nodules distributed around areas of quiescent AFUs containing globules of compact thyroglobulin (Tg) and surrounded by a hypotrophic microvasculature. Upon TSH stimulation, quiescent AFUs are activated with Tg globules undergoing fragmentation into soluble Tg, proteins involved in TH biosynthesis being expressed and the local microvascular network extending. Over time and depending on physiological needs, AFUs may undergo repetitive phases of high, moderate, or low cell and tissue activity, which may ultimately culminate in multinodular goiters. PMID:23349248

Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues.

PubMed

Padron, Alvaro Souto; Neto, Ruy Andrade Louzada; Pantaleão, Thiago Urgal; de Souza dos Santos, Maria Carolina; Araujo, Renata Lopes; de Andrade, Bruno Moulin; da Silva Leandro, Monique; de Castro, João Pedro Saar Werneck; Ferreira, Andrea Claudia Freitas; de Carvalho, Denise Pires

2014-06-01

In general, 3,5-diiodothyronine (3,5-T2) increases the resting metabolic rate and oxygen consumption, exerting short-term beneficial metabolic effects on rats subjected to a high-fat diet. Our aim was to evaluate the effects of chronic 3,5-T2 administration on the hypothalamus-pituitary-thyroid axis, body mass gain, adipose tissue mass, and body oxygen consumption in Wistar rats from 3 to 6 months of age. The rats were treated daily with 3,5-T2 (25, 50, or 75 μg/100 g body weight, s.c.) for 90 days between the ages of 3 and 6 months. The administration of 3,5-T2 suppressed thyroid function, reducing not only thyroid iodide uptake but also thyroperoxidase, NADPH oxidase 4 (NOX4), and thyroid type 1 iodothyronine deiodinase (D1 (DIO1)) activities and expression levels, whereas the expression of the TSH receptor and dual oxidase (DUOX) were increased. Serum TSH, 3,3',5-triiodothyronine, and thyroxine were reduced in a 3,5-T2 dose-dependent manner, whereas oxygen consumption increased in these animals, indicating the direct action of 3,5-T2 on this physiological variable. Type 2 deiodinase activity increased in both the hypothalamus and the pituitary, and D1 activities in the liver and kidney were also increased in groups treated with 3,5-T2. Moreover, after 3 months of 3,5-T2 administration, body mass and retroperitoneal fat pad mass were significantly reduced, whereas the heart rate and mass were unchanged. Thus, 3,5-T2 acts as a direct stimulator of energy expenditure and reduces body mass gain; however, TSH suppression may develop secondary to 3,5-T2 administration. © 2014 The authors.

Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism.

PubMed

Badziong, Julia; Ting, Saskia; Synoracki, Sarah; Tiedje, Vera; Brix, Klaudia; Brabant, Georg; Moeller, Lars Christian; Schmid, Kurt Werner; Fuhrer, Dagmar; Zwanziger, Denise

2017-09-01

Thyroid hormone (TH) transporters are expressed in thyrocytes and most play a role in TH release. We asked whether expression of the monocarboxylate transporter 8 (MCT8) and the L-type amino acid transporters LAT2 and LAT4 is changed with thyrocyte dedifferentiation and in hyperfunctioning thyroid tissues. Protein expression and localization of transporters was determined by immunohistochemistry in human thyroid specimen including normal thyroid tissue (NT, n  = 19), follicular adenoma (FA, n  = 44), follicular thyroid carcinoma (FTC, n  = 45), papillary thyroid carcinoma (PTC, n  = 40), anaplastic thyroid carcinoma (ATC, n  = 40) and Graves' disease (GD, n  = 50) by calculating the 'hybrid' (H) score. Regulation of transporter expression was investigated in the rat follicular thyroid cell line PCCL3 under basal and thyroid stimulating hormone (TSH) conditions. MCT8 and LAT4 were localized at the plasma membrane, while LAT2 transporter showed cytoplasmic localization. MCT8 expression was downregulated in benign and malignant thyroid tumours as compared to NT. In contrast, significant upregulation of MCT8, LAT2 and LAT4 was found in GD. Furthermore, a stronger expression of MCT8 was demonstrated in PCCL3 cells after TSH stimulation. Downregulation of MCT8 in thyroid cancers qualifies MCT8 as a marker of thyroid differentiation. The more variable expression of LATs in distinct thyroid malignancies may be linked with other transporter properties relevant to altered metabolism in cancer cells, i.e. amino acid transport. Consistent upregulation of MCT8 in GD is in line with increased TH release in hyperthyroidism, an assumption supported by our in vitro results showing TSH-dependent upregulation of MCT8. © 2017 European Society of Endocrinology.

Exposure to non-ionizing radiation provokes changes in rat thyroid morphology and expression of HSP-90

PubMed Central

Misa-Agustiño, Maria J; Jorge-Mora, Teresa; Jorge-Barreiro, Francisco J; Suarez-Quintanilla, Juan; Moreno-Piquero, Eduardo; Ares-Pena, Francisco J

2015-01-01

Non-ionizing radiation at 2.45 GHz may modify the morphology and expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Diathermy is the therapeutic application of non-ionizing radiation to humans for its beneficial effects in rheumatological and musculo-skeletal pain processes. We used a diathermy model on laboratory rats subjected to maximum exposure in the left front leg, in order to study the effects of radiation on the nearby thyroid tissue. Fifty-six rats were individually exposed once or repeatedly (10 times in two weeks) for 30 min to 2.45 GHz radiation in a commercial chamber at different non-thermal specific absorption rates (SARs), which were calculated using the finite difference time domain technique. We used immunohistochemistry methods to study the expression of HSP-90 and morphological changes in thyroid gland tissues. Ninety minutes after radiation with the highest SAR, the central and peripheral follicles presented increased size and the thickness of the peripheral septa had decreased. Twenty-four hours after radiation, only peripheral follicles radiated at 12 W were found to be smaller. Peripheral follicles increased in size with repeated exposure at 3 W power. Morphological changes in the thyroid tissue may indicate a glandular response to acute or repeated stress from radiation in the hypothalamic–pituitary–thyroid axis. Further research is needed to determine if the effect of this physical agent over time may cause disease in the human thyroid gland. PMID:25649190

Changes of Serum Angiotensin-Converting Enzyme Activity During Treatment of Patients with Graves’ Disease*

PubMed Central

Lee, Dong Soo; Chung, June-Key; Cho, Bo Youn; Koh, Chang-Soon; Lee, Munho

1986-01-01

Serum angiotensin-converting enzyme activity was measured spectrophotometrically, and serum thyrotropin-binding-inhibitory immunoglobulin (TBII) activity was measured by radioreceptor assay in normal subjects and in patients with Graves’ disease serially before and during treatment, and these activities were compared with each other and with thyroid hormone levels in various thyroid functional status. Correlation between serum angiotensin-converting enzyme activity and serum thyroid hormone level was pursued with relation to the changes of thyroid functional status in patients with Graves’ disease during treatment. Serum angiotensin-converting enzyme activity was significantly elevated in patients with hyperthyroid Graves’ disease before the start of treatment (35 ± 13 nmol/min/ml, n=50), and not in patients with Graves’ disease, euthyroid state during treatment with antithyroid drugs or radioactive iodine (23 ± 9 nmol/min/ml, n=12), but decreased significantly in patients with Graves’ disease, hypothyroid state transiently during treatment (15 ± 4 nmol/min/ml, n=12), respectively in comparison with normal control subjects. Serum angiotensin-converting enzyme activity was positively correlated with the log value of serum T3 concentration (r=0.62, p<0.001, n=95), and with the log value of free thyroxine index (r=0.66, p<0.001, n=91) but not statistically significantly with serum TBII activity. Serum angiotensin-converting enzyme activity was followed in 11 patients with initially increased activity and the activity decreased in proportion to serum thyroid hormone level during treatment, irrespective of treatment modality. It is suggested that thyroid hormones play a role in the increase and decrease of serum angiotensin-converting enzyme activity directly or indirectly influencing the peripheral tissues (probably reticuloendothelial cells or peripheral endothelial cells) in patients with Graves’ disease. PMID:15759385

Sodium/iodide symporter: a key transport system in thyroid cancer cell metabolism.

PubMed

Filetti, S; Bidart, J M; Arturi, F; Caillou, B; Russo, D; Schlumberger, M

1999-11-01

The recent cloning of the gene encoding the sodium/iodide symporter (NIS) has enabled better characterization of the molecular mechanisms underlying iodide transport, thus opening the way to clarifying its role in thyroid diseases. Several studies, at both the mRNA and the protein expression levels, have demonstrated that TSH, the primary regulator of iodide uptake, upregulates NIS gene expression and NIS protein abundance, both in vitro and in vivo. However, other factors, including iodide, retinoic acid, transforming growth factor-beta, interleukin-1alpha and tumour necrosis factor alpha, may participate in the regulation of NIS expression. Investigation of NIS mRNA expression in different thyroid tissues has revealed increased levels of expression in Graves' disease and toxic adenomas, whereas a reduction or loss of NIS transcript was detected in differentiated thyroid carcinomas, despite the expression of other specific thyroid markers. NIS mRNA was also detected in non-thyroid tissues able to concentrate radioiodine, including salivary glands, stomach, thymus and breast. The production of specific antibodies against the NIS has facilitated study of the expression of the symporter protein. Despite of the presence of high levels of human (h)NIS mRNA, normal thyroid glands exhibit a heterogeneous expression of NIS protein, limited to the basolateral membrane of the thyrocytes. By immunohistochemistry, staining of hNIS protein was stronger in Graves' and toxic adenomas and reduced in thyroid carcinomas. Measurement of iodide uptake by thyroid cancer cells is the cornerstone of the follow-up and treatment of patients with thyroid cancer. However, radioiodide uptake is found only in about 67% of patients with persistent or recurrent disease. Several studies have demonstrated a decrease in or a loss of NIS expression in primary human thyroid carcinomas, and immunohistochemical studies have confirmed this considerably decreased expression of the NIS protein in thyroid cancer tissues, suggesting that the low expression of NIS may represent an early abnormality in the pathway of thyroid cell transformation, rather than being a consequence of cancer progression. The relationship between radioiodine uptake and NIS expression by thyroid cancer cells require further study. New strategies, based on manipulation of NIS expression, to obtain NIS gene reactivation or for use as NIS gene therapy in the treatment of radiosensitive cancer, are also being investigated.

Using Acoustic Structure Quantification During B-Mode Sonography for Evaluation of Hashimoto Thyroiditis.

PubMed

Rhee, Sun Jung; Hong, Hyun Sook; Kim, Chul-Hee; Lee, Eun Hye; Cha, Jang Gyu; Jeong, Sun Hye

2015-12-01

This study aimed to evaluate the usefulness of Acoustic Structure Quantification (ASQ; Toshiba Medical Systems Corporation, Nasushiobara, Japan) values in the diagnosis of Hashimoto thyroiditis using B-mode sonography and to identify a cutoff ASQ level that differentiates Hashimoto thyroiditis from normal thyroid tissue. A total of 186 thyroid lobes with Hashimoto thyroiditis and normal thyroid glands underwent sonography with ASQ imaging. The quantitative results were reported in an echo amplitude analysis (Cm(2)) histogram with average, mode, ratio, standard deviation, blue mode, and blue average values. Receiver operating characteristic curve analysis was performed to assess the diagnostic ability of the ASQ values in differentiating Hashimoto thyroiditis from normal thyroid tissue. Intraclass correlation coefficients of the ASQ values were obtained between 2 observers. Of the 186 thyroid lobes, 103 (55%) had Hashimoto thyroiditis, and 83 (45%) were normal. There was a significant difference between the ASQ values of Hashimoto thyroiditis glands and those of normal glands (P < .001). The ASQ values in patients with Hashimoto thyroiditis were significantly greater than those in patients with normal thyroid glands. The areas under the receiver operating characteristic curves for the ratio, blue average, average, blue mode, mode, and standard deviation were: 0.936, 0.902, 0.893, 0.855, 0.846, and 0.842, respectively. The ratio cutoff value of 0.27 offered the best diagnostic performance, with sensitivity of 87.38% and specificity of 95.18%. The intraclass correlation coefficients ranged from 0.86 to 0.94, which indicated substantial agreement between the observers. Acoustic Structure Quantification is a useful and promising sonographic method for diagnosing Hashimoto thyroiditis. Not only could it be a helpful tool for quantifying thyroid echogenicity, but it also would be useful for diagnosis of Hashimoto thyroiditis. © 2015 by the American Institute of Ultrasound in Medicine.

Thyroid nodule ultrasound: technical advances and future horizons.

PubMed

McQueen, Andrew S; Bhatia, Kunwar S S

2015-04-01

Thyroid nodules are extremely common and the vast majority are non-malignant; therefore the accurate discrimination of a benign lesion from malignancy is challenging. Ultrasound (US) characterisation has become the key component of many thyroid nodule guidelines and is primarily based on the detection of key features by high-resolution US. The thyroid imager should be familiar with the strengths and limitations of this modality and understand the technical factors that create and alter the imaging characteristics. Specific advances in high-resolution US are discussed with reference to individual features of thyroid cancer and benign disease. Potential roles for three-dimensional thyroid ultrasound and computer-aided diagnosis are also considered. The second section provides an overview of current evidence regarding thyroid ultrasound elastography (USE). USE is a novel imaging technique that quantifies tissue elasticity (stiffness) non-invasively and has potential utility because cancers cause tissue stiffening. In recent years, there has been much research into the value of thyroid USE for distinguishing benign and malignant nodules. Preliminary findings from multiple pilot studies and meta-analyses are promising and suggest that USE can augment the anatomical detail provided by high-resolution US. However, a definite role remains controversial and is discussed. • High-resolution US characterises thyroid nodules by demonstration of specific anatomical features • Technical advances heavily influence the key US features of thyroid nodules • Most papillary carcinomas appear stiffer than benign thyroid nodules on US elastography (USE) • Thyroid USE is controversial because of variation in the reported accuracies for malignancy • Combined grey-scale US/USE may lower the FNAC rate in benign nodules.

Serum microRNA profiles in athyroid patients on and off levothyroxine therapy.

PubMed

Massolt, Elske T; Chaker, Layal; Visser, Theo J; Gillis, Ad J M; Dorssers, Lambert C J; Beukhof, Carolien M; Kam, Boen L R; Franssen, Gaston J; Brigante, Giulia; van Ginhoven, Tessa M; Visser, W Edward; Looijenga, Leendert H J; Peeters, Robin P

2018-01-01

Levothyroxine replacement treatment in hypothyroidism is unable to restore physiological thyroxine and triiodothyronine concentrations in serum and tissues completely. Normal serum thyroid stimulating hormone (TSH) concentrations reflect only pituitary euthyroidism and, therefore, novel biomarkers representing tissue-specific thyroid state are needed. MicroRNAs (miRNAs), small non-coding regulatory RNAs, exhibit tissue-specific expression patterns and can be detectable in serum. Previous studies have demonstrated differential expression of (precursors of) miRNAs in tissues under the influence of thyroid hormone. To study if serum miRNA profiles are changed in different thyroid states. We studied 13 athyroid patients (6 males) during TSH suppressive therapy and after 4 weeks of thyroid hormone withdrawal. A magnetic bead capture system was used to isolate 384 defined miRNAs from serum. Subsequently, the TaqMan Array Card 3.0 platform was used for profiling after individual target amplification. Mean age of the subjects was 44.0 years (range 20-61 years). Median TSH levels were 88.9 mU/l during levothyroxine withdrawal and 0.006 mU/l during LT4 treatment with a median dosage of 2.1 μg/kg. After normalization to allow inter-sample analysis, a paired analysis did not demonstrate a significant difference in expression of any of the 384 miRNAs analyzed on and off LT4 treatment. Although we previously showed an up-regulation of pri-miRNAs 133b and 206 in hypothyroid state in skeletal muscle, the present study does not supply evidence that thyroid state also affects serum miRNAs in humans.

Hyperthyroidism

PubMed Central

Sharma, Mala; Aronow, Wilbert S.; Patel, Laxesh; Gandhi, Kaushang; Desai, Harit

2011-01-01

Summary Hyperthyroidism is a pathological syndrome in which tissue is exposed to excessive amounts of circulating thyroid hormone. The most common cause of this syndrome is Graves’ disease, followed by toxic multinodular goitre, and solitary hyperfunctioning nodules. Autoimmune postpartum and subacute thyroiditis, tumors that secrete thyrotropin, and drug-induced thyroid dysfunction, are also important causes. PMID:21455118

Polybrominated Diphenyl Ether (DE-71)Interferes with Thyroid Hormone Action Independent Of Effects On Circulating Levels of Thyroid Hormone in Male Rats

EPA Science Inventory

Polybrominated diphenyl ethers (PBDEs) are routinely found in human tissues including cord blood and breast milk. PBDEs may interfere with thyroid hormone (TH) during development, which could produce neurobehavioral deficits. An assumption in experimental and epidemiological stud...

Analysis of thyroid hormones in biological samples using stable isotope dilution liquid chromatography-tandem mass spectrometry

EPA Science Inventory

This poster presentation will describe analytical chemistry methods for measuring thyroid hormones and related precursors and metabolites in very small tissue or plasma samples. These methods are amenable to measure thyroid hormones in amphibian tadpoles or small mammals used as ...

Septic shock non-thyroidal illness syndrome causes hypothyroidism and conditions for reduced sensitivity to thyroid hormone.

PubMed

Castro, Isabel; Quisenberry, Leah; Calvo, Rosa-Maria; Obregon, Maria-Jesus; Lado-Abeal, Joaquin

2013-04-01

Non-thyroidal illness syndrome (NTIS) is part of the neuroendocrine response to stress, but the significance of this syndrome remains uncertain. The aim of this study was to investigate the effect of lipopolysaccharide (LPS)-induced NTIS on thyroid hormone (TH) levels and TH molecular targets, as well as the relationship between septic shock nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) activation and TH receptor β (THRB) gene expression at a multi-tissue level in a pig model. Prepubertal domestic pigs were given i.v. saline or LPS for 48 h. Serum and tissue TH was measured by chemiluminescence and RIA. Expression of THRs and cofactors was measured by real-time PCR, and deiodinase (DIO) activity was measured by enzyme assays. Tissue NF-kB nuclear binding activity was evaluated by EMSA. LPS-treated pigs had decreased TH levels in serum and most tissues. DIO1 expression in liver and kidney and DIO1 activity in kidney decreased after LPS. No changes in DIO2 activity were observed between groups. LPS induced an increase in hypothalamus, thyroid, and liver DIO3 activity. Among the other studied genes, monocarboxylate transporter 8 and THRB were the most commonly repressed in endotoxemic pigs. LPS-induced NF-kB activation was associated with a decrease in THRB gene expression only in frontal lobe, adrenal gland, and kidney cortex. We conclude that LPS-induced NTIS in pigs is characterized by hypothyroidism and tissue-specific reduced TH sensitivity. The role of NF-kB in regulating THRB expression during endotoxemia, if any, is restricted to a limited number of tissues.

Genes that characterize T3-predominant Graves' thyroid tissues.

PubMed

Matsumoto, Chisa; Ito, Mitsuru; Yamada, Hiroya; Yamakawa, Noriko; Yoshida, Hiroshi; Date, Arisa; Watanabe, Mikio; Hidaka, Yoh; Iwatani, Yoshinori; Miyauchi, Akira; Takano, Toru

2013-02-01

3,5,3'-Triiodothyronine (T(3))-predominant Graves' disease is characterized by the increasing volume of thyroid goiter resulting in poor prognosis. Although type 1 and type 2 iodothyronine deiodinases (DIO1 and DIO2 respectively) are known to be overexpressed in the thyroid tissues of T(3)-predominant Graves' disease, the pathogenesis of this disease is still unclear. The aim of our study is to identify genes that characterize T(3)-predominant Graves' disease tissue in order to clarify the molecular mechanism of this disease. mRNAs from two thyroid tissues of both typical T(3)-predominant and common-type Graves' disease were analyzed with DNA microarrays with probes for 28 869 genes. Genes identified to be differentially expressed between the two groups were further analyzed in the second and third screenings using 70 Graves' thyroid tissues by real-time quantitative RT-PCR. Twenty-three candidate genes were selected as being differentially expressed in the first screening with microarrays. Among these, seven genes, leucine-rich repeat neuronal 1 (LRRN1), bone morphogenetic protein 8a (BMP8A), N-cadherin (CDH2), phosphodiesterase 1A (PDE1A), creatine kinase mitochondrial 2 (CKMT2), integrin beta-3 (ITGB3), and protein tyrosine phosphatase non-receptor type 4 (PTPN4), were confirmed to be differentially expressed in DIO1 or DIO2 over- and underexpressing Graves' tissues. These genes are related to the characteristics of T(3)-predominant Graves' disease, such as high titer level of serum anti-TSH receptor antibody, high free T(3) to free thyroxine ratio, and a large goiter size. They might play a role in the pathogenesis of T(3)-predominant Graves' disease.

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.

Excess iodine promotes apoptosis of thyroid follicular epithelial cells by inducing autophagy suppression and is associated with Hashimoto thyroiditis disease.

PubMed

Xu, Chengcheng; Wu, Fei; Mao, Chaoming; Wang, Xuefeng; Zheng, Tingting; Bu, Ling; Mou, Xiao; Zhou, Yuepeng; Yuan, Guoyue; Wang, Shengjun; Xiao, Yichuan

2016-12-01

The incidence of the autoimmune thyroid disease Hashimoto thyroiditis (HT) has increased in recent years, and increasing evidence supports the contribution of excess iodine intake to thyroid disease. In this study, we examined the status of autophagy and apoptosis in thyroid tissues obtained from patients with HT, and we determined the effects of excessive iodine on the autophagy and apoptosis of thyroid follicular cells (TFCs) in an attempt to elucidate the effects of excess iodine on HT development. Our results showed decreases in the autophagy-related protein LC3B-II, and increases in caspase-3 were observed in thyroid tissues from HT patients. Interestingly, the suppression of autophagy activity in TFCs was induced by excess iodine in vitro, and this process is mediated through transforming growth factor-β1 downregulation and activation of the Akt/mTOR signaling pathway. In addition, excess iodine induced autophagy suppression and enhanced reactive oxygen species (ROS) production and apoptosis of TFCs, which could be rescued by the activation of autophagy. Taken together, our results demonstrated that excess iodine contributed to autophagy suppression and apoptosis of TFCs, which could be important factors predisposing to increased risk of HT development. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Effects of thyroidal, gonadal and adrenal hormones on tissue respiration of streaked frog, Rana limnocharis, at low temperature.

PubMed

Gupta, B B; Chakrabarty, P

1990-01-01

In vivo and in vitro effects of thyroidal, gonadal and adrenal hormones were studied on the rate of liver and skeletal muscle respiration in both the sexes of R. limnocharis during active and inactive phases of the annual activity cycle. Triiodothyronine (L-T3) and thyroxine (L-T4) did not stimulate tissue (liver and muscle) respiration in any of the experiments irrespective of season, sex and temperature. Testosterone, estradiol and corticosterone stimulated O2 uptake significantly irrespective of season, sex and temperature. Adrenaline and nor-adrenaline also stimulated tissue respiration significantly during the winter month. Since the ambient temperature was low even during the active phase (max. temperature 21 degrees C), it seems that the frog might have developed tissue sensitivity for gonadal and adrenal hormones at low temperatures when thyroid hormones are calorigenically ineffective.

Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer.

PubMed

Gurgul, Edyta; Kasprzak, Aldona; Blaszczyk, Agata; Biczysko, Maciej; Surdyk-Zasada, Joanna; Seraszek-Jaros, Agnieszka; Ruchala, Marek

2015-01-01

Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis.

PubMed

Kleinstreuer, Nicole C; Dix, David J; Houck, Keith A; Kavlock, Robert J; Knudsen, Thomas B; Martin, Matthew T; Paul, Katie B; Reif, David M; Crofton, Kevin M; Hamilton, Kerry; Hunter, Ronald; Shah, Imran; Judson, Richard S

2013-01-01

Thousands of untested chemicals in the environment require efficient characterization of carcinogenic potential in humans. A proposed solution is rapid testing of chemicals using in vitro high-throughput screening (HTS) assays for targets in pathways linked to disease processes to build models for priority setting and further testing. We describe a model for predicting rodent carcinogenicity based on HTS data from 292 chemicals tested in 672 assays mapping to 455 genes. All data come from the EPA ToxCast project. The model was trained on a subset of 232 chemicals with in vivo rodent carcinogenicity data in the Toxicity Reference Database (ToxRefDB). Individual HTS assays strongly associated with rodent cancers in ToxRefDB were linked to genes, pathways, and hallmark processes documented to be involved in tumor biology and cancer progression. Rodent liver cancer endpoints were linked to well-documented pathways such as peroxisome proliferator-activated receptor signaling and TP53 and novel targets such as PDE5A and PLAUR. Cancer hallmark genes associated with rodent thyroid tumors were found to be linked to human thyroid tumors and autoimmune thyroid disease. A model was developed in which these genes/pathways function as hypothetical enhancers or promoters of rat thyroid tumors, acting secondary to the key initiating event of thyroid hormone disruption. A simple scoring function was generated to identify chemicals with significant in vitro evidence that was predictive of in vivo carcinogenicity in different rat tissues and organs. This scoring function was applied to an external test set of 33 compounds with carcinogenicity classifications from the EPA's Office of Pesticide Programs and successfully (p = 0.024) differentiated between chemicals classified as "possible"/"probable"/"likely" carcinogens and those designated as "not likely" or with "evidence of noncarcinogenicity." This model represents a chemical carcinogenicity prioritization tool supporting targeted testing and functional validation of cancer pathways.

[Clinical features of myasthenia gravis with thyroid disease with 106 patients].

PubMed

Meng, Chao; Jing, Yun; Li, Ran; Zhang, Xiaojun; Wang, Jiawei

2016-03-22

To report the presentation, clinical course and prognosis of myasthenia gravis (MG) with thyroid disease. Retrospective data analysis was conducted.Between 2004 and 2013, we reviewed a total of 106 patients with MG. We analyzed the clinical features, the relationship between the thyroid function, antibodies and the clinical course, prognosis. (1) In our study, 20/106 (18.87%) patients were thyroid function-abnormal, 37/106 (34.91) were thyroglobulin antibodies (TGAb) and/or thyroid microsomal antibody (TMAb)-positive, and abnormality was observed in 46 (43.40%) of the thyroid gland. Thyroid antibody positive rate was higher than abnormal thyroid function rate, and the difference was significant (P=0.036). (2) The thyroid stimulating hormone (TSH) level ((2.9±4.0) mIU/L) of ocular MG was higher than the level ((1.5±1.1) mIU/L) of generalized MG (P=0.01). (3) The transformation time of 52 ocular type to generalized type was longer in higher antibody group than in normal group (P=0.04). And there were no significant differences between the elevated TSH type and the normal TSH type, the abnormal thyroid function type and normal thyroid function type, the abnormal thyroid type and the normal thyroid type. (4) Comparing the TSH level, total antibody level, TGAb, and TMAb level between the ease group and the unease group in the course of 1 year, 2 years, 5 years, there were no significant differences (all P>0.05). MG is often companied with thyroid abnormalities. MG patients are more susceptible to hashimoto thyroiditis and other autoimmune thyroid diseases. Ocular type patients are more likely to suffer from thyroid function decrease than the generalized type. MG patients with hashimoto thyroiditis and other autoimmune thyroid diseases are more sensitive to respond to therapy means like glucocorticoid therapy, and the short-term prognosis is relatively good. There are no significant correlations between the MG remission rate and TSH level, total antibody level, TGAb and TMAb level.

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.

Role of thyroidal and testicular hormones in regulation of tissue respiration in male air-breathing fish, Clarias batrachus (Linn.).

PubMed

Lynshiang, D S; Gupta, B B

2000-07-01

In vivo and in vitro effects of thyroidal hormones (MIT, DIT, T3, T4), propyl thiouracil (PTU), testosterone and cyproterone acetate were studied on the rate of tissue (liver, muscle, kidney and brain) respiration of adult male C. batrachus during winter and summer/rainy seasons. Monoiodotyrosine (MIT) and diiodothyrosine (DIT) increased the respiratory rate in a dose-dependent and temperature-independent manner. Triiodothyronine (T3) and thyroxine (T4) stimulated tissue respiration during summer/rainy months but not during winter. PTU decreased tissue respiration during summer/rainy season and also at simulated low temperature. Testosterone invariably stimulated the rate of respiration of the tissues, while in vivo treatment with cyproterone acetate significantly decreased the metabolic rate of all the tissues. The findings suggest that in C. batrachus MIT and DIT may be more important than T3 and T4 at low temperature, endogenous thyroid hormones are involved indirectly in energy metabolism even during winter/at low temperature and testicular hormones are actively involved in the respiration.

MOK, a pharmacopuncture medicine, regulates thyroid dysfunction in L-thyroxin-induced hyperthyroidism in rats through the regulation of oxidation and the TRPV1 ion channel.

PubMed

Hwang, Ji Hye; Kang, Seok Yong; Kang, An Na; Jung, Hyo Won; Jung, Chul; Jeong, Jin-Ho; Park, Yong-Ki

2017-12-15

In this study, we evaluated the therapeutic effect of MOK, a pharmacopuncture medicine, on thyroid dysfunction in L-thyroxin (LT4)-induced hyperthyroidism rats. The experimental hyperthyroidism model was prepared by the intraperitoneal injection of LT4 (0.5 mg/kg) once daily for 2 weeks in SD rats. MOK extract was injected at doses of 0.3 or 3 mg/kg on acupuncture points in the thyroid glands of LT4-induced hypothyroidism rats once a day for 2 weeks. The body temperature, body weight, and food/water intake were measured once a week for 2 weeks. The levels of thyroid hormones, total cholesterol, LDL-cholesterol, GOT, and GPT were measured in the sera of rats using ELISA and an automatic blood analyzer. The histological changes of thyroid tissues were observed by H&E staining. The expression of thermo-regulating protein, TRPV1 was determined by western blot in dorsal root ganglion (DRG) and brain tissues. We also measured the contents of GSH in the liver and antioxidant enzymes, SOD, and catalase in the liver, heart, and brain tissues by enzyme-based assay and Western blot, respectively. The acupuncture of MOK extract on the thyroid gland of LT4-induced hyperthyroidism rats significantly decreased the body temperature, and did not change body weight and food and water intakes. MOK acupuncture significantly increased the level of TSH, and decreased the levels of T3 and T4 in hyperthyroidism rats. The expression of TRPV1 was inhibited in both DRG and brain tissues after MOK acupuncture, and the levels of GOT, GPT, total cholesterol, and LDL-cholesterol were also decreased. MOK acupuncture also inhibited the pathological feature with follicular lining epithelial thicknesses and increased follicular colloid depositions in the thyroid glands of hypothyroidism. MOK acupuncture significantly increased hepatic GSH levels and decreased the expression of SOD and catalase in the liver, heart, and brain tissues of hyperthyroidism rats. These results suggest that the pharmacopuncture with MOK extract in hyperthyroidism can improve the pathophysiological changes through regulating the body temperature, thyroid hormones imbalance, lipid accumulation, and oxidation. This anti-hyperthyroidism effect of MOK pharmacopuncture is thought to be related to the control of thermo-regulating protein TRPV1 in DRG and brain.

Technetium 99m pertechnetate scans in congenital hypothyroidism

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

Bauman, R.A.; Bode, H.H.; Hayek, A.

1976-08-01

Goiters are rarely palpable in infants with congenital hypothyroidism except in the case of maternal ingestion of iodide. The presence or absence of glandular tissue is, however, important for genetic and prognostic counseling and for acceleration of diagnosis in other affected siblings. The detection of thyroid tissue by /sup 99m/Tc pertechnetate scans in a significant number of our patients heretofore considered athyreotic establishes that physical findings and traditional laboratory data are not adequate to determine whether or not thyroid tissue is present.

A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses.

PubMed

Nasreldin, Magda H A; Ibrahim, Eman A; Saad El-Din, Somaia A

2016-01-01

Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations.

A Case Report: A Third/Fourth Branchial Pouch Anomaly Presented by Solid Thyroid and Lateral Cervical Neck Masses

PubMed Central

Nasreldin, Magda H. A.; Ibrahim, Eman A.; Saad El-Din, Somaia A.

2016-01-01

Branchial pouch-derived anomalies may arise from remnants of the first, second, or third/fourth branchial arches. Branchial pouch-related structures are found within the thyroid gland in the form of solid cell rests, epithelial lined cyst with or without an associated lymphoid component, thymic and/or parathyroid tissue, and less commonly in the form of heterotopic cartilage. We present a rare case of left solid thyroid swelling nearby two cervical nodules in a seven-year-old female with a clinical diagnosis suggestive of malignant thyroid tumor with metastasis to the cervical lymph nodes. Histopathological examination revealed that it was compatible with third/fourth branchial pouch-derived anomaly composed of mature cartilage and thymic and parathyroid tissues for clinical and radiological correlations. PMID:26819565

Radioisotope imaging for the evaluation of thyroid neoplasia and hypothyroidism in a dog

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

Branam, J.E.; Leighton, R.L.; Hornof, W.J.

1982-05-01

An 11-year-old dog was diagnosed as having concurrent unilateral follicular thyroid carcinoma and hypothyroidism. Radioisotope imaging with /SUP 99m/Tc as sodium pertechnatate identified the extent of thyroid tissue involvement. A combination of surgical resection and hormonal supplementation resulted in a favorable clinical response.

Neither bST nor Growth Hormone Releasing Factor Alter Expression of Thyroid Hormone Receptors in Liver and Mammary Tissues

USDA-ARS?s Scientific Manuscript database

Physiological effects of thyroid hormones are mediated primarily by binding of triiodothyronine, to specific nuclear receptors. It has been hypothesized that organ-specific changes in production of triiodothyronine from its prohormone, thyroxine, target the action of thyroid hormones to the mammary...

TRANSCRIPTIONAL RESPONSES IN THYROID TISSUES FROM RATS TREATED WITH A TUMORIGENIC AND A NON-TUMORIGENIC TRIAZOLE CONAZOLE FUNGICIDE

EPA Science Inventory

Conazoles are fungicides that are used in agriculture and medicine. Conazoles can induce follicular cell adenomas of the thyroid in rats after chronic bioassay and are considered to pose a hazard to humans. Pathways and networks of genes that were associated with thyroid cancer w...

Studies on Changes of β-Adrenergic Receptors in Polymorphonuclear Cell and Mononuclear Cell with the Changes of Thyroid Function

PubMed Central

Lee, Jong Do; You, Myung Hee; Kim, Young Seol; Kim, Jin Woo; Kim, Kwang Won; Kim, Sun Woo; Choi, Young Kil

1986-01-01

Although it has been well established that thyroid hormones increase β-adrenergic receptors of various tissues in the animal studies, there are controversies about the β-adrenergic receptor changes of human mononuclear cells and polymorphonuclear cells. The present study was performed to analyze the change of β-adrenergic receptor of those cells according to the thyroid functional status and to evaluate their usefulness in assessment of sympathetic hyperactivity. We measured [3H]-dihydroalprenolol binding to circulating mononuclear and polymorphonuclear cells from 18 patients with hyperthyrodism, 7 with hypothyroidism, 8 with euthyroid goiter and 21 normal controls. Only with polymorphonuclear cells the receptor concentration was significantly higher (P<0.01) in hyperthyroidism (46.07±4.78 fmol/mg protein) than in the normal control (28.42±2.06 fmol/mg protein) and the affinity constants of both cells were comparable to normal control values. And serum concentrations of T3 were not correlated well with the changes of receptor concentrations in hyperthyroidism. The patients with hypothyroidism and euthyroid goiter showed no significant difference in the receptor concentration and the affinity constants with both cell binding assays. These results indicate that thyroid hormones increase the receptor concentration in polymorphonuclear cells which might be responsible for the symptoms of sympathetic hyperactivity and the polymorphornuclear cells are useful for β-adrenergic receptor assay. PMID:15759381

Thyroid Hormone and Leptin in the Testis

PubMed Central

Ramos, Cristiane Fonte; Zamoner, Ariane

2014-01-01

Leptin is primarily expressed in white adipose tissue; however, it is expressed in the hypothalamus and reproductive tissues as well. Leptin acts by activating the leptin receptors (Ob-Rs). Additionally, the regulation of several neuroendocrine and reproductive functions, including the inhibition of glucocorticoids and enhancement of thyroxine and sex hormone concentrations in human beings and mice are leptin functions. It has been suggested that thyroid hormones (TH) could directly regulate leptin expression. Additionally, hypothyroidism compromises the intracellular integration of leptin signaling specifically in the arcuate nucleus. Two TH receptor isoforms are expressed in the testis, TRa and TRb, with TRa being the predominant one that is present in all stages of development. The effects of TH involve the proliferation and differentiation of Sertoli and Leydig cells during development, spermatogenesis, and steroidogenesis. In this context, TH disorders are associated with sexual dysfunction. An endocrine and/or direct paracrine effect of leptin on the gonads inhibits testosterone production in Leydig cells. Further studies are necessary to clarify the effects of both hormones in the testis during hypothyroidism. The goal of this review is to highlight the current knowledge regarding leptin and TH in the testis. PMID:25505448

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

Increased expression of G-protein-coupled receptor kinases 3 and 4 in hyperfunctioning thyroid nodules.

PubMed

Voigt, Carsten; Holzapfel, Hans-Peter; Meyer, Silke; Paschke, Ralf

2004-07-01

G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis. While G-protein-coupled receptor kinases 2 and 5 have been shown to be involved in the desensitization of the rat thyrotropin receptor (TSHR), their role in the pathophysiology of hyperfunctioning thyroid nodules (HTNs) is unknown. Therefore, we analyzed the expression pattern of the known GRKs in human thyroid tissue and investigated their function in the pathology of HTNs. The expression of different GRKs in human thyroid and HTNs was measured by Western blotting. The influence of GRK expression on TSHR function was analyzed by coexpression experiments in HEK 293 cells. We demonstrate that in addition to GRKs 2, 5 and 6, GRKs 3 and 4 are also expressed in the human thyroid. GRKs 2, 3, 5 and 6 are able to desensitize the TSHR in vitro. This GRK-induced desensitization is amplified by the additional over-expression of beta-arrestin 1 or 2. We did not find any mutations in the GRKs 2, 3 and 5 from 14 HTNs without TSHR mutations and Gsalpha mutations. The expression of GRKs 3 and 4 was increased in HTNs independently from the existence of TSHR mutations or Gsalpha mutations. In conclusion, the increased expression of GRK 3 in HTNs and the ability of GRK 3 to desensitize the TSHR in vitro, suggest a potential role for GRK 3 as a negative feedback regulator for the constitutively activated cAMP pathway in HTNs.

[Changes in muscle tissue in hypothyroidism].

PubMed

Jiskra, J

2001-09-01

This article offers a synopsis of detailed analysis of the functional and structural changes in muscle tissue in manifest and subclinical hypothyroidism. There is a brief overview of the division between mypathy and myositis, with emphasis on endocrinological and metabolic disorders. The necessity of endocrinological examination in each case of myopathy the etiology of which is indefinite is stressed, and this especially before the instigation of non-specific immunosuppressive treatment (e.g., corticosteroids) as this treatment has the risk of undesirable side-effects. In conclusion, it emphasises the negative influence of the nexus of hypothyroidism and the administering of a hypolipidemic in tandem on muscle tissue, as in rare cases this can lead to the disintegration of muscle tissue, i.e., rhabdomyolysis. The administering of hypolipidemic drugs to patients with hypothyroidism is indicated only in those cases where persists hyperlipoproteinemia after the normalisation of the thyroid function by substitutional treatment.

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.

Methamphetamine-associated dysregulation of the hypothalamic-pituitary-thyroid axis.

PubMed

Jones, Deborah L; Carrico, Adam W; Babayigit, Suat; Rodriguez, Violeta J; Aguila, Carlos; Kumar, Mahendra

2018-05-17

Methamphetamine and HIV impair thyroid function, but few studies have investigated their combined effects on thyroid dysregulation. This study examined the associations of methamphetamine use alone and in combination with HIV on thyroid function among men in South Florida. Measures of thyroid function in methamphetamine-using, HIV-infected (METH+HIV+; n = 127) and HIV-negative (METH+HIV-; n = 46) men who have sex with men (MSM) were compared to non-methamphetamine-using, HIV-negative men (METH-HIV-; n = 136). Thyroid function was dysregulated in methamphetamine-using MSM, irrespective of HIV status. Both meth-using groups had greater odds of abnormal thyroid stimulating hormone levels and significantly higher mean free triiodothyronine (T3) levels. Elevated free T3 was associated with greater depressive symptoms. Overall, outcomes have important implications for assessment of thyroid function in methamphetamine users, particularly among those presenting with depression.

The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing.

PubMed

Lan, Xiabin; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Cao, Jun; Zhu, Xuhang; Ge, Minghua

2018-05-25

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776-, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895- being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047-, chr9: 16435553-16437522-, and chr22: 36006931-36007153- being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

[Effects of maternal hyperthyroidism and antithyroid drug therapy on thyroid function of newborn infants].

PubMed

Lian, Xiao-lan; Bai, Yao; Xun, Yun-hua; Dai, Wei-xin; Guo, Zhi-sheng

2005-12-01

To evaluate the relationship between the incidence of abnormal thyroid function of newborns and maternal hyperthyroidism with antithyroid drug therapy. The clinical data of 35 neonates born to mothers with hyperthyroidism from 1983 to 2003 in Peking Union Medical College Hospital were retrospectively analyzed. According to the maternal thyroid function and the antithyroid drugs taken during pregnancy, subjects were divided into different groups. The proportion of abnormal thyroid function in newborn was 48.6% (17/35). The prevalences of primary hypothyroidism, subclinical hypothyroidism, hypothyroxinemia, and central hypothyroidism were 29.4%, 29.4%, 35.3%, and 5.9%, respectively. The incidence of abnormal thyroid function of neonates whose mothers did not take the antithyroid drugs (ATDs) until the third trimester of pregnancy was significantly higher than those without and with ATDs during the first or second trimester (P < 0.01). The incidence of abnormal thyroid function significantly increased in premature neonates, neonates whose mothers with modest or heavy pregnant hypertension, or neonates whose core serum thyroid-stimulating hormone or serum anti-thyroid peroxidase antibodies levels were abnormal. The risk of abnormal thyroid function of infants whose hyperthyroid mothers did not take ATDs until the third trimester of pregnancy may be increased. Prompt diagnosis and appropriate treatment of hyperthyroidism in pregnant women are essential for the prevention of neonatal thyroid functional abnormality.

Postotic and preotic cranial neural crest cells differently contribute to thyroid development.

PubMed

Maeda, Kazuhiro; Asai, Rieko; Maruyama, Kazuaki; Kurihara, Yukiko; Nakanishi, Toshio; Kurihara, Hiroki; Miyagawa-Tomita, Sachiko

2016-01-01

Thyroid development and formation vary among species, but in most species the thyroid morphogenesis consists of five stages: specification, budding, descent, bilobation and folliculogenesis. The detailed mechanisms of these stages have not been fully clarified. During early development, the cranial neural crest (CNC) contributes to the thyroid gland. The removal of the postotic CNC (corresponding to rhombomeres 6, 7 and 8, also known as the cardiac neural crest) results in abnormalities of the cardiovascular system, thymus, parathyroid glands, and thyroid gland. To investigate the influence of the CNC on thyroid bilobation process, we divided the CNC into two regions, the postotic CNC and the preotic CNC (from the mesencephalon to rhombomere 5) regions and examined. We found that preotic CNC-ablated embryos had a unilateral thyroid lobe, and confirmed the presence of a single lobe or the absence of lobes in postotic CNC-ablated chick embryos. The thyroid anlage in each region-ablated embryos was of a normal size at the descent stage, but at a later stage, the thyroid in preotic CNC-ablated embryos was of a normal size, conflicting with a previous report in which the thyroid was reduced in size in the postotic CNC-ablated embryos. The postotic CNC cells differentiated into connective tissues of the thyroid in quail-to-chick chimeras. In contrast, the preotic CNC cells did not differentiate into connective tissues of the thyroid. We found that preotic CNC cells encompassed the thyroid anlage from the specification stage to the descent stage. Finally, we found that endothelin-1 and endothelin type A receptor-knockout mice and bosentan (endothelin receptor antagonist)-treated chick embryos showed bilobation anomalies that included single-lobe formation. Therefore, not only the postotic CNC, but also the preotic CNC plays an important role in thyroid morphogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Cell division cycle 45 promotes papillary thyroid cancer progression via regulating cell cycle.

PubMed

Sun, Jing; Shi, Run; Zhao, Sha; Li, Xiaona; Lu, Shan; Bu, Hemei; Ma, Xianghua

2017-05-01

Cell division cycle 45 was reported to be overexpressed in some cancer-derived cell lines and was predicted to be a candidate oncogene in cervical cancer. However, the clinical and biological significance of cell division cycle 45 in papillary thyroid cancer has never been investigated. We determined the expression level and clinical significance of cell division cycle 45 using The Cancer Genome Atlas, quantitative real-time polymerase chain reaction, and immunohistochemistry. A great upregulation of cell division cycle 45 was observed in papillary thyroid cancer tissues compared with adjacent normal tissues. Furthermore, overexpression of cell division cycle 45 positively correlates with more advanced clinical characteristics. Silence of cell division cycle 45 suppressed proliferation of papillary thyroid cancer cells via G1-phase arrest and inducing apoptosis. The oncogenic activity of cell division cycle 45 was also confirmed in vivo. In conclusion, cell division cycle 45 may serve as a novel biomarker and a potential therapeutic target for papillary thyroid cancer.

Genetic Alterations in Hungarian Patients with Papillary Thyroid Cancer.

PubMed

Tobiás, Bálint; Halászlaki, Csaba; Balla, Bernadett; Kósa, János P; Árvai, Kristóf; Horváth, Péter; Takács, István; Nagy, Zsolt; Horváth, Evelin; Horányi, János; Járay, Balázs; Székely, Eszter; Székely, Tamás; Győri, Gabriella; Putz, Zsuzsanna; Dank, Magdolna; Valkusz, Zsuzsanna; Vasas, Béla; Iványi, Béla; Lakatos, Péter

2016-01-01

The incidence of thyroid cancers is increasing worldwide. Some somatic oncogene mutations (BRAF, NRAS, HRAS, KRAS) as well as gene translocations (RET/PTC, PAX8/PPAR-gamma) have been associated with the development of thyroid cancer. In our study, we analyzed these genetic alterations in 394 thyroid tissue samples (197 papillary carcinomas and 197 healthy). The somatic mutations and translocations were detected by Light Cycler melting method and Real-Time Polymerase Chain Reaction techniques, respectively. In tumorous samples, 86 BRAF (44.2%), 5 NRAS (3.1%), 2 HRAS (1.0%) and 1 KRAS (0.5%) mutations were found, as well as 9 RET/PTC1 (4.6%) and 1 RET/PTC3 (0.5%) translocations. No genetic alteration was seen in the non tumorous control thyroid tissues. No correlation was detected between the genetic variants and the pathological subtypes of papillary cancer as well as the severity of the disease. Our results are only partly concordant with the data found in the literature.

Weight gain - unintentional

MedlinePlus

... Cushing syndrome Underactive thyroid, or low thyroid (hypothyroidism) Polycystic ovary syndrome Menopause Pregnancy Bloating, or swelling due to a buildup of fluid in the tissues can cause weight gain. This may be due to menstruation, heart ...

A misdiagnosed Riedel's thyroiditis successfully treated by thyroidectomy and tamoxifen.

PubMed

Wang, Chih-Jung; Wu, Ta-Jen; Lee, Chung-Ta; Huang, Shih-Ming

2012-12-01

Riedel's thyroiditis, known as invasive fibrous thyroiditis, is a very rare form of chronic thyroiditis. It is hard to make the diagnosis without surgical biopsy. We present a case of Riedel's thyroiditis in a 52-year-old female with past history of Hashimoto's thyroiditis. She suffered from bilateral neck pain, which radiated to both lower jaws. The erythrocyte sedimentation rate was 125 mm/hour. Subacute thyroiditis superimposed on Hashimoto's thyroiditis was diagnosed and treated with steroid. However the response was poor and she had a history of severe peptic ulcer. To avoid inducing the peptic ulcer by steroid, she received bilateral subtotal thyroidectomy. During surgery, the thyroid had severe adhesion to surrounding soft tissue and the pathology showed Riedel's thyroiditis. The neck pain improved after thyroidectomy. Tamoxifen has been given for 8 months and the size of remnant thyroid decreased to 8 mm. We concluded that combined thyroidectomy and tamoxifen successfully cured a patient with Riedel's thyroiditis. Copyright © 2012. Published by Elsevier B.V.

Hyperthyroidism increases brown fat metabolism in humans.

PubMed

Lahesmaa, Minna; Orava, Janne; Schalin-Jäntti, Camilla; Soinio, Minna; Hannukainen, Jarna C; Noponen, Tommi; Kirjavainen, Anna; Iida, Hidehiro; Kudomi, Nobuyuki; Enerbäck, Sven; Virtanen, Kirsi A; Nuutila, Pirjo

2014-01-01

Thyroid hormones are important regulators of brown adipose tissue (BAT) development and function. In rodents, BAT metabolism is up-regulated by thyroid hormones. The purpose of this article was to investigate the impact of hyperthyroidism on BAT metabolism in humans. This was a follow-up study using positron emission tomography imaging. Glucose uptake (GU) and perfusion of BAT, white adipose tissue, skeletal muscle, and thyroid gland were measured using [18F]2-fluoro-2-deoxy-D-glucose and [15O]H2O and positron emission tomography in 10 patients with overt hyperthyroidism and in 8 healthy participants. Five of the hyperthyroid patients were restudied after restoration of euthyroidism. Supraclavicular BAT was quantified with magnetic resonance imaging or computed tomography and energy expenditure (EE) with indirect calorimetry. Compared with healthy participants, hyperthyroid participants had 3-fold higher BAT GU (2.7±2.3 vs 0.9±0.1 μmol/100 g/min, P=.0013), 90% higher skeletal muscle GU (P<.005), 45% higher EE (P<.005), and a 70% higher lipid oxidation rate (P=.001). These changes were reversible after restoration of euthyroidism. During hyperthyroidism, serum free T4 and free T3 were strongly associated with EE and lipid oxidation rates (P<.001). TSH correlated inversely with BAT and skeletal muscle glucose metabolism (P<.001). Hyperthyroidism had no effect on BAT perfusion, whereas it stimulated skeletal muscle perfusion (P=.04). Thyroid gland GU did not differ between hyperthyroid and euthyroid study subjects. Hyperthyroidism increases GU in BAT independently of BAT perfusion. Hyperthyroid patients are characterized by increased skeletal muscle metabolism and lipid oxidation rates.

Thyroid Hormone, Cancer, and Apoptosis.

PubMed

Lin, Hung-Yun; Chin, Yu-Tan; Yang, Yu-Chen S H; Lai, Husan-Yu; Wang-Peng, Jacqueline; Liu, Leory F; Tang, Heng-Yuan; Davis, Paul J

2016-06-13

Thyroid hormones play important roles in regulating normal metabolism, development, and growth. They also stimulate cancer cell proliferation. Their metabolic and developmental effects and growth effects in normal tissues are mediated primarily by nuclear hormone receptors. A cell surface receptor for the hormone on integrin [alpha]vβ3 is the initiation site for effects on tumor cells. Clinical hypothyroidism may retard cancer growth, and hyperthyroidism was recently linked to the prevalence of certain cancers. Local levels of thyroid hormones are controlled through activation and deactivation of iodothyronine deiodinases in different organs. The relative activities of different deiodinases that exist in tissues or organs also affect the progression and development of specific types of cancers. In this review, the effects of thyroid hormone on signaling pathways in breast, brain, liver, thyroid, and colon cancers are discussed. The importance of nuclear thyroid hormone receptor isoforms and of the hormone receptor on the extracellular domain of integrin [alpha]vβ3 as potential cancer risk factors and therapeutic targets are addressed. We analyze the intracellular signaling pathways activated by thyroid hormones in cancer progression in hyperthyroidism or at physiological concentrations in the euthyroid state. Determining how to utilize the deaminated thyroid hormone analog (tetrac), and its nanoparticulate derivative to reduce risks of cancer progression, enhance therapeutic outcomes, and prevent cancer recurrence is also deliberated. © 2016 American Physiological Society. Compr Physiol 6:1221-1237, 2016. Copyright © 2016 John Wiley & Sons, Inc.

Maternal transfer of methimazole and effects on thyroid hormone availability in embryonic tissues.

PubMed

Van Herck, Stijn L J; Geysens, Stijn; Bald, Edward; Chwatko, Grazyna; Delezie, Evelyne; Dianati, Elham; Ahmed, R G; Darras, Veerle M

2013-07-01

Methimazole (MMI) is an anti-thyroid drug used in the treatment of chronic hyperthyroidism. There is, however, some debate about its use during pregnancy as MMI is known to cross the mammalian placenta and reach the developing foetus. A similar problem occurs in birds, where MMI is deposited in the egg and taken up by the developing embryo. To investigate whether maternally derived MMI can have detrimental effects on embryonic development, we treated laying hens with MMI (0.03% in drinking water) and measured total and reduced MMI contents in the tissues of hens and embryos at different stages of development. In hens, MMI was selectively increased in the thyroid gland, while its levels in the liver and especially brain remained relatively low. Long-term MMI treatment induced a pronounced goitre with a decrease in thyroxine (T₄) content but an increase in thyroidal 3,5,3'-triiodothyronine (T₃) content. This resulted in normal T₃ levels in tissues except in the brain. In chicken embryos, MMI levels were similar in the liver and brain. They gradually decreased during development but always remained above those in the corresponding maternal tissues. Contrary to the situation in hens, T₄ availability was only moderately affected in embryos. Peripheral T₃ levels were reduced in 14-day-old embryos but normal in 18-day-old embryos, while brain T₃ content was decreased at all embryonic stages tested. We conclude that all embryonic tissues are exposed to relatively high doses of MMI and its oxidised metabolites. The effect of maternal MMI treatment on embryonic thyroid hormone availability is most pronounced for brain T₃ content, which is reduced throughout the embryonic development period.

Medicinal values of fruit peels from Citrus sinensis, Punica granatum, and Musa paradisiaca with respect to alterations in tissue lipid peroxidation and serum concentration of glucose, insulin, and thyroid hormones.

PubMed

Parmar, Hamendra Singh; Kar, Anand

2008-06-01

Peel extracts from Citrus sinensis, Punica granatum, and Musa paradisiaca were investigated for their effects on tissue lipid peroxidation (LPO) and on the concentration of thyroid hormones, insulin, and glucose in male rats. In vitro inhibition of H(2)O(2)-induced LPO in red blood cells of rats by 0.25, 0.50, 1.0, and 2.0 microg/mL C. sinensis, P. granatum, and M. paradisiaca peel extracts was observed in a dose-specific manner. Maximum inhibition was observed at 0.50 microg/mL C. sinensis, 2.0 microg/mL P. granatum, and 1.0 microg/mL M. paradisiaca. In the in vivo investigation, out of four different concentrations of each peel extract, 25, 200, and 100 mg/kg C. sinensis, P. granatum, and M. paradisiaca, respectively, were found to maximally inhibit hepatic LPO. The most effective doses were further evaluated for effects on serum triiodothyronine (T(3)), thyroxine (T(4)), insulin, and glucose concentrations. C. sinensis exhibited antithyroidal, hypoglycemic, and insulin stimulatory activities, in addition to inhibition of LPO, as it significantly decreased the serum T(4) (P < .05) and glucose (P < .001) concentrations with a concomitant increase in insulin levels (P < .05). P. granatum decreased LPO in hepatic, cardiac, and renal tissues (P < .01, P < .001, and P < .05, respectively) and serum glucose concentration (P < .01). M. paradisiaca strongly inhibited the serum level of thyroid hormones (P < .01 for both T(3) and T(4)) but increased the level of glucose (P < .05). These findings reveal the hitherto unknown potential of the tested peel extracts in the regulation of thyroid function and glucose metabolism. Besides antiperoxidative activity, C. sinensis extract has antithyroidal, hypoglycemic, and insulin stimulatory properties, which suggest its potential to ameliorate both hyperthyroidism and diabetes mellitus.

Effect of cell phone-like electromagnetic radiation on primary human thyroid cells.

PubMed

Silva, Veronica; Hilly, Ohad; Strenov, Yulia; Tzabari, Cochava; Hauptman, Yirmi; Feinmesser, Raphael

2016-01-01

To evaluate the potential carcinogenic effects of radiofrequency energy (RFE) emitted by cell phones on human thyroid primary cells. Primary thyroid cell culture was prepared from normal thyroid tissue obtained from patients who underwent surgery at our department. Subconfluent thyroid cells were irradiated under different conditions inside a cell incubator using a device that simulates cell phone-RFE. Proliferation of control and irradiated cells was assessed by the immunohistochemical staining of antigen Kiel clone-67 (Ki-67) and tumor suppressor p53 (p53) expression. DNA ploidy and the stress biomarkers heat shock protein 70 (HSP70) and reactive oxygen species (ROS) was evaluated by fluorescence-activated cell sorting (FACS). Our cells highly expressed thyroglobulin (Tg) and sodium-iodide symporter (NIS) confirming the origin of the tissue. None of the irradiation conditions evaluated here had an effect neither on the proliferation marker Ki-67 nor on p53 expression. DNA ploidy was also not affected by RFE, as well as the expression of the biomarkers HSP70 and ROS. Our conditions of RFE exposure seem to have no potential carcinogenic effect on human thyroid cells. Moreover, common biomarkers usually associated to environmental stress also remained unchanged. We failed to find an association between cell phone-RFE and thyroid cancer. Additional studies are recommended.

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.

Differential expression of mucins 1-6 in papillary thyroid carcinoma: evidence for transformation-dependent post-translational modifications of MUC1 in situ.

PubMed

Magro, Gaetano; Schiappacassi, Monica; Perissinotto, Daniela; Corsaro, Antonella; Borghese, Cinzia; Belfiore, Antonino; Colombatti, Alfonso; Grasso, Sebastiano; Botti, Carlo; Bombardieri, Emilio; Perris, Roberto

2003-07-01

Mucins are primary glycoproteins of epithelia that are known to undergo major changes in their post-translational processing during neoplastic transformation. This study has examined the expression pattern of seven primary mucins, ie mucin (MUC) 1, 2, 3, 4, 5AC, 5B and 6, in normal, hyperplastic, benign neoplastic, and papillary-type carcinoma (PTC) tissues of the thyroid. MUC1 and MUC5B were the only mucins to be widely transcribed in both benign and malignant tissues. In contrast, MUC4 transcripts were undetectable in normal thyroids, and were present in only 40% of the hyperplastic and malignant thyroid tissues. In PTC, MUC1 was identified as a single mRNA transcript, rejecting the idea that this mucin may undergo transformation-dependent alternative splicing in thyroid tumours. The tissue distribution of MUC1 and MUC4 proteins was highly heterogeneous: this largely paralleled their mRNA expression profiles and supported the conclusion that whereas MUC1 was ubiquitously expressed in PTC, MUC4 was detectable in less than 20% of the cases analysed. In order to determine whether post-translational modifications of MUC1, putatively associated with malignancy, also occurred in the mucin produced by PTC, immunohistochemistry was performed with a panel of well-characterized anti-MUC1 antibodies in conjunction with digestion of the tissue sections with deglycosylating enzymes. These experiments, which were supported by immunochemical analyses of the MUC1 and MUC4 glycoforms extracted from tissues, collectively demonstrated markedly divergent MUC1 glycosylation profiles in normal and benign thyroid tissues when compared with PTC. Characteristically, these latter neoplastic cells produced mucin molecules carrying complex poly-N-lactosamine-type glycans capped with fucose and neuraminic acid residues. The present study also found evidence in PTC for the potential presence of proteolytically processed MUC1 isoforms which differ in their post-translational traits depending on whether they are retained on the cell surface or secreted into the extracellular space. It is proposed that the observed differences in the glycosylation properties of normal and neoplastic MUC1 may be exploitable as an ancillary tool in the diagnosis of PTC. Copyright 2003 John Wiley & Sons, Ltd.

The advent of ultrasound-guided ablation techniques in nodular thyroid disease: towards a patient-tailored approach.

PubMed

Papini, Enrico; Pacella, Claudio M; Misischi, Irene; Guglielmi, Rinaldo; Bizzarri, Giancarlo; Døssing, Helle; Hegedus, Laszlo

2014-08-01

Surgery is the long-established therapeutic option for benign thyroid nodules, which steadily grow and become symptomatic. The cost of thyroid surgery, the risk of temporary or permanent complications, and the effect on quality of life, however, remain relevant concerns. Therefore, various minimally invasive treatments, directed towards office-based management of symptomatic nodules, without requiring general anaesthesia, and with negligible damage to the skin and cervical tissues, have been proposed during the past two decades. Today, ultrasound-guided percutaneous ethanol injection and thermal ablation with laser or radiofrequency have been thoroughly evaluated, and are accessible procedures in specialized centres. In clinical practice, relapsing thyroid cysts are effectively managed with percutaneous ethanol injection treatment, which should be considered therapy of choice. In solid non-functioning thyroid nodules that grow or become symptomatic, trained operators may safely induce, with a single session of laser ablation treatment or radiofrequency ablation, a 50% volume decrease and, in parallel, improve local symptoms. In contrast, hyperfunctioning nodules remain best treated with radioactive iodine, which results in a better control of hyperthyroidism, also in the long-term, and fewer side-effects. Currently, minimally invasive treatment is also investigated for achieving local control of small size neck recurrences of papillary thyroid carcinoma in patients who are poor candidates for repeat cervical lymph node dissection. This particular use should still be considered experimental. Copyright © 2014 Elsevier Ltd. All rights reserved.

The pharmacists' role in improving guideline compliance for thyroid function testing in patients with heart failure.

PubMed

Ziman, Melanie E; Bui, Hien T; Smith, Craig S; Tsukiji, Lori A; Asmatey, Veda M; Chu, Steven B; Miano, John S

2012-04-01

This single-center retrospective pilot program's objective was to utilize outpatient pharmacists to improve laboratory test adherence in chronic heart failure (CHF) patients overdue for thyroid function testing, thereby demonstrating the value of the outpatient pharmacist and justifying possible clinical role expansion. Thyroid disorders may contribute to CHF development, progression, and exacerbation. Testing is the standard of care in CHF patients per American Heart Association's 2009 Guidelines. Delinquency was defined as labs not conducted within 1 year in patients with euthyroid history, within 6 months in patients with thyroid dysfunction, abnormal labs at any time without follow-up, or lab absence after thyroid medication initiation, adjustment, or discontinuation. Targeted 80 nonpregnant adult CHF patients with delinquent thyroid function tests were counseled to get thyroid labs at point of sale, via telephone, e-mail, or letter. In collaboration with physicians, pharmacists ordered thyroid-stimulating hormone (TSH) and free T4 (FT4) labs. For patients with abnormal laboratory results, pharmacists coordinated drug therapy and follow-up labs. Data were collected from November 1, 2009 to March 30, 2010. Seventy-two patients (90%) previously delinquent for thyroid function testing received relevant thyroid labs. Ten patients (12.5%) with abnormal thyroid function tests not on prior drug therapy received treatment.

Development of a microRNA-based molecular assay for the detection of papillary thyroid carcinoma in aspiration biopsy samples.

PubMed

Mazeh, Haggi; Mizrahi, Ido; Halle, David; Ilyayev, Nadia; Stojadinovic, Alexander; Trink, Barry; Mitrani-Rosenbaum, Stella; Roistacher, Marina; Ariel, Ilana; Eid, Ahmed; Freund, Herbert R; Nissan, Aviram

2011-02-01

Although thyroid nodules are common and diagnosed in over 5% of the adult population, only 5% harbor malignancy. Patients with clinically suspicious thyroid nodules need to undergo fine-needle aspiration biopsy (FNAB). The main limitation of FNAB remains indeterminate cytopathology. Only 20%-30% of the indeterminate nodules harbor malignancy, and therefore up to 80% of patients undergo unnecessary thyroidectomy. The aim of this study was to identify and validate a panel of microRNAs (miRNAs) that could serve as a platform for an FNAB-based diagnostic for thyroid neoplasms. The study population included 27 consecutive patients undergoing total thyroidectomy for FNAB-based papillary thyroid cancer (n = 20) and benign disorders (n = 7). Aspiration biopsy was performed from the index lesion and from the opposite lobe normal tissue in all study patients at the time of operation. RNA was extracted from all aspiration biopsy samples. Quantitative polymerase chain reaction on a panel of previously selected miRNAs was performed. Polymerase chain reaction results were compared with final histopathology. miRNA from tumor tissues was amplified using the highest value of each miRNA expression in normal tissue as a threshold for malignancy detection. Diagnostic characteristics were most favorable for mir-221 in differentiating benign from malignant thyroid pathology. mir-221 was overexpressed in 19 patients (p < 0.0001) with a sensitive yield of 95%. Specificity, negative and positive predictive value, and accuracy of the miRNA panel were 100%, 96%, 100%, and 98%, respectively. miRNA quantification for differential diagnosis of thyroid neoplasms within aspiration biopsy samples is feasible and may improve the accuracy of FNAB cytology.

Expression of Simple Mucin Type Antigens and Lewis Type 1 and Type 2 Chain Antigens in the Thyroid Gland: An Immunohistochemical Study of Normal Thyroid Tissues, Benign Lesions, and Malignant Tumors.

PubMed

Fonseca, Elsa; Castanhas, Salome; Sobrinho-Simoes, Manuel

1996-01-01

In order to characterize the pattern of expression of carbohydrate structures in several types of thyroid tissues and to evaluate the putative usefulness of the detection of such antigens in diagnostic surgical pathology, we undertook the immunohistochemical study of simple mucin type antigens (T, Tn, and sialyl Tn), Lewis type I antigens (Lewis a, sialyl Lewis a, and Lewis b), and Lewis type 2 related antigens (precursor type 2, H type 2, Lewis x, sialyl Lewis x, and Lewis y) in thyroid samples obtained from 65 patients. The material consisted on paraffin sections of normal thyroid (n = 43), benign lesions (13 goiters/hyperplastic lesions and 15 adenomas), and malignant tumors (12 follicular carcinomas and 27 papillary carcinomas, 5 of which had lymph node metastases) of the thyroid follicular epithelium. Tn, T, and precursor type 2 antigens were the only antigens that were detected and very rarely in normal thyroid. Benign lesions were similar to normal thyroid despite displaying a higher prevalence of immunoreactivity for several antigens of the three groups. Thyroid carcinomas presented a significantly higher level of expression of all types of simple mucin, Lewis type 1, and Lewis type 2 antigens than the normal thyroid and benign lesions. The expression of sialyl Tn was restricted to malignant tumors, and the expression of sialyl Lewis x was closely associated, though not exclusively, to papillary carcinomas. The immunoreactivity was stronger and the number of positive cases was higher in papillary than in follicular carcinomas. No differences were found between primary tumors and the respective metastases. The existence of distinct patterns of expression of carbohydrate antigens in different types of thyroid lesions points to the usefulness of the detection of some of these antigens in thyroid surgical pathology. The putative role of such antigens in the peculiar metastatic properties of thyroid carcinomas remains unsettled.

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

Synthesis of a high molecular weight thyroglobulin dimer by two ovine thyroid cell lines: the OVNIS.

PubMed

Hovsépian, S; Aouani, A; Fayet, G

1986-05-01

The OVNIS 6H and 5H thyroid cells, 2 permanent cell lines isolated 3 years ago from ovine tissue, synthesize a high molecular weight glycosylated protein, immunologically related to ovine thyroglobulin, which is similar to the prothyroid hormone dimer (17-19) S: thyroglobulin. Using sucrose gradient centrifugation and cell labelling with [14C]Leu or [3H]GlNH2, radioactivity was observed in proteins purified from cell layers and from cell culture media. Addition of thyrotropin to or removal from the media resulted respectively in an increase (+773%) or decrease (-1090%) of the total radioactivity detected in the (17-19)S thyroglobulin fraction. Estimation of thyroglobulin by RIA gave similar though less pronounced effects. These experiments prove (1) that thyroglobulin is still expressed in these OVNIS thyroid cell lines even after 3 years of permanent culture, (2) that TSH modulates the level of this protein through a TSH-receptor functional system.

The role of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment.

PubMed

Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

2004-11-01

To review the literature on the roles of thyroid hormone in trophoblast function, early pregnancy maintenance, and fetal neurodevelopment. MEDLINE was searched for English-language papers published from 1971 to 2003, using the key words "brain," "hypothyroidism," "placenta," "pregnancy," "threatened abortion," "thyroid hormone," "thyroid hormone receptor," "thyroid hormone replacement therapy," "thyroid hormone-responsive gene," and "trophoblast." Transplacental transfer of thyroid hormone occurs before the onset of fetal thyroid hormone secretion. Thyroid hormone receptors and iodothyronine deiodinases are present in the placenta and the fetal central nervous system early in pregnancy, and thyroid hormone plays a crucial role both in trophoblast function and fetal neurodevelopment. Maternal hypothyroxinemia is associated with a high rate of spontaneous abortion and long-term neuropsychological deficits in children born of hypothyroid mothers. Maternal iodine deficiency also causes a wide spectrum of neuropsychological disorders in children, ranging from subclinical deficits in cognitive motor and auditory functions to hypothyroid-induced cognitive impairment in infants. However, these conditions are preventable when iodine supplementation is initiated before the second trimester. Although thyroid hormone replacement therapy is effective for reducing the adverse effects complicated by maternal hypothyroidism, the appropriate dose of thyroid hormone is mandatory in protecting the early stage of pregnancy. Close monitoring of maternal thyroid hormone status and ensuring adequate maternal thyroid hormone levels in early pregnancy are of great importance to prevent miscarriage and neuropsychological deficits in infants.

Thyroid function, reduced kidney function and incident chronic kidney disease in a community-based population: the Atherosclerosis Risk in Communities study.

PubMed

Schultheiss, Ulla T; Daya, Natalie; Grams, Morgan E; Seufert, Jochen; Steffes, Michael; Coresh, Josef; Selvin, Elizabeth; Köttgen, Anna

2017-11-01

Reduced kidney function is a common public health problem that increases risk for a wide variety of adverse outcomes, making the identification of potentially modifiable factors associated with the development of incident chronic kidney disease (CKD) important. Alterations in the hypothalamic-pituitary-thyroid axis have been linked to reduced kidney function, but the association of thyroid function with the development of incident CKD is largely uncharacterized. Concentrations of thyroid stimulating hormone (TSH), free thyroxine (FT4), triiodothyronine (T3) and thyroid peroxidase antibody (TPOAb) were quantified in 12 785 black and white participants of the ongoing community-based prospective Atherosclerosis Risk in Communities study. Thyroid markers and clinical categories of thyroid dysfunction (euthyroidism, combined subclinical and overt hypothyroidism, combined subclinical and overt hyperthyroidism) were also evaluated for their association with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1.73 m2) at study baseline and with incident CKD over a median follow-up time of 19.6 years. Higher TSH and FT4 as well as lower T3 concentrations were strongly and independently associated with reduced kidney function at study baseline. The clinical entities hypothyroidism and hyperthyroidism were also associated with higher odds of baseline reduced kidney function, but this was not significant. However, none of the markers of thyroid function nor different clinical categories of thyroid dysfunction (hypothyroidism, hyperthyroidism or TPOAb positivity) were associated with incident CKD in adjusted analyses. Elevated TSH, FT4 and reduced T3 concentrations were associated with reduced kidney function cross-sectionally. The lack of association with the development of incident CKD suggests that altered thyroid function in the general population is not causally related to CKD development, but screening for thyroidal status may be especially relevant in persons with reduced kidney function. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The Evolution of Thyroid Function after Presenting with Hashimoto Thyroiditis Is Different between Initially Euthyroid Girls with and Those without Turner Syndrome.

PubMed

Wasniewska, Malgorzata; Salerno, Mariacarolina; Corrias, Andrea; Mazzanti, Laura; Matarazzo, Patrizia; Corica, Domenico; Aversa, Tommaso; Messina, Maria Francesca; De Luca, Filippo; Valenzise, Mariella

2016-01-01

To prospectively investigate, during a 5-year follow-up, whether the prognosis of thyroid function with Hashimoto thyroiditis (HT) is different in euthyroid girls with Turner syndrome (TS) than in euthyroid girls without TS. In 66 TS girls and 132 non-TS girls with euthyroid HT and similar thyroid functional test results at HT diagnosis, we followed up the evolution of thyroid status over time. At the end of follow-up, the TS girls exhibited higher TSH levels, lower fT4 levels, and lower prevalence rates of both euthyroidism and subclinical hypothyroidism, but higher prevalence rates of both overt hypothyroidism and hyperthyroidism, irrespective of the karyotype. An association with TS is able to impair the long-term prognosis of thyroid function in girls with HT. Such an effect occurs irrespective of thyroid functional test results at HT diagnosis and is not necessarily linked with a specific karyotype. © 2016 S. Karger AG, Basel.

Pathogenesis of Hyperthyroidism.

PubMed

Singh, Ishita; Hershman, Jerome M

2016-12-06

Hyperthyroidism is a form of thyrotoxicosis in which there is excess thyroid hormone synthesis and secretion. Multiple etiologies can lead to a common clinical state of "thyrotoxicosis," which is a consequence of the high thyroid hormone levels and their action on different tissues of the body. The most common cause of thyrotoxicosis is Graves' disease, an autoimmune disorder in which stimulating thyrotropin receptor antibodies bind to thyroid stimulating hormone (TSH) receptors on thyroid cells and cause overproduction of thyroid hormones. Other etiologies include: forms of thyroiditis in which inflammation causes release of preformed hormone, following thyroid gland insult that is autoimmune, infectious, mechanical or medication induced; secretion of human chorionic gonadotropin in the setting of transient gestational thyrotoxicosis and trophoblastic tumors; pituitary thyrotropin release, and exposure to extra-thyroidal sources of thyroid hormone that may be endogenous or exogenous. © 2017 American Physiological Society. Compr Physiol 7:67-79, 2017. Copyright © 2017 John Wiley & Sons, Inc.

Thyroid Hormones and Growth in Health and Disease

PubMed Central

Tarım, Ömer

2011-01-01

Thyroid hormones regulate growth by several mechanisms. In addition to their negative feedback effect on the stimulatory hormones thyrotropin-releasing hormone (TRH) and thyrotropin (TSH), thyroid hormones also regulate their receptors in various physiological and pathological conditions. Up-regulation and down-regulation of the thyroid receptors fine-tune the biological effects exerted by the thyroid hormones. Interestingly, the deiodinase enzyme system is another intrinsic regulator of thyroid physiology that adjusts the availability of thyroid hormones to the tissues, which is essential for normal growth and development. Almost all chronic diseases of childhood impair growth and development. Every disease may have a unique mechanism to halt linear growth, but reduced serum concentration or diminished local availability of thyroid hormones seems to be a common pathway. Therefore, the effects of systemic diseases on thyroid physiology must be taken into consideration in the evaluation of growth retardation in affected children. Conflict of interest:None declared. PMID:21750631

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1.

PubMed

Casey, Mary B; Lohse, Christine M; Lloyd, Ricardo V

2003-01-01

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.

Differential effects of human interferon alpha and interferon gamma on xenografted human thyroid tissue in severe combined immunodeficient mice and nude mice.

PubMed

Kawai, K; Enomoto, T; Fornasier, V; Resetkova, E; Volpé, R

1997-03-01

We have studied the in vivo effects of human interferon alpha (IFN-alpha) and interferon gamma (IFN-gamma) administration on human thyroid tissue xenografted into two mouse strains: severe combined immunodeficient (SCID) mice and nude mice. Human lymphocytes survive in SCID mice but are lysed in nude mice. Thyroid tissues from Graves' disease or Hashimoto's thyroiditis, or paranodular [normal, (N)] tissue was xenografted into SCID mice (0.8 g/mouse) pretreated with anti-asialo GM-1 antiserum and radiation and also into nude mice. One week after xenografting, SCID and nude mice were divided into three groups. Group A was treated with IFN-alpha intraperitoneally (2,000 units/mouse) three times weekly; group B was treated with IFN-gamma similarly; group C was treated with phosphate buffered saline (PBS) only (control). Autologous human peripheral blood mononuclear cells (PBMCs) were added to mice receiving N xenografts. Blood was taken every 2 weeks for levels of IgG and thyroid antibodies (TAb). After 6 weeks of treatment, mice were sacrificed, and xenograft thyrocyte histocompatibility leukocyte antigen (HLA-DR) and intercellular adhesion molecule (ICAM-1) expression were measured. In addition, thyrocyte cultures were stimulated in vitro with 200 units/ml of either IFN-alpha or IFN-gamma or PBS (control). SCID mice xenografted with autoimmune thyroid disease (AITD) in group A showed a significantly higher TAb production than group C, whereas in group B, TAb production was not statistically increased compared to control (group C). SCID mice xenografted with N did not produce TAb in any group, nor did nude mice xenografted with AITD. Thyrocyte HLA-DR expression was markedly increased in group A and B in SCID mice xenografted with Graves' disease, Hashimoto's thyroiditis, and N tissue compared to group C. In contrast, only group B (IFN-gamma) showed an increase in thyrocyte HLA-DR in nude mice. In the in vitro studies, only IFN-gamma (not IFN-alpha) stimulated thyrocyte HLA-DR and ICAM-1 expression in Graves' disease, Hashimoto's thyroiditis, and N tissues. We concluded that in SCID mice, IFN-alpha causes TAB production in AITD xenografts but not in N xenografts, while increasing thyrocyte HLA-DR expression in both. Also, IFN-gamma does not cause a statistically increased TAb in AITD xenografts in SCID mice, despite a sharp rise in thyrocyte HLA-DR expression. In addition, because IFN-alpha has no effect in nude mice or in vitro on thyrocyte HLA-DR expression, its effects in SCID mice must be mediated via local infiltrating lymphocytes. Finally, IFN-gamma has a direct effect on thyrocytes to increase HLA-DR expression (and, in vitro, ICAM-1 expression) but may not stimulate TAb production.

Multifocal fibrosing thyroiditis and its association with papillary thyroid carcinoma using BRAF pyrosequencing.

PubMed

Frank, Renee; Baloch, Zubair W; Gentile, Caren; Watt, Christopher D; LiVolsi, Virginia A

2014-09-01

Multifocal fibrosing thyroiditis (MFT) is characterized by numerous foci of fibrosis in a stellate configuration with fibroelastotic and fibroblastic centers entrapping epithelial structures. MFT has been proposed as a risk factor for papillary thyroid carcinoma (PTC) development. We attempted to identify whether MFT showed such molecular changes and could possibly be related to PTC. We identified seven cases of PTC with MFT in our institutional pathology database and personal consult service of one of the authors (VAL) for the years 1999 to 2012. Areas of PTC, MFT, and normal tissue were selected for BRAF analysis. Macro-dissection, DNA extraction and PCR amplification, and pyrosequencing were performed to detect BRAF mutations in codon 600. All of the MFT lesions and normal thyroid tissue were negative for BRAF mutations. Of the seven PTCs analyzed, five (71 %) were negative for BRAF mutations, while two cases were positive. In our study, none of the MFT lesions harbored BRAF mutations, whereas 29 % (two of seven) PTCs in the same gland were positive. Hence, in this small study, we found no evidence that the MFT lesion is a direct precursor to PTC. It is likely an incidental bystander in the process and a reflection of the background thyroiditis.

Hypothalamic-Pituitary-Thyroid Axis Perturbations in Male Mice by CNS-Penetrating Thyromimetics.

PubMed

Ferrara, Skylar J; Bourdette, Dennis; Scanlan, Thomas S

2018-07-01

Thyromimetics represent a class of experimental drugs that can stimulate tissue-selective thyroid hormone action. As such, thyromimetics should have effects on the hypothalamic-pituitary-thyroid (HPT) axis, but details of this action and the subsequent effects on systemic thyroid hormone levels have not been reported to date. Here, we compare the HPT-axis effects of sobetirome, a well-studied thyromimetic, with Sob-AM2, a newly developed prodrug of sobetirome that targets sobetirome distribution to the central nervous system (CNS). Similar to endogenous thyroid hormone, administration of sobetirome and Sob-AM2 suppress HPT-axis gene transcript levels in a manner that correlates to their specific tissue distribution properties (periphery vs CNS, respectively). Dosing male C57BL/6 mice with sobetirome and Sob-AM2 at concentrations ≥10 μg/kg/d for 29 days induces a state similar to central hypothyroidism characterized by depleted circulating T4 and T3 and normal TSH levels. However, despite the systemic T4 and T3 depletion, the sobetirome- and Sob-AM2-treated mice do not show signs of hypothyroidism, which may result from the presence of the thyromimetic in the thyroid hormone-depleted background.

Review and hypothesis: does Graves' disease develop in non-human great apes?

PubMed

McLachlan, Sandra M; Alpi, Kristine; Rapoport, Basil

2011-12-01

Graves' disease, caused by stimulatory thyrotropin receptor (TSHR) autoantibodies, has not been observed in animals. In contrast, Hashimoto's thyroiditis develops in chickens, rats, mice, dogs, and marmosets. Attempts to induce an immune response in mice to the luteinizing-hormone receptor suggested that autoantigen glycosylation was one parameter involved in breaking self-tolerance. Over evolution, TSHR glycosylation increased from three asparagine-linked-glycans (N-glycans) in fish to six N-glycans in humans and great apes. All other placental mammals lack one N-glycan in the shed TSHR A-subunit, the primary Graves' disease autoantigen. We hypothesized that (a) lesser TSHR A-subunit glycosylation reduces immunogenicity, accounting for the absence of Graves' disease in most placental mammals; (b) due to human-like A-subunit glycosylation, Graves' disease might arise in great apes. Here, we review and analyze the literature on this subject and report the results of a survey of veterinarians at primate centers and zoos in North America. Previous experimental data from induced TSHR antibodies in mice support a role for A-subunit glycosylation in breaking self-tolerance. An extensive search of the great-ape literature revealed five reports of noncongenital thyroid dysfunction, four with hypothyroidism and one with hyperthyroidism. The latter was a gorilla who was treated with anti-thyroid drugs but is now deceased. Neither serum nor thyroid tissue from this gorilla were available for analysis. The survey of veterinarians revealed that none of the 979 chimpanzees in primate research centers had a diagnosis of noncongenital thyroid dysfunction and among ∼1100 great apes (gorillas, orangutans, and chimpanzees) in U.S. zoos, only three were hypothyroid, and none were hyperthyroid. Graves' disease appears to be either very rare or does not occur in great apes based on the literature and a survey of veterinarians. Although the available data do not advance our hypothesis, there is a paucity of information regarding thyroid function tests and thyroid autoantibodies in the great apes In addition, these primates may be protected against TSHR autoimmunity by the absence of genetic polymorphisms and putative environmental triggers. Finally, larger numbers of great apes need to be followed, and tests of thyroid function and thyroid autoantibodies be performed, to confirm that spontaneous Graves' disease is restricted to humans.

Hyperthyroidism: Diagnosis and Treatment.

PubMed

Kravets, Igor

2016-03-01

Hyperthyroidism is an excessive concentration of thyroid hormones in tissues caused by increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an endogenous or exogenous extrathyroidal source. The most common causes of an excessive production of thyroid hormones are Graves disease, toxic multinodular goiter, and toxic adenoma. The most common cause of an excessive passive release of thyroid hormones is painless (silent) thyroiditis, although its clinical presentation is the same as with other causes. Hyperthyroidism caused by overproduction of thyroid hormones can be treated with antithyroid medications (methimazole and propylthiouracil), radioactive iodine ablation of the thyroid gland, or surgical thyroidectomy. Radioactive iodine ablation is the most widely used treatment in the United States. The choice of treatment depends on the underlying diagnosis, the presence of contraindications to a particular treatment modality, the severity of hyperthyroidism, and the patient's preference.

Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis.

PubMed

Johnson, Elizabeth O; Kamilaris, Themis C; Calogero, Aldo E; Gold, Philip W; Chrousos, George P

2005-07-01

Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mug of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH, corticosterone and thyroid indices were also determined. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism. The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased.

Activated Leukocyte Cell Adhesion Molecule Expression and Shedding in Thyroid Tumors

PubMed Central

Miccichè, Francesca; Da Riva, Luca; Fabbi, Marina; Pilotti, Silvana; Mondellini, Piera; Ferrini, Silvano; Canevari, Silvana; Pierotti, Marco A.; Bongarzone, Italia

2011-01-01

Activated leukocyte cell adhesion molecule (ALCAM, CD166) is expressed in various tissues, cancers, and cancer-initiating cells. Alterations in expression of ALCAM have been reported in several human tumors, and cell adhesion functions have been proposed to explain its association with cancer. Here we documented high levels of ALCAM expression in human thyroid tumors and cell lines. Through proteomic characterization of ALCAM expression in the human papillary thyroid carcinoma cell line TPC-1, we identified the presence of a full-length membrane-associated isoform in cell lysate and of soluble ALCAM isoforms in conditioned medium. This finding is consistent with proteolytically shed ALCAM ectodomains. Nonspecific agents, such as phorbol myristate acetate (PMA) or ionomycin, provoked increased ectodomain shedding. Epidermal growth factor receptor stimulation also enhanced ALCAM secretion through an ADAM17/TACE-dependent pathway. ADAM17/TACE was expressed in the TPC-1 cell line, and ADAM17/TACE silencing by specific small interfering RNAs reduced ALCAM shedding. In addition, the CGS27023A inhibitor of ADAM17/TACE function reduced ALCAM release in a dose-dependent manner and inhibited cell migration in a wound-healing assay. We also provide evidence for the existence of novel O-glycosylated forms and of a novel 60-kDa soluble form of ALCAM, which is particularly abundant following cell stimulation by PMA. ALCAM expression in papillary and medullary thyroid cancer specimens and in the surrounding non-tumoral component was studied by western blot and immunohistochemistry, with results demonstrating that tumor cells overexpress ALCAM. These findings strongly suggest the possibility that ALCAM may have an important role in thyroid tumor biology. PMID:21364949

The Na+/I− Symporter (NIS): Mechanism and Medical Impact

PubMed Central

Portulano, Carla; Paroder-Belenitsky, Monika

2014-01-01

The Na+/I− symporter (NIS) is the plasma membrane glycoprotein that mediates active I− transport in the thyroid and other tissues, such as salivary glands, stomach, lactating breast, and small intestine. In the thyroid, NIS-mediated I− uptake plays a key role as the first step in the biosynthesis of the thyroid hormones, of which iodine is an essential constituent. These hormones are crucial for the development of the central nervous system and the lungs in the fetus and the newborn and for intermediary metabolism at all ages. Since the cloning of NIS in 1996, NIS research has become a major field of inquiry, with considerable impact on many basic and translational areas. In this article, we review the most recent findings on NIS, I− homeostasis, and related topics and place them in historical context. Among many other issues, we discuss the current outlook on iodide deficiency disorders, the present stage of understanding of the structure/function properties of NIS, information gleaned from the characterization of I− transport deficiency-causing NIS mutations, insights derived from the newly reported crystal structures of prokaryotic transporters and 3-dimensional homology modeling, and the novel discovery that NIS transports different substrates with different stoichiometries. A review of NIS regulatory mechanisms is provided, including a newly discovered one involving a K+ channel that is required for NIS function in the thyroid. We also cover current and potential clinical applications of NIS, such as its central role in the treatment of thyroid cancer, its promising use as a reporter gene in imaging and diagnostic procedures, and the latest studies on NIS gene transfer aimed at extending radioiodide treatment to extrathyroidal cancers, including those involving specially engineered NIS molecules. PMID:24311738

Deficiency in the manganese efflux transporter SLC30A10 induces severe hypothyroidism in mice.

PubMed

Hutchens, Steven; Liu, Chunyi; Jursa, Thomas; Shawlot, William; Chaffee, Beth K; Yin, Weiling; Gore, Andrea C; Aschner, Michael; Smith, Donald R; Mukhopadhyay, Somshuvra

2017-06-09

Manganese is an essential metal that becomes toxic at elevated levels. Loss-of-function mutations in SLC30A10, a cell-surface-localized manganese efflux transporter, cause a heritable manganese metabolism disorder resulting in elevated manganese levels and parkinsonian-like movement deficits. The underlying disease mechanisms are unclear; therefore, treatment is challenging. To understand the consequences of loss of SLC30A10 function at the organism level, we generated Slc30a10 knock-out mice. During early development, knock-outs were indistinguishable from controls. Surprisingly, however, after weaning and compared with controls, knock-out mice failed to gain weight, were smaller, and died prematurely (by ∼6-8 weeks of age). At 6 weeks, manganese levels in the brain, blood, and liver of the knock-outs were ∼20-60-fold higher than controls. Unexpectedly, histological analyses revealed that the brain and liver of the knock-outs were largely unaffected, but their thyroid exhibited extensive alterations. Because hypothyroidism leads to growth defects and premature death in mice, we assayed for changes in thyroid and pituitary hormones. At 6 weeks and compared with controls, the knock-outs had markedly reduced thyroxine levels (∼50-80%) and profoundly increased thyroid-stimulating hormone levels (∼800-1000-fold), indicating that Slc30a10 knock-out mice develop hypothyroidism. Importantly, a low-manganese diet produced lower tissue manganese levels in the knock-outs and rescued the phenotype, suggesting that manganese toxicity was the underlying cause. Our unanticipated discovery highlights the importance of determining the role of thyroid dysfunction in the onset and progression of manganese-induced disease and identifies Slc30a10 knock-out mice as a new model for studying thyroid biology. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

The synthetic gestagen levonorgestrel directly affects gene expression in thyroid and pituitary glands of Xenopus laevis tadpoles.

PubMed

Lorenz, Claudia; Opitz, Robert; Trubiroha, Achim; Lutz, Ilka; Zikova, Andrea; Kloas, Werner

2016-08-01

The synthetic gestagen levonorgestrel (LNG) was previously shown to perturb thyroid hormone-dependent metamorphosis in Xenopus laevis. However, so far the mechanisms underlying the anti-metamorphic effects of LNG remained unknown. Therefore, a series of in vivo and ex vivo experiments was performed to identify potential target sites of LNG action along the pituitary-thyroid axis of X. laevis tadpoles. Prometamorphic tadpoles were treated in vivo with LNG (0.01-10nM) for 72h and brain-pituitary and thyroid tissue was analyzed for marker gene expression. While no treatment-related changes were observed in brain-pituitary tissue, LNG treatment readily affected thyroidal gene expression in tadpoles including decreased slc5a5 and iyd mRNA expression and a strong induction of dio2 and dio3 expression. When using an ex vivo organ explant culture approach, direct effects of LNG on both pituitary and thyroid gland gene expression were detecTable Specifically, treatment of pituitary explants with 10nM LNG strongly stimulated dio2 expression and concurrently suppressed tshb expression. In thyroid glands, ex vivo LNG treatment induced dio2 and dio3 mRNA expression in a thyrotropin-independent manner. When thyroid explants were cultured in thyrotropin-containing media, LNG caused similar gene expression changes as seen after 72h in vivo treatment including a very strong repression of thyrotropin-induced slc5a5 expression. Concerning the anti-thyroidal activity of LNG as seen under in vivo conditions, our ex vivo data provide clear evidence that LNG directly affects expression of genes important for thyroidal iodide handling as well as genes involved in negative feedback regulation of pituitary tshb expression. Copyright © 2016 Elsevier B.V. All rights reserved.

Riedel's thyroiditis and multifocal fibrosclerosis are part of the IgG4-related systemic disease spectrum.

PubMed

Dahlgren, Mollie; Khosroshahi, Arezou; Nielsen, G Petur; Deshpande, Vikram; Stone, John H

2010-09-01

Riedel's thyroiditis is a chronic fibrosing disorder of unknown etiology often associated with "multifocal fibrosclerosis." IgG4-related systemic disease is characterized by IgG4+ plasma cell infiltration and fibrosis throughout many organs. We hypothesized that Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. We searched our institution's pathology database using the terms "Riedel's," "struma," "thyroid," and "fibrosis," and identified 3 cases of Riedel's thyroiditis. Riedel's thyroiditis was diagnosed if there was a fibroinflammatory process involving all or a portion of the thyroid gland, with evidence of extension of the process into surrounding tissues. Immunohistochemical stains for IgG4 and IgG were performed. The histopathologic and immunohistochemical features of each involved organ were evaluated. The clinical features of one patient with multiple organ system disease were described. All 3 thyroidectomy samples stained positively for IgG4-bearing plasma cells. One patient had extensive extrathyroidal involvement diagnostic of IgG4-related systemic disease, including cholangitis, pseudotumors of both the lung and lacrimal gland, and a lymph node contiguous to the thyroid that stained intensely for IgG4+ plasma cells. The histologic features of all organs involved were consistent with IgG4-related systemic disease. Patient 3 had 10 IgG4+ plasma cells per high-power field initially, but rebiopsy 2 years later demonstrated no IgG4+ plasma cells. That patient's second biopsy, characterized by fibrosis and minimal residual inflammation, further solidifies the link between IgG4-bearing plasma cells in tissue and the histologic evolution to Riedel's thyroiditis. Riedel's thyroiditis is part of the IgG4-related systemic disease spectrum. In many cases, multifocal fibrosclerosis and IgG4-related systemic disease are probably the same entity.

Biochemical and immunohistochemical characterization of proteins in Hürthle cell carcinoma.

PubMed

De Keyser, L; Layfield, L; Van Herle, A; Costin, A; Lewin, K

1984-10-01

The present study reports the biochemical and immunohistochemical findings in the cytosol of a Hürthle cell carcinoma as compared with that of normal thyroid tissue. Sephadex G-200 chromatography of the extract derived from a Hürthle cell carcinoma and from normal thyroid tissue revealed three identical pools. Pool I consisted mainly of thyroglobulin (Tg), pool II corresponded to albumin, while pool III contained unidentified low molecular weight fragments which could not be studied further. Hürthle cell carcinoma, pool I, had a Tg content of 12.9 micrograms Tg/mg equivalent tissue and a 127I content of 5,6 mole/mole of Tg. Its sialic acid content was undetectable, however. In pool I of the normal thyroid gland, the respective values were 62.8 micrograms Tg/mg equivalent tissue, 21.3 +/mole 127I/mole Tg, and 15.4 mole sialic acid/mole Tg. The albumin contained in both pools II was shown to be ioidinated at the following levels: 0.025 mole 127I/mole albumin in Hürthle tumor pool II vs 1.28 mole 127I/mole albumin in normal thyroid pool II. Immunohistochemical studies confirmed the presence of Tg and albumin in the malignant Hürthle cells and acini and colloid. Thus, Hürthle cell carcinoma contained Tg and albumin. The Tg content was five times less compared with control tissue. Both proteins (Tg and albumin) were poorly iodinated in Hürthle carcinoma tissue, and the iodination of albumina seemed to be more severely impaired. The site of synthesis of both proteins could not be derived from the present studies.

Novel neural pathways for metabolic effects of thyroid hormone.

PubMed

Fliers, Eric; Klieverik, Lars P; Kalsbeek, Andries

2010-04-01

The relation between thyrotoxicosis, the clinical syndrome resulting from exposure to excessive thyroid hormone concentrations, and the sympathetic nervous system remains enigmatic. Nevertheless, beta-adrenergic blockers are widely used to manage severe thyrotoxicosis. Recent experiments show that the effects of thyrotoxicosis on hepatic glucose production and insulin sensitivity can be modulated by selective hepatic sympathetic and parasympathetic denervation. Indeed, thyroid hormone stimulates hepatic glucose production via a sympathetic pathway, a novel central pathway for thyroid hormone action. Rodent studies suggest that similar neural routes exist for thyroid hormone analogues (e.g. thyronamines). Further elucidation of central effects of thyroid hormone on autonomic outflow to metabolic organs, including the thyroid and brown adipose tissue, will add to our understanding of hyperthyroidism. Copyright 2009 Elsevier Ltd. All rights reserved.

Low-activity 124I-PET/low-dose CT versus 99mTc-pertechnetate planar scintigraphy or 99mTc-pertechnetate single-photon emission computed tomography of the thyroid: a pilot comparison.

PubMed

Darr, Andreas M; Opfermann, Thomas; Niksch, Tobias; Driesch, Dominik; Marlowe, Robert J; Freesmeyer, Martin

2013-10-01

The standard thyroid functional imaging method, 99mTc-pertechnetate (99mTc-PT) planar scintigraphy, has technical drawbacks decreasing its sensitivity in detecting nodules or anatomical pathology. 124I-PET, lacking these disadvantages and allowing simultaneous CT, may have greater sensitivity for these purposes. We performed a blinded pilot comparison of 124I-PET(/CT) versus 99mTc-PT planar scintigraphy or its cross-sectional enhancement, 99mTc-PT single-photon emission CT (SPECT), in characterizing the thyroid gland with benign disease. Twenty-one consecutive adults with goiter underwent low-activity (1 MBq/0.027 mCi) 124I-PET/low-dose (30 mAs) CT, 99mTc-PT planar scintigraphy, and 99mTc-PT-SPECT. Endpoints included the numbers of “hot spots” with/without central photopenia and “cold spots” detected, the proportion of these lesions with morphological correlates, the mean volume and diameter of visualized nodules, and the number of cases of lobus pyramidalis or retrosternal thyroid tissue identified. 124I-PET detected significantly more “hot spots” with/without central photopenia (P < 0.001), significantly more nodules (P < 0.001), and more “cold spots” than did 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT, including all lesions seen on the 99mTc-PT modalities. Ultrasonographic correlates were found for all nodules visualized on all 3 modalities and 92.5% of nodules seen only on 124I-PET. Nodules discernible only on 124I-PET had significantly smaller mean volume or diameter (P < 0.001) than did those visualized on 99mTc-PT planar scintigraphy or 99mTc-PT-SPECT. 124I-PET(/CT) identified significantly more patients with a lobus pyramidalis (P < 0.001) or retrosternal thyroid tissue (P < 0.05). 124I-PET(/CT) may provide superior imaging of benign thyroid disease compared to planar or cross-sectional 99mTc-PT scintigraphy.

Effect of neurological monitoring in postoperative 5-15 days residual thyroidectomy after primary thyroid cancer surgery.

PubMed

Long, Miao-Yun; Diao, Fei-Yu; Peng, Li-Na; Tan, Lang-Ping; Zhu, Yue; Huang, Kai; Li, Hong-Hao

2018-05-16

To explore the application of intraoperative neurological monitoring in residual thyroidectomy 5-15 days after thyroid cancer operation and the influence on postoperative serum thyroglobulin (Tg), recurrent laryngeal nerve and function of parathyroid glands. Material of patients receiving thyroid surgery from January 2010 to December 2016 was retrospectively analyzed. Cases meeting with standards were enrolled for analysis and the patients were divided into neurological monitoring group and non-neurological monitoring group in line with the use of neurological monitoring during the operation. Recurrent laryngeal nerve-injured hoarseness, hypoparathyroidism and concentration of serum Tg before and after the surgery were collected and analyzed. Four-hundred and thirty-five patients met with standards, among which 227 from neurological monitoring group and 208 from non-neurological monitoring group. Temporary hoarseness rate of non-neurological monitoring group and neurological monitoring group was 8.67% and 2.2%. Permanent hoarseness rate of non-neurological monitoring group and neurological monitoring group was 1.92% and 0.44%. Temporary hypoparathyroidism rate of non-neurological monitoring group and neurological monitoring group was 18.75% and 7.48%. Permanent hypoparathyroidism rate of non-neurological monitoring group and neurological monitoring group was 1.92% and 0.88%. Average Tg concentration 1 month after the surgery in non-neurological monitoring group and neurological monitoring group was 2.82 and 1.37 ng/mL, respectively. Rate of average Tg concentration less than 1 ng/mL 1 month after the surgery in non-neurological monitoring group and neurological monitoring group was 45.06% and 67.4%. Intraoperative neurological monitoring can be adopted in residual thyroidectomy in postoperative 5-15 days after primary thyroid cancer surgery, as to reduce incidence rate of recurrent laryngeal nerve injury and hypoparathyroidism and to enhance thorough removal of thyroid tissues and cancer tissues. © 2018 John Wiley & Sons Australia, Ltd.

Congenital hypothyroidism with goiter in Tenterfield terriers.

PubMed

Dodgson, S E; Day, R; Fyfe, J C

2012-01-01

A cluster of cases of congenital hypothyroidism with goiter (CHG) in Tenterfield Terriers was identified and hypothesized to be dyshormonogenesis of genetic etiology with autosomal recessive inheritance. To describe the phenotype, thyroid histopathology, biochemistry, mode of inheritance, and causal mutation of CHG in Tenterfield Terriers. Thyroid tissue from 1 CHG-affected Tenterfield Terriers, 2 affected Toy Fox Terriers, and 7 normal control dogs. Genomic DNA from blood or buccal brushings of 114 additional Tenterfield Terriers. Biochemical and genetic segregation analysis of functional gene candidates in a Tenterfield Terrier kindred. Thyroid peroxidase (TPO) iodide oxidation activity was measured, and TPO protein and SDS-resistant thyroglobulin aggregation were assessed on western blots. TPO cDNA was amplified from thyroid RNA and sequenced. Exons and flanking splice sites were amplified from genomic DNA and sequenced. Variant TPO allele segregation was assessed by restriction enzyme digestion of PCR products. Thyroid from an affected pup had lesions consistent with dyshormonogenesis. TPO activity was absent, but normal sized immunocrossreactive TPO protein was present. Affected dog cDNA and genomic sequences revealed a homozygous TPO missense mutation in exon 9 (R593W) that was heterozygous in all obligate carriers and in 31% of other clinically normal Tenterfield Terriers. The mutation underlying CHG in Tenterfield Terriers was identified, and a convenient carrier test made available for screening Tenterfield Terriers used for breeding. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients.

PubMed

Arici, Merve; Oztas, Ezgi; Yanar, Fatih; Aksakal, Nihat; Ozcinar, Beyza; Ozhan, Gul

2018-03-28

Thyroid hormones play a vital role in the human body for growth and differentiation, regulation of energy metabolism, and physiological function. Hypothyroidism is a common endocrine disorder, which generally results from diminished normal circulating concentrations of serum thyroxine (fT4) and triiodothyronine (fT3). The primary choice in hypothyroidism treatment is oral administration of levothyroxine (L-T4), a synthetic T4 hormone, as approximately 100-125 μg/day. Generally, dose adjustment is made by trial and error approach. However, there are several factors which might influence bioavailability of L-T4 treatment. Genetic background could be an important factor in hypothyroid patients as well as age, gender, concurrent medications and patient compliance. The concentration of thyroid hormones in tissue is regulated by both deiodinases enzyme and thyroid hormone transporters. In the present study, it was aimed to evaluate the effects of genetic differences in the proteins and enzymes (DIO1, DIO2, TSHR, THR and UGT) which are efficient in thyroid hormone metabolism and bioavailability of L-T4 in Turkish population. According to our findings, rs225014 and rs225015 variants in DIO2, which catalyses the conversion of thyroxine (pro-hormone) to the active thyroid hormone, were associated with TSH levels. It should be given lower dose to the patients with rs225014 TT and rs225015 GG genotypes in order to provide proper treatment with higher effectivity and lower toxicity.

An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+/I- symporter (NIS) knockout mice.

PubMed

Ferrandino, Giuseppe; Kaspari, Rachel R; Reyna-Neyra, Andrea; Boutagy, Nabil E; Sinusas, Albert J; Carrasco, Nancy

2017-07-13

The sodium/iodide symporter (NIS) mediates active iodide (I - ) accumulation in the thyroid, the first step in thyroid hormone (TH) biosynthesis. Mutations in the SLC5A5 gene encoding NIS that result in a non-functional protein lead to congenital hypothyroidism due to I - transport defect (ITD). ITD is a rare autosomal disorder that, if not treated promptly in infancy, can cause mental retardation, as the TH decrease results in improper development of the nervous system. However, in some patients, hypothyroidism has been ameliorated by unusually large amounts of dietary I - . Here we report the first NIS knockout (KO) mouse model, obtained by targeting exons 6 and 7 of the Slc5a5 gene. In NIS KO mice, in the thyroid, stomach, and salivary gland, NIS is absent, and hence there is no active accumulation of the NIS substrate pertechnetate ( 99m TcO 4 - ). NIS KO mice showed undetectable serum T 4 and very low serum T 3 levels when fed a diet supplying the minimum I - requirement for rodents. These hypothyroid mice displayed oxidative stress in the thyroid, but not in the brown adipose tissue or liver. Feeding the mice a high-I - diet partially rescued TH biosynthesis, demonstrating that, at high I - concentrations, I - enters the thyroid through routes other than NIS.

Fetal cell carcinogenesis of the thyroid: a modified theory based on recent evidence.

PubMed

Takano, Toru

2014-01-01

Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARγ1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.

Q-elastography in the presurgical diagnosis of thyroid nodules with indeterminate cytology.

PubMed

Cantisani, Vito; Ulisse, Salvatore; Guaitoli, Eleonora; De Vito, Corrado; Caruso, Riccardo; Mocini, Renzo; D'Andrea, Vito; Ascoli, Valeria; Antonaci, Alfredo; Catalano, Carlo; Nardi, Francesco; Redler, Adriano; Ricci, Paolo; De Antoni, Enrico; Sorrenti, Salvatore

2012-01-01

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the "Sapienza" University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient's thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule's malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients' presurgical selection.

Q-Elastography in the Presurgical Diagnosis of Thyroid Nodules with Indeterminate Cytology

PubMed Central

Guaitoli, Eleonora; De Vito, Corrado; Caruso, Riccardo; Mocini, Renzo; D’Andrea, Vito; Ascoli, Valeria; Antonaci, Alfredo; Catalano, Carlo; Nardi, Francesco; Redler, Adriano; Ricci, Paolo; De Antoni, Enrico; Sorrenti, Salvatore

2012-01-01

Quantitative ultrasound (US) elastography (Q-USE), able to evaluate tissue stiffness has been indicated as a new diagnostic tool to differentiate benign from malignant thyroid lesions. Aim of this prospective study, conducted at the Department of Surgical Sciences, of the “Sapienza” University of Rome, was to evaluate the diagnostic accuracy of Q-USE, compared with US parameters, in thyroid nodules with indeterminate cytology (Thy3).The case study included 140 nodules from 140 consecutive patients. Patient’s thyroid nodules were evaluated by Q-USE, measuring the strain ratio (SR) of stiffness between nodular and surrounding normal thyroid tissue, and conventional US parameters prior fine-needle aspiration cytology. Those with Thy3 diagnosis were included in the study. Forty of the nodules analyzed harbored a malignant lesion. Q-USE demonstrated that malignant nodules have a significant higher stiffness with respect to benign one and an optimun SR cut-off value of 2.05 was individuated following ROC analysis. Univariate analysis showed that hypoechogenicity, irregular margins and SR >2.05 associated with malignancy, with an accuracy of 67.2%, 81,0% and 89.8%, respectively. Data were unaffected by nodule size or thyroiditis. These findings were confirmed in multivariate analysis demonstrating a significant association of the SR and the irregular margins with thyroid nodule’s malignancy. In conclusion, we demonstrated the diagnostic utility of Q-USE in the differential diagnosis of thyroid nodules with indeterminate cytology that, if confirmed, could be of major clinical utility in patients’ presurgical selection. PMID:23209819

An animal model of marginal iodine deficiency during development: the thyroid axis and neurodevelopmental outcome.

PubMed

Gilbert, Mary E; Hedge, Joan M; Valentín-Blasini, Liza; Blount, Benjamin C; Kannan, Kurunthachalam; Tietge, Joseph; Zoeller, R Thomas; Crofton, Kevin M; Jarrett, Jeffrey M; Fisher, Jeffrey W

2013-03-01

Thyroid hormones (THs) are essential for brain development, and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low-level TH disruption. This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment. Diets deficient in iodine were prepared by adding 975, 200, 125, 25, or 0 µg/kg potassium iodate to the base casein diet to produce five nominal iodine levels ranging from ample (Diet 1: 1000 μg iodine/kg chow, D1) to deficient (Diet 5: 25 µg iodine/kg chow, D5). Female Long Evans rats were maintained on these diets beginning 7 weeks prior to breeding until the end of lactation. Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN) 21. Fetal tissue was harvested from the dams, and pups were sacrificed on PN14 and PN21. Blood, thyroid gland, and brain were collected for analysis of iodine, TH, and TH precursors and metabolites. Serum and thyroid gland iodine and TH were reduced in animals receiving two diets that were most deficient in iodine. T4 was reduced in the fetal brain but was not altered in the neonatal brain. Neurobehavior, assessed by acoustic startle, water maze learning, and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus in animals receiving two diets that were most deficient in iodine. A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in adults. These findings have implications for regulation of TH-disrupting chemicals and suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption.

Contribution of Brain Tissue Oxidative Damage in Hypothyroidism-associated Learning and Memory Impairments

PubMed Central

Baghcheghi, Yousef; Salmani, Hossein; Beheshti, Farimah; Hosseini, Mahmoud

2017-01-01

The brain is a critical target organ for thyroid hormones, and modifications in memory and cognition happen with thyroid dysfunction. The exact mechanisms underlying learning and memory impairments due to hypothyroidism have not been understood yet. Therefore, this review was aimed to compress the results of previous studies which have examined the contribution of brain tissues oxidative damage in hypothyroidism-associated learning and memory impairments. PMID:28584813

The Chernobyl Tissue Bank — A Repository for Biomaterial and Data Used in Integrative and Systems Biology Modeling the Human Response to Radiation

PubMed Central

Thomas, Geraldine; Unger, Kristian; Krznaric, Marko; Galpine, Angela; Bethel, Jackie; Tomlinson, Christopher; Woodbridge, Mark; Butcher, Sarah

2012-01-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer post Chernobyl, the Chernobyl Tissue Bank (CTB: www.chernobyltissuebank.com) was established in 1998. Thus far it is has collected biological samples from 3,861 individuals, and provided 27 research projects with 11,254 samples. The CTB was designed from its outset as a resource to promote the integration of research and clinical data to facilitate a systems biology approach to radiation related thyroid cancer. The project has therefore developed as a multidisciplinary collaboration between clinicians, dosimetrists, molecular biologists and bioinformaticians and serves as a paradigm for tissue banking in the omics era. PMID:24704918

Integrating Research on Thyroid Cancer after Chernobyl — the Chernobyl Tissue Bank

PubMed Central

Thomas, G.A.; Bethel, J.A.; Galpine, A.; Krznaric, M.; Unger, K.

2011-01-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl, the Chernobyl Tissue Bank was established. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 21 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated cooperation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age. PMID:21345659

The Risk of Preeclampsia According to High Thyroid Function in Pregnancy Differs by hCG Concentration.

PubMed

Korevaar, Tim I M; Steegers, Eric A P; Chaker, Layal; Medici, Marco; Jaddoe, Vincent W V; Visser, Theo J; de Rijke, Yolanda B; Peeters, Robin P

2016-12-01

During pregnancy, there is an increased demand for thyroid hormone. The pregnancy hormone human chorionic gonadotropin (hCG) is an important physiological stimulator of thyroid function. Already high-normal maternal free T 4 concentrations are associated with a higher risk of preeclampsia. The objective of the investigation was to study our hypothesis that hCG concentrations can distinguish a physiological form of high thyroid function from a more pathological form of high thyroid function and that the risk of preeclampsia would differ accordingly. TSH, free T 4 , hCG, or thyroperoxidase antibody concentrations were determined in pregnant women participating in a population-based prospective cohort study. The study was conducted in the general community. A nonselected sample of 5146 pregnant women participated in the study. There were no interventions. Preeclampsia was measured. Women with high hCG-associated high thyroid function did not have a higher risk of preeclampsia than women with normal thyroid function. In contrast, women with low hCG and high thyroid function had a 3.4- to 11.1-fold higher risk of preeclampsia. These risk estimates were amplified in women with a high body mass index. Women with a low hCG and suppressed TSH (<0.10 mU/L) had a 3.2- to 8.9-fold higher risk of preeclampsia. hCG was not associated with preeclampsia, and results remained similar after exclusion of thyroperoxidase antibody-positive women. This study suggests that, in contrast to women with a high hCG associated high thyroid function, women with low hCG and high thyroid function during pregnancy are at a higher risk of developing preeclampsia. The additional measurement of hCG may therefore help to distinguish a more pathological form of high thyroid function and women at a high risk of preeclampsia.

Thyroid hormone and retinoid X receptor function and expression during sea lamprey (Petromyzon marinus) metamorphosis.

PubMed

Manzon, Lori A; Youson, John H; Holzer, Guillaume; Staiano, Leopoldo; Laudet, Vincent; Manzon, Richard G

2014-08-01

Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be important for lamprey metamorphosis, however, serum TH concentrations are elevated in the larval phase, decline rapidly during early metamorphosis and remain low until metamorphosis is complete; these TH fluctuations are contrary to those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH treatments disrupt natural metamorphosis in P. marinus. Given that THs exert their effects by binding to TH nuclear receptors (TRs) that often act as heterodimers with retinoid X receptors (RXRs), we cloned and characterized these receptors from P. marinus and examined their expression during metamorphosis. Two TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA. Phylogenetic analyses group the PmTRs together on a branch prior to the gnathostome TRα/β split. The three RXRs also group together, but our data indicated that these transcripts are most likely either allelic variants of the same gene locus, or the products of a lamprey-specific duplication event. Importantly, these P. marinus receptors more closely resemble vertebrate as opposed to invertebrate chordate receptors. Functional analysis revealed that PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated with nanomolar concentrations of TH and they have distinct pharmacological profiles reminiscent of vertebrate TRβ and TRα, respectively. Also similar to other metamorphosing vertebrates, expression patterns of the PmTRs during lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific expression pattern that correlates with tissue morphogenesis and biochemical changes and PmTR2 has a more uniform expression pattern. This TR expression data suggests that THs, either directly or via a metabolite, may function to positively modulate changes at the tissue or organ levels during lamprey metamorphosis. Collectively the results presented herein support the hypothesis that THs have a dual functional role in the lamprey life cycle whereby high levels promote larval feeding, growth and lipogenesis and low levels promote metamorphosis. Copyright © 2014 Elsevier Inc. All rights reserved.

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 parameters are the key for diagnosis of other forms of thyroiditis. PMID:29686830

Carcinoma showing thymus-like elements of the thyroid gland: report of three cases including one case with breast cancer history.

PubMed

Zhang, Guanjun; Liu, Xi; Huang, Wei; Li, Xiaofeng; Johnstone, Marianne; Deng, Yuan; Ke, Yongqiang; Nunes, Quentin M; Wang, Hongyan; Wang, Yili; Zhang, Xuebin

2015-01-01

Carcinoma showing thymus-like elements (CASTLE) is a rare malignant tumor of the thyroid or adjacent neck soft tissues, whose histogenesis is still debated. It may resemble other primary or metastatic poorly differentiated tumors histologically and the differential diagnosis is crucial for CASTLE has a better prognosis. However, CASTLE as a second primary tumor has not been reported in the literature. We report three cases of thyroid CASTLE, including a unique tumor following breast-conserving surgery for early-stage breast invasive carcinoma. There were two female and one male. All three tumors were located in the right lobe of the thyroid, and one tumor showed extension into the surrounding soft tissue. Histologically, all tumors showed expansive growth and consisted of cords, nests or sheets of epithelial cells divided into irregularly shaped lobules by fibrous connective tissue with lymphoplasmacytic infiltration. Focal squamous differentiation resembling Hassall's corpuscles were observed. All cases stained positively for CD5, CD117, high molecular weight cytokeratin, cytokeratin, P63, carcinoembryonic antigen and epithelial membrane antigen. Positive staining for Bcl-2 in two cases and chromogranin A in one case was noted. Ki-67 expression ranged from 15 to 25%. Thyroid transcription factor and CD3 were negative. There was no evidence of recurrent or metastatic disease at following surgery. These features demonstrated CASTLE may arise from branchial pouch remnants, the thyroid solid cell nests. CASTLE is a rare entity, awareness of its occurrence as a second primary tumor is important to avoid overtreatment because it is associated with a favorable prognosis.

The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats

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

Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.

Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that ismore » neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor {alpha} and {beta}, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk assessments for AA.« less

Clinical Features of Nivolumab-Induced Thyroiditis: A Case Series Study.

PubMed

Yamauchi, Ichiro; Sakane, Yoriko; Fukuda, Yorihide; Fujii, Toshihito; Taura, Daisuke; Hirata, Masakazu; Hirota, Keisho; Ueda, Yohei; Kanai, Yugo; Yamashita, Yui; Kondo, Eri; Sone, Masakatsu; Yasoda, Akihiro; Inagaki, Nobuya

2017-07-01

The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international Phase 3 studies and national post-marketing surveillance of nivolumab in Japan. This study analyzed five consecutive cases with thyroid dysfunction associated with nivolumab therapy. Second, it examined the mRNA and protein expressions of PD-L1 and PD-L2 by reverse transcription polymerase chain reaction and Western blotting. All patients were diagnosed with painless thyroiditis. Thyrotoxicosis developed within four weeks from the first administration of nivolumab and normalized within four weeks of onset in three of the five patients. Hypothyroidism after transient thyrotoxicosis developed in two patients, and preexisting hypothyroidism persisted in one patient. The other two patients were treated with glucocorticoids and discontinued nivolumab therapy for comorbid adverse events. One did not develop hypothyroidism, and the other developed mild, transient hypothyroidism. In addition, it was verified that normal thyroid tissue expresses PD-L1 and PD-L2 mRNA and those proteins. In the present cases, nivolumab-induced thyrotoxicosis seemed to be associated with painless thyroiditis, while no patient with Graves' disease was observed. A transient and rapid course with subsequent hypothyroidism was observed in nivolumab-induced thyroiditis. In addition, it was verified that PD-L1 and PD-L2 are expressed in normal thyroid tissue. This suggests that nivolumab therapy reduces immune tolerance, even in normal thyroid tissue, and leads to the development of thyroiditis. Treating thyrotoxicosis with only supportive care and considering levothyroxine replacement therapy once subsequent hypothyroidism occurs is proposed. Further investigations are required to confirm whether glucocorticoid therapy and discontinuation of nivolumab therapy prevent subsequent hypothyroidism.

Thyroid function and the risk of dementia: The Rotterdam Study.

PubMed

Chaker, Layal; Wolters, Frank J; Bos, Daniel; Korevaar, Tim I M; Hofman, Albert; van der Lugt, Aad; Koudstaal, Peter J; Franco, Oscar H; Dehghan, Abbas; Vernooij, Meike W; Peeters, Robin P; Ikram, M Arfan

2016-10-18

To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI. Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function. We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI. High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia. © 2016 American Academy of Neurology.

Iodine-131 for therapy of thyroid diseases. Physical and biological basis.

PubMed

Wyszomirska, Anna

2012-08-28

Iodine-131 is successfully used in the treatment of hyperthyroidism and differentiated thyroid cancer. Thyroid is the critical organ for iodine. Iodine is taken up by the thyroid follicular cells. Radioactive isotope iodine-131 simultaneously emits two types of radiation: radiation beta minus (β-) used for the treatment and gamma (γ) used for diagnosis. Due to the penetration of beta particles in tissue, damaging effect of β-radiation is restricted to thyroid cells. In this article, characteristic of iodine-131, mechanism of action and mechanism of tissue damage is presented. HIGH energy γ-ray emission, contributes to the dose of both: patient's body and the personnel. In accordance with the principles of radiation protection, reducing exposure to ionizing radiation should be achieved by: use of proper shieldings, organization of work, appropriate distance from the radiation source and reducing the time of exposure. Treatment with I-131, depending on medical indications, may be carried out on stationary or outpatient basis. All activities conducted in the exposure to radiation must comply with the principles of radiation protection, in accordance with the applicable regulations, that are also presented in this article.

Assessment of renal function and electrolytes in patients with thyroid dysfunction in Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Abebe, Nardos; Kebede, Tedla; Wolde, Mistire

2016-01-01

Studies demonstrated that abnormal thyroid functions may result in decreased or increased kidney size, kidney weight, and affect renal functions. In this regard, studies on the association of abnormal thyroid functions and renal function tests are scarcely found in Ethiopia. To assess renal function and electrolytes in patients with thyroid dysfunction, in Addis Ababa, Ethiopia. Cross sectional study was conducted from March 21/2015-May 27/2015 at Arsho Advanced Medical Laboratory. During the study period, 71 patients with thyroid dysfunction were eligible, and socio demographic data collected by structured questionnaire. Then blood sample was collected for thyroid function tests, renal function and blood electrolyte analysis. The collected data was analyzed by SPSS version 20. ANOVA and binary logistic regression were employed to evaluate the mean deference and associations of thyroid hormone with renal function and electrolyte balances. Among the renal function tests, serum uric acid, and creatinine mean values were significantly decreased in hyperthyroid patients; whereas, eGFR mean value was significantly increased in hyperthyroid study patients (P<0.05). Meanwhile, from the electrolyte measurements made, only the mean serum sodium value was significantly increased in hyperthyroid study participants. Binary logistic regression analysis on the association of thyroid dysfunction with electrolyte balance and renal function tests indicated that serum sodium, creatinine, eGFR values and hyperthyroidism have a statistical significant association at AOR 95% CI of 0.141(0.033-0.593, P=0.008); 16.236(3.481-75.739, P=0.001), and 13.797(3.261-58.67, P=0.001) respectively. The current study reveals, thyroid abnormalities may lead to renal function alterations and also may disturb electrolyte balance. Knowledge of this significant association has worthwhile value for clinicians, to manage their patients' optimally.

Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity.

PubMed

Sosic-Jurjevic, Branka; Filipovic, Branko; Renko, Kostja; Ajdzanovic, Vladimir; Manojlovic-Stojanoski, Milica; Milosevic, Verica; Köhrle, Josef

2012-11-01

Endogenous androgens are involved in regulation of thyroid function and metabolism of thyroid hormones. As serum testosterone level progressively declines with age, this regulation may change. We tested how androgen deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery, animals were decapitated. Thyroids were used for histomorphometric and ultrastructural examinations and together with livers and pituitaries for real-time quantitative PCR and deiodinase (DIO) activity measurements. Serum testosterone, TSH, l-thyroxine (T(4)), and cholesterol (Chol) levels were determined. As expected, middle-aged control rats had lower (P<0.05) testosterone and T(4) compared with 3-month-old males. In the Orx middle-aged group, we detected diminished serum testosterone (P<0.05), no change in TSH and T(4) levels, and higher Chol level (P<0.05), in comparison with age-matched controls. Histomorphometric analysis of thyroid tissue revealed decreased relative volume densities of follicles and colloid (P<0.05). Relevant gene expressions and DIO1 enzyme activity were not changed in the thyroids of Orx rats. Liver Dio1 gene expression and DIO1 activity were decreased (P<0.05) in comparison with the control values. Pituitary levels of TSHβ, Dio1, and Dio2 mRNAs did not change, while DIO2 activity decreased (P<0.05). In conclusion, orchidectomy of middle-aged rats affected thyroid structure with no effect on serum T(4) and TSH. However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate compensatory-adaptive changes in local T(3) production.

Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

PubMed

Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

2016-12-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Anxiety- and Depression-like Behaviors and Hyperactivity in a Type 3 Deiodinase-Deficient Mouse Showing Brain Thyrotoxicosis and Peripheral Hypothyroidism

PubMed Central

Stohn, J. Patrizia; Martinez, M. Elena; Hernandez, Arturo

2016-01-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 −/− mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 −/− mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 −/− mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. PMID:27580013

Circulating levels of irisin is elevated in hypothyroidism, a case-control study.

PubMed

Ateş, İhsan; Altay, Mustafa; Topçuoğlu, Canan; Yılmaz, Fatma Meriç

2016-04-01

Objective Our objective in this study was to determine the relationship between irisin hormone, which has a similar effect with thyroid hormones on adipose tissue and the metabolism, and the thyroid functions and the obesity secondary to thyroid disease. Subjects and methods Seventy-four patients were included in the study, of the patients, 37 were newly diagnosed with Hashimoto's thyroiditis related hypothyroidism but not started on a treatment yet, and the remaining 37 were healthy volunteers without a known disease. Serum thyroid stimulating hormone (TSH), free thyroxin (fT4), anti-thyroglobulin and anti-thyroid peroxidase were measured and thyroid ultrasonography was performed in both groups. Serum irisin levels were measured using the commercially available ELISA kit. The hypothyroidism group had higher levels of irisin compared to the control group (2.77 ng/mL vs. 2.15 ng/mL respectively; p = 0.017). Results The hypothyroidism group had higher median levels of irisin in the obese patients than those in the control group (3.10 ng/mL vs. 2.10 ng/mL respectively; p = 0.013). Irisin level was negatively correlated with age in the whole population and patients with hypothyroidism (r = -0.255, p = 0.028; r = -0.346, p = 0.036 respectively). Irisin level was positively correlated with TSH (r = 0.247, p = 0.034) but negatively correlated with the fT4 (r = -0.316, p = 0.006) in the whole population. Obesity, fT4 and irisin levels were identified to be independent predictors in the diagnosis of hypothyroidism in the multivariable logistic regression analysis. Conclusion To the best of our knowledge, this study is the first in literature to identify that obesity, irisin level and fT4 level are independent risk factors for hypothyroidism.

Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

PubMed Central

Yokoi, N; Hidaka, S; Tanabe, S; Ohya, M; Ishima, M; Takagi, Y; Masui, N; Seino, S

2012-01-01

Although the MHC class II ‘u' haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a' and ‘u' haplotypes on the Komeda diabetes-prone (KDP) genetic background. The u/u homozygous animals developed T1D similar to the original KDP rat; a/u heterozygous animals did develop T1D but with delayed onset and low frequency. In contrast, none of the a/a homozygous animals developed T1D; about half of the animals with a/u heterozygous or a/a homozygous genotypes showed autoimmune thyroiditis. To investigate the role of genetic background in the development of thyroiditis, we also produced a congenic strain carrying Cblb mutation of the KDP rat on the PVG.R23 genetic background (MHC class II ‘a' haplotype). The congenic rats with homozygous Cblb mutation showed autoimmune thyroiditis without T1D and slight to severe alopecia, a clinical symptom of hypothyroidism such as Hashimoto's thyroiditis. These data indicate that MHC class II is involved in the tissue-specific development of autoimmune diseases, including T1D and thyroiditis. PMID:21918539

A Hormonally Active Malignant Struma Ovarii

PubMed Central

Lara, Carolina; Salame, Latife; Padilla-Longoria, Rafael

2016-01-01

Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii. PMID:27882257

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 ...

Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development.

PubMed

Goodman, Julie E; Kerper, Laura E; Boyce, Catherine Petito; Prueitt, Robyn L; Rhomberg, Lorenz R

2010-10-01

Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case-control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development. Copyright (c) 2010 Elsevier Inc. All rights reserved.

A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

PubMed

Porcu, Eleonora; Medici, Marco; Pistis, Giorgio; Volpato, Claudia B; Wilson, Scott G; Cappola, Anne R; Bos, Steffan D; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M; Nolte, Ilja M; O'Connell, Jeffrey R; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J; Buckley, Brendan M; Camaschella, Clara; de Craen, Anton J M; Davies, Gail; de Visser, Marieke C H; Ford, Ian; Forsen, Tom; Frayling, Timothy M; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T; Hermus, Ad R; Hofman, Albert; Houwing-Duistermaat, Jeanine J; Jensen, Richard A; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D; Nagaraja, Ramaiah; Netea-Maier, Romana T; Palotie, Aarno; Persani, Luca; Piras, Maria G; Psaty, Bruce M; Räikkönen, Katri; Richards, J Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M; Sattar, Naveed; Shields, Beverley M; Soranzo, Nicole; Starr, John M; Stott, David J; Sweep, Fred C G J; Usala, Gianluca; van der Klauw, Melanie M; van Heemst, Diana; van Mullem, Alies; Vermeulen, Sita H; Visser, W Edward; Walsh, John P; Westendorp, Rudi G J; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J; Eriksson, Johan G; Ferrucci, Luigi; Fox, Caroline S; Jukema, J Wouter; Kiemeney, Lambertus A; Pramstaller, Peter P; Schlessinger, David; Shuldiner, Alan R; Slagboom, Eline P; Uitterlinden, André G; Vaidya, Bijay; Visser, Theo J; Wolffenbuttel, Bruce H R; Meulenbelt, Ingrid; Rotter, Jerome I; Spector, Tim D; Hicks, Andrew A; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

Natural History of Thyroid Function in Adults with Down Syndrome--10-Year Follow-Up Study

ERIC Educational Resources Information Center

Prasher, V.; Gomez, G.

2007-01-01

Background: The natural history of thyroid function in adults with Down syndrome (DS) is unknown. Method: This study investigated annual thyroid function tests in 200 adults with DS over a 10-year period. Results: Transient and persistent thyroid dysfunction was common. The 5- and 10-year incidence of definite hypothyroidism was 0.9%-1.64% and…

Intrinsic Regulation of Thyroid Function by Thyroglobulin

PubMed Central

Sellitti, Donald F.

2014-01-01

Background: The established paradigm for thyroglobulin (Tg) function is that of a high molecular weight precursor of the much smaller thyroid hormones, triiodothyronine (T3) and thyroxine (T4). However, speculation regarding the cause of the functional and morphologic heterogeneity of the follicles that make up the thyroid gland has given rise to the proposition that Tg is not only a precursor of thyroid hormones, but that it also functions as an important signal molecule in regulating thyroid hormone biosynthesis. Summary: Evidence supporting this alternative paradigm of Tg function, including the up- or downregulation by colloidal Tg of the transcription of Tg, iodide transporters, and enzymes employed in Tg iodination, and also the effects of Tg on the proliferation of thyroid and nonthyroid cells, is examined in the present review. Also discussed in detail are potential mechanisms of Tg signaling in follicular cells. Conclusions: Finally, we propose a mechanism, based on experimental observations of Tg effects on thyroid cell behavior, that could account for the phenomenon of follicular heterogeneity as a highly regulated cycle of increasing and decreasing colloidal Tg concentration that functions to optimize thyroid hormone production through the transcriptional activation or suppression of specific genes. PMID:24251883

Thyroid-adrenergic interactions: physiological and clinical implications.

PubMed

Silva, J Enrique; Bianco, Suzy D C

2008-02-01

The sympathoadrenal system, including the sympathetic nervous system and the adrenal medulla, interacts with thyroid hormone (TH) at various levels. Both systems are evolutionary old and regulate independent functions, playing probably independent roles in poikilothermic species. With the advent of homeothermy, TH acquired a new role, which is to stimulate thermogenic mechanisms and synergize with the sympathoadrenal system to produce heat and maintain body temperature. An important part of this new function is mediated through coordinated and, most of the time, synergistic interactions with the sympathoadrenal system. Catecholamines can in turn activate TH in a tissue-specific manner, most notably in brown adipose tissue. Such interactions are of great adaptive value in cold adaptation and in states needing high-energy output. Conversely, in states of emergency where energy demand should be reduced, such as disease and starvation, both systems are turned down. In pathological states, where one of the systems is fixed at a high or a low level, coordination is lost with disruption of the physiology and development of symptoms. Exaggerated responses to catecholamines dominate the manifestations of thyrotoxicosis, while hypothyroidism is characterized by a narrowing of adaptive responses (e.g., thermogenic, cardiovascular, and lipolytic). Finally, emerging results suggest the possibility that disrupted interactions between the two systems contribute to explain metabolic variability, for example, fuel efficiency, energy expenditure, and lipolytic responses.

Age impact on autoimmune thyroid disease in females

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.

PubMed

Kero, Jukka; Ahmed, Kashan; Wettschureck, Nina; Tunaru, Sorin; Wintermantel, Tim; Greiner, Erich; Schütz, Günther; Offermanns, Stefan

2007-09-01

The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.

Exposure to polybrominated diphenyl ethers (PBDEs): Changes in thyroid, vitamin A, glutathione homeostasis, and oxidative stress in American kestrels (Falco sparverius)

USGS Publications Warehouse

Fernie, K.J.; Shutt, J.L.; Mayne, G.; Hoffman, D.; Letcher, R.J.; Drouillard, K.G.; Ritchie, I.J.

2005-01-01

Polybrominated diphenyl ethers (PBDEs), a class of additive flame retardants, are temporally increasing in wildlife tissues and capable of disrupting normal endocrine function. We determined whether in ovo and post-hatch exposure of captive American kestrels (Falco sparverius) to environmentally relevant PBDEs alter thyroid, retinol, and oxidative stress measures. Control eggs were injected with safflower oil and subsequent nestlings fed the same vehicle; dosed eggs received PBDE congeners (BDE-47, -99, -100, -153), which mainly comprise the Penta-BDE commercial mixture, dissolved in safflower oil at concentrations (1500 ng/g total [Sigma] PBDEs) approximating those in Great Lakes gull eggs. Nestlings hatching from dosed eggs were orally exposed for 29 days to variable Sigma PBDE concentrations that are similar to levels reported in tissues of Great Lakes trout (100 ng/g). Treatment kestrels had lower plasma thyroxine (T-4), plasma retinol, and hepatic retinol and retinyl palmitate concentrations, but unaltered triiodothyronine (T-3) concentrations and thyroid glandular structure. BDE-47, -100, and -99 were negatively associated with plasma T-4, plasma retinol (BDE-100, -99) and hepatic retinol (BDE-47). Despite an antioxidant-rich diet, PBDE exposure induced hepatic oxidative stress, particularly in females, with an increased hepatic GSSG:GSH ratio, a marginal increase in lipid peroxidation, and increased oxidized glutathione. Positive associations were found between concentrations of BDE-183 and thiols and, in males, between BDE-99 and reduced GSH, but a negative association occurred between BDE-99 and TBARS. Subsequently, concentrations of PBDE congeners in wild birds may alter thyroid hormone and vitamin A concentrations, glutathione metabolism and oxidative stress.

Characterization of the novel tumor-suppressor gene CCDC67 in papillary thyroid carcinoma.

PubMed

Yin, De Tao; Xu, Jianhui; Lei, Mengyuan; Li, Hongqiang; Wang, Yongfei; Liu, Zhen; Zhou, Yubing; Xing, Mingzhao

2016-02-02

Some studies showed an association of coiled-coil domain-containing (CCDC) genes with cancers. Our previous limited data specifically suggested a possible pathogenic role of CCDC67 in papillary thyroid cancer (PTC), but this has not been firmly established. The present study was to further investigate and establish this role of CCDC67 in PTC. The expression of CCDC67, both at mRNA and protein levels, was sharply down-regulated in PTC compared with normal thyroid tissues. Lower CCDC67 expression was significantly associated with aggressive tumor behaviors, such as advanced tumor stages and lymph node metastasis, as well as BRAF mutation. Introduced expression of CCDC67 in TPC-1 cells robustly inhibited cell proliferation, colony formation and migration, induced G1 phase cell cycle arrest, and increased cell apoptosis. Primary PTC tumors and matched normal thyroid tissues were obtained from 200 unselected patients at the initial surgery for detection of CCDC67 mRNA and protein by RT-PCR and Western blotting analyses, respectively. Genomic DNA sequencing was performed to detect BRAF mutation in PTC tumors. Clinicopathological data were retrospectively reviewed for correlation analyses. PTC cell line TPC-1 with stable transfection of CCDC67 was used to investigate the functions of CCDC67. This large study demonstrates down-regulation of CCDC67 in PTC, an inverse relationship between CCDC67 expression and PTC aggressiveness and BRAF mutation, and a robust inhibitory effect of CCDC67 on PTC cellular activities. These results are consistent with CCDC67 being a novel and impaired tumor suppressor gene in PTC, providing important prognostic and therapeutic implications for this cancer.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

PubMed

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

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

Quantitative analysis of collagen change between normal and cancerous thyroid tissues based on SHG method

NASA Astrophysics Data System (ADS)

Chen, Xiwen; Huang, Zufang; Xi, Gangqin; Chen, Yongjian; Lin, Duo; Wang, Jing; Li, Zuanfang; Sun, Liqing; Chen, Jianxin; Chen, Rong

2012-03-01

Second-harmonic generation (SHG) is proved to be a high spatial resolution, large penetration depth and non-photobleaching method. In our study, SHG method was used to investigate the normal and cancerous thyroid tissue. For SHG imaging performance, system parameters were adjusted for high-contrast images acquisition. Each x-y image was recorded in pseudo-color, which matches the wavelength range in the visible spectrum. The acquisition time for a 512×512-pixels image was 1.57 sec; each acquired image was averaged four frames to improve the signal-to-noise ratio. Our results indicated that collagen presence as determined by counting the ratio of the SHG pixels over the whole pixels for normal and cancerous thyroid tissues were 0.48+/-0.05, 0.33+/-0.06 respectively. In addition, to quantitatively assess collagen-related changes, we employed GLCM texture analysis to the SHG images. Corresponding results showed that the correlation both fell off with distance in normal and cancerous group. Calculated value of Corr50 (the distance where the correlation crossed 50% of the initial correlation) indicated significant difference. This study demonstrates that SHG method can be used as a complementary tool in thyroid histopathology.

Transient hyperthyroidism of hyperemesis gravidarum.

PubMed

Tan, Jackie Y L; Loh, Keh Chuan; Yeo, George S H; Chee, Yam Cheng

2002-06-01

To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum. Prospective observational study. Hospital inpatient gynaecological ward. Women admitted with hyperemesis gravidarum and found to have hyperthyroidism. Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation. Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes). Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile. In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.

Long non-coding RNA BANCR regulates cancer stem cell markers in papillary thyroid cancer via the RAF/MEK/ERK signaling pathway.

PubMed

Wang, Yuanyuan; Lin, Xiangde; Fu, Xinghao; Yan, Wei; Lin, Fusheng; Kuang, Penghao; Luo, Yezhe; Lin, Ende; Hong, Xiaoquan; Wu, Guoyang

2018-06-18

Thyroid cancer is one of the most common malignant tumors of the endocrine system. Among all thyroid cancers, papillary thyroid carcinoma (PTC) is the most common type. The BRAF-activated non-coding RNA (BANCR) is a 693-bp nucleotide transcript which was first identified in melanoma. However, the role of BANCR in the development of thyroid cancer remains unclear. Therefore, the present study investigated the potential involvement of BANCR in the development of thyroid cancer in vitro using patient tissue samples and a panel of thyroid cancer cell lines, and in vivo using a xenograft mouse model. We observed that BANCR was expressed at a higher level in human thyroid tumor tissues than that noted in the adjacent normal tissues. The expression level of BANCR differed between cultured thyroid cancer cell lines; BANCR expression was lower in the BCPAP cell line than that observed in the CAL-62, WRO and FTC-133 cell lines. Western blot analysis and flow cytometry revealed that overexpression of BANCR in the BCPAP cell line resulted in increased expression of the cancer stem cell markers, LGR5 and EpCAM. Single-clone formation experiments showed that upregulated expression of BANCR in the BCPAP cell line promoted an increase in the number of clones formed. Similarly, in microsphere formation experiments, overexpression of BANCR resulted in increased number and size of microspheres compared with the control cell line. Western blotting experiments showed that BANCR overexpression in BCPAP upregulated the expression of phosphorylated c-Raf, MEK1/2 and ERK1/2. Inhibition of c-Raf via U0126 decreased the expression of LGR5 and EpCAM, as well as phosphorylated levels of c-Raf, MEK1/2 and ERK1/2 in the BCPAP cells, compared to levels in the DMSO controls. In the xenograft mouse model, BANCR overexpression in the thyroid cancer cells significantly increased tumor growth. Taken together, these results suggest that BANCR plays a role in PTC development by regulating the expression of cancer stem cell markers LGR5 and EpCAM via the c-Raf/MEK/ERK signaling pathway. Therefore, BANCR may be used as a novel prognostic marker for PTC.

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.

Effect of different doses of monosodium glutamate on the thyroid follicular cells of adult male albino rats: a histological study

PubMed Central

Khalaf, Hanaa A; Arafat, Eetmad A

2015-01-01

Monosodium glutamate (MSG) is a major flavor enhancer used as a food additive. The present study investigates the effects of different doses of MSG on the morphometric and histological changes of the thyroid gland. 28 male albino rats were used. The rats were divided into four groups: group I control, group II, III and IV treated with MSG (0.25 g/kg, 3 g/kg, 6 g/kg daily for one month) respectively. The thyroid glands were dissected out and prepared for light and electron microscopic examination. Light microscopic examination of thyroid gland of group II revealed increase in follicular epithelial height. Groups III & IV showed decrease in the follicular diameter and irregularity in the shape of some follicles with discontinuity of basement membrane. Follicular hyperplasia was detected in some follicles with appearance of multiple pyknotic nuclei in follicular and interfollicular cells and multiple exfoliated cells in the colloid. In addition, areas of loss of follicular pattern were appeared in group IV. Immunohistochemical examination of BCL2 immunoexpression of the thyroid glands of groups III & IV reveals weak positive reaction in the follicular cells cytoplasm. Ultrathin sections examination of groups III & IV revealed follicular cells with irregular hyperchromatic nuclei, marked dilatation of rER and increased lysosomes with areas of short or lost apical microvilli. In addition, vacuolation of mitochondria was detected in group IV. The results displayed that MSG even at low doses is capable of producing alterations in the body weights and thyroid tissue function and histology. PMID:26884820

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.

Vasovagal reflex emergency caused by Riedel's thyroiditis: A case report and review of the literature.

PubMed

Cai, Wei; Kang, Hua; Hai, Tao

2016-01-01

Riedel's thyroiditis is a rare type of chronic thyroiditis, associated with fibroinflammatory process and invasion into surrounding tissues, leading to compressive symptoms. A 45-year-old man had a left thyroid mass, presenting with hypotension and bradycardia many times. He was diagnosed with vasovagal reflex caused by cervical vessel compression due to a thyroid lesion. We performed the emergency operation, and most of the left thyroid was removed to relieve the compression on cervical vessels. The result of pathology proved to be Riedel's thyroiditis. The vasovagal reflex did not occur any more during the 28-month follow up, except on the 3(rd) day after the surgery. Six months after the thyroidectomy, the patient was found to have retroperitoneal fibrosis, diagnosed by biopsy during a laparotomy for biliary disease. Riedel's thyroiditis can lead to a vasovagal episode and might not be a primary thyroid disease but rather a manifestation of the systemic disorder, multifocal fibrosclerosis. Copyright © 2013. Published by Elsevier Taiwan.

Estrogen-Related Receptor Alpha Modulates Lactate Dehydrogenase Activity in Thyroid Tumors

PubMed Central

Mirebeau-Prunier, Delphine; Le Pennec, Soazig; Jacques, Caroline; Fontaine, Jean-Fred; Gueguen, Naig; Boutet-Bouzamondo, Nathalie; Donnart, Audrey; Malthièry, Yves; Savagner, Frédérique

2013-01-01

Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis. PMID:23516535

Hashimoto thyroiditis onset after laparoscopic removal of struma ovarii: an overview to unravel a rare and intriguing finding.

PubMed

Laganà, A S; Santoro, G; Triolo, O; Giacobbe, V; Certo, R; Palmara, V

2015-01-01

Struma ovarii is an uncommon type of ovarian tumor derived by germinal cells, characterized by the predominance of thyroid tissue (> 50%); 90-95% of these formations are benign and mainly affect the left ovary, while in 6% of the cases struma ovarii is bilateral. The malignant transformation is a rare condition that often occurs after 50 years. In most instances, diagnosis of malignant struma ovarii is made postoperatively during histological analysis. This tumor appears to derive by one germinal cell through loss of heterozygosity of the androgen receptor gene and of the X chromosome. Clinical symptoms comprise abdominopelvic mass, lower abdominal pain, abnormal vaginal bleeding, and ascites (the occurrence of this condition has been observed in one-third of the cases). The patients with struma ovarii generally do not manifest symptoms related to thyroid hyperfunction, reported only in 8% of the cases, and due to hyperstimulation of the thyroid by auto-antibodies. Thyroid tissue of the struma ovarii, often embedded in a teratoma, may be papillary, follicular or with mixed pattern and it can include elements of mucinous cystoadenomas, Brenner's tumor or carcinoid or melanomas cells. Here the authors report their experience with an unusual case of Hashimoto thyroiditis onset after laparoscopic removal of struma ovarii.

Estrogen receptor (ER)-beta, but not ER-alpha, is present in thyroid vessels: immunohistochemical evaluations in multinodular goiter and papillary thyroid carcinoma.

PubMed

Ceresini, Graziano; Morganti, Simonetta; Graiani, Virna; Saccani, Maria; Milli, Bruna; Usberti, Elisa; Valenti, Giorgio; Ceda, Gian Paolo; Corcione, Luigi

2006-12-01

Estrogen receptors (ERs) have been demostrated in the vessel structures of several systems. Little is known on the presence of ERs in the thyroid vessels. We immunohistochemically evaluated both ER-alpha and ER-beta immunoreactivity (IR) in both vascular and follicular thyroid cells in tissue samples from 17 cases of multinodular goiter (MNG) and 17 cases of papillary thyroid carcinoma (PTC). ER-alpha IR was undetectable in either tissue examined. In 100% of MNG samples, nuclear ER-beta IR was detected in both endothelial and follicular cells. In PTC samples, endothelial nuclear ER-beta IR was found in 100% of cases, whereas the nuclear staining of follicular cells was found in 83% of cases. The intensity of staining of the endothelial ER-beta IR was comparable between MNG and PTC. However, when follicular cells were considered, a tendency toward a decrease in nuclear staining and a significant increase in cytoplasmic staining were found in PTC lesions as compared to MNG. This study demonstrated that ER-beta, but not ER-alpha, IR is present in the endothelium of thyroid vessels. Furthermore, although data need to be confirmed in larger observations, these results suggest the lack of differences in the pattern of vascular ER-beta IR between MNG and PTC.

Multiplex analysis of cytokines as biomarkers that differentiate benign and malignant thyroid diseases

PubMed Central

Linkov, Faina; Ferris, Robert L.; Yurkovetsky, Zoya; Marrangoni, Adele; Velikokhatnaya, Lyudmila; Gooding, William; Nolan, Brian; Winans, Matthew; Siegel, Eric R.; Lokshin, Anna; Stack, Brendan C.

2008-01-01

Thyroid cancer incidence is increasing, and its diagnosis can be challenging. Fine needle biopsy, the principal clinical tool to make a tissue diagnosis, leads to inconclusive diagnoses in up to 30% of the cases, leading to surgery. Advances in proteomics are improving abilities to diagnose malignant conditions using small samples of tissue or body fluids. We hypothesized that analysis of serum growth factors would uncover diagnostically informative differences between benign and malignant thyroid conditions. Using xMAP profiling, we evaluated concentrations of 19 cytokines, chemokines, and growth factors. We used sera from 23 patients with cancer (Malignant group), 24 patients with benign nodular thyroid disease (Benign group), and 23 healthy subjects (Normal group). In univariate analysis, five factors (epithelial growth factor, hepatocyte growth factor, Interleukins-5 and -8, and regulated upon activation, normally T-expressed and presumably secreted (RANTES) distinguished subjects with thyroid disease from the Normal group. In multivariate analysis, the set {Interleukin-8, hepatocyte growth factor, monocyte-induced γ interferon, interleukin-12 p40} achieved noteworthy discrimination between Benign and Malignant groups (area under the receiver operating characteristics curve was 0.81 (95% confidence interval: 0.65–0.90)). Multiplex panels of serum biomarkers may be promising tools to diagnose cancer in patients presenting with evidence of nodular thyroid disease. PMID:19234619

Activating thyrotropin receptor mutations are present in nonadenomatous hyperfunctioning nodules of toxic or autonomous multinodular goiter.

PubMed

Tonacchera, M; Agretti, P; Chiovato, L; Rosellini, V; Ceccarini, G; Perri, A; Viacava, P; Naccarato, A G; Miccoli, P; Pinchera, A; Vitti, P

2000-06-01

Toxic multinodular goiter, a heterogeneous disease producing hyperthyroidism, is frequently found in iodine-deficient areas. The pathogenesis of this common clinical entity is still unclear. The aim of the present study was to search for activating TSH receptor (TSHr) or Gs alpha mutations in areas of toxic or functionally autonomous multinodular goiters that appeared hyperfunctioning at thyroid scintiscan but did not clearly correspond to definite nodules at physical or ultrasonographic examination. Surgical tissue specimens from nine patients were carefully dissected, matching thyroid scintiscan and thyroid ultrasonography, to isolate hyperfunctioning and nonfunctioning areas even if they did not correspond to well-defined nodules. TSHr and Gs alpha mutations were searched for by direct sequencing after PCR amplification of genomic DNA. Only 2 adenomas were identified at microscopic examination, whereas the remaining 18 hyperfunctioning areas corresponded to hyperplastic nodules containing multiple aggregates of micromacrofollicules not surrounded by a capsule. Activating TSHr mutations were detected in 14 of these 20 hyperfunctioning areas, whereas no mutation was identified in nonfunctioning nodules or areas contained in the same gland. No Gs alpha mutation was found. In conclusion, activating TSHr mutations are present in the majority of nonadenomatous hyperfunctioning nodules scattered throughout the gland in patients with toxic or functionally autonomous multinodular goiter.

Effects of hypothyroidism on vascular /sup 125/I-albumin permeation and blood flow in rats

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

Tilton, R.G.; Pugliese, G.; Chang, K.

1989-05-01

Effects of hypothyroidism on vascular 125I-albumin permeation and on blood flow were assessed in multiple tissues of male Sprague-Dawley rats rendered hypothyroid by dietary supplementation with 0.5% (wt/wt) 2-thiouracil or by thyroidectomy. In both thiouracil-treated and thyroidectomized rats, body weights, kidney weight, arterial blood pressure, and pulse rate were decreased significantly v age-matched controls. After 10 to 12 weeks of thiouracil treatment, 125I-albumin permeation was increased significantly in the kidney, aorta, eye (anterior uvea, choroid, retina), skin, and new granulation tissue, remained unchanged in brain, sciatic nerve, and heart, and was decreased in forelimb skeletal muscle. A similar pattern wasmore » observed in thyroidectomized rats, except that increases in 125I-albumin permeation for all tissues were smaller than those observed in thiouracil-treated rats, and 125I-albumin permeation in retina did not differ from controls. In both thiouracil-treated and thyroidectomized rats, changes in blood flow (assessed with 15-microns, 85Sr-labeled microspheres) relative to the decrease in arterial blood pressure were indicative of a decrease in regional vascular resistance except in the choroid and in the kidney, in which vascular resistance was increased significantly. Glomerular filtration rate was decreased, but filtration fraction and urinary excretion of albumin remained unchanged by thiouracil treatment and thyroidectomy. These results indicate that vascular hemodynamics and endothelial cell barrier functional integrity are modulated in many different tissues by the thyroid. In view of the correspondence of hypothyroid- and diabetes-induced vascular permeability changes, these results raise the possibility that altered thyroid function in diabetes may play a role in the pathogenesis of diabetic vascular disease.« less

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.

Influence of lake trophic structure on iodine-131 accumulation and subsequent cumulative radiation dose to trout thyroids.

PubMed

Martinez, Nicole E; Johnson, Thomas E; Pinder, John E

2014-05-01

Iodine-131 is a major component of the atmospheric releases following reactor accidents, and the passage of (131)I through food chains from grass to human thyroids has been extensively studied. By comparison, the fate and effects of (131)I deposition onto lakes and other aquatic systems have been less studied. In this study we: (1) reanalyze 1960s data from experimental releases of (131)I into two small lakes; (2) compare the effects of differences in lake trophic structures on the accumulation of (131)I by fish; (3) relate concentrations in fish and fish tissues to that in the water column using empirically estimated uptake (L kg(-1) d(-1)) and loss (d(-1)) parameters; and (4) show that the largest concentrations in the thyroids of trout (Oncorhynchus mykiss) may occur from 8 to 32 days after initial release. Iodine-131 concentration in trout thyroids at 30-days post release may be >1000 times that in the water. Estimates of cumulative radiation dose (mGy) to thyroids computed using an anatomically-appropriate model of trout thyroid structure within the Monte Carlo N-particle modeling software predicted cumulative thyroid doses that increased approximately linearly after the first 8 days and resulted in 32-day cumulative thyroid doses that ranged from 6 mGy g(-1) to 18 mGy g(-1) per 1 Bq mL(-1) of initial (131)I in the water depending upon fish size. The majority of this dose is due to beta emissions, and the dose varies with positions in the thyroid tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effect of low level laser on anaplastic thyroid cancer

NASA Astrophysics Data System (ADS)

Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

2015-02-01

Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

Expression of immunoregulatory molecules by thyrocytes protects nonobese diabetic-H2h4 mice from developing autoimmune thyroiditis.

PubMed

Nakahara, Mami; Nagayama, Yuji; Saitoh, Ohki; Sogawa, Rintaro; Tone, Shigenobu; Abiru, Norio

2009-03-01

One approach to prevent tissue destruction by autoimmune attack in organ-specific autoimmune diseases is to protect the target tissue from autoimmune reaction, regardless of its persistent activity. To provide proof-of-principle for the feasibility of this approach, the immunoregulatory molecules, TNF-related apoptosis-inducing ligand (TRAIL) and indoleamine 2, 3-dioxygenase, were expressed in the thyroid glands using adenovirus vector in nonobese diabetic-H2(h4) mice that spontaneously develop thyroiditis. Mice were anesthetized, and the thyroid glands were exposed by neck dissection, followed by in situ infection with adenovirus vector (5 x 10(10) particles per mouse) twice or thrice, starting 1 d or 4 wk before mice were supplied with sodium iodine (NaI) water. After 8 wk NaI provision, the extent of thyroiditis, serum titers of antithyroglobulin antibodies, and cytokine expression in the spleen were examined. In situ infection of adenovirus expressing TRAIL or indoleamine 2, 3-dioxygenase, but not green fluorescent protein, significantly suppressed thyroiditis scores. However, antithyroglobulin antibody titers and expression levels of cytokines (interferon-gamma and IL-4) in the spleen remained unaltered. Importantly, adenovirus infection 4 wk after NaI provision was also effective at suppressing thyroiditis. The suppressive effect of TRAIL appears to be mediated at least partly by accumulation of CD4(+)Foxp3(+) regulatory T cells into the thyroid glands. Thus, localized expression of immunoregulatory molecules efficiently protected the thyroid glands from autoimmune attack without changing the systemic autoimmunity in nonobese diabetic-H2(h4) mice. This kind of immunological intervention, although it does not suppress autoimmune reactivity, may have a potential for treating organ-specific autoimmune diseases.

The thyroid hormone receptor-associated protein TRAP220 is required at distinct embryonic stages in placental, cardiac, and hepatic development.

PubMed

Landles, Christian; Chalk, Sara; Steel, Jennifer H; Rosewell, Ian; Spencer-Dene, Bradley; Lalani, El-Nasir; Parker, Malcolm G

2003-12-01

Recent work indicates that thyroid hormone receptor-associated protein 220 (TRAP220), a subunit of the multiprotein TRAP coactivator complex, is essential for embryonic survival. We have generated TRAP220 conditional null mice that are hypomorphic and express the gene at reduced levels. In contrast to TRAP220 null mice, which die at embryonic d 11.5 (E11.5), hypomorphic mice survive until E13.5. The reduced expression in hypomorphs results in hepatic necrosis, defects in hematopoiesis, and hypoplasia of the ventricular myocardium, similar to that observed in TRAP220 null embryos at an earlier stage. The embryonic lethality of null embryos at E11.5 is due to placental insufficiency. Tetraploid aggregation assays partially rescues embryonic development until E13.5, when embryonic loss occurs due to hepatic necrosis coupled with poor myocardial development as observed in hypomorphs. These findings demonstrate that, for normal placental function, there is an absolute requirement for TRAP220 in extraembryonic tissues at E11.5, with an additional requirement in embryonic tissues for hepatic and cardiovascular development thereafter.

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 blood. • Weighted quantile sum (WQS) regression examined complex mixture effect. • WQS identified an inverse association between the exposure mixture and maternal TSH. • Perchlorate indicated as the ‘bad actor’ of the mixture.« less

Evaluation of residual radioactivity in human tissues associated with weapons testing at the nevada test site. Technical report, 1 June 1981-31 March 1989

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

Wrenn, M.E.; Singh, N.P.; Paschoa, A.S.

1992-11-01

Residual radioactivity consisting of 239 Pu were measured by radiochemistry and alpha spectrometry in samples of bone and soft tissues from 100 autopsies or surgeries from northern and southwestern Utah and from control areas in Colorado and Pennsylvania. Based upon the isotopic ratio 240 Pu/239 Pu contamination was attributable to atmospheric weapons tests at the Nevada Test Site (NTS). In addition, 110 thyroid tissue samples obtained from tissue blocks made at autopsy of veterans dying at the VA hospital in Salt Lake City in the 1940's and 1950's were measured for 129 I (half life 16 million year) and 127more » I (stable) by neutron activation. The results were analyzed by year of death, by periods before and during atmospheric nuclear weapons testing at the NTS and by origin of usual residence. A model was developed to relate thyroid dose from 131 I to the measured 124/127 I ratios, and thyroid dose estimates were made based upon the measured ratios.« less

Effects of drugs on the efficacy of radioiodine (|) therapy in hyperthyroid patients.

PubMed

Oszukowska, Lidia; Knapska-Kucharska, Małgorzata; Lewiński, Andrzej

2010-03-01

The treatment of hyperthyroidism is targeted at reducing the production of thyroid hormones by inhibiting their synthesis or suppressing their release, as well as by controlling their influence on peripheral tissue (conservative therapy, medical treatment). Radical treatment includes surgical intervention to reduce the volume of thyroid tissue or damage of the mechanisms of thyroid hormone synthesis by radioiodine ((131)|) administration. Radioiodine ((131)|) is a reactor radionuclide, produced as a result of uranium decomposition and emission of β and γ radiation. The therapeutic effects of the isotope are obtained by the emission of β radiation. In the paper, the effects of administered drugs (antithyroid, glucocorticosteroids, lithium carbonate, inorganic iodine, β-blockers) on the final outcome of radioiodine therapy in patients with hyperthyroidism are discussed.

Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis

PubMed Central

Bonett, Ronald M.; Hoopfer, Eric D.; Denver, Robert J.

2010-01-01

Corticosteroids (CS) act synergistically with thyroid hormone (TH) to accelerate amphibian metamorphosis. Earlier studies showed that CS increase nuclear 3,5,3′-triiodothyronine (T3) binding capacity in tadpole tail, and 5′ deiodinase activity in tadpole tissues, increasing the generation of T3 from thyroxine (T4). In the present study we investigated CS synergy with TH by analyzing expression of key genes involved in TH and CS signaling using tadpole tail explant cultures, prometamorphic tadpoles, and frog tissue culture cells (XTC-2 and XLT-15). Treatment of tail explants with T3 at 100 nM, but not at 10 nM caused tail regression. Corticosterone (CORT) at three doses (100, 500, 3400 nM) had no effect or increased tail size. T3 at 10 nM plus CORT caused tails to regress similar to 100 nM T3. Thyroid hormone receptor beta (TRβ) mRNA was synergistically upregulated by T3 plus CORT in tail explants, tail and brain in vivo, and tissue culture cells. The activating 5′ deiodinase type 2 (D2) mRNA was induced by T3 and CORT in tail explants and tail in vivo. Thyroid hormone increased expression of glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNAs. Our findings support that the synergistic actions of TH and CS in metamorphosis occur at the level of expression of genes for TRβ and D2, enhancing tissue sensitivity to TH. Concurrently, TH enhances tissue sensitivity to CS by upregulating GR and MR. Environmental stressors can modulate the timing of tadpole metamorphosis in part by CS enhancing the response of tadpole tissues to the actions of TH. PMID:20338173

A review on cardiovascular diseases originated from subclinical hypothyroidism.

PubMed

Mansourian, Azad Reza

2012-01-15

Thyroid hormones play an important role on the cardiovascular systems and thyroid disorder ultimately have a profound adverse effects on myocardium and vascular functions. There are extensive reports on the role of overt thyroid dysfunction which adversely can modify the cardiovascular metabolism but even at the present of some controversial reports, the subclinical thyroid disorders are able also to manipulate cardiovascular system to some extent. The aim of this study is to review the cardiovascular disorders accompanied with subclinical hypothyroidism. It is concluded that adverse effect of thyroid malfunction on myocardium and vascular organs are through the direct role of thyroid hormone and dyslipidemia on heart muscle cells at nuclear level and vascular system, respectively. It seems many cardiovascular disorders initially would not have been occurred in the first place if the thyroid of affected person had functioned properly, therefore thyroid function tests should be one of a prior laboratory examinations in cardiovascular disorders.

Update on the Management of Thyroid Disease during Pregnancy.

PubMed

Yim, Chang Hoon

2016-09-01

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant; however, these complications can be prevented by optimal treatment of maternal overt thyroid dysfunction. Although several studies have demonstrated that maternal subclinical hypothyroidism is associated with obstetric complications and neurocognitive impairments in offspring, there is limited evidence that levothyroxine treatment can improve these complications. Therefore, most professional societies do not recommend universal screening for thyroid dysfunction during pregnancy, and instead recommend a case-finding approach in which only high-risk women are tested. However, recent studies have estimated that targeted thyroid function testing misses approximately 30% to 55% of hypothyroidism cases in pregnant women, and some associations and researchers have recommended universal screening of pregnant women to facilitate the early detection and treatment of overt hypothyroidism. This review summarizes recent data on thyroid function test changes, thyroid functional disorder management, and thyroid screening during pregnancy.

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

Gao, Xuemei; Hubei Province Key Laboratory of Molecular Imaging, Wuhan 430022, Hubei Province; Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province

Thyroid cancer is a common malignancy of the endocrine system. Although radioiodine {sup 131}I treatment on differentiated thyroid cancer is widely used, many patients still fail to benefit from {sup 131}I therapy. Therefore, exploration of novel targeted therapies to suppress tumor growth and improve radioiodine uptake remains necessary. Bromodomain-containing protein 4 (BRD4) is an important member of the bromodomain and extra terminal domain family that influences transcription of downstream genes by binding to acetylated histones. In the present study, we found that BRD4 was up-regulated in thyroid cancer tissues and cell lines. Inhibition of BRD4 in thyroid cancer cells bymore » JQ1 resulted in cell cycle arrest at G0/G1 phase and enhanced {sup 131}I uptake in vitro and suppressed tumor growth in vivo. Moreover, JQ1 treatment suppressed C-MYC but enhanced NIS expression. We further demonstrated that BRD4 was enriched in the promoter region of C-MYC, which could be markedly blocked by JQ1 treatment. In conclusion, our findings revealed that the aberrant expression of BRD4 in thyroid cancer is possibly involved in tumor progression, and JQ1 is potentially an effective chemotherapeutic agent against human thyroid cancer. - Highlights: • BRD4 is upregulated in thyroid cancer tissues and cell lines. • Inhibition of BRD4 induced cell cycle arrest and enhanced radioiodine uptake in vitro and impaired tumor growth in vivo. • JQ1 suppressed the expression of C-MYC and promoted the expression of NIS and P21. • JQ1 attenuated the recruitment of BRD4 to MYC promoter in thyroid cancer.« less

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

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

High Body Mass Index Is an Indicator of Maternal Hypothyroidism, Hypothyroxinemia, and Thyroid-Peroxidase Antibody Positivity during Early Pregnancy

PubMed Central

Han, Cheng; Li, Chenyan; Mao, Jinyuan; Wang, Weiwei; Xie, Xiaochen; Zhou, Weiwei; Li, Chenyang; Xu, Bin; Bi, Lihua; Meng, Tao; Du, Jianling; Zhang, Shaowei; Gao, Zhengnan; Zhang, Xiaomei; Yang, Liu; Fan, Chenling; Teng, Weiping; Shan, Zhongyan

2015-01-01

Background. Maternal thyroid dysfunction in early pregnancy may increase the risk of adverse pregnancy complications and neurocognitive deficiencies in the developing fetus. Currently, some researchers demonstrated that body mass index (BMI) is associated with thyroid function in nonpregnant population. Hence, the American Thyroid Association recommended screening thyroid function in obese pregnant women; however, the evidence for this is weak. For this purpose, our study investigated the relationship between high BMI and thyroid functions during early pregnancy in Liaoning province, an iodine-sufficient region of China. Methods. Serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) concentration, urinary iodine concentration (UIC), and BMI were determined in 6303 pregnant women. Results. BMI ≥ 25 kg/m2 may act as an indicator of hypothyroxinemia and TPOAb positivity and BMI ≥ 30 kg/m2 was associated with increases in the odds of hypothyroidism, hypothyroxinemia, and TPOAb positivity. The prevalence of isolated hypothyroxinemia increased among pregnant women with BMI > 24 kg/m2. Conclusions. High BMI during early pregnancy may be an indicator of maternal thyroid dysfunction; for Asian women whose BMI > 24 kg/m2 and who are within 8 weeks of pregnancy, thyroid functions should be assessed especially. PMID:26273610

Quantitative single-photon emission computed tomography/computed tomography for technetium pertechnetate thyroid uptake measurement

PubMed Central

Lee, Hyunjong; Kim, Ji Hyun; Kang, Yeon-koo; Moon, Jae Hoon; So, Young; Lee, Won Woo

2016-01-01

Abstract Objectives: Technetium pertechnetate (99mTcO4) is a radioactive tracer used to assess thyroid function by thyroid uptake system (TUS). However, the TUS often fails to deliver accurate measurements of the percent of thyroid uptake (%thyroid uptake) of 99mTcO4. Here, we investigated the usefulness of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) after injection of 99mTcO4 in detecting thyroid function abnormalities. Materials and methods: We retrospectively reviewed data from 50 patients (male:female = 15:35; age, 46.2 ± 16.3 years; 17 Graves disease, 13 thyroiditis, and 20 euthyroid). All patients underwent 99mTcO4 quantitative SPECT/CT (185 MBq = 5 mCi), which yielded %thyroid uptake and standardized uptake value (SUV). Twenty-one (10 Graves disease and 11 thyroiditis) of the 50 patients also underwent conventional %thyroid uptake measurements using a TUS. Results: Quantitative SPECT/CT parameters (%thyroid uptake, SUVmean, and SUVmax) were the highest in Graves disease, second highest in euthyroid, and lowest in thyroiditis (P < 0.0001, Kruskal–Wallis test). TUS significantly overestimated the %thyroid uptake compared with SPECT/CT (P < 0.0001, paired t test) because other 99mTcO4 sources in addition to thyroid, such as salivary glands and saliva, contributed to the %thyroid uptake result by TUS, whereas %thyroid uptake, SUVmean and SUVmax from the SPECT/CT were associated with the functional status of thyroid. Conclusions: Quantitative SPECT/CT is more accurate than conventional TUS for measuring 99mTcO4 %thyroid uptake. Quantitative measurements using SPECT/CT may facilitate more accurate assessment of thyroid tracer uptake. PMID:27399139

Common variants in the G protein beta3 subunit gene and thyroid disorders in a formerly iodine-deficient population.

PubMed

Völzke, Henry; Bornhorst, Alexa; Rimmbach, Christian; Petersenn, Holger; Geissler, Ingrid; Nauck, Matthias; Wallaschofski, Henri; Kroemer, Heyo K; Rosskopf, Dieter

2009-10-01

Heterotrimeric G proteins are key mediators of signals from membrane receptors-including the thyroid-stimulating hormone (TSH) receptor-to cellular effectors. Gain-of-function mutations in the TSH receptor and the Galpha(S) subunit occur frequently in hyperfunctioning thyroid nodules and differentiated thyroid carcinomas, whereby the T allele of a common polymorphism (825C>T, rs5443) in the G protein beta3 subunit gene (GNB3) is associated with increased G protein-mediated signal transduction and a complex phenotype. The aim of this study was to investigate whether this common polymorphism affects key parameters of thyroid function and morphology and influences the pathogenesis of thyroid diseases in the general population. The population-based cross-sectional Study of Health in Pomerania is a general health survey with focus on thyroid diseases in northeast Germany, a formerly iodine-deficient area. Data from 3428 subjects (1800 men and 1628 women) were analyzed for an association of the GNB3 genotype with TSH, free triiodothyronine and thyroxine levels, urine iodine and thiocyanate excretion, and thyroid ultrasound morphology including thyroid volume, presence of goiter, and thyroid nodules. There was no association between GNB3 genotype status and the functional or morphological thyroid parameters investigated, neither in crude analyses nor upon multivariable analyses including known confounders of thyroid disorders. Based on the data from this large population-based survey, we conclude that the GNB3 825C>T polymorphism does not affect key parameters of thyroid function and morphology in the general population of a formerly iodine-deficient area.

Sorafenib induced thyroiditis in two patients with hepatocellular carcinoma.

PubMed

van Doorn, Leni; Eskens, Ferry A L M; Visser, Theo J; van der Lugt, Aad; Mathijssen, Ron H J; Peeters, Robin P

2011-02-01

Sorafenib is a multi-targeted tyrosine kinase inhibitor licensed for the treatment of hepatocellular carcinoma and renal cell carcinoma. Thyroid function test abnormalities have been reported for different tyrosine kinase inhibitors, but only limited data on thyroid function test abnormalities related to sorafenib are available, demonstrating the occurrence of hypothyroidism in patients treated with sorafenib. We describe two patients who developed temporary hyperthyroidism during the course of sorafenib treatment, which was followed by overt and subclinical hypothyroidism, respectively. Thyroid ultrasonography showed an atrophic thyroid gland in patient 1 , and signs of thyroiditis in patient 2 . Detailed reassessment of thyroid volumes on routinely performed computerized tomography scans showed a gradual decrease in thyroid volume during sorafenib treatment in one patient, suggesting progressive thyroid destruction. This case report describes in detail and for the first time two cases of sorafenib-induced thyroiditis. We assume that this sorafenib-induced destructive thyroiditis is an important cause of sorafenib-induced hypothyroidism.

Atherosclerosis affecting vision: therapy.

PubMed

Eggers, H

1966-05-01

The visual consequences and the pathogenesis and therapy of atherosclerosis are discussed. Atherosclerosis apparently is the result of hepatic failure to produce a stable suspension of cholesterol esters in the plasma. In some instances this represents an inherent metabolic defect. Usually it represents improper diet, namely, the excessive intake of saturated fatty acids and the inadequate intake of polyunsaturated fatty acids. Excessive ingestion of carbohydrates, insufficient physical exercise and reduced thyroid function are contributing causes. The final common denominators leading to tissue injury and destruction are vascular insufficiency and hypoxia. Hypertension is a separate disease, often concurrent with atherosclerosis. In diabetes, also a separate disease, atherosclerosis is one of the sequelae. Therapy primarily consists of the reduction or elimination of meat and milk fats from the diet, and the inclusion or increase of marine fats and vegetable oils. Simultaneously, carbohydrate intake is restricted. Adequate thyroid function, a normal hemoglobin level, and sufficient physical exercise are important. A supplementary intake of vitamins B6 and E, and of lipotropic substances is recommended.

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

Laparoscopic gastric bypass in patients on thyroid replacement therapy for subnormal thyroid function - prevalence and short-term outcome.

PubMed

Szomstein, Samuel; Avital, Shmuel; Brasesco, Oscar; Mehran, Amir; Cabral, Jose M; Rosenthal, Raul

2004-01-01

Hypothyroidism is associated with increased body weight. Weight gain may occur despite normal levels of serum thyroid stimulating hormone (TSH) and thyroxine (T4) achieved by replacement therapy. We evaluated the prevalence of patients on thyroid replacement for subnormal thyroid function who were operated on for morbid obesity and monitored their postoperative weight loss pattern. Data was identified from a prospectively accrued database of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) or laparoscopic adjustable gastric banding (LAGB) for morbid obesity from February 2000 to November 2001. All patients with subnormal thyroid function, diagnosed by past thyroid function tests and treated by an endocrinologist, who were on thyroid replacement therapy, were identified; 5 of these were matched for age, gender, preoperative body mass index (BMI) and surgical procedure (LRYGBP) to 5 non-hypothyroid patients. Weight loss at 3 and 9 months after surgery was compared between the 2 groups. 192 patients underwent LRYGBP (n=155) or LAGB (n=37). Of the 21 patients (10.9%) on thyroid replacement identified, 14 were primary, 4 were postablative, and 3 were post-surgical; 17 underwent LRYGBP. All patients had normal preoperative serum levels of TSH and T4. Comparison of the 2 matched groups of patients revealed no difference in weight loss at 3 and 9 months after surgery (P=1.0). The prevalence of euthyroid patients on thyroid replacement for subnormal thyroid function who undergo surgical intervention for morbid obesity is high. Short-term weight loss in these patients is comparable to normal thyroid patients. Longer follow-up may be necessary to demonstrate the weight loss pattern in this group.

Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

PubMed

Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

2016-12-01

Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

Comparison of the Light Charged Particles on Scatter Radiation Dose in Thyroid Hadron Therapy

PubMed Central

Azizi, M; Mowlavi, AA

2014-01-01

Background: Hadron therapy is a novel technique of cancer radiation therapy which employs charged particles beams, 1H and light ions in particular. Due to their physical and radiobiological properties, they allow one to obtain a more conformal treatment, sparing better the healthy tissues located in proximity of the tumor and allowing a higher control of the disease. Objective: As it is well known, these light particles can interact with nuclei in the tissue, and produce the different secondary particles such as neutron and photon. These particles can damage specially the critical organs behind of thyroid gland. Methods: In this research, we simulated neck geometry by MCNPX code and calculated the light particles dose at distance of 2.14 cm in thyroid gland, for different particles beam: 1H, 2H, 3He, and 4He. Thyroid treatment is important because the spine and vertebrae is situated right behind to the thyroid gland on the posterior side. Results: The results show that 2H has the most total flux for photon and neutron, 1.944E-3 and 1.7666E-2, respectively. Whereas 1H and 3He have best conditions, 8.88609E-4 and 1.35431E-3 for photon, 4.90506E-4 and 4.34057E-3 for neutron, respectively. The same calculation has obtained for energy depositions for these particles. Conclusion: In this research, we investigated that which of these light particles can deliver the maximum dose to the normal tissues and the minimum dose to the tumor. By comparing these results for the mentioned light particles, we find out 1H and 3He is the best therapy choices for thyroid glands whereas 2H is the worst. PMID:25505774

IMPORTANCE OF THE DETERMINATION OF THE WEIGHT OF THE THYROID GLAND AND THE CLINICAL BIOLOGICAL FACTORS IN THE TREATMENT OF HYPERTHYRODISM WITH $sup 131$I

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

Clode, W.; Sobral, V.; Baptista, A.M.

1959-10-31

Clinical results are reviewed for a group of 117 patients treated for hyperthyroidism with iodine-131. The importance of clinical, biological, and physical factors on results is stressed. Various methods for determining thyroid mass are discussed. A visualization technique, called pneumothyroid, is described in which the thyroid volume is determined from a series of x rays and tomographs following the injection of air into the tissue surrounding the thyroid capsule. The apparatus used resembles that used in pneumothorax. This method was found superior to palpation for estimations of thyroid weight prior to calculation of iodine-131 dose. (C.H.)

Cytomorphology and sonographic features of ectopic thymic tissue diagnosed in paediatric FNA biopsies.

PubMed

Escobar, F A; Pantanowitz, L; Picarsic, J L; Craig, F E; Simons, J P; Viswanathan, P A; Yilmaz, S; Monaco, S E

2018-03-26

Ectopic thymic tissue can arise as an asymptomatic neck mass, which may be detected on imaging studies. The aim of this study was to determine the incidence of ectopic thymic tissue in paediatric FNAs and to the correlate clinical, radiological and cytomorphological findings. FNAs in children with neck and mediastinal lesions performed between January 2012 and July 2016 were reviewed for cases of ectopic thymus. These were then evaluated and correlated with the cytology findings. Of 739 FNAs, 13 (1.8%) cases from 11 patients showed ectopic thymic tissue. The targeted lesions were in the thyroid (n = 7), submandibular region (n = 1), superior mediastinum (n = 1) and paratracheal region (n = 1). The most common indication was for microcalcifications concerning for papillary thyroid carcinoma on ultrasound (n = 6). Imaging findings included fusiform lesions with linear and punctuate bright echoes. The cytology evaluation showed small lymphocytes with discohesive epithelioid cells in most cases, and proteinaceous fluid in the cystic case. There were rare macrophages and Hassall's corpuscles. Flow cytometry and/or immunostains were performed in all cases, supporting thymic origin. Ectopic thymic tissue is rarely present as a neck mass or thyroid nodule on FNA biopsy. The ultrasound imaging findings reveal a well-defined fusiform lesion with punctate bright echoes that could be misinterpreted as papillary thyroid carcinoma. The aspirates show a small lymphoid population, immunophenotypically compatible with thymic T-cells, in addition to scattered epithelial cells. Therefore, knowledge of the typical ultrasonographic and cytopathological features can help make a definitive diagnosis and avoid more invasive procedures in paediatric patients. © 2018 John Wiley & Sons Ltd.

Assessment of thyroid function in dogs with low plasma thyroxine concentration.

PubMed

Diaz Espineira, M M; Mol, J A; Peeters, M E; Pollak, Y W E A; Iversen, L; van Dijk, J E; Rijnberk, A; Kooistra, H S

2007-01-01

Differentiation between hypothyroidism and nonthyroidal illness in dogs poses specific problems, because plasma total thyroxine (TT4) concentrations are often low in nonthyroidal illness, and plasma thyroid stimulating hormone (TSH) concentrations are frequently not high in primary hypothyroidism. The serum concentrations of the common basal biochemical variables (TT4, freeT4 [fT4], and TSH) overlap between dogs with hypothyroidism and dogs with nonthyroidal illness, but, with stimulation tests and quantitative measurement of thyroidal 99mTcO4(-) uptake, differentiation will be possible. In 30 dogs with low plasma TT4 concentration, the final diagnosis was based upon histopathologic examination of thyroid tissue obtained by biopsy. Fourteen dogs had primary hypothyroidism, and 13 dogs had nonthyroidal illness. Two dogs had secondary hypothyroidism, and 1 dog had metastatic thyroid cancer. The diagnostic value was assessed for (1) plasma concentrations of TT4, fT4, and TSH; (2) TSH-stimulation test; (3) plasma TSH concentration after stimulation with TSH-releasing hormone (TRH); (4) occurrence of thyroglobulin antibodies (TgAbs); and (5) thyroidal 99mTcO4(-) uptake. Plasma concentrations of TT4, fT4, TSH, and the hormone pairs TT4/TSH and fT4/TSH overlapped in the 2 groups, whereas, with TgAbs, there was 1 false-negative result. Results of the TSH- and TRH-stimulation tests did not meet earlier established diagnostic criteria, overlapped, or both. With a quantitative measurement of thyroidal 99mTcO4(-) uptake, there was no overlap between dogs with primary hypothyroidism and dogs with nonthyroidal illness. The results of this study confirm earlier observations that, in dogs, accurate biochemical diagnosis of primary hypothyroidism poses specific problems. Previous studies, in which the TSH-stimulation test was used as the "gold standard" for the diagnosis of hypothyroidism may have suffered from misclassification. Quantitative measurement of thyroidal 99mTcO- uptake has the highest discriminatory power with regard to the differentiation between primary hypothyroidism and nonthyroidal illness.

Influence of thyroid function on glomerular filtration rate and other estimates of kidney function in two pediatric patients.

PubMed

Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki

2018-05-01

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

Thyroid hormones and deiodinase activity in plasma and tissues in relation to high levels of organohalogen contaminants in East Greenland polar bears (Ursus maritimus).

PubMed

Gabrielsen, Kristin Møller; Krokstad, Julie Stene; Villanger, Gro Dehli; Blair, David A D; Obregon, Maria-Jesus; Sonne, Christian; Dietz, Rune; Letcher, Robert J; Jenssen, Bjørn Munro

2015-01-01

Previous studies have shown relationships between organohalogen contaminants (OHCs) and circulating levels of thyroid hormones (THs) in arctic wildlife. However, there is a lack of knowledge concerning the possible functional effects of OHCs on TH status in target tissues for TH-dependent activity. The relationships between circulating (plasma) levels of OHCs and various TH variables in plasma as well as in liver, muscle and kidney tissues from East Greenland sub-adult polar bears (Ursus maritimus) sampled in 2011 (n=7) were therefore investigated. The TH variables included 3.3',5.5'-tetraiodothyronine or thyroxine (T4), 3.3',5-triiodothyronine (T3) and type 1 (D1) and type 2 (D2) deiodinase activities. Principal component analysis (PCA) combined with correlation analyses demonstrated negative relationships between individual polychlorinated biphenyls (PCBs) and their hydroxylated (OH-) metabolites and T4 in both plasma and muscle. There were both positive and negative relationships between individual OHCs and D1 and D2 activities in muscle, liver and kidney tissues. In general, PCBs, OH-PCBs and polybrominated dipehenyl ethers (PBDEs) were positively correlated to D1 and D2 activities, whereas organochlorine pesticides and byproducts (OCPs) were negatively associated with D1 and D2 activities. These results support the hypothesis that OHCs can affect TH status and action in the target tissues of polar bears. TH levels and deiodinase activities in target tissues can be sensitive endpoints for exposure of TH-disrupting compounds in arctic wildlife, and thus, tissue-specific responses in target organs should be further considered when assessing TH disruption in wildlife studies. Copyright © 2014 Elsevier Inc. All rights reserved.

Knockdown of BAG3 induces epithelial-mesenchymal transition in thyroid cancer cells through ZEB1 activation.

PubMed

Meng, X; Kong, D-H; Li, N; Zong, Z-H; Liu, B-Q; Du, Z-X; Guan, Y; Cao, L; Wang, H-Q

2014-02-27

The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial-mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis.

Knockdown of BAG3 induces epithelial–mesenchymal transition in thyroid cancer cells through ZEB1 activation

PubMed Central

Meng, X; Kong, D-H; Li, N; Zong, Z-H; Liu, B-Q; Du, Z-X; Guan, Y; Cao, L; Wang, H-Q

2014-01-01

The process by which epithelial features are lost in favor of a mesenchymal phenotype is referred to as epithelial–mesenchymal transition (EMT). Most carcinomas use this mechanism to evade into neighboring tissues. Reduction or a loss of E-cadherin expression is a well-established hallmark of EMT. As a potent suppressor of E-cadherin, transcription factor ZEB1 is one of the key inducers of EMT, whose expression promotes tumorigenesis and metastasis of carcinomas. Bcl-2-associated athanogene 3 (BAG3) affects multifaceted cellular functions, including proliferation, apoptosis, cell adhesion and invasion, viral infection, and autophagy. Recently, we have reported a novel role of BAG3 implicated in EMT, while the mechanisms are poorly elucidated. The current study demonstrated that knockdown of BAG3 induced EMT, and increased cell migratory and invasiveness in thyroid cancer cells via transcriptional activation of ZEB1. We also found that BAG3 knockdown led to nuclear accumulation of β-catenin, which was responsible for the transcriptional activation of ZEB1. These results indicate BAG3 as a regulator of ZEB1 expression in EMT and as a regulator of metastasis in thyroid cancer cells, providing potential targets to prevent and/or treat thyroid cancer cell invasion and metastasis. PMID:24577090

Downregulation of Notch-regulated Ankyrin Repeat Protein Exerts Antitumor Activities against Growth of Thyroid Cancer.

PubMed

Chu, Bing-Feng; Qin, Yi-Yu; Zhang, Sheng-Lai; Quan, Zhi-Wei; Zhang, Ming-Di; Bi, Jian-Wei

2016-07-05

The Notch-regulated ankyrin repeat protein (NRARP) is recently found to promote proliferation of breast cancer cells. The role of NRARP in carcinogenesis deserves extensive investigations. This study attempted to investigate the expression of NRARP in thyroid cancer tissues and assess the influence of NRARP on cell proliferation, apoptosis, cell cycle, and invasion in thyroid cancer. Thirty-four cases with thyroid cancer were collected from the Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine between 2011 and 2012. Immunohistochemistry was used to detect the level of NRARP in cancer tissues. Lentivirus carrying NRARP-shRNA (Lenti-NRARP-shRNA) was applied to down-regulate NRARP expression. Cell viability was tested after treatment with Lenti-NRARP-shRNA using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle distribution were determined by flow cytometry. Cell invasion was tested using Transwell invasion assay. In addition, expressions of several cell cycle-associated and apoptosis-associated proteins were examined using Western blotting after transfection. Student's t-test, one-way analysis of variance (ANOVA), or Kaplan-Meier were used to analyze the differences between two group or three groups. NRARP was highly expressed in thyroid cancer tissues. Lenti-NRARP-shRNA showed significantly inhibitory activities against cell growth at a multiplicity of infection of 10 or higher (P < 0.05). Lenti-NRARP-shRNA-induced G1 arrest (BHT101: 72.57% ± 5.32%; 8305C: 75.45% ± 5.26%) by promoting p21 expression, induced apoptosis by promoting bax expression and suppressing bcl-2 expression, and inhibited cell invasion by suppressing matrix metalloproteinase-9 expression. Downregulation of NRARP expression exerts significant antitumor activities against cell growth and invasion of thyroid cancer, that suggests a potential role of NRARP in thyroid cancer targeted therapy.

APE/Ref-1 is increased in nuclear fractions of human thyroid hyperfunctioning nodules.

PubMed

Russo, D; Celano, M; Bulotta, S; Bruno, R; Arturi, F; Giannasio, P; Filetti, S; Damante, G; Tell, G

2002-08-30

Apurinic/apyrimidinic endonuclease APE/Ref-1 is a multifunctional protein provided with DNA repair, transcription-factor regulation and anti-apoptotic activities. We have previously reported that, in thyroid cells, TSH regulates both the synthesis and nuclear translocation of APE/Ref-1. We have also shown that nuclear levels of this protein are reduced both in thyroid carcinoma tissues and cell lines. In the present study, APE/Ref-1 expression and cellular localization were analysed by Western blot in hyperfunctioning thyroid nodules from patients with toxic adenoma and/or toxic multinodular goiter. The total content of APE/Ref-1 protein was increased in the majority of the hyperfunctioning tissues with respect to normal adjacent tissue. There was also an increase in the nuclear levels of APE/Ref-1, suggesting enhanced cytoplasm-to-nucleus translocation of the protein in addition to its increased rate of synthesis. These results demonstrate that the phenomenon of nuclear translocation of APE/Ref-1 hypothesized on the basis of cell culture experiments does actually occur in vivo. Together with previous observations in thyroid carcinomas and tumoral cell lines, our findings suggest a two-stage model of APE/Ref-1 behaviour during malignant thyrocyte transformation: an early stage characterized by simple hyperplasia and upregulation of APE/Ref-1 in the nuclear compartment of the cell and a later stage in which nuclear levels of the protein drop to below-normal levels as the cell becomes progressively undifferentiated.

Need of tetraiodothyronine supplemental therapy in pregnant women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid hormones are essential for fetal development. Normal thyroid function in pregnant women adjusts by itself in cases of pregnancy, phenomenon that is deficient in cases of previous maternal thyroid disease. The study group was represented by 120 females, with reproductive age, with known thyroid disease, that had a up to delivery pregnancy. Thyroid ultrasound parameters and functional parameters were follow-up during the 9-month of gestation. The study proposes a mathematical model of predicting the need and the amount of tetraiodothyronine treatment in pregnant women with prevalent thyroid disease.

Diagnostic and functional structure of a high-resolution thyroid nodule clinic.

PubMed

Fernández-García, José Carlos; Mancha-Doblas, Isabel; Ortega-Jiménez, María Victoria; Ruiz-Escalante, José Francisco; Castells-Fusté, Ignasi; Tofé-Povedano, Santiago; Argüelles-Jiménez, Iñaki; Tinahones, Francisco José

2014-01-01

Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a high-resolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

PubMed Central

Volpato, Claudia B.; Wilson, Scott G.; Cappola, Anne R.; Bos, Steffan D.; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M.; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M.; Nolte, Ilja M.; O'Connell, Jeffrey R.; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J.; Buckley, Brendan M.; Camaschella, Clara; de Craen, Anton J. M.; Davies, Gail; de Visser, Marieke C. H.; Ford, Ian; Forsen, Tom; Frayling, Timothy M.; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T.; Hermus, Ad R.; Hofman, Albert; Houwing-Duistermaat, Jeanine J.; Jensen, Richard A.; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M.; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D.; Nagaraja, Ramaiah; Netea-Maier, Romana T.; Palotie, Aarno; Persani, Luca; Piras, Maria G.; Psaty, Bruce M.; Räikkönen, Katri; Richards, J. Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M.; Sattar, Naveed; Shields, Beverley M.; Soranzo, Nicole; Starr, John M.; Stott, David J.; Sweep, Fred C. G. J.; Usala, Gianluca; van der Klauw, Melanie M.; van Heemst, Diana; van Mullem, Alies; H.Vermeulen, Sita; Visser, W. Edward; Walsh, John P.; Westendorp, Rudi G. J.; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J.; Eriksson, Johan G.; Ferrucci, Luigi; Fox, Caroline S.; Jukema, J. Wouter; Kiemeney, Lambertus A.; Pramstaller, Peter P.; Schlessinger, David; Shuldiner, Alan R.; Slagboom, Eline P.; Uitterlinden, André G.; Vaidya, Bijay; Visser, Theo J.; Wolffenbuttel, Bruce H. R.; Meulenbelt, Ingrid; Rotter, Jerome I.; Spector, Tim D.; Hicks, Andrew A.; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P.; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism. PMID:23408906

Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality.

PubMed

Mammen, Jennifer S; McGready, John; Ladenson, Paul W; Simonsick, Eleanor M

2017-11-01

Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time. Individual patterns of changing TSH and free thyroxine (fT4) were determined in 640 participants in the Baltimore Longitudinal Study of Aging who had at least three measures of serum TSH and fT4, not on medications, over an average of seven years of follow-up. Participants with changing phenotypes were identified based on quintiles for both slopes. Those with alterations in primary thyroid gland function demonstrated intact negative feedback (rising TSH with declining fT4 or declining TSH with rising fT4). Other participants had a parallel rise or fall of TSH and fT4 levels, consistent with pituitary dysfunction. Predictors of phenotype were analyzed by logistic regression. Differential survival between thyroid aging phenotypes was analyzed using multivariate Cox regression. While the majority of participants at all ages had stable thyroid function, changes were more common among older adults, with 32.3% of those aged >80 years but only 9.5% of those aged <60 years demonstrating thyroid function changes in the highest and lowest quintiles. Regression to the mean accounts for some of the changes, for example increased baseline TSH was associated with a falling TSH pattern (odds ratio = 1.4 [confidence interval 1.1-1.7] per 1 mIU/L). Importantly, changing thyroid function in either the upper or lower quintiles of slope for TSH and fT4 was associated with increased risk of death compared to stable thyroid status (hazard ratio = 5.4 [confidence interval 3.1-9.5]). Changing thyroid hormone function is increasingly common at older ages and is associated with decreased survival. Nonetheless, the tendency for abnormal thyroid function tests to resolve, along with altered pituitary responsiveness underlying some TSH elevations, suggests that an elevated TSH level should be not assumed to represent subclinical hypothyroidism in older adults. Thus, caution is appropriate when determining the need for thyroid hormone supplements in older adults.

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...

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

Serum apelin levels in patients with thyroid dysfunction

PubMed Central

Gürel, Ali; Doğantekin, Akif; Özkan, Yusuf; Aydın, Süleyman

2015-01-01

Adipocytes are not only for energy storage, but are also functionally active cells, producing biologically active peptides called adipocytokines. Adipocytokines control nutrition, thermogenesis, immunity, thyroid and reproductive hormones, and neuroendocrine functions. One of the most important new members of this family is apelin. In patients with thyroid dysfunctions, there are usually changes in weight, thermogenesis and adipose tissue lipolysis. Here, we investigated the serum apelin levels in different thyroid hormone states. Our study group consisted of the following patients: 32 thyrotoxicosis, 32 subclinical hyperthyroidism, 31 hypothyroidism, 34 subclinical hypothyroidism and 31 healthy control cases. In addition to routine blood tests, serum free T3 (FT3), free T4 (FT4), TSH and apelin levels were measured, and the body mass index (BMI) was recorded. In terms of the demographic characteristics, age and BMI, there was no statistically significant difference between the groups (P>0.05). The mean serum apelin levels of the groups were as follows: thyrotoxicosis group, 4.6±1.9 ng/ml; subclinical hyperthyroidism group, 3.7±1.9 ng/ml; hypothyroid group, 4.8±2.5 ng/ml; subclinical hypothyroidism group, 4.3±2.2 ng/mL; and control group, 3.4±1.4 ng/ml, respectively. There was no statistically significant difference in terms of the mean apelin levels between the groups (P>0.05). The hypothyroid group had the highest and the control group had the lowest mean apelin levels. As a result, the apelin levels were higher in both the patients with hypothyroidism and hyperthyroidism, in comparison with the normal population, but without statistical significance. PMID:26629164

[Clinical importance of thyroid gland cytology].

PubMed

Ting, S; Synoracki, S; Bockisch, A; Führer, D; Schmid, K W

2015-11-01

The cytological evaluation of fine needle biopsies (FNB) of the thyroid gland crucially depends on a close cooperation between clinicians and cytopathologists. Scintigraphy, sonography as well as clinical data and patient history are necessary for a correct interpretation of the indications for FNB; moreover, these data are of outstanding importance for cytopathologists for the correct interpretation of the cytomorphological findings. This overview describes the present standards in the acquisition, technical workup and cytopathological interpretation of thyroid gland tissue obtained by FNB, particularly focusing on the rapidly growing relevance of additional molecular pathological investigations to increase the diagnostic accuracy of thyroid FNB.

[Treatment of hyperthyroidism with radioiodine during hemodialysis: Report of one case].

PubMed

Hurtado, Claudia; Báez, María Soledad; Bate, Anabel; Opazo, Claudio; Troncoso, Mauricio

2017-05-01

Although radioiodine (131-I) can be used as treatment of hyperthyroidism for patients in hemodialysis, its use is limited and the experience is mainly related to differentiated thyroid carcinoma. We report a 58 years old female on hemodialysis with recurrent hyperthyroidism after propylthiouracil treatment. She was successfully treated with 131-I and four months after the intervention her euthyroid state was confirmed. We measured 131-I activity in blood, dialysate liquid and other waste products, as well as patient radiation exposure rates. We found that 131-I elimination was prolonged through time with no major dependence on hemodialysis, as opposed to the elimination of 131-I in patients with thyroid carcinoma. This was probably due to high radiotracer uptake in hyper functioning thyroid tissue. Conversely, radiation content in dialysate wastes or equipment was minimal. Furthermore, the rate of both environmental exposure and exposure of nursing staff in charge of hemodialysis sessions, was minimal and met international security standards. In conclusion, I-131 therapy showed both appropriate effectiveness and safety in this case and may be considered as a suitable treatment alternative to thyroidectomy when antithyroid drugs are unsuccessful.

Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care.

PubMed

Sheehan, Michael T

2016-06-01

Disorders of thyroid function are common, and screening, diagnosis, and management are often performed by primary care providers. While management of significant biochemical abnormalities is reasonably straight forward, laboratory tests only slightly outside, or even within, the normal range are becoming more difficult to appropriately manage. A large part of this increasing difficulty in appropriate management is caused by patients requesting, and even demanding, certain tests or treatments that may not be indicated. Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population. This, along with a growing body of information available to patients via the lay press and internet suggesting that traditional thyroid function testing is not reliable, has fostered some degree of patient mistrust. Increasingly, when a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry. This review aims to clarify the interpretation of normal and mild abnormalities of thyroid function tests by describing pituitary-thyroid physiology and through an in depth review of, arguably, the three most important biochemical tests of thyroid function: TSH, free T4, and anti-TPO antibodies. It is important for primary care providers to have an understanding of the shortcomings and proper interpretation of these tests to be better able to discuss thyroid function with their patients. © 2016 Marshfield Clinic.

Follicular adenoma in ectopic thyroid. A case-report.

PubMed

Consalvo, Vincenzo; Barbieri, Gerarda; Rossetti, Amalia Rosaria Rita; Romano, Mafalda; Contieri, Rosaria; Tramontano, Salvatore; Rescigno, Carmela; Infranzi, Massimo; Lombardi, Domenico

2017-01-01

The term ectopic thyroid refers to the presence of thyroid tissue located far from its usual anatomic placement and with no vascular connection to the main gland. The presence of swelling in atypical locations is diagnostically differentiated from other pathologies like pleomorphic adenoma or carcinoma, inflammatory lesions like sialadenitis, neurogenic tumors, paraganglioma, fibrolipoma and lymphadenopaties of diverse etiologies. Here we present the case of a submandibular ectopic thyroid in a 67year old woman. She came to our attention for a left submandibular swelling. The anamnesis did not show related pathologies, as well as blood tests. Diagnostic image studies and a FNAC were performed. The mass was surgically removed and histopatology showed a follicular adenoma in the contest of the capsulated lesion. It is important to not underestimate these types of lesions and procede with hematochemical, instrumental tests and above all surgery that can eliminate any diagnostic uncertainty and on the whole be therapeutic. It should not be forgotten that ectopic thyroid tissue can be a site for adenoma or papillary carcinoma and thus any watch and wait strategy should be avoided. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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.

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

Cho, Nancy L., E-mail: nlcho@partners.org; Lin, Chi-Iou; Du, Jinyan

Highlights: Black-Right-Pointing-Pointer Kinome profiling is a novel technique for identifying activated kinases in human cancers. Black-Right-Pointing-Pointer Src activity is increased in invasive thyroid cancers. Black-Right-Pointing-Pointer Inhibition of Src activity decreased proliferation and invasion in vitro. Black-Right-Pointing-Pointer Further investigation of Src targeted therapies in thyroid cancer is warranted. -- Abstract: Background: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using amore » bead-based, high-throughput system. Methods: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room. Protein lysates were analyzed using the Luminex immunosandwich, a bead-based kinase phosphorylation assay. Data was analyzed using GenePattern 3.0 software and clustered according to histology, demographic factors, and tumor status regarding capsular invasion, size, lymphovascular invasion, and extrathyroidal extension. Survival and invasion assays were performed to determine the effect of Src inhibition in papillary thyroid cancer (PTC) cells. Results: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Supervised clustering of well-differentiated tumors by histology, gender, age, or size did not reveal significant differences in tyrosine kinase activity. However, supervised clustering by the presence of invasive disease showed increased Src activity in invasive tumors relative to non-invasive tumors (60% v. 0%, p < 0.05). In vitro, we found that Src inhibition in PTC cells decreased cell invasion and proliferation. Conclusion: Global kinome analysis enables the discovery of novel targets for thyroid cancer therapy. Further investigation of Src targeted therapy for advanced thyroid cancer is warranted.« less

Integrating research on thyroid cancer after Chernobyl--the Chernobyl Tissue Bank.

PubMed

Thomas, G A; Bethel, J A; Galpine, A; Mathieson, W; Krznaric, M; Unger, K

2011-05-01

The only unequivocal radiological effect of the Chernobyl accident on human health is the increase in thyroid cancer in those exposed in childhood or early adolescence. In response to the scientific interest in studying the molecular biology of thyroid cancer after Chernobyl, the Chernobyl Tissue Bank was established. The project is supported by the governments of Ukraine and Russia, and financially supported (in total around US$3 million) by the European Commission, the National Cancer Institute of the USA and the Sasakawa Memorial Health Foundation of Japan. The project began collecting a variety of biological samples from patients on 1 October 1988, and has supplied material to 21 research projects in Japan, the USA and Europe. The establishment of the Chernobyl Tissue Bank has facilitated co-operation between these research projects and the combination of clinical and research data provides a paradigm for cancer research in the molecular biological age. Copyright © 2011 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Association of Pro-apoptotic Bad Gene Expression Changes with Benign Thyroid Nodules.

PubMed

Gül, Nurdan; Temel, Berna; Ustek, Duran; Sirma-Ekmekçi, Sema; Kapran, Yersu; Tunca, Fatih; Giles-Şenyürek, Yasemin; Özbek, Uğur; Alagöl, Faruk

2018-01-01

This study aimed to investigate the role of the mitochondrial apoptotic pathway in benign thyroid nodules. Paired samples of nodular and normal tissues were collected from 26 patients with nodular goiters undergoing thyroidectomy. Variable expression of Bcl-2, Bax and Bad genes were evaluated by quantitative PCR. Expression level of Bad gene in nodules was found to be significantly decreased compared to normal tissues (p=0.049). A positive correlation was observed between nodule size and Bad expression levels (correlation coefficient=0.563, p=0.004); and this correlation was stronger in hot nodules (n=18, correlation coefficient=0.689, p=0.003). No significant difference was observed between nodular and normal tissue expressions of Bax and Bcl-2. These results suggest that Bad expression correlates with the size of benign thyroid nodules and also its relatively lower expression in nodules, warrant further investigation. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

PubMed

Takano, Toru; Miyauchi, Akira; Ito, Yasuhiro; Amino, Nobuyuki

2006-06-01

We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

[Effects of mercazolyl and L-thyroxine on the antiedematous activity of immunotropic preparations during development of toxic brain edema and swelling].

PubMed

Platonov, I A; Anashchenkova, T A; Andreeva, T A

2008-01-01

Dysfunction of thyroid gland plays an important role in the pathogenesis of brain edema and swelling. Toxic brain edema and swelling was modeled under condition of hypo- and hyperfunction of thyroid gland. Mercazolyl and L-thyroxine ambiguously influence the development of toxic brain edema and swelling in rats. L-thyroxin (35.7 microg/kg) favors increase in the water content in brain tissue, which can be considered as synergism with the edematous factor and the formation of brain tissue susceptibility to the development of brain edema and swelling. The administration of mercazolyl (5 mg/kg) and L-thyroxin (35.7 microg/kg) with thymogen (10 microg/kg), thymalin (1.2 mg/kg), cycloferon (0.5 mg/kg) results in decreasing brain tissue density as compared to intact animals. Dysfunction of the thyroid gland leads to changes in pharmacodynamics of immune preparations, which results in a decrease of their antiedematous activity.

Upregulation of uncoupling proteins by oral administration of capsiate, a nonpungent capsaicin analog.

PubMed

Masuda, Yoriko; Haramizu, Satoshi; Oki, Kasumi; Ohnuki, Koichiro; Watanabe, Tatsuo; Yazawa, Susumu; Kawada, Teruo; Hashizume, Shu-ichi; Fushiki, Tohru

2003-12-01

Capsiate is a nonpungent capsaicin analog, a recently identified principle of the nonpungent red pepper cultivar CH-19 Sweet. In the present study, we report that 2-wk treatment of capsiate increased metabolic rate and promoted fat oxidation at rest, suggesting that capsiate may prevent obesity. To explain these effects, at least in part, we examined uncoupling proteins (UCPs) and thyroid hormones. UCPs and thyroid hormones play important roles in energy expenditure, the maintenance of body weight, and thermoregulation. Two-week treatment of capsiate increased the levels of UCP1 protein and mRNA in brown adipose tissue and UCP2 mRNA in white adipose tissue. This dose of capsiate did not change serum triiodothyronine or thyroxine levels. A single dose of capsiate temporarily raised both UCP1 mRNA in brown adipose tissue and UCP3 mRNA in skeletal muscle. These results suggest that UCP1 and UCP2 may contribute to the promotion of energy metabolism by capsiate, but that thyroid hormones do not.

Imaging of connective tissue diseases of the head and neck

PubMed Central

2016-01-01

We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren’s syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still’s disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders. PMID:26988082

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab

PubMed Central

Jansen, Yanina; Schreuer, Max; Everaert, Hendrik; Velkeniers, Brigitte; Neyns, Bart; Bravenboer, Bert

2016-01-01

Context: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. Objective: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. Design and Setting: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. Patients: Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. Main Outcome Measures: Patient characteristics, thyroid function (TSH, free T4), thyroid autoantibodies, and 18FDG-PET/CT. Results: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. Conclusions: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates. PMID:27571185

Skin findings in autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls.

PubMed

Takir, Mümtaz; Özlü, Emin; Köstek, Osman; Türkoğlu, Zafer; Mutlu, Hasan Hüseyin; Uzunçakmak, Tuğba Kevser; Akdeniz, Necmettin; Karadağ, Ayşe Serap

2017-06-12

Thyroid disorders are associated with a wide variety of skin disorders that respond to treatment of hormone imbalance in most cases and thus are of vital importance to dermatologists. This study aimed to evaluate skin findings associated with autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls. A total of 300 consecutive patients with either autoimmune (n = 173) or nonautoimmune (n = 127) thyroid disease and 100 healthy control subjects were included in this cross-sectional study. Data on patient demographics, thyroid function tests, and skin findings were recorded for patient and control groups. Compared to control subjects, patients had higher proportions in populations with alopecia (P < 0.001), nail thinning (P = 0.02), brittle nails (P = 0.001), pruritus (P < 0.001), diffuse hyperhidrosis (P = 0.01), flushing (P = 0.001), and xerosis (P < 0.001). Onycholysis (P = 0.02), yellow skin (P = 0.04), periorbital edema (P = 0.03), psoriasis (P = 0.001), and palmoplantar hyperkeratosis (P = 0.007) were significantly more common in patients with autoimmune than nonautoimmune thyroid disease. A significantly higher percentage of patients with autoimmune rather than nonautoimmune thyroid disease had overall skin findings (P = 0.03) among the hyperthyroid patients.Conclusions: Our findings indicate that the presence of skin findings in a majority of thyroid patients significantly differs for certain cutaneous manifestations with respect to controls, autoimmune etiology, and thyroid functional status.

Bipedicled strap muscle transposition for vocal fold deficit after laser cordectomy in early glottic cancer patients.

PubMed

Su, Chih-Ying; Chuang, Hui-Ching; Tsai, Shang-Shyue; Chiu, Jeng-Fen

2005-03-01

In treating early glottic carcinomas, the outcomes of endoscopic laser cordectomy have been proven to be valuable in local control, survival, and vocal function preservation. In some extended cases, however, laser cordectomy may leave patients with poor vocal function because of vocal fold deficit. This work assesses the vocal outcome of medialization laryngoplasty with bipedicled strap muscle transposition for vocal fold deficit resulting from laser cordectomy in early glottic cancer patients. A prospective clinical series. Thirteen early glottic cancer patients who had vocal fold deficit caused by previous laser cordectomy underwent medialization laryngoplasty with bipedicled strap muscle transposition. The thyroid lamina on the cordectomy side was paramedially separated. The inner perichondrium was circumspectly raised from the overlying thyroid cartilage. After separating the thyrohyoid and cricothyroid membranes, the lamina was retracted laterally. A bipedicled strap muscle flap was then transposed into the area between the lamina and the paraglottic soft tissue. The thyroid cartilages were carefully sutured back in position. All patients received pre- and postoperative voice assessments comprising laryngostroboscopy and vocal function studies. Vocal enhancement was present in 92% (12/13) of patients after medialization laryngoplasty with strap muscle transposition. The glottal closure and maximal phonation time were noticeably improved by surgery. No dyspnea or other significant complications were observed in any patients. The outcomes show that bipedicled strap muscle transposition is a prosthesis-free, safe, and valuable laryngoplastic technique for correcting glottal incompetence caused by endoscopic laser cordectomy in early glottic cancer patients.

Xenopus laevis deiodinase 3 expression for in vitro screening of potential chemical inhibitors

EPA Science Inventory

Thyroid hormones are essential for normal sequential development and metamorphosis of amphibian tissues and organs. Critical to this process are the deiodinase (DIO) enzymes which catalyze the removal of an iodine from thyroid hormones to either activate or inactivate the hormone...

Physiological serum 25-hydroxyvitamin D concentrations are associated with improved thyroid function-observations from a community-based program.

PubMed

Mirhosseini, Naghmeh; Brunel, Ludovic; Muscogiuri, Giovanna; Kimball, Samantha

2017-12-01

Vitamin D deficiency has been associated with an increased risk of hypothyroidism and autoimmune thyroid disease. Our aim was to investigate the influence of vitamin D supplementation on thyroid function and anti-thyroid antibody levels. We constructed a database that included 11,017 participants in a health and wellness program that provided vitamin D supplementation to target physiological serum 25-hydroxyvitmain D [25(OH)D] concentrations (>100 nmol/L). Participant measures were compared between entry to the program (baseline) and follow-up (12 ± 3 months later) using an intent-to-treat analysis. Further, a nested case-control design was utilized to examine differences in thyroid function over 1 year in hypothyroid individuals and euthyroid controls. More than 72% of participants achieved serum 25(OH)D concentrations >100 nmol/L at follow-up, with 20% above 125 nmol/L. Hypothyroidism was detected in 2% (23% including subclinical hypothyroidism) of participants at baseline and 0.4% (or 6% with subclinical) at follow-up. Serum 25(OH)D concentrations ≥125 nmol/L were associated with a 30% reduced risk of hypothyroidism and a 32% reduced risk of elevated anti-thyroid antibodies. Hypothyroid cases were found to have higher mean serum 25(OH)D concentrations at follow-up, which was a significant positive predictor of improved thyroid function. The results of the current study suggest that optimal thyroid function might require serum 25(OH)D concentrations above 125 nmol/L. Vitamin D supplementation may offer a safe and economical approach to improve thyroid function and may provide protection from developing thyroid disease.

Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals.

PubMed

de Jongh, Renate T; Lips, Paul; van Schoor, Natasja M; Rijs, Kelly J; Deeg, Dorly J H; Comijs, Hannie C; Kramer, Mark H H; Vandenbroucke, Jan P; Dekkers, Olaf M

2011-10-01

To what extent endogenous subclinical thyroid disorders contribute to impaired physical and cognitive function, depression, and mortality in older individuals remains a matter of debate. A population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. TSH and, if necessary, thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older. Participants were classified according to clinical categories of thyroid function. Participants with overt thyroid disease or use of thyroid medication were excluded, leaving 1219 participants for analyses. Outcome measures were physical and cognitive function, depressive symptoms (cross-sectional), and mortality (longitudinal) Sixty-four (5.3%) individuals had subclinical hypothyroidism and 34 (2.8%) individuals had subclinical hyperthyroidism. Compared with euthyroidism (n=1121), subclinical hypo-, and hyper-thyroidism were not significantly associated with impairment of physical or cognitive function, or depression. On the contrary, participants with subclinical hypothyroidism did less often report more than one activity limitation (odds ratio 0.44, 95% confidence interval (CI) 0.22-0.86). After a median follow-up of 10.7 years, 601 participants were deceased. Subclinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk (hazard ratio 0.89, 95% CI 0.59-1.35 and 0.69, 95% CI 0.40-1.20 respectively). This study does not support disadvantageous effects of subclinical thyroid disorders on physical or cognitive function, depression, or mortality in an older population.

An analytical method to screen for six thyreostatic drug residues in the thyroid gland and muscle tissues of food producing animals by liquid chromatography with ultraviolet absorption detection and liquid chromatography/mass spectrometry.

PubMed

Asea, Philip E; MacNeil, James D; Boison, Joe O

2006-01-01

A method was developed and validated to screen for residues of the thyreostatic drugs, tapazole (TAP), mercaptobenzimidazole (MBI), thiouracil (TU), methylthiouracil (MTU), propylthiouracil (PrTU), and phenylthiouracil (PhTU) in bovine, equine, ovine, and porcine thyroid and muscle tissues at concentrations > or = 5 ng/g using 2-methoxy-mercaptobenzimidazole (MeMBI) and dimethylthiouracil (DMTU) as internal standards. In this method, the drugs were solvent extracted from thyroid and muscle tissue and cleaned up on an amino-propyl solid-phase extraction (SPE) cartridge. The unretained fraction containing TAP and MBI and the internal standard, MeMBI, was collected as Fraction 1. The retained fraction containing TU, MTU, PrTU, PhTU, and the internal standard, DMTU, was eluted with 3% acetic acid-isopropanol as Fraction 2. Fraction 1 was further cleaned up on an alumina B SPE cartridge and analyzed by gradient elution on a C18 high-performance liquid chromatography (HPLC) column with ultraviolet detection at wavelengths of 255 and 300 nm. Fraction 2 was taken to dryness, derivatized with 4-chloro-7-nitrobenzo-2-furazan at pH 8, and analyzed by gradient elution on a C18 LC column with mass spectrometry (MS) detection. Any "presumptive positive" test results were submitted for further analysis by LC/MS/MS. The validated method was applied to the analysis of over 300 thyroid tissue samples.

CD8+ TIL recruitment may revert the association of MAGE A3 with aggressive features in thyroid tumors.

PubMed

Martins, Mariana Bonjiorno; Marcello, Marjory Alana; Batista, Fernando de Assis; Cunha, Lucas Leite; Morari, Elaine Cristina; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

2014-01-01

We aimed to investigate a possible role of MAGE A3 and its associations with infiltrated immune cells in thyroid malignancy, analyzing their utility as a diagnostic and prognostic marker. We studied 195 malignant tissues: 154 PTCs and 41 FTCs; 102 benign tissues: 51 follicular adenomas and 51 goiter and 17 normal thyroid tissues. MAGE A3 and immune cell markers (CD4 and CD8) were evaluated using immunohistochemistry and compared with clinical pathological features. The semiquantitative analysis and ACIS III analysis showed similar results. MAGE A3 was expressed in more malignant than in benign lesions (P < 0.0001), also helping to discriminate follicular-patterned lesions. It was also higher in tumors in which there was extrathyroidal invasion (P = 0.0206) and in patients with stage II disease (P = 0.0107). MAGE A3+ tumors were more likely to present CD8+ TIL (P = 0.0346), and these tumors were associated with less aggressive features, that is, extrathyroidal invasion and small size. There was a trend of MAGE A3+ CD8+ tumors to evolve free of disease. We demonstrated that MAGE A3 and CD8+ TIL infiltration may play an important role in malignant thyroid nodules, presenting an interesting perspective for new researches on DTC immunotherapy.

Effects of hyperthyroidism, hypothyroidism, and thyroid autoimmunity on female sexual function.

PubMed

Oppo, A; Franceschi, E; Atzeni, F; Taberlet, A; Mariotti, S

2011-06-01

Thyroid hormones affect male and female sexual functions, but data in hypo- and hyperthyroid women are scanty. To investigate sexual function in hypo- and hyperthyroid women before and immediately after restoration of euthyroidism and in women with euthyroid Hashimoto's thyroiditis (HT). Fifty-six women with thyroid diseases (age 19-50 yr; 22 with hyperthyroidism, 17 with hypothyroidism, and 17 with euthyroid HT) and 30 age-matched healthy women. Hypoactive sexual desire, disorders of sexual arousal, vaginal lubrication, orgasm, satisfaction, and sexual pain (SPD) were assessed by Female Sexual Function Index. Serum TSH, free T4 (FT4) and thyroid autoantibodies (anti-thyroglobulin, anti-thyroperoxidase, and TSH-receptor antibodies) were assessed at the diagnosis; FT4 and TSH were repeated after treatment to confirm normalization of thyroid function. All sexual domains scores were significantly reduced (p ranging <0.0001-<0.05) in both hypo- and hyperthyroid women. Correction of hypothyroidism was associated to normalization of desire, satisfaction, and pain, while arousal and orgasm remained unchanged. In hyperthyroid women therapy normalized sexual desire, arousal/lubrication, satisfaction, and pain, while orgasm remained significantly impaired. Interestingly, euthyroid HT women displayed a significant decrease in sexual desire (p<0.0005), with no changes in the other sexual domains. Both hypo- and hyperthyroidism markedly impair female sexual function. A rapid improvement is observed with the restoration of euthyroidism, although a longer period of time may be needed for full normalization. Preliminary data suggest that thyroid autoimmunity may selectively impair sexual desire, independently from thyroid function.

Autoimmune thyrotoxicosis: diagnostic challenges.

PubMed

Ponto, Katharina A; Kahaly, George J

2012-09-01

Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. Copyright © 2012. 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.

Typical thyroid-type carcinoma arising in struma ovarii: a report of 4 cases and review of the literature.

PubMed

Roth, Lawrence M; Miller, Alexander W; Talerman, Aleksander

2008-10-01

Struma ovarii has elicited considerable interest because of its many unique features since Ludwig Pick first elucidated its relationship to teratoma in the early part of the 20th century. In this article, we report 3 cases of papillary and 1 of follicular thyroid carcinoma; 2 of these cases were associated with mature cystic teratoma. Metastases occurred in 2 patients, and 1 died of neoplasm. In regard to the occurrence of thyroid-type carcinoma in struma ovarii, precise terminology should be used, and the expression malignant struma ovarii was avoided as a diagnostic term. Upon review of the literature, papillary carcinoma and follicular carcinoma are the most frequent types of malignancy to occur in ovarian struma; other forms of thyroid carcinoma occur only rarely. The diagnostic criteria for cases of papillary carcinoma are similar to those described in the cervical thyroid gland and are based primarily on nuclear and architectural features. In reference to follicular carcinoma, invasion into the surrounding ovarian tissue, vascular invasion, or metastasis is evidence of malignancy. Histological malignancy in a struma does not necessarily equate with biological malignancy, and the majority of thyroid-type carcinomas do not spread beyond the ovary. Occasionally, metastases of ovarian struma have an innocuous histological appearance, and such cases are referred to as highly differentiated follicular carcinoma of ovarian origin (HDFCO). Because its histological appearance resembles that of nonneoplastic thyroid, HDFCO characteristically cannot be diagnosed until the neoplasm spreads beyond the ovary. In this article, we apply the term typical thyroid carcinoma to those forms of thyroid malignancy arising in ovarian struma that closely resemble the types described in the cervical thyroid gland to distinguish them from HDFCO. Typical follicular carcinoma is more aggressive than the somewhat more common papillary carcinoma, and HDFCO is the least aggressive of these tumor types. Cases of thyroid-type carcinoma arising in the ovary sometimes lack evidence of preexisting struma. The more aggressive thyroid-type neoplasms can arise in thyroid tissue within a mature cystic teratoma, or they may overgrow and replace the struma. Primary thyroid-type carcinoma must be distinguished from rare instances of ovarian metastases that originate in the cervical thyroid gland and the less differentiated forms from other ovarian neoplasms such as clear cell adenocarcinoma and tumors with an oxyphilic appearance. In the differential diagnosis with other ovarian neoplasms, cases of thyroid-type carcinoma associated with strumal carcinoid should not be diagnosed as malignant strumal carcinoid because the latter diagnosis might lead to suboptimal therapy.

Radioactive iodine therapy in cats with hyperthyroidism

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

Turrel, J.M.; Feldman, E.C.; Hays, M.

Eleven cats with hyperthyroidism were treated with radioactive iodine (/sup 131/I). Previous unsuccessful treatments for hyperthyroidism included hemithyroidectomy (2 cats) and an antithyroid drug (7 cats). Two cats had no prior treatment. Thyroid scans, using technetium 99m, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 5 cats and in both lobes in 6 cats. Serum thyroxine concentrations were high and ranged from 4.7 to 18 micrograms/dl. Radioactive iodine tracer studies were used to determine peak radioactive iodine uptake (RAIU) and effective and biological half-lives. Activity of /sup 131/I administered was calculated from peak RAIU, effective half-life, andmore » estimated thyroid gland weight. Activity of /sup 131/I administered ranged from 1.0 to 5.9 mCi. The treatment goal was to deliver 20,000 rad to hyperactive thyroid tissue. However, retrospective calculations based on peak RAIU and effective half-life obtained during the treatment period showed that radiation doses actually ranged from 7,100 to 64,900 rad. Complete ablation of the hyperfunctioning thyroid tissue and a return to euthyroidism were seen in 7 cats. Partial responses were seen in 2 cats, and 2 cats became hypothyroid. It was concluded that /sup 131/I ablation of thyroid tumors was a reasonable alternative in the treatment of hyperthyroidism in cats. The optimal method of dosimetry remains to be determined.« less

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

Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland?

PubMed

Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

2013-01-01

Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD.

Partial resection and reconstruction of the sternum for treatment of metachronous sternal metastasis of thyroid carcinoma: A case report.

PubMed

Lan, Hong-Jing; Wu, Zhi-Qiang; Gong, Dong-Ge; Zheng, Wang-Yong; Jin, Yun

2017-11-01

Metachronous sternal metastasis of thyroid carcinoma was a rare disease. There was no consensus in the treatment for bone metastasis after the initial thyroid carcinoma surgery. A 53-year-old female patient was hospitalized due to recurrent dull chest pains, with a history of radical right side thyroid carcinoma 4 years ago. On examination, there was an irregular mass on the lower left half of the sternum. Computerized tomography scan showed sternal bone destruction with a soft tissue mass. Metachronous sternal metastasis of thyroid carcinoma. Partial resection of the sternum and reconstruction with a titanium alloy mesh were performed. After a 3-year follow-up, the patient had no recurrence. Surgical resection may be a sufficient treatment for metachronous sternal metastasis of thyroid carcinoma. Biosynthesis material mesh is preferred to be used.

The microRNA-processing enzyme Dicer is essential for thyroid function.

PubMed

Frezzetti, Daniela; Reale, Carla; Calì, Gaetano; Nitsch, Lucio; Fagman, Henrik; Nilsson, Ola; Scarfò, Marzia; De Vita, Gabriella; Di Lauro, Roberto

2011-01-01

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.

How reliably can computed tomography predict thyroid invasion prior to laryngectomy?

PubMed

Harris, Andrew S; Passant, Carl D; Ingrams, Duncan R

2018-05-01

There is little evidence to support the removal of thyroid tissue during total laryngectomy. Although oncological control of the tumor is the priority, thyroidectomy can lead to hypothyroidism and hypoparathyroidism. This study aimed to test the usefulness of preoperative computed tomography in predicting histological invasion of the thyroid. Ambispective cohort study. All patients undergoing total laryngectomy for squamous cell carcinoma at one center from 2006 to 2016 were included. Data were recorded prospectively as part of the patients' standard care, but were collated retrospectively, giving this study an ambispective design. The histology report for thyroid invasion was taken as the gold standard. The computed tomography report was categorized by invasion of tumor into intralaryngeal, laryngeal cartilage involvement, and extralaryngeal tissues. Seventy-nine patients were included. Nine patients had thyroid involvement on histology, translating to an incidence of 11.29% in this population. The positive predictive value for cartilage involvement on computed tomography for thyroid invasion was 52.9% (95% confidence interval [CI]: 28.5%-76.1%) and the negative predictive value was 100% (95% CI: 92.7%-100%).The positive predictive value for extralaryngeal spread on computed tomography for thyroid involvement was 100% (95% CI: 62.9%-100%), and the negative predictive value was also 100% (95% CI: 93.5%-100%). This study has shown that preoperative computed tomography is an effective method of ruling out thyroid gland invasion. The absence of extralaryngeal spread on computed tomography has been shown to be the most useful finding, with a high negative predictive value and a narrow 95% CI. 4. Laryngoscope, 128:1099-1102, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Applications of Raman spectroscopy in life science

NASA Astrophysics Data System (ADS)

Martin, Airton A.; T. Soto, Cláudio A.; Ali, Syed M.; Neto, Lázaro P. M.; Canevari, Renata A.; Pereira, Liliane; Fávero, Priscila P.

2015-06-01

Raman spectroscopy has been applied to the analysis of biological samples for the last 12 years providing detection of changes occurring at the molecular level during the pathological transformation of the tissue. The potential use of this technology in cancer diagnosis has shown encouraging results for the in vivo, real-time and minimally invasive diagnosis. Confocal Raman technics has also been successfully applied in the analysis of skin aging process providing new insights in this field. In this paper it is presented the latest biomedical applications of Raman spectroscopy in our laboratory. It is shown that Raman spectroscopy (RS) has been used for biochemical and molecular characterization of thyroid tissue by micro-Raman spectroscopy and gene expression analysis. This study aimed to improve the discrimination between different thyroid pathologies by Raman analysis. A total of 35 thyroid tissues samples including normal tissue (n=10), goiter (n=10), papillary (n=10) and follicular carcinomas (n=5) were analyzed. The confocal Raman spectroscopy allowed a maximum discrimination of 91.1% between normal and tumor tissues, 84.8% between benign and malignant pathologies and 84.6% among carcinomas analyzed. It will be also report the application of in vivo confocal Raman spectroscopy as an important sensor for detecting advanced glycation products (AGEs) on human skin.

Evaluation of Serum Vascular Adhesion Protein-1 as a Potential Biomarker in Thyroid Cancer

PubMed Central

Zhao, Pengxin; Zhang, Kaili

2016-01-01

Vascular adhesion protein-1 (VAP-1) is a glycoprotein that mediates tissue-selective lymphocyte adhesion. The prognostic value of VAP-1 has been determined in gastric cancer. The aim of this study was to evaluate the changes and the predictive value of serum VAP-1 in patients with thyroid cancer. A total of 126 patients with thyroid nodules and 53 healthy controls participated in this study. The patients were further divided into subgroup 1 (69 cases with benign thyroid nodules) and subgroup 2 (57 cases with thyroid cancer). Serum VAP-1 was measured by time-resolved immunofluorometric assay. Diagnostic value of presurgical VAP-1 for thyroid cancer was conducted by receiver operating characteristic (ROC) curves. Serum levels of VAP-1 were significantly lower in thyroid cancer group than in healthy control and benign thyroid nodule groups. VAP-1 concentrations negatively correlated with serum thyroglobulin (Tg) levels in thyroid cancer patients (r = −0.81; p < 0.001). The optimum cut-off value of VAP-1 was 456.6 ng/mL with a 77.4% specificity and 66.7% sensitivity for thyroid cancer diagnosis. Serum VAP-1 decreased in thyroid cancer patients and VAP-1 could be a potential useful adjunct biomarker in the diagnosis of thyroid cancer. PMID:27446209

Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

PubMed Central

Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

2015-01-01

Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

A single nucleotide polymorphism associated with isolated cleft lip and palate, thyroid cancer and hypothyroidism alters the activity of an oral epithelium and thyroid enhancer near FOXE1

PubMed Central

Lidral, Andrew C.; Liu, Huan; Bullard, Steven A.; Bonde, Greg; Machida, Junichiro; Visel, Axel; Uribe, Lina M. Moreno; Li, Xiao; Amendt, Brad; Cornell, Robert A.

2015-01-01

Three common diseases, isolated cleft lip and cleft palate (CLP), hypothyroidism and thyroid cancer all map to the FOXE1 locus, but causative variants have yet to be identified. In patients with CLP, the frequency of coding mutations in FOXE1 fails to account for the risk attributable to this locus, suggesting that the common risk alleles reside in nearby regulatory elements. Using a combination of zebrafish and mouse transgenesis, we screened 15 conserved non-coding sequences for enhancer activity, identifying three that regulate expression in a tissue specific pattern consistent with endogenous foxe1 expression. These three, located −82.4, −67.7 and +22.6 kb from the FOXE1 start codon, are all active in the oral epithelium or branchial arches. The −67.7 and +22.6 kb elements are also active in the developing heart, and the −67.7 kb element uniquely directs expression in the developing thyroid. Within the −67.7 kb element is the SNP rs7850258 that is associated with all three diseases. Quantitative reporter assays in oral epithelial and thyroid cell lines show that the rs7850258 allele (G) associated with CLP and hypothyroidism has significantly greater enhancer activity than the allele associated with thyroid cancer (A). Moreover, consistent with predicted transcription factor binding differences, the −67.7 kb element containing rs7850258 allele G is significantly more responsive to both MYC and ARNT than allele A. By demonstrating that this common non-coding variant alters FOXE1 expression, we have identified at least in part the functional basis for the genetic risk of these seemingly disparate disorders. PMID:25652407

Thyrotoxicosis induced by excessive 3,5,3'-triiodothyronine in a dog.

PubMed

Morré, Wendy A; Panciera, David L; Daniel, Gregory B; Refsal, Kent R; Rick, Markus; Arrington, Kathy

2017-06-15

CASE DESCRIPTION A 7-year-old castrated male Havanese was evaluated at a veterinary teaching hospital because of a 12-week history of hyperactivity, aggression, and progressive weight loss despite a healthy appetite. CLINICAL FINDINGS Tachycardia was the only remarkable finding during physical examination. Serum 3,5,3'-triiodothyronine (T3) and free T3 concentrations were markedly increased, and thyroxine (T4), free T4, and thyroid-stimulating hormone concentrations were at or decreased from the respective reference ranges. Thyroid scintigraphy revealed suppressed uptake of sodium pertechnetate Tc 99m by the thyroid gland but no ectopic thyroid tissue, which was indicative of thyrotoxicosis induced by an exogenous source of T3. TREATMENT AND OUTCOME The dog was hospitalized for 24 hours, and its diet was changed, after which the clinical signs rapidly resolved and serum T3 and free T3 concentrations returned to within the respective reference ranges. This raised suspicion of an exogenous source of T3 in the dog's home environment. Analysis of the commercial beef-based canned food the dog was being fed revealed a high concentration of T3 (1.39 μg/g) and an iodine (82.44 μg/g) concentration that exceeded industry recommendations. No other source of T3 was identified in the dog's environment. CLINICAL RELEVANCE To our knowledge, this is the first report of clinical thyrotoxicosis in a dog induced by exogenous T3, although the source of exogenous T3 was not identified. This case highlights the importance of measuring serum T3 and thyroid-stimulating hormone concentrations in addition to T4 and free T4 concentrations when there is incongruity between clinical findings and thyroid function test results.

12-month efficacy of a single radiofrequency ablation on autonomously functioning thyroid nodules.

PubMed

Bernardi, Stella; Stacul, Fulvio; Michelli, Andrea; Giudici, Fabiola; Zuolo, Giulia; de Manzini, Nicolò; Dobrinja, Chiara; Zanconati, Fabrizio; Fabris, Bruno

2017-09-01

Radiofrequency ablation has been advocated as an alternative to radioiodine and/or surgery for the treatment of autonomously functioning benign thyroid nodules. However, only a few studies have measured radiofrequency ablation efficacy on autonomously functioning benign thyroid nodules. The aim of this work was to evaluate the 12-month efficacy of a single session of radiofrequency ablation (performed with the moving shot technique) on solitary autonomously functioning benign thyroid nodules. Thirty patients with a single, benign autonomously functioning benign thyroid nodules, who were either unwilling or ineligible to undergo surgery and radioiodine, were treated with radiofrequency ablation between April 2012 and May 2015. All the patients underwent a single radiofrequency ablation, performed with the 18-gauge needle and the moving shot technique. Clinical, laboratory, and ultrasound evaluations were scheduled at baseline, and after 1, 3, 6, and 12 months from the procedure. A single radiofrequency ablation reduced thyroid nodule volume by 51, 63, 69, and 75 % after 1, 3, 6, and 12 months, respectively. This was associated with a significant improvement of local cervical discomfort and cosmetic score. As for thyroid function, 33 % of the patients went into remission after 3 months, 43 % after 6 months, and 50 % after 12 months from the procedure. This study demonstrates that a single radiofrequency ablation allowed us to withdraw anti-thyroid medication in 50 % of the patients, who remained euthyroid afterwards. This study shows that a single radiofrequency ablation was effective in 50 % of patients with autonomously functioning benign thyroid nodules. Patients responded gradually to the treatment. It is possible that longer follow-up studies might show greater response rates.

Low thyroid function is not associated with an accelerated deterioration in renal function.

PubMed

Meuwese, Christiaan L; van Diepen, Merel; Cappola, Anne R; Sarnak, Mark J; Shlipak, Michael G; Bauer, Douglas C; Fried, Linda P; Iacoviello, Massimo; Vaes, Bert; Degryse, Jean; Khaw, Kay-Tee; Luben, Robert N; Åsvold, Bjørn O; Bjøro, Trine; Vatten, Lars J; de Craen, Anton J M; Trompet, Stella; Iervasi, Giorgio; Molinaro, Sabrina; Ceresini, Graziano; Ferrucci, Luigi; Dullaart, Robin P F; Bakker, Stephan J L; Jukema, J Wouter; Kearney, Patricia M; Stott, David J; Peeters, Robin P; Franco, Oscar H; Völzke, Henry; Walsh, John P; Bremner, Alexandra; Sgarbi, José A; Maciel, Rui M B; Imaizumi, Misa; Ohishi, Waka; Dekker, Friedo W; Rodondi, Nicolas; Gussekloo, Jacobijn; den Elzen, Wendy P J

2018-04-18

Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

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.

High-intensity focused ultrasound ablation of thyroid nodules: first human feasibility study.

PubMed

Esnault, Olivier; Franc, Brigitte; Ménégaux, Fabrice; Rouxel, Agnès; De Kerviler, Eric; Bourrier, Pierre; Lacoste, François; Chapelon, Jean-Yves; Leenhardt, Laurence

2011-09-01

Thyroid surgery is common, but complications may occur. High-intensity focused ultrasound (HIFU) is a minimally invasive alternative to surgery. We hypothesized that an optimized HIFU device could be safe and effective for ablating benign thyroid nodules without affecting neighboring structures. In this open, single-center feasibility study, 25 patients were treated with HIFU with real-time ultrasound imaging 2 weeks before a scheduled thyroidectomy for multinodular goiter. Thyroid ultrasonography imaging, thyroid function, were evaluated before and after treatment. Adverse events were carefully recorded. Each patient received HIFU for one thyroid nodule, solid or mixed, with mean diameter ≥8 mm, and no suspicion of malignancy. The HIFU device was progressively adjusted with stepwise testing. The energy level for ablation ranged from 35 to 94 J/pulse for different groups of patients. One pathologist examined all removed thyroids. Three patients discontinued treatment due to pain or skin microblister. Among the remaining 22 patients, 16 showed significant changes by ultrasound. Macroscopic and histological examinations showed that all lesions were confined to the targeted nodule without affecting neighboring structures. At pathological analysis, the extent of nodule destruction ranged from 2% to 80%. Five out of 22 patients had over 20% pathological lesions unmistakably attributed to HIFU. Seventeen cases had putative lesions including nonspecific necrosis, hemorrhage, nodule detachment, cavitations, and cysts. Among these 17 cases, 12 had both ultrasound changes and cavitation at histology that may be expected for an HIFU effect. In the last three patients ablated at the highest energy level, significant ultrasound changes and complete coagulative necrosis were observed in 80%, 78%, and 58% of the targeted area, respectively. There were no major complications of ablation. This study showed the potential efficacy of HIFU for human thyroid nodule ablation. Lesions were clearly visible by histology and ultrasound after high energy treatments, and safety and tolerability were good. We identified a power threshold for optimal necrosis of the target thyroid tissue. Further studies are ongoing to assess nodule changes at longer follow-up times.

Function of the Alpha6 in Breast Carcinoma

DTIC Science & Technology

1999-10-01

Miao , J., S. Araki, K. Kaji, and H . Hayashi. 1997. Integrin P34 is involved in apoptotic signal transduction in endothelial cells. Biochem. and Biophys...cadherin expression in neoplasatic verus normal thyroid tissue. J. Natl. Cancer Inst. 88:442-449. 6. Shaw, L. M., I. Rabinovitz, H . H .-F. Wang, A. Toker, and...Integrin and cAMP Metabolism Kathleen L. O’Connor, Bao-Kim Nguyen and Arthur M. Mercurio Department of Medicine, Beth Israel Deaconess Medical Center and

Left ventricular functions in children with newly diagnosed Graves' disease. A single-center study from Upper Egypt.

PubMed

Metwalley, Kotb Abbass; Farghaly, Hekma Saad; Abdelhamid, Abdelrahman

2018-01-01

This study aimed to evaluate the left ventricular (LV) functions in a cohort of children with Graves' disease (GD). This is a cross-sectional case-control study. It included 36 children with GD and 36 healthy children matched for age and gender. Thyroid hormones (TSH, FT4, and FT3) and anti-thyroid autoantibodies [anti-thyroid peroxidase (anti-TPO), thyrotropin receptor (TRAbs), and thyroglobulin antibodies] were measured. Conventional and tissue Doppler imaging (TDI) echocardiographies were used to assess left ventricular systolic and diastolic functions. LV mass index (LVMI) and myocardial performance index (MPI) were also measured. Compared to healthy children, conventional echocardiography of patients with GD revealed higher LVMI (P = 0.001) indicating LV hypertrophy but normal LV functions while TDI revealed lower Em/Am ratio indicating LV diastolic dysfunction (P = 0.001). Significant correlations were reported between FT4 with LVMI (P = 0.05), Em/Am (P = 0.01), and MPI (P = 0.01). In multivariate analysis, a positive correlation was identified between FT4 with MPI (OR = 1.17; 95% CI = 1.09-1.15; P = 0.001). Children with newly diagnosed GD may have significant subclinical changes in LV structure and function (diastolic and global). TDI is more sensitive than conventional Doppler in detecting LV dysfunction. These findings highlight the importance of early monitoring of children with GD for left ventricular mass index and diastolic function. What is Known: • There is an increased risk for cardiac abnormalities in children with Graves' disease (GD). • Limited studies assessed left ventricular function in patients with GD. What is New: • Children with newly diagnosed GD may have significant subclinical changes in left ventricular structure and functions. • Children with newly diagnosed GD should be monitored for left ventricular mass index and diastolic function.

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

Palliative Care

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

Factors associated with serum thyroglobulin levels in a population living in Belarus

PubMed Central

Cahoon, Elizabeth K; Rozhko, Alexander; Hatch, Maureen; Polyanskaya, Olga; Ostroumova, Evgenia; Tang, Min; Nadirov, Eldar; Yauseyenka, Vasilina; Savasteeva, Irina; McConnell, Robert J; Pfeiffer, Ruth M; Brenner, Alina V

2013-01-01

SUMMARY Objective Serum thyroglobulin (Tg) has been associated with a number of thyroid disorders and has been proposed as an indicator of iodine deficiency in a population. However, few studies have addressed the epidemiology of Tg in a population-based setting or in the context of exposure to radioactive iodine-131 (I-131). Our objective was to evaluate baseline levels of Tg in relation to socio-demographic characteristics, iodine status, and thyroid function for individuals exposed to I-131. Design A population-based cohort assembled in Belarus following the Chornobyl accident provided demographic factors, clinical data, and physiological measurements. Participants Our analytic sample included 10,344 subjects of whom 7,890 had no thyroid disease and 2,454 had evidence of structural or functional thyroid abnormality. Measurements Standardized assays were used to measure serum Tg, urinary iodine, TSH, and antibodies to Tg and thyroid peroxidase. Ultrasound was used to assess the presence of nodules and estimate thyroid volume. Results In the fully adjusted model, percent change in Tg was significantly increased among females, smokers, and subjects of older age and Tg increased with decreasing urinary iodine concentration, increasing serum TSH and increasing thyroid volume (p-values for trend < 0.0001), and presence of thyroid nodules (p < 0.05). We found a complex interaction between region of residence, rural/urban living, presence/absence of thyroid abnormalities, and serum Tg (p < 0.0001). Conclusions In residents of Belarus, serum Tg is significantly related to presence of thyroid abnormalities as well as indicators of thyroid function and iodine deficiency and, therefore, could be used to characterize the iodine status and thyroid function of individuals in the context of epidemiological study. PMID:23190420

Potential Influence of Selenium, Copper, Zinc and Cadmium on L-Thyroxine Substitution in Patients with Hashimoto Thyroiditis and Hypothyroidism.

PubMed

Rasic-Milutinovic, Z; Jovanovic, D; Bogdanovic, G; Trifunovic, J; Mutic, J

2017-02-01

Background: Besides genetic factors, it is known that some trace elements, as Selenium, Copper, and Zinc are essential for thyroid gland fuction and thyroid hormone metabolism. Moreover, there were some metals effect that suggested patterns associated with overt thyroid disease. Aim of study: Hashimoto thyroiditis (HT), chronic autoimune inflamation of thyroid gland with cosequtive hipothyroidism, is common disease in Serbia, and we thought it is worthwile to explore potential effects of essential and toxic metals and metalloides on thyroid function and ability to restore euthyroid status of them. Results: This cross-sectional, case-control, study investigated the status of essential elements (Selenium,Copper,and Zinc) and toxic metals and metalloides (Al, Cr, Mn, Co, As, Cd, Sb, Ba, Be, Pb and Ni) from the blood of 22 female, patients with Hashimoto thyroiditis and overt hypothyroidism, and compared it with those of 55 female healthy persons. We tried to establish the presence of any correlation between previous mentioned elements and thyroid function in hypothyroid patients and healthy participants. Conclusions: The results of our study suggested that the blood concentration of essential trace elements, especially the ratio of Copper, and Selenium may influence directly thyroid function in patients with HT and overt hypothyroidism.Thus, our findings may have implication to life-long substitution therapy in terms of l-thyroxine dose reduction. Furthermore, for the first time, our study shown potential toxic effect of Cadmium on thyroid function in HT patients, which may implicate the dose of l-thyroxine substitution. © Georg Thieme Verlag KG Stuttgart · New York.

Pathological findings of thyroid nodules after percutaneous laser ablation : a series of 22 cases with cyto-histological correlation.

PubMed

Piana, Simonetta; Riganti, Fabrizio; Froio, Elisabetta; Andrioli, Massimiliano; Pacella, Claudio M; Valcavi, Roberto

2012-06-01

Ultrasound (US)-guided percutaneous laser ablation (LA) of benign thyroid nodules may be a potential alternative to surgery in patients with compressive symptoms, at high surgical risk, or in patients who refuse to undergo surgery. We evaluated the morphological effects of LA procedure on 22 patients and compared the cytological findings before and after LA with the histological features on surgical specimens. Twenty-two (4.9%; 19 women, three men, mean age 53.2 years) out of 452 patients treated with LA for benign thyroid nodules in our Hospital underwent surgery after LA procedure, either because nodule regrowth (treatment failure, n = 17) or indeterminate cytology (Thy3) after LA (n = 5). Morphological findings varied according to the time between LA and surgical intervention. Within 2 months, the area was occasionally cavitated and filled in with dark amorphous material. The inflammatory response was abundant and composed of neutrophils, lymphocytes, and macrophages. After 18 months or more since LA, the expected laser-induced histologic changes in thyroid morphology consisted of a well-defined area surrounded by a fibrous capsule and filled in by amorphous material. No significant pathologic features were found in the thyroid tissue adjacent to the treated area. Histological evaluation of thyroid tissues after LA shows that thermal damage is restricted to the ablated area, with no involvement of the nearby parenchyma. Our long-term histopathological findings indicate that LA treatment of benign thyroid nodules is safe, and patients undergoing LA may also be followed up by fine needle aspiration.

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

PubMed Central

Lee, Bradford W.; Kumar, Virender B.; Biswas, Pooja; Ko, Audrey C.; Alameddine, Ramzi M.; Granet, David B.; Ayyagari, Radha; Kikkawa, Don O.; Korn, Bobby S.

2018-01-01

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents. PMID:29760827

Relapse or Recurrence

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

Tests and Procedures

MedlinePlus

... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...

Hybrid SPECT-CT and PET-CT imaging of differentiated thyroid carcinoma.

PubMed

Wong, K K; Zarzhevsky, N; Cahill, J M; Frey, K A; Avram, A M

2009-10-01

Hybrid imaging modalities such as radioiodine single photon emission CT with integrated CT ((131)I SPECT-CT) and 2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography with integrated CT (FDG PET-CT) allow the rapid and efficient fusion of functional and anatomic images, and provide diagnostic information that may influence management decisions in patients with differentiated thyroid carcinoma (DTC). Diagnostic localisation and therapy of these tumours are dependent upon their capacity to concentrate radioiodine ((131)I) via uptake through the sodium-iodide symporter and retention within the tumour. The prognosis for most patients with DTC is favourable, although controversy exists regarding the role of post-operative (131)I therapy in patients at low-risk for disease. Accurate identification of functional thyroid tissue (benign or malignant) using diagnostic (131)I planar scintigraphy complemented by SPECT-CT imaging enables the completion of post-operative staging and patient risk stratification prior to (131)I therapy administration. In patients with non-iodine-avid tumours (negative (131)I scan but elevated thyroglobulin indicative of persistent or recurrent disease), FDG PET-CT is used to identify tumours with enhanced glucose metabolism and to localise the source of thyroglobulin production. The CT component of this hybrid technology provides anatomic localisation of activity and allows CT-based attenuation correction of PET images. Images from 15 patients illustrate the applications of (131)I SPECT-CT and FDG PET-CT.

Functional Analyses of c.2268dup in Thyroid Peroxidase Gene Associated with Goitrous Congenital Hypothyroidism

PubMed Central

Harun, Fatimah; Jalaludin, Muhammad Yazid; Lim, Chor Yin; Ng, Khoon Leong

2014-01-01

The c.2268dup mutation in thyroid peroxidase (TPO) gene was reported to be a founder mutation in Taiwanese patients with dyshormonogenetic congenital hypothyroidism (CH). The functional impact of the mutation is not well documented. In this study, homozygous c.2268dup mutation was detected in two Malaysian-Chinese sisters with goitrous CH. Normal and alternatively spliced TPO mRNA transcripts were present in thyroid tissues of the two sisters. The abnormal transcript contained 34 nucleotides originating from intron 12. The c.2268dup is predicted to generate a premature termination codon (PTC) at position 757 (p.Glu757X). Instead of restoring the normal reading frame, the alternatively spliced transcript has led to another stop codon at position 740 (p.Asp739ValfsX740). The two PTCs are located at 116 and 201 nucleotides upstream of the exons 13/14 junction fulfilling the requirement for a nonsense-mediated mRNA decay (NMD). Quantitative RT-PCR revealed an abundance of unidentified transcripts believed to be associated with the NMD. TPO enzyme activity was not detected in both patients, even though a faint TPO band of about 80 kD was present. In conclusion, the c.2268dup mutation leads to the formation of normal and alternatively spliced TPO mRNA transcripts with a consequential loss of TPO enzymatic activity in Malaysian-Chinese patients with goitrous CH. PMID:24745015

Increased incidence of thyroid dysfunction and autoimmunity in patients with vernal keratoconjunctivitis.

PubMed

Stagi, Stefano; Pucci, Neri; Di Grande, Laura; de Libero, Cinzia; Caputo, Roberto; Pantano, Stefano; Mattei, Ivan; Mori, Francesca; de Martino, Maurizio; Novembre, Elio

2014-01-01

Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; P<0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; P<0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, P<0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity.

Increased Incidence of Thyroid Dysfunction and Autoimmunity in Patients with Vernal Keratoconjunctivitis

PubMed Central

Stagi, Stefano; Pucci, Neri; Di Grande, Laura; de Libero, Cinzia; Caputo, Roberto; Pantano, Stefano; Mattei, Ivan; Mori, Francesca; de Martino, Maurizio; Novembre, Elio

2014-01-01

Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; P<0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; P<0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, P<0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity. PMID:25140177

Is the use of the cervical vertebrae maturation method justified to determine skeletal age? A comparison of radiation dose of two strategies for skeletal age estimation.

PubMed

Patcas, Raphael; Signorelli, Luca; Peltomäki, Timo; Schätzle, Marc

2013-10-01

The aim of this study was to assess effective doses of a lateral cephalogram radiograph with and without thyroid shield and compare the differences with the radiation dose of a hand-wrist radiograph. Thermoluminescent dosimeters were placed at 19 different sites in the head and neck of a tissue-equivalent human skull (RANDO phantom). Analogue lateral cephalograms with and without thyroid shield (67 kV, 250 mA, 10 mAs) and hand-wrist radiographs (40 kV, 250 mA, 10 mAs) were obtained. The effective doses were calculated using the 2007 International Commission on Radiological Protection recommendations. The effective dose for conventional lateral cephalogram without a thyroid shield was 5.03 microsieverts (µSv). By applying a thyroid shield to the RANDO phantom, a remarkable dose reduction of 1.73 µSv could be achieved. The effective dose of a conventional hand-wrist radiograph was calculated to be 0.16 µSv. Adding the effective dose of the hand-wrist radiograph to the effective dose of the lateral cephalogram with thyroid shield resulted in a cumulative effective dose of 3.46 µSv. Without thyroid shield, the effective dose of a lateral cephalogram was approximately 1.5-fold increased than the cumulative effective dose of a hand-wrist radiograph and a lateral cephalogram with thyroid shield. Thyroid is an organ that is very sensitive to radiation exposure. Its shielding will significantly reduce the effective dose. An additional hand-wrist radiograph, involving no vulnerable tissues, however, causes very little radiation risk. In accordance with the ALARA (As Low As Reasonably Achievable) principle, if an evaluation of skeletal age is indicated, an additional hand-wrist radiograph seems much more justifiable than removing the thyroid shield.

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