Gene transcription ontogeny of hypothalamic-pituitary-thyroid axis development in early-life stage fathead minnow and zebrafish.

PubMed

Vergauwen, Lucia; Cavallin, Jenna E; Ankley, Gerald T; Bars, Chloé; Gabriëls, Isabelle J; Michiels, Ellen D G; Fitzpatrick, Krysta R; Periz-Stanacev, Jelena; Randolph, Eric C; Robinson, Serina L; Saari, Travis W; Schroeder, Anthony L; Stinckens, Evelyn; Swintek, Joe; Van Cruchten, Steven J; Verbueken, Evy; Villeneuve, Daniel L; Knapen, Dries

2018-05-04

The hypothalamic-pituitary-thyroid (HPT) axis is known to play a crucial role in the development of teleost fish. However, knowledge of endogenous transcription profiles of thyroid-related genes in developing teleosts remains fragmented. We selected two model teleost species, the fathead minnow (Pimephales promelas) and the zebrafish (Danio rerio), to compare the gene transcription ontogeny of the HPT axis. Control organisms were sampled at several time points during embryonic and larval development until 33 days post-fertilization. Total RNA was extracted from pooled, whole fish, and thyroid-related mRNA expression was evaluated using quantitative polymerase chain reaction. Gene transcripts examined included: thyrotropin-releasing hormone receptor (trhr), thyroid-stimulating hormone receptor (tshr), sodium-iodide symporter (nis), thyroid peroxidase (tpo), thyroglobulin (tg), transthyretin (ttr), deiodinases 1, 2, 3a, and 3b (dio1, dio2, dio3a and 3b), and thyroid hormone receptors alpha and beta (thrα and β). A loess regression method was successful in identifying maxima and minima of transcriptional expression during early development of both species. Overall, we observed great similarities between the species, including maternal transfer, at least to some extent, of almost all transcripts (confirmed in unfertilized eggs), increasing expression of most transcripts during hatching and embryo-larval transition, and indications of a fully functional HPT axis in larvae. These data will aid in the development of hypotheses on the role of certain genes and pathways during development. Furthermore, this provides a background reference dataset for designing and interpreting targeted transcriptional expression studies both for fundamental research and for applications such as toxicology. Copyright © 2018 Elsevier Inc. All rights reserved.

Thyroid-disrupting chemicals and brain development: an update

PubMed Central

Mughal, Bilal B; Fini, Jean-Baptiste; Demeneix, Barbara A

2018-01-01

This review covers recent findings on the main categories of thyroid hormone–disrupting chemicals and their effects on brain development. We draw mostly on epidemiological and experimental data published in the last decade. For each chemical class considered, we deal with not only the thyroid hormone–disrupting effects but also briefly mention the main mechanisms by which the same chemicals could modify estrogen and/or androgen signalling, thereby exacerbating adverse effects on endocrine-dependent developmental programmes. Further, we emphasize recent data showing how maternal thyroid hormone signalling during early pregnancy affects not only offspring IQ, but also neurodevelopmental disease risk. These recent findings add to established knowledge on the crucial importance of iodine and thyroid hormone for optimal brain development. We propose that prenatal exposure to mixtures of thyroid hormone–disrupting chemicals provides a plausible biological mechanism contributing to current increases in the incidence of neurodevelopmental disease and IQ loss. PMID:29572405

Thyroid Disorders in Children and Adolescents: A Review.

PubMed

Hanley, Patrick; Lord, Katherine; Bauer, Andrew J

2016-10-01

Normal thyroid gland function is critical for early neurocognitive development, as well as for growth and development throughout childhood and adolescence. Thyroid disorders are common, and attention to physical examination findings, combined with selected laboratory and radiologic tools, aids in the early diagnosis and treatment. To provide a practical review of the presentation, evaluation, and treatment of thyroid disorders commonly encountered in a primary care practice. We performed a literature review using the PubMed database. Results focused on reviews and articles published from January 1, 2010, through December 31, 2015. Articles published earlier than 2010 were included when appropriate for historical perspective. Our review emphasized evidence-based management practices for the clinician, as well as consensus statements and guidelines. A total of 479 articles for critical review were selected based on their relevance to the incidence, pathophysiology, laboratory evaluation, radiological assessment, and treatment of hypothyroidism, hyperthyroidism, thyroid nodules, and thyroid cancer in children and adolescents. Eighty-three publications were selected for inclusion in this article based on their relevance to these topics. The primary care physician is often the first health care professional responsible for initiating the evaluation of a thyroid disorder in children and adolescents. Patients may be referred secondary to an abnormal newborn screening, self-referred after a caregiver raises concern, or identified to be at risk of a thyroid disorder based on findings from a routine well-child visit. Irrespective of the path of referral, knowledge of the signs and symptoms of hypothyroidism, hyperthyroidism, and thyroid nodules, as well as the general approach to evaluation and management, will help the primary care physician complete an initial assessment and determine which patients would benefit from referral to a pediatric endocrinologist. Early identification and treatment of thyroid disease in children and adolescents is critical to optimize growth and development. The primary care physician plays a critical role in identifying patients at risk. An understanding of risk factors, clinical signs and symptoms, and interpretation of screening laboratories ensures an efficient and accurate diagnosis of these common disorders. Regular communication between the primary care physician and the subspecialist is critical to optimize outcome because the majority of patients with thyroid disorders will require long-term to lifelong medical therapy and/or surveillance.

Peripheral thyroid hormone levels and hepatic thyroid hormone deiodinase gene expression in dairy heifers on the day of ovulation and during the early peri-implantation period.

PubMed

Meyerholz, Marie Margarete; Mense, Kirsten; Linden, Matthias; Raliou, Mariam; Sandra, Olivier; Schuberth, Hans-Joachim; Hoedemaker, Martina; Schmicke, Marion

2016-09-08

Before the onset of fetal thyroid hormone production, the transplacental delivery of maternal thyroid hormones is necessary for embryonic and fetal development. Therefore, the adaptation of maternal thyroid hormone metabolism may be important for pregnancy success and embryo survival. The aims of this study were to determine the thyroid hormone levels during the early peri-implantation period until day 18 and on the day of ovulation, to determine whether pregnancy success is dependent on a "normothyroid status" and to determine whether physiological adaptations in maternal thyroid hormone metabolism occur, which may be necessary to provide sufficient amounts of biologically active T3 to support early pregnancy. Therefore, blood samples obtained on the day of ovulation (day 0) and days 14 and 18 of the Holstein-Friesian heifers (n = 10) during the respective pregnant, non-pregnant and negative control cycles were analyzed for thyroid-stimulating-hormone (TSH), thyroxine (T4) and triiodothyronine (T3). Liver biopsies (day 18) from pregnant and respective non-pregnant heifers were analyzed for mRNA expression of the most abundant hepatic thyroid hormone deiodinase (DIO1) by real time qPCR. Although liver DIO1 mRNA expression did not differ between the pregnant and non-pregnant heifers on day 18, the serum concentrations of TSH and T3 on day 18 were higher in non-pregnant heifers compared to pregnant heifers (P < 0.05). Moreover, T3 decreased between day 0 and 18 in pregnant heifers (P < 0.001). In conclusion, no associations between thyroid hormone patterns on day 18 and pregnancy success were detected. During the early peri-implantation period, TSH and T3 may be affected by the pregnancy status because both TSH and T3 were lower on day 18 in pregnant heifers compared to non-pregnant dairy heifers. In further studies, the thyroid hormone axis should be evaluated throughout the entire gestation to confirm these data and identify other possible effects of pregnancy on the thyroid hormone axis in cattle.

Influence of thyroid in nervous system growth.

PubMed

Mussa, G C; Mussa, F; Bretto, R; Zambelli, M C; Silvestro, L

2001-08-01

Nervous system growth and differentiation are closely correlated with the presence of iodine and thyroid hormones in initial development stages. In the human species, encephalon maturation during the first quarter of pregnancy is affected according to recent studies by the transplacenta passage of maternal thyroid hormones while it depends on initial iodiothyronin secretion by the foetal gland after the 12th week of pregnancy. Thyroid hormone deficiency during nervous system development causes altered noble nervous cells, such as the pyramidal cortical and Purkinje cells, during glial cell proliferation and differentiation alike. Neurons present cell hypoplasia with reduced axon count, dendritic branching, synaptic spikes and interneuron connections. Oligodendrocytes decrease in number and average myelin content consequently drops. Biochemical studies on hypothyroid rats have demonstrated alterations to neuron intraplasmatic microtubule content and organisation, changed mitochondria number and arrangement and anomalies in T3 nuclear and citoplasmatic receptor maturation. Alterations to microtubules are probably responsible for involvement of the axon-dendrite system, and are the consequence of deficient thyroid hormone action on the mitochondria, the mitochondria enzymes and proteins associated with microtubules. Nuclear and citoplasmatic receptors have been identified and gene clonation studies have shown two families of nuclear receptors that include several sub-groups in their turn. A complex scheme of temporal and spatial expression of these receptors exists, so they probably contribute with one complementary function, although their physiological role differs. The action of thyroid hormones occurs by changing cell protein levels because of their regulation at the transcriptional or post-transcriptional level. Genes submitted to thyroid hormone control are either expressed by oligodendrytes, which are myelin protein coders or glial differentiation mediators, or are nervous cell specific, genes coding neurotropins or proteins involved in synaptic excitation. The use of new PMRS and MRI non-invasive techniques has enabled identification of metabolic and biochemical markers for alterations in the encephalon of untreated hypothyroid children. Even an excess of thyroid hormones during early nervous system development can cause permanent effects. Hyperthyroidism in fact initially induces accelerated maturation process including cell migration and differentiation, extension of dendritic processes and synaptogenesis but a later excess of thyroid hormones causes reduction of the total number of dendritic spikes, due to early interruption of neuron proliferation. Experimental studies and clinical research have clarified not only the correlation between nervous system maturation and thyroid function during early development stages and the certain finding from this research is that both excess and deficient thyroid hormones can cause permanent anatomo-functional alterations to the nervous system.

Developmental Thyroid Hormone Insufficiency Impairs Visual Contrast Sensitivity in Adult Male Offspring.

EPA Science Inventory

Severe thyroid hormone (TH) insufficiency during early development results in alterations in brain structure and function. Many environmental agents produce subtle alterations in TH status, but the dose-response relationships for such effects are unclear. We have previously demon...

Zebrafish hhex, nk2.1a, and pax2.1 regulate thyroid growth and differentiation downstream of Nodal-dependent transcription factors.

PubMed

Elsalini, Osama A; von Gartzen, Julia; Cramer, Matthias; Rohr, Klaus B

2003-11-01

During zebrafish development, the thyroid primordium initiates expression of molecular markers such as hhex and nk2.1a in the endoderm prior to pharynx formation. As expected for an endodermally derived organ, initiation of thyroid development depends on Nodal signalling. We find that it also depends on three downstream effectors of Nodal activity, casanova (cas), bonnie and clyde (bon), and faust (fau)/gata5. Despite their early Nodal-dependent expression in the endoderm, both hhex and nk2.1a are only required relatively late during thyroid development. In hhex and nk2.1a loss-of-function phenotypes, thyroid development is initiated and arrests only after the primordium has evaginated from the pharyngeal epithelium. Thus, like pax2.1, both hhex and nk2.1a have similarly late roles in differentiation or growth of thyroid follicular cells, and here, we show that all three genes act in parallel rather than in a single pathway. Our functional analysis suggests that these genes have similar roles as in mammalian thyroid development, albeit in a different temporal mode of organogenesis.

Recombinant Protein Production from TPO Gen Cloning and Expression for Early Detection of Autoimmune Thyroid Diseases

NASA Astrophysics Data System (ADS)

Aulanni'am, Aulanni'am; Kinasih Wuragil, Dyah; Wahono Soeatmadji, Djoko; Zulkarnain; Marhendra, Agung Pramana W.

2018-01-01

Autoimmune Thyroid Disease (AITD) is an autoimmune disease that has many clinical symptoms but is difficult to detect at the onset of disease progression. Most thyroid autoimmune disease patients are positive with high titre of thyroid autoantibodies, especially thyroid peroxidase (TPO). The detection AITD are still needed because these tests are extremely high cost and have not regularly been performed in most of clinical laboratories. In the past, we have explored the autoimmune disease marker and it has been developed as source of polyclonal antibodies from patient origin. In the current study, we develop recombinant protein which resulted from cloning and expression of TPO gene from normal person and AITD patients. This work flows involves: DNA isolation and PCR to obtain TPO gene from human blood, insertion of TPO gene to plasmid and transformation to E. coli BL21, Bacterial culture to obtain protein product, protein purification and product analysis. This products can use for application to immunochromatography based test. This work could achieved with the goal of producing autoimmune markers with a guaranteed quality, sensitive, specific and economically. So with the collaboration with industries these devices could be used for early detection. Keywords: recombinant protein, TPO gene, Autoimmune thyroid diseases (AITD)ction of the diseases in the community.

Gene expression profiling at early organogenesis reveals both common and diverse mechanisms in foregut patterning

PubMed Central

Fagman, Henrik; Amendola, Elena; Parrillo, Luca; Zoppoli, Pietro; Marotta, Pina; Scarfò, Marzia; De Luca, Pasquale; de Carvalho, Denise Pires; Ceccarelli, Michele; De Felice, Mario; Di Lauro, Roberto

2011-01-01

The thyroid and lungs originate as neighboring bud shaped outgrowths from the midline of the embryonic foregut. When and how organ specific programs regulate development into structures of distinct shapes, positions and functions is incompletely understood. To characterize, at least in part, the genetic basis of these events, we have employed laser capture microdissection and microarray analysis to define gene expression in the mouse thyroid and lung primordia at E10.5. By comparing the transcriptome of each bud to that of the whole embryo as well as to each other, we broadly describe the genes that are preferentially expressed in each developing organ as well as those with an enriched expression common to both. The results thus obtained provide a valuable resource for further analysis of genes previously unrecognized to participate in thyroid and lung morphogenesis and to discover organ specific as well as common developmental mechanisms. As an initial step in this direction we describe a regulatory pathway involving the anti-apoptotic gene Bcl2 that controls cell survival in early thyroid development. PMID:21924257

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.

Maternal Thyroid Function in Early Pregnancy and Neuropsychological Performance of the Child at 5 Years of Age.

PubMed

Andersen, Stine Linding; Andersen, Stig; Liew, Zeyan; Vestergaard, Peter; Olsen, Jørn

2018-02-01

Abnormal maternal thyroid function in pregnancy may impair fetal brain development, but more evidence is needed to refine and corroborate the hypothesis. To estimate the association between maternal thyroid function in early pregnancy and neuropsychological performance of the child at 5 years of age. Follow-up study. A cohort of 1153 women and their children sampled from the Danish National Birth Cohort. Maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) were measured in stored biobank sera from early pregnancy. Child neuropsychological test results (Wechsler Intelligence Scale/Test of Everyday Attention), test of motor function (Movement Assessment Battery), and results of parent and teacher reports (Behavior Rating Inventory of Executive Function/Strengths and Difficulties Questionnaire). Altogether 145 children (12.6%) were born to mothers with abnormal thyroid function in the early pregnancy. High maternal TSH and low fT4 were associated with lower child verbal intelligence quotient (adjusted mean difference TSH ≥ 10 mIU/L vs 0.1 to 2.49 mIU/L, -8.9 [95% confidence interval (CI), -15 to -2.4]; fT4 < 10 pmol/l vs 12.0 to 18.99 pmol/l, -13 [95% CI, -19 to -7.3]). Abnormal maternal thyroid function was also associated with adverse motor function and teacher-reported problems of executive function and behavior, and these associations were dominated by exposure to maternal hypothyroxinemia. Maternal thyroid hormone abnormalities were associated with adverse neuropsychological function of the child at 5 years of age. For intelligence, marked hypothyroidism was important, whereas for motor function and executive and behavior problems, maternal hypothyroxinemia was predominant. Copyright © 2017 Endocrine Society

Early Phthalates Exposure in Pregnant Women Is Associated with Alteration of Thyroid Hormones

PubMed Central

Tsai, Chih-Hsin; Liang, Wei-Yen; Li, Sih-Syuan; Huang, Han-Bin

2016-01-01

Introduction Previous studies revealed that phthalate exposure could alter thyroid hormones during the last trimester of pregnancy. However, thyroid hormones are crucial for fetal development during the first trimester. We aimed to clarify the effect of phthalate exposure on thyroid hormones during early pregnancy. Method We recruited 97 pregnant women who were offered an amniocentesis during the early trimester from an obstetrics clinic in southern Taiwan from 2013 to 2014. After signing an informed consent form, we collected amniotic fluid and urine samples from pregnant women to analyze 11 metabolites, including mono-ethyl phthalate (MEP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-(2-ethylhexyl) phthalate (MEHP), mono-butyl phthalate (MnBP), of 9 phthalates using liquid chromatography/ tandem mass spectrometry. We collected blood samples from each subject to analyze serum thyroid hormones including thyroxine (T4), free T4, and thyroid-binding globulin (TBG). Results Three phthalate metabolites were discovered to be >80% in the urine samples of the pregnant women: MEP (88%), MnBP (81%) and MECPP (86%). Median MnBP and MECPP levels in pregnant Taiwanese women were 21.5 and 17.6 μg/g-creatinine, respectively, that decreased after the 2011 Taiwan DEHP scandal. Results of principal component analysis suggested two major sources (DEHP and other phthalates) of phthalates exposure in pregnant women. After adjusting for age, gestational age, TBG, urinary creatinine, and other phthalate metabolites, we found a significantly negative association between urinary MnBP levels and serum T4 (β = –5.41; p-value = 0.012; n = 97) in pregnant women using Bonferroni correction. Conclusion We observed a potential change in the thyroid hormones of pregnant women during early pregnancy after DnBP exposure. Additional study is necessitated to clarify these associations. PMID:27455052

Methylation Markers for Early Detection and Differentiation of Follicular Thyroid Cancer Subtypes

PubMed Central

Stephen, Josena K.; Chen, Kang Mei; Merritt, Jason; Chitale, Dhananjay; Divine, George; Worsham, Maria J.

2016-01-01

Thyroid cancer has the fastest rising incidence rates and is the fifth most common cancer in women. There are four main types of which the papillary and follicular types together account for >90%, followed by medullary cancers (3%−5%) and anaplastic carcinomas (<3%). For individuals who present with early stage disease of papillary and follicular cancers, there are no accurate markers to predict whether they will develop metastatic or recurrent disease. Our immediate goal is to molecularly differentiate follicular cancer subtypes for enhanced classification. Promoter methylation status of genes with reported associations in thyroid cancer (CASP8, CDKN2A, DAPK1, ESR1, NIS, RASSF1 and TIMP3) were examined in a cohort of follicular thyroid cancers comprising of 26 Hurthle and 27 Classic subtypes utilizing quantitative methylation-specific PCR. RASSF1 was differentially methylated in Classic tumor tissue compared to Hurthle (p<0.001). Methylation of RASSF1 pointed to racial group differences between African Americans and Caucasian Americans (p=0.05). Extra thyroidal extension was found to be associated with DAPK1 (p=0.014) and ESR1 (p=0.036) methylation. Late stage disease was associated with older age (p<0.001) and methylation of DAPK1 (p=0.034) and ESR1 (p=0.035). The methylation status of RASSF1, DAPK1 and ESR1 suggests the utility of methylation markers to molecularly differentiate thyroid cancer subtypes for enhanced classification and early detection of thyroid cancer. PMID:27158284

Development of a Human Neurovascular Unit Organotypic Systems Model of Early Brain Development

EPA Science Inventory

The inability to model human brain and blood-brain barrier development in vitro poses a major challenge in studies of how chemicals impact early neurogenic periods. During human development, disruption of thyroid hormone (TH) signaling is related to adverse morphological effects ...

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.

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.

Early thyroxine treatment in Down syndrome and thyroid function later in life.

PubMed

Zwaveling-Soonawala, Nitash; Witteveen, M Emma; Marchal, Jan Pieter; Klouwer, Femke C C; Ikelaar, Nadine A; Smets, Anne M J B; van Rijn, Rick R; Endert, Erik; Fliers, Eric; van Trotsenburg, A S Paul

2017-05-01

The hypothalamus-pituitary-thyroid (HPT) axis set point develops during the fetal period and first two years of life. We hypothesized that thyroxine treatment during these first two years, in the context of a randomized controlled trial (RCT) in children with Down syndrome, may have influenced the HPT axis set point and may also have influenced the development of Down syndrome-associated autoimmune thyroiditis. We included 123 children with Down syndrome 8.7 years after the end of an RCT comparing thyroxine treatment vs placebo and performed thyroid function tests and thyroid ultrasound. We analyzed TSH and FT4 concentrations in the subgroup of 71 children who were currently not on thyroid medication and had no evidence of autoimmune thyroiditis. TSH concentrations did not differ, but FT4 was significantly higher in the thyroxine-treated group than that in the placebo group (14.1 vs 13.0 pmol/L; P  = 0.02). There was an increase in anti-TPO positivity, from 1% at age 12 months to 6% at age 24 months and 25% at age 10.7 years with a greater percentage of children with anti-TPO positivity in the placebo group (32%) compared with the thyroxine-treated group (18.5%) ( P  = 0.12). Thyroid volume at age 10.7 years (mean: 3.4 mL; range: 0.5-7.5 mL) was significantly lower ( P  < 0.01) compared with reference values (5.5 mL; range: 3-9 mL) and was similar in the thyroxine and placebo group. Thyroxine treatment during the first two years of life led to a mild increase in FT4 almost 9 years later on and may point to an interesting new mechanism influencing the maturing HPT axis set point. Furthermore, there was a trend toward less development of thyroid autoimmunity in the thyroxine treatment group, suggesting a protective effect of the early thyroxine treatment. Lastly, thyroid volume was low possibly reflecting Down-specific thyroid hypoplasia. © 2017 European Society of Endocrinology.

Maternal hypothyroxinemia during pregnancy and growth of the fetal and infant head.

PubMed

van Mil, Nina H; Steegers-Theunissen, Régine P M; Bongers-Schokking, Jacoba J; El Marroun, Hanan; Ghassabian, Akhgar; Hofman, Albert; Jaddoe, Vincent W V; Visser, Theo J; Verhulst, Frank C; de Rijke, Yolanda B; Steegers, Eric A P; Tiemeier, Henning

2012-12-01

Severe maternal thyroid dysfunction during pregnancy affects fetal brain growth and corticogenesis. This study focused on the effect of maternal hypothyroxinemia during early pregnancy on growth of the fetal and infant head. In a population-based birth cohort, we assessed thyroid status in early pregnancy (median 13.4, 90% range 10.8-17.2), in 4894 women, and measured the prenatal and postnatal head size of their children at 5 time points. Hypothyroxinemia was defined as normal thyroid-stimulating hormone levels and free thyroxine-4 concentrations below the 10th percentile. Statistical analysis was performed using linear generalized estimating equation. Maternal hypothyroxinemia was associated with larger fetal and infant head size (overall estimate β: 1.38, 95% confidence interval 0.56; 2.19, P = .001). In conclusion, in the general population, even small variations in maternal thyroid function during pregnancy may affect the developing head of the young child.

TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA.

PubMed

Wang, Na; Liu, Tiantian; Sofiadis, Anastasios; Juhlin, C Christofer; Zedenius, Jan; Höög, Anders; Larsson, Catharina; Xu, Dawei

2014-10-01

The telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have been found in many malignancies, including in thyroid carcinomas. However, it is unclear how early these mutations occur in thyroid tumorigenesis. The study included primary tumors from 58 patients initially diagnosed with follicular thyroid adenoma (FTA), a benign entity, 18 with atypical FTA (AFTA) having an uncertain malignant potential, and 52 with follicular thyroid carcinoma (FTC). Sanger sequencing was used to investigate the mutational status of the TERT promoter. Telomere length and TERT messenger RNA (mRNA) expression were determined using quantitative polymerase chain reaction (PCR). Telomerase activity was assessed using a Telomerase PCR enzyme-linked immunosorbent assay kit. The C228T mutation was identified in 1 of 58 FTA (2%) and 3 of 18 AFTA (17%) samples. These 4 tumors all expressed TERT mRNA and telomerase activity, whereas the majority of C228T-negative adenomas lacked TERT expression (C228T versus wild-type, P = .008). The C228T mutation was associated with NRAS gene mutations (P = .016). The patient with C228T-mutated FTA later developed a scar recurrence and died of FTC, whereas none of the remaining 57 patients with FTA had recurrence. No recurrence occurred in 3 patients with AFTA who carried C228T during the follow-up period (36-285 months). Nine of the 52 FTCs (17%) exhibited the TERT mutation (8 of 9 C228T and 1 of 9 C250T), and the presence of the mutation was associated with shorter patient survival. TERT promoter mutations may occur as an early genetic event in thyroid follicular tumors that have not developed malignant features on routine histopathological workup. © 2014 American Cancer Society.

DOSE-DEPENDENT REDUCTIONS IN SPATIAL LEARING AND SYNAPTIC FUNCTION IN THE DENTATE GYRUS OF ADULT RATS FOLLOWING DEVELOPMENTAL THYROID HORMONE INSUFFICIENCY.

EPA Science Inventory

The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

Thyroid Storm in a Patient with Trauma - A Challenging Diagnosis for the Emergency Physician: Case Report and Literature Review.

PubMed

Wang, Hsiang-I; Yiang, Giou-Teng; Hsu, Chin-Wang; Wang, Jen-Chun; Lee, Chien-Hsing; Chen, Yu-Long

2017-03-01

Thyroid storm, an endocrine emergency, remains a diagnostic and therapeutic challenge. It is recognized to develop as a result of several factors, including infection, surgery, acute illness, and rarely, trauma. Recognition of thyroid storm in a trauma patient is difficult because the emergency physician usually focuses on managing more obvious injuries. We present a case of trauma-related thyroid storm and review the previous literature on posttraumatic thyroid storm to delineate risk factors of the disease. The case occurred in a 32-year-old man after a motorcycle accident. Careful investigation of patient history and risk factors of trauma-related thyroid storms and utilization of the scoring system may facilitate early diagnosis. Traumatically induced thyroid storm usually responds to medical treatment developed for hyperthyroidism. Surgical intervention may be needed for patients who failed medical treatment or those with direct thyroid gland injuries. The outcome is usually fair under appropriate management. We present a case of trauma-related thyroid storm to illustrate the diagnostic and therapeutic approach with a summary of the previous literature. Emergency physicians should be aware of the clinical presentation and risk factors of patients with trauma-related thyroid storm to reduce the rate of misdiagnosis and prevent catastrophic outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.

[Papillary thyroid carcinoma in a child with congenital dyshormonogenetic hypothyroidism. Case report].

PubMed

Orellana, María José; Fulle, Angelo; Carrillo, Diego; Escobar, Lucía; Ebensperger, Alicia; Martínez, Raúl; Rumié Carmi, Hana

Papillary thyroid carcinoma (PTC) is a rare childhood disease. The development of PTC in dyshormonogenetic congenital hypothyroidism (CH) is infrequent, with very few case reports in literature. To report a case of PTC in a boy with dyshormonogenetic CH without goitre and exposed to ionising radiation. To evaluate relationships between these factors and development of PTC. We present a boy with dyshormonogenetic CH since birth. Early hormonal substitution was initiated, with subsequent normal levels of thyrotropin and thyroid hormones. He has also congenital cardiomyopathy, exposed to interventional treatment with 10 heart catheterisations, and approximately 26 chest X-rays at paediatric doses. A thyroid nodule was found in thyroid echography at the age of 6 years old. Fine needle aspiration biopsy confirmed high probability of thyroid carcinoma (Bethesda 5). The pre-surgical thorax and cerebral scan showed no evidence of metastasis. The patient underwent total thyroidectomy. Pathological examination revealed a 0.5cm papillary thyroid micro-carcinoma in the right lobe, with no evidence of dissemination. Genetic mutations and radiation exposure may play an important role in the development of PTC. There may be common pathways between dyshormonogenetic CH and thyroid carcinoma that need further investigation. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

The effects of methimazole on development of the fathead minnow, Pimephales promelas, from embryo to adult.

PubMed

Crane, Helen M; Pickford, Daniel B; Hutchinson, Thomas H; Brown, J Anne

2006-10-01

The importance of thyroid hormones in regulating early developmental processes of many amphibian and fish species is well known, but the impacts of exposure to disrupters of thyroid homeostasis during the embryo-larval-juvenile transitions are unclear. To investigate these impacts, fathead minnows, Pimephales promelas, were exposed to a model thyroid axis disrupter, methimazole, an inhibitor of thyroid hormone synthesis, at control (0), 32, 100, and 320 mug/l, starting at <24-h postfertilization, for 28, 56, and 83/84 days postfertilization (dpf). Thyroid disruption was evident at 28 dpf, when survival was significantly reduced by 32 or 100 mug/l methimazole concomitant with a reduced thyroxine (T(4)) content. However, the T(3) content of these fish was similar to that of control fish, and body mass was unaffected (as in all groups), suggesting compensatory mechanisms overcame reduced T(4) synthesis. At the highest concentration of methimazole (320 mug/l), activation of feedback mechanisms on the hypothalamic-pituitary-thyroid axis was suggested by the normal T(4) content after 28 dpf exposure to methimazole, although triiodothyronine (T(3)) content of these fish was significantly reduced. The generally less pronounced disruption of thyroid hormone homeostasis after 56 days exposure to methimazole also suggests compensatory mechanisms in juvenile/adult fish that may regulate T(4) content, despite exposure to methimazole at 32 or 100 mug/l (in fish held in 320 mug/l methimazole, the T(4) content was significantly higher than in controls). Whole body T(3) content at 56 dpf was significantly depressed only in fish held in 100 mug/l methimazole. By 83/84 dpf, length, body mass, and thyroid hormone concentrations were similar in all experimental groups and controls, indicating that adult fish may achieve regulation of their thyroid axis despite prolonged exposures to thyroid disruptors throughout early development.

Bipolar disorder and antithyroid antibodies: review and case series.

PubMed

Bocchetta, Alberto; Traccis, Francesco; Mosca, Enrica; Serra, Alessandra; Tamburini, Giorgio; Loviselli, Andrea

2016-12-01

Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms.

Epigenetic modulators of thyroid cancer.

PubMed

Rodríguez-Rodero, Sandra; Delgado-Álvarez, Elías; Díaz-Naya, Lucía; Martín Nieto, Alicia; Menéndez Torre, Edelmiro

2017-01-01

There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

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.

[Factors associated with advanced thyroid cancer in pediatric patients in a high specialty medical unit in Northeast Mexico].

PubMed

García-Castillo, Lizbeth Ariana; Bahena-García, Ana Laura; Sánchez-Sánchez, Luz María; del Carmen Palacios-Saucedo, Gerardo

2015-01-01

Thyroid cancer represents 2% of all childhood malignances. Its incidence rises 1.1% per year. In comparison with adults, childhood thyroid cancer is detected in a more advanced stage, but with a survival rate above 95%. The objective of this study was to evaluate whether there are factors associated with advanced stages of thyroid cancer in pediatric patients. Nineteen patients were included, 13 (68.4%) were female and six male, all between 7-15 years, with a median of 11 years. Fifteen in advanced and four in early stage. The median age of patients in advanced stage at time of diagnosis was 10.6 years (7-15) and 13.2 (12-14) were in early stage (p=0.075). There was a delay of nine months to get a diagnosis in advanced stage, and 7.2 in early stage (p=0.931). Three of the patients with advanced stage and two with early stage were from Nuevo León (Mexico) and the rest were foreign (p=0.567). In the group with advanced stage, two had thyroid cancer familiar history, and none in the early stage group (p=0.452). Nine patients in advanced stage and three in early stage presented thyroid nodule as the first sign of illness. Six patients in advanced stage and one in early stage presented goiter (p=0.590). None of the studied patients had radiation history. Six patients in advanced stage and one in early stage suffered from Hashimoto's Thyroiditis (p=0.590). Eleven in advanced stage and one in early stage had papillary histologic variety. Four in advanced stage and three in early stage had papillary histologic variety with a follicular patter (p=0.083). Eight patients presented lung metastasis at time of diagnosis (p=0.061). There are no factors associated with advanced stage thyroid cancer in pediatric populations. Although half of studied patients presented lung metastasis, treatment response and survival is satisfactory.

Thyroid-related neurological disorders and complications in children.

PubMed

Nandi-Munshi, Debika; Taplin, Craig E

2015-04-01

Thyroid hormones exert critical roles throughout the body and play an important and permissive role in neuroendocrine, neurological, and neuromuscular function. We performed a PubMed search through June 2014 with search terms including "hypothyroidism," "hyperthyroidism," "neurological complications," "neuropathy," "myopathy," "congenital hypothyroidism," and "encephalopathy." Relevant publications reviewed included case series, individual case reports, systematic reviews, retrospective analyses, and randomized controlled trials. The neurological outcomes of congenital hypothyroidism were reviewed, along with the clinical features of associated neuromuscular syndromes of both hypothyroidism and hyperthyroidism, including other autoimmune conditions. Evidence for, and pathophysiological controversies surrounding, Hashimoto encephalopathy was also reviewed. The establishment of widespread newborn screening programs has been highly successful in attenuating or preventing early and irreversible neurological harm resulting from congenital thyroid hormone deficiency, but some children continue to display neuromuscular, sensory, and cognitive defects in later life. Acquired disorders of thyroid function such as Hashimoto thyroiditis and Graves' disease are associated with a spectrum of central nervous system and/or neuromuscular dysfunction. However, considerable variation in clinical phenotype is described, and much of our knowledge of the role of thyroid disease in childhood neurological disorders is derived from adult case series. Early and aggressive normalization of thyroxine levels in newborn infants with congenital hypothyroidism is important in minimizing neurological sequelae, but maternal thyroid hormone sources are also critically important to the early developing brain. A spectrum of neurological disorders has been reported in older children with acquired thyroid disease, but the frequency with which these occur remains poorly defined in the literature, and much must be extrapolated from adult data. A high index of suspicion for acquired thyroid disease is paramount in the investigation of many neurological disorders of youth, as many reported sequelae of hypothyroidism and hyperthyroidism are reversible with appropriate endocrine management. Copyright © 2015 Elsevier Inc. All rights reserved.

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma.

PubMed

Song, Hai; Lin, Chuwen; Yao, Erica; Zhang, Kuan; Li, Xiaoling; Wu, Qingzhe; Chuang, Pao-Tien

2017-03-03

Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRP CreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53 , Rb , and Pten , in mature parafollicular C cells via an inducible Cre recombinase from CGRP CreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53 / Rb -induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRP CreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Thyroid disorders associated with pregnancy: etiology, diagnosis, and management.

PubMed

Lazarus, John H

2005-01-01

Pregnancy has an effect on thyroid economy with significant changes in iodine metabolism, serum thyroid binding proteins, and the development of maternal goiter especially in iodine-deficient areas. Pregnancy is also accompanied by immunologic changes, mainly characterized by a shift from a T helper-1 (Th1) lymphocyte to a Th2 lymphocyte state. Thyroid peroxidase antibodies are present in 10% of women at 14 weeks' gestation, and are associated with (i) an increased pregnancy failure (i.e. abortion), (ii) an increased incidence of gestational thyroid dysfunction, and (iii) a predisposition to postpartum thyroiditis. Thyroid function should be measured in women with severe hyperemesis gravidarum but not in every patient with nausea and vomiting during pregnancy. Graves hyperthyroidism during pregnancy is best managed with propylthiouracil administered throughout gestation. Thyroid-stimulating hormone-receptor antibody measurements at 36 weeks' gestation are predictive of transient neonatal hyperthyroidism, and should be checked even in previously treated patients receiving thyroxine. Postpartum exacerbation of hyperthyroidism is common, and should be evaluated in women with Graves disease not on treatment. Radioiodine therapy in pregnancy is absolutely contraindicated. Hypothyroidism (including subclinical hypothyroidism) occurs in about 2.5% of pregnancies, and may lead to obstetric and neonatal complications as well as being a cause of infertility. During the last few decades, evidence has been presented to underpin the critical importance of adequate fetal thyroid hormone levels in order to ensure normal central and peripheral nervous system maturation. In iodine-deficient and iodine-sufficient areas, low maternal circulating thyroxine levels have been associated with a significant decrement in child IQ and development. These data suggest the advisability of further evaluation for a screening program early in pregnancy to identify women with hypothyroxinemia, and the initiation of prompt treatment for its correction. Hypothyroidism in pregnancy is treated with a larger dose of thyroxine than in the nonpregnant state. Postpartum thyroid dysfunction (PPTD) occurs in 50% of women found to have thyroid peroxidase antibodies in early pregnancy. The hypothyroid phase of PPTD is symptomatic and requires thyroxine therapy. A high incidence (25-30%) of permanent hypothyroidism has been noted in these women. Women having transient PPTD with hypothyroidism should be monitored frequently, as there is a 50% chance of these patients developing hypothyroidism during the next 7 years.

Absent 99mTc-MIBI Uptake in the Thyroid Gland during Early Phase of Parathyroid Scintigraphy in Patients with Primary and Secondary Hyperparathyroidism.

PubMed

Jovanovska, Anamarija; Stoilovska, Bojana; Mileva, Magdalena; Miladinova, Daniela; Majstorov, Venjamin; Ugrinska, Ana

2018-05-20

Thyroid uptake of technetium-99m methoxyisobutylisonitrile ( 99m Tc-MIBI) during parathyroid scintigraphy can be affected by various conditions. To evaluate the frequency of absent 99m Tc-MIBI uptake by the thyroid gland in the early phase of dual-phase parathyroid scintigraphy. The early planar images of dual phase Tc 99m MIBI parathyroid scintigraphy from 217 patients performed between 2014 and 2017 were retrospectively analysed. Patients were divided into two groups. The first group included 147 patients with primary hyperparathyroidism and the second group included 70 patients with chronic renal failure. Patient records, laboratory and ultrasonographic data were analysed in all patients. Descriptive statistic was used for data analysis. Out of all patients in the first group, 18 patients (12.24%) showed absent thyroid uptake. Thyroidectomy was performed in 44.4% of these patients, and the rest of them had some thyroid disease. Only one patient had no thyroid or another chronic disease. In the second group, 8 patients (11.42%) presented with absent thyroid uptake of MIBI. Among them, 5 patients had no history of thyroid disease and had been on hemodialysis programme, and 3 patients had hypothyroidism. Absent 99m Tc-MIBI uptake in the thyroid during the early phase of parathyroid scintigraphy is most frequently related to thyroid disease. A small proportion of patients with chronic renal failure can present with absent 99m Tc-MIBI uptake in the thyroid as well. The mechanism for this alteration is still unclear and needs further investigation.

Gravity Plays an Important Role in Muscle Development and the Differentiation of Contractile Protein Phenotype

NASA Technical Reports Server (NTRS)

Adams, Gregory A.; Haddad, Fadia; Baldwin, Kenneth M.

2003-01-01

Several muscles in the body exist mainly to work against gravity. Whether gravity is important in the development of these muscles is not known. By examining the basic proteins that compose muscle, questions about the role of gravity in muscle development can be answered. Myosin heavy chains (MHCs) are a family of proteins critically important for muscle contraction. Several types of MHCs exist (e.g., neonatal, slow, fast), and each type is produced by a particular gene. Neonatal MHCs are produced early in life. Slow MHCs are important in antigravity muscles, and fast MHCs are found in fast-twitch power muscles. The gene that is turned on or expressed will determine which MHC is produced. Early in development, antigravity skeletal muscles (muscles that work against gravity) normally produce a combination of the neonatal/embryonic MHCs. The expression of these primitive MHCs is repressed early in development; and the adult slow and fast MHC genes become fully expressed. We tested the hypothesis that weightbearing activity is critical for inducing the normal expression of the slow MHC gene typically expressed in adult antigravity muscles. Also, we hypothesized that thyroid hormone, but not opposition to gravity, is necessary for expressing the adult fast IIb MHC gene essential for high-intensity muscle performance. Groups of normal thyroid and thyroid-deficient neonatal rats were studied after their return from the 16-day Neurolab mission and compared to matched controls. The results suggest: (1) Weightlessness impaired body and limb skeletal muscle growth in both normal and thyroid-deficient animals. Antigravity muscles were impaired more than those used primarily for locomotion andor nonweightbearing activity. (2) Systemic and muscle expression of insulin-like growth factor-I (IGF-I), an important body and tissue growth factor, was depressed in flight animals. (3) Normal slow, type I MHC gene expression was markedly repressed in the normal thyroid flight group. (4) Fast IIb MHC gene expression was enhanced in fast-twitch muscles of normal thyroid animals exposed to spaceflight; however, thyroid deficiency markedly repressed expression of this gene independently of spaceflight. In summary, the absence of gravity, when imposed at critical stages of development, impaired body and skeletal muscle growth, as well as expression of the MHC gene family of motor proteins. This suggests that normal weightbearing activity is essential for establishing body and muscle growth in neonatal animals, and for expressing the motor gene essential for supporting antigravity functions.

Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Initial investigation of a hypothesized link between thyroid peroxidase inhibition and fish early-life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

IgG4-Related Disease of the Thyroid Gland Requiring Emergent Total Thyroidectomy: A Case Report.

PubMed

Zhao, Zitong; Lee, Yu Jin; Zheng, Shuwei; Khor, Li Yan; Lim, Kok Hing

2018-05-31

IgG4-related disease of the thyroid gland is a recently recognized subtype of thyroiditis, often with rapid progression requiring surgical treatment. It is considered as a spectrum of disease varying from early IgG4-related Hashimoto's thyroiditis (HT) pattern to late fibrosing HT or Riedel's thyroiditis patterns. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over 3 years and subclinical hypothyroidism. Computed tomography (CT) scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed a limited number of follicular epithelial cell groups with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of 'atypia of undetermined significance'. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate and fibrosis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. The overall features suggest the diagnosis of IgG4-related disease of the thyroid gland in the form of IgG4-related HT. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids for treatment of IgG4-related disease.

A case with atrophic autoimmune thyroiditis-related hypothyroidism causing multisystem involvement in early childhood.

PubMed

Kurnaz, Erdal; Savaş-Erdeve, Şenay; Keskin, Melikşah; Doğan, Vehbi; Çetinkaya, Semra; Aycan, Zehra

2016-01-01

The most common reason of acquired hypothyroidism is autoimmune (Hashimoto) thyroiditis. Autoimmune thyroiditis can be atrophic or goitrogenic. Atrophic autoimmune thyroiditis (ATT) related acquired hypothyroidism causes interruption of growth, obesity, and bone age retardation in early ages while goitrogenic thyroiditis has a higher incidence rate and mostly presents with diffuse goiter. We discuss the effects of hypothyroidism on various systems through a case found to have pericardial effusion during the echocardiography performed after cardiac murmur was detected and later diagnosed with ATT related hypothyroidism.

Effects of prolonged exposure to perchlorate on thyroid and reproductive function in zebrafish

USGS Publications Warehouse

Mukhi, S.; Patino, R.

2007-01-01

The objectives of this study were to determine the effects of prolonged exposure to perchlorate on (1) thyroid status and reproductive performance of adult zebrafish (Danio rerio) and (2) F1 embryo survival and early larval development. Using a static-renewal procedure, mixed sex populations of adult zebrafish were exposed to 0, 10, and 100 mg/l nominal concentrations of waterborne perchlorate for 10 weeks. Thyroid histology was qualitatively assessed, and females and males were separated and further exposed to their respective treatments for six additional weeks. Eight females in each tank replicate (n = 3) were paired weekly with four males from the same respective treatment, and packed-egg (spawn) volume (PEV) was measured each of the last five weeks. At least once during weeks 14-16 of exposure, other end points measured included fertilization rate, fertilized egg diameter, hatching rate, standard length, and craniofacial development of 4-day-postfertilization larvae and thyroid hormone content of 3.5-h embryos and of exposed mothers. At 10 weeks of exposure, perchlorate at both concentrations caused thyroidal hypertrophy and colloid depletion. A marked reduction in PEV was observed toward the end of the 6-week spawning period, but fertilization and embryo hatching rates were unaffected. Fertilized egg diameter and larval length were increased by parental exposure to perchlorate. Larval head depth was unaffected but the forward protrusion of the lower jaw-associated cartilage complexes, Meckel's and ceratohyal, was decreased. Exposure to both concentrations of perchlorate inhibited whole-body thyroxine content in mothers and embryos, but triiodothyronine content was unchanged. In conclusion, prolonged exposure of adult zebrafish to perchlorate not only disrupts their thyroid endocrine system but also impairs reproduction and influences early F1 development. ?? 2007 Oxford University Press.

Concurrence of Grave's disease and Hashimoto's thyroiditis.

PubMed Central

Sato, T; Takata, I; Taketani, T; Saida, K; Nakajima, H

1977-01-01

Early histological changes in the thyroid gland were examined in 30 patients with juvenile thyrotoxicosis, by means of needle biopsy. Based on the degree of lymphocytic infiltration and degenerative changes in follicular epithelium, results were classified into four groups. A: hyperplastic changes without cellular infiltration (6 patients, 20%); B: hyperplastic changes with areas of focal thyroiditis less than 30% of specimen (10 patients, 33%); C: those with 30 to 60% areas ot thyroiditis (10 patients, 33%); D: almost diffuse thyroiditis (4 patients, 13%). Moderate to severe lymphocytic thyroiditis was frequently present in the early stage of hyperplastic thyroid glands. The clinical significance of the 4 histological groups was evaluated. Neither clinical signs nor routine laboratory tests could differentiate these groups except group D, in which thyrotoxic signs were mild and transient. However, serum antithyroid antibodies tended to increase in accordance with severity of thyroiditis. The rate of remission was high in groups C and D, whereas relapse was frequent in group A. These results suggest that Grave's disease and chronic lymphocytic thyroiditis are closely related in the early stage of thyrotoxicosis in children, and that the clinical course may be considerably altered by the degree of associated thyroiditis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 3 PMID:580172

Why is the thyroid so prone to autoimmune disease?

PubMed

Saranac, L; Zivanovic, S; Bjelakovic, B; Stamenkovic, H; Novak, M; Kamenov, B

2011-01-01

The thyroid gland plays a major role in the human body; it produces the hormones necessary for appropriate energy levels and an active life. These hormones have a critical impact on early brain development and somatic growth. At the same time, the thyroid is highly vulnerable to autoimmune thyroid diseases (AITDs). They arise due to the complex interplay of genetic, environmental, and endogenous factors, and the specific combination is required to initiate thyroid autoimmunity. When the thyroid cell becomes the target of autoimmunity, it interacts with the immune system and appears to affect disease progression. It can produce different growth factors, adhesion molecules, and a large array of cytokines. Preventable environmental factors, including high iodine intake, selenium deficiency, and pollutants such as tobacco smoke, as well as infectious diseases and certain drugs, have been implicated in the development of AITDs in genetically predisposed individuals. The susceptibility of the thyroid to AITDs may come from the complexity of hormonal synthesis, peculiar oligoelement requirements, and specific capabilities of the thyroid cell's defense system. An improved understanding of this interplay could yield novel treatment pathways, some of which might be as simple as identifying the need to avoid smoking or to control the intake of some nutrients. Copyright © 2011 S. Karger AG, Basel.

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.

The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe.

PubMed

de Jong, Frank Jan; Peeters, Robin P; den Heijer, Tom; van der Deure, Wendy M; Hofman, Albert; Uitterlinden, André G; Visser, Theo J; Breteler, Monique M B

2007-02-01

Thyroid function has been related to Alzheimer disease (AD) and neuroimaging markers thereof. Whether thyroid dysfunction contributes to or results from developing AD remains unclear. Variations in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes that potentially alter thyroid hormone bioactivity may help in elucidating the role of thyroid function in AD. We investigated the association of recently identified polymorphisms in the DIO1 (D1a-C/T, D1b-A/G) and DIO2 (D2-ORFa-Gly3Asp, D2-Thr92Ala) genes with circulating thyroid parameters and early neuroimaging markers of AD. The Rotterdam Scan Study is a population-based cohort study among 1,077 elderly individuals aged 60-90 yr. DIO1 and DIO2 polymorphisms and serum TSH, free T4, T3, and reverse T3 (rT3) levels were determined in 995 nondemented elderly, including 473 persons with assessments of hippocampal and amygdalar volume on brain magnetic resonance imaging. Carriers of the D1a-T allele had higher serum free T4 and rT3, lower T3, and lower T3/rT3. The D1b-G allele was associated with higher serum T3 and T3/rT3. The DIO2 variants were not associated with serum thyroid parameters. No associations were found with hippocampal or amygdalar volume. This is the first study to report an association of D1a-C/T and D1b-A/G polymorphisms with iodothyronine levels in the elderly. Polymorphisms in the DIO1 and DIO2 genes are not associated with early magnetic resonance imaging markers of AD. This suggests that the previously reported association between iodothyronine levels and brain atrophy reflects comorbidity or nonthyroidal illness rather than thyroid hormones being involved in developing AD.

Temperature induced variation in gene expression of thyroid hormone receptors and deiodinases of European eel (Anguilla anguilla) larvae.

PubMed

Politis, S N; Servili, A; Mazurais, D; Zambonino-Infante, J-L; Miest, J J; Tomkiewicz, J; Butts, I A E

2018-04-01

Thyroid hormones (THs) are key regulators of growth, development, and metabolism in vertebrates and influence early life development of fish. TH is produced in the thyroid gland (or thyroid follicles) mainly as T4 (thyroxine), which is metabolized to T3 (3,5,3'-triiodothyronine) and T2 (3,5-diiodothyronine) by deiodinase (DIO) enzymes in peripheral tissues. The action of these hormones is mostly exerted by binding to a specific nuclear thyroid hormone receptor (THR). In this study, we i) cloned and characterized thr sequences, ii) investigated the expression pattern of the different subtypes of thrs and dios, and iii) studied how temperature affects the expression of those genes in artificially produced early life history stages of European eel (Anguilla anguilla), reared in different thermal regimes (16, 18, 20 and 22 °C) from hatch until first-feeding. We identified 2 subtypes of thr (thrα and thrβ) with 2 isoforms each (thrαA, thrαB, thrβA, thrβB) and 3 subtypes of deiodinases (dio1, dio2, dio3). All thr genes identified showed high similarity to the closely related Japanese eel (Anguilla japonica). We found that all genes investigated in this study were affected by larval age (in real time or at specific developmental stages), temperature, and/or their interaction. More specifically, the warmer the temperature the earlier the expression response of a specific target gene. In real time, the expression profiles appeared very similar and only shifted with temperature. In developmental time, gene expression of all genes differed across selected developmental stages, such as at hatch, during teeth formation or at first-feeding. Thus, we demonstrate that thrs and dios show sensitivity to temperature and are involved in and during early life development of European eel. Copyright © 2017 Elsevier Inc. All rights reserved.

[Thyroid disorders during pregnancy].

PubMed

Gärtner, R

2009-01-01

Thyroid disorders may not only be the cause infertility but also increases the incidence of miscarriages and the morbidity of the pregnancies. During pregnancy the demand of thyroid hormones increases to about 30 - 50 % and the thyroid has to cope with this increase. In Germany the iodine intake has improved significantly during the last 20 years, but still is borderline low with an mean intake of about 120 microg iodide per day. Therefore it is still recommended that pregnant women are supplemented with about 100 - 150 microg of iodide during pregnancy and the time of breast-feeding, to avoid hypothyroidism of the foetus with concomitant delay of the brain development. Not only women with subclinical hypothyroidism, but only elevated TPO antibodies have a significant increase in early miscarriage and preterm delivery. An early supplementation with Levothyroxin despite euthyroidism might reduce these risks. Those women also more frequently develop postpartum thyroiditis. This risk can be reduced by a supplementation with selenium during and after pregnancy. Graves' disease is a rare disorder and only about 0,1 - 0,4 pregnancies are affected. The course of the disease is biphasic, with an exacerbation within the first trimester and an improvement thereafter, but a recurrence after delivery. Overt thyrotoxicosis has to be treated with propylthiouracil, to maintain euthyroidism during pregnancy. The TSH receptor antibodies are transferred to the foetus with the risk of thyrotoxicosis. Special care of the foetus is therefore necessary. Transient mild hyperthyroidism may occur in women with very high HCG levels during the first three months of pregnancy. This often is associated with hyperemesis gravidarum. Subclinical hypothyroidism of the mother will disturb the normal development of the foetus and therefore has to be treated even when TSH is within the upper normal level. Special care is necessary in women with elevated TPO antibodies, because these more often develop postpartum thyroiditis.

[Thyroid emergencies : Thyroid storm and myxedema coma].

PubMed

Spitzweg, C; Reincke, M; Gärtner, R

2017-10-01

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

Thyroid hormones states and brain development interactions.

PubMed

Ahmed, Osama M; El-Gareib, A W; El-Bakry, A M; Abd El-Tawab, S M; Ahmed, R G

2008-04-01

The action of thyroid hormones (THs) in the brain is strictly regulated, since these hormones play a crucial role in the development and physiological functioning of the central nervous system (CNS). Disorders of the thyroid gland are among the most common endocrine maladies. Therefore, the objective of this study was to identify in broad terms the interactions between thyroid hormone states or actions and brain development. THs regulate the neuronal cytoarchitecture, neuronal growth and synaptogenesis, and their receptors are widely distributed in the CNS. Any deficiency or increase of them (hypo- or hyperthyroidism) during these periods may result in an irreversible impairment, morphological and cytoarchitecture abnormalities, disorganization, maldevelopment and physical retardation. This includes abnormal neuronal proliferation, migration, decreased dendritic densities and dendritic arborizations. This drastic effect may be responsible for the loss of neurons vital functions and may lead, in turn, to the biochemical dysfunctions. This could explain the physiological and behavioral changes observed in the animals or human during thyroid dysfunction. It can be hypothesized that the sensitive to the thyroid hormones is not only remarked in the neonatal period but also prior to birth, and THs change during the development may lead to the brain damage if not corrected shortly after the birth. Thus, the hypothesis that neurodevelopmental abnormalities might be related to the thyroid hormones is plausible. Taken together, the alterations of neurotransmitters and disturbance in the GABA, adenosine and pro/antioxidant systems in CNS due to the thyroid dysfunction may retard the neurogenesis and CNS growth and the reverse is true. In general, THs disorder during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems that leads to a multitude of irreversible morphological and biochemical abnormalities (pathophysiology). Thus, further studies need to be done to emphasize this concept.

Perigastric lymph node metastasis from papillary thyroid carcinoma in a patient with early gastric cancer: the first case report.

PubMed

Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok

2014-09-01

Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.

Thyroid storm associated with Graves' disease covered by diabetic ketoacidosis: A case report.

PubMed

Osada, Erika; Hiroi, Naoki; Sue, Mariko; Masai, Natsumi; Iga, Ryo; Shigemitsu, Rika; Oka, Reiko; Miyagi, Masahiko; Iso, Kaoru; Kuboki, Koji; Yoshino, Gen

2011-04-14

Thyroid storm is a condition in which multiple organ dysfunction results from failure of the compensatory mechanisms of the body owing to excessive thyroid hormone activity induced by some factors in patients with thyrotoxicosis. While diabetic ketoacidosis (DKA) is an important trigger for thyroid storm, simultaneous development of DKA and thyroid storm is rare. A 59-year-old woman with no history of either diabetes mellitus or thyroid disease presented to our hospital because of developing nausea, vomiting and diarrhea for 2 days. Physical examination showed mild disturbance of consciousness, fever, and tachycardia. There were no other signs of thyrotoxicosis. Laboratory studies revealed elevation of random blood glucose and glycosylated hemoglobin, strongly positive of urine acetone, and metabolic acidosis. Since DKA was diagnosed, we initiated the patient on treatment with administration of insulin and adequate fluid replacement. Although the hyperglycemia and acidosis were immediately relieved, the disturbance of consciousness and tachycardia remained persistent. Levels of FT3 and FT4 were extremely high and TSH was below the detectable limit. TRAb was positive. The thyroid storm score of Burch & Wartofsky was 75/140, and the thyroid storm diagnostic criteria of the Japan Thyroid Association were satisfied. Oral administration of thiamazole, potassium iodide and propranolol resulted in immediate relief of the tachycardia. We encountered a case of thyroid storm associated with Graves' disease covered by DKA. Thyroid storm and DKA are both potentially fatal, and the prognosis varies depending on whether or not these conditions are detected and treated sufficiently early. The thyroid storm diagnostic criteria prepared in 2008 by the Japan Thyroid Association are very simple as compared to the Burch & Wartofsky scoring system for thyroid storm. The Japanese criteria may be useful in the diagnosis of this condition since they enable clinicians to identify a broad range of cases with thyroid storm. When dealing with cases of DKA or thyroid storm, it seems essential to bear in mind the possibility of the coexistence of these two diseases.

Maternal Thyroid Dysfunction and Risk of Seizure in the Child: A Danish Nationwide Cohort Study

PubMed Central

Laurberg, Peter; Wu, Chun Sen; Olsen, Jørn

2013-01-01

Thyroid hormones are essential for brain development, and maternal thyroid disease may affect child neurocognitive development. Some types of seizures may also depend upon early exposure of the developing central nervous system, and we hypothesized that maternal thyroid dysfunction could increase the risk of seizure in the child. In a Danish population-based study we included 1,699,693 liveborn singletons, and from the Danish National Hospital Register we obtained information on maternal diagnosis of hyper- or hypothyroidism and neonatal seizure, febrile seizure, and epilepsy in the child. Maternal diagnosis of thyroid dysfunction before or after birth of the child was registered in two percent of the singleton births. In adjusted analyses, maternal hyperthyroidism and hypothyroidism first time diagnosed after birth of the child were associated with a significant increased risk of epilepsy in the child. Moreover, hypothyroidism diagnosed after birth of the child was associated with a significant increased risk of neonatal and febrile seizures. No significant association was seen for maternal diagnosis prior to birth of the child. We speculate if some degree of maternal thyroid dysfunction was already present during the pregnancy in mothers diagnosed after birth of the child and if this untreated condition may present a neurodevelopmental risk. PMID:23984072

Maternal thyroid dysfunction and risk of seizure in the child: a Danish nationwide cohort study.

PubMed

Andersen, Stine Linding; Laurberg, Peter; Wu, Chun Sen; Olsen, Jørn

2013-01-01

Thyroid hormones are essential for brain development, and maternal thyroid disease may affect child neurocognitive development. Some types of seizures may also depend upon early exposure of the developing central nervous system, and we hypothesized that maternal thyroid dysfunction could increase the risk of seizure in the child. In a Danish population-based study we included 1,699,693 liveborn singletons, and from the Danish National Hospital Register we obtained information on maternal diagnosis of hyper- or hypothyroidism and neonatal seizure, febrile seizure, and epilepsy in the child. Maternal diagnosis of thyroid dysfunction before or after birth of the child was registered in two percent of the singleton births. In adjusted analyses, maternal hyperthyroidism and hypothyroidism first time diagnosed after birth of the child were associated with a significant increased risk of epilepsy in the child. Moreover, hypothyroidism diagnosed after birth of the child was associated with a significant increased risk of neonatal and febrile seizures. No significant association was seen for maternal diagnosis prior to birth of the child. We speculate if some degree of maternal thyroid dysfunction was already present during the pregnancy in mothers diagnosed after birth of the child and if this untreated condition may present a neurodevelopmental risk.

Cardiorespiratory Failure in Thyroid Storm: Case Report and Literature Review

PubMed Central

Nai, Qiang; Ansari, Mohammad; Pak, Stella; Tian, Yufei; Amzad-Hossain, Mohammed; Zhang, Yanhong; Lou, Yali; Sen, Shuvendu; Islam, Mohammed

2018-01-01

Thyroid storm is a potentially fatal manifestation of thyrotoxicosis. Cardiopulmonary failure is the most common cause of death in thyroid storm. Clinicians should keep in mind that thyroid storm complicated with cardiopulmonary failure can be the first presentation of thyrotoxicosis. As early intervention is associated with improved patient outcome, prompt diagnosis based on clinical grounds is of paramount importance in the management of thyrotoxicosis. A high index of suspicion and the ability of early recognition of impending thyroid storm depends on a thorough knowledge of both the typical and atypical clinical features of this illness. Herein, we report a case of thyroid storm presenting as cardiopulmonary failure in a 51-year-old woman with undiagnosed Grave’s disease. Additionally, we review the pathophysiology of cardiopulmonary failure associated with thyrotoxicosis and various treatment modalities for thyroid storm. PMID:29511425

Cardiorespiratory Failure in Thyroid Storm: Case Report and Literature Review.

PubMed

Nai, Qiang; Ansari, Mohammad; Pak, Stella; Tian, Yufei; Amzad-Hossain, Mohammed; Zhang, Yanhong; Lou, Yali; Sen, Shuvendu; Islam, Mohammed

2018-04-01

Thyroid storm is a potentially fatal manifestation of thyrotoxicosis. Cardiopulmonary failure is the most common cause of death in thyroid storm. Clinicians should keep in mind that thyroid storm complicated with cardiopulmonary failure can be the first presentation of thyrotoxicosis. As early intervention is associated with improved patient outcome, prompt diagnosis based on clinical grounds is of paramount importance in the management of thyrotoxicosis. A high index of suspicion and the ability of early recognition of impending thyroid storm depends on a thorough knowledge of both the typical and atypical clinical features of this illness. Herein, we report a case of thyroid storm presenting as cardiopulmonary failure in a 51-year-old woman with undiagnosed Grave's disease. Additionally, we review the pathophysiology of cardiopulmonary failure associated with thyrotoxicosis and various treatment modalities for thyroid storm.

Foetal and neonatal thyroid disorders.

PubMed

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

2002-10-01

Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes recently identified are represented by TSH receptor mutations leading to constitutively activated TSH receptor. Infants born to mothers with Graves' history may develop neonatal thyrotoxicosis. Foetal/neonatal disease is due to transplacental thyrotrophin receptor stimulating antibodies (TRAb) passage. It's extremely important recognizing and treating Graves' disease in mothers as soon as possible, because a thyrotoxic state may have adverse effects on the outcome of pregnancy and both on the foetus and newborn. Thyrotoxic foetuses may develop goitre, tachycardia, hydrops associated with heart failure, growth retardation, craniosynostosis, increased foetal motility and accelerated bone maturation. Neonatal Graves' disease tends to resolve spontaneously within 3-12 weeks as maternal thyroid stimulating immunoglobulins are cleared from the circulation but subsequent development may be impaired by perceptual motor difficulties. Hashimoto's thyroiditis is a very common autoimmune thyroid disease. In presence of maternal Hashimoto's thyroiditis, there are usually no consequences on foetal thyroid, even if antiTPO and antiTg antibodies can be found in the newborn due to transplacental passage. However there are some literature reports describing foetal and neonatal hyperthyroidism in the affected mothers' offspring.

Estimation of thyroid radiation doses for the hanford thyroid disease study: results and implications for statistical power of the epidemiological analyses.

PubMed

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

2004-07-01

Residents of eastern Washington, northeastern Oregon, and western Idaho were exposed to I released into the atmosphere from operations at the Hanford Nuclear Site from 1944 through 1972, especially in the late 1940's and early 1950's. This paper describes the estimated doses to the thyroid glands of the 3,440 evaluable participants in the Hanford Thyroid Disease Study, which investigated whether thyroid morbidity was increased in people exposed to radioactive iodine from Hanford during 1944-1957. The participants were born during 1940-1946 to mothers living in Benton, Franklin, Walla Walla, Adams, Okanogan, Ferry, or Stevens Counties in Washington State. Whenever possible someone with direct knowledge of the participant's early life (preferably the participant's mother) was interviewed about the participant's individual dose-determining characteristics (residence history, sources and quantities of food, milk, and milk products consumed, production and processing techniques for home-grown food and milk products). Default information was used if no interview respondent was available. Thyroid doses were estimated using the computer program Calculation of Individual Doses from Environmental Radionuclides (CIDER) developed by the Hanford Environmental Dose Reconstruction Project. CIDER provided 100 sets of doses to represent uncertainty of the estimates. These sets were not generated independently for each participant, but reflected the effects of uncertainties in characteristics shared by participants. Estimated doses (medians of each participant's 100 realizations) ranged from 0.0029 mGy to 2823 mGy, with mean and median of 174 and 97 mGy, respectively. The distribution of estimated doses provided the Hanford Thyroid Disease Study with sufficient statistical power to test for dose-response relationships between thyroid outcomes and exposure to Hanford's I.

Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone

PubMed Central

Petersen, Ann M.; Dillon, Danielle; Bernhardt, Richard A.; Torunsky, Roberta; Postlethwait, John H.; von Hippel, Frank A.; Buck, C. Loren; Cresko, William A.

2014-01-01

Perchlorate, an environmental contaminant, disrupts normal functioning of the thyroid. We previously showed that perchlorate disrupts behavior and gonad development, and induces external morphological changes in a vertebrate model organism, the threespine stickleback. Whether perchlorate alters these phenotypes via a thyroid-mediated mechanism, and the extent to which the effects depend on dose, are unknown. To address these questions, we chronically exposed stickleback to control conditions and to three concentrations of perchlorate (10, 30 and 100 ppm) at various developmental stages from fertilization to reproductive maturity. Adults chronically exposed to perchlorate had increased numbers of thyroid follicles and decreased numbers of thyrocytes. Surprisingly, T4 and T3 levels in larval, juvenile, and adult whole fish chronically exposed to perchlorate did not differ from controls, except at the lowest perchlorate dose, suggesting a non-monotonic dose response curve. We found no detectable abnormalities in external phenotype at any dose of perchlorate, indicating that the increased number of thyroid follicles compensated for the disruptive effects of these doses. In contrast to external morphology, gonadal development was altered substantially, with the highest dose of perchlorate causing the largest effects. Perchlorate increased the number both of early stage ovarian follicles in females and of advanced spermatogenic stages in males. Perchlorate also disrupted embryonic androgen levels. We conclude that chronic perchlorate exposure may not result in lasting adult gross morphological changes but can produce lasting modifications to gonads when compensation of T3 and T4 levels occurs by thyroid follicle hyperplasia. Perchlorate may therefore affect vertebrate development via both thyroidal and non-thyroidal mechanisms. PMID:25448260

Analysis and functional characterization of sequence variations in ligand binding domain of thyroid hormone receptors in autism spectrum disorder (ASD) patients.

PubMed

Kalikiri, Mahesh Kumar; Mamidala, Madhu Poornima; Rao, Ananth N; Rajesh, Vidya

2017-12-01

Autism spectrum disorder (ASD) is a neuro developmental disorder, reported to be on a rise in the past two decades. Thyroid hormone-T3 plays an important role in early embryonic and central nervous system development. T3 mediates its function by binding to thyroid hormone receptors, TRα and TRβ. Alterations in T3 levels and thyroid receptor mutations have been earlier implicated in neuropsychiatric disorders and have been linked to environmental toxins. Limited reports from earlier studies have shown the effectiveness of T3 treatment with promising results in children with ASD and that the thyroid hormone levels in these children was also normal. This necessitates the need to explore the genetic variations in the components of the thyroid hormone pathway in ASD children. To achieve this objective, we performed genetic analysis of ligand binding domain of THRA and THRB receptor genes in 30 ASD subjects and in age matched controls from India. Our study for the first time reports novel single nucleotide polymorphisms in the THRA and THRB receptor genes of ASD individuals. Autism Res 2017, 10: 1919-1928. ©2017 International Society for Autism Research, Wiley Periodicals, Inc. Thyroid hormone (T3) and thyroid receptors (TRα and TRβ) are the major components of the thyroid hormone pathway. The link between thyroid pathway and neuronal development is proven in clinical medicine. Since the thyroid hormone levels in Autistic children are normal, variations in their receptors needs to be explored. To achieve this objective, changes in THRA and THRB receptor genes was studied in 30 ASD and normal children from India. The impact of some of these mutations on receptor function was also studied. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

Image analysis for TSH mRNA in situ hybridization in pituitary glands from rats with thyroid follicular cell hypertrophy after treatment with three different test compounds.

PubMed

Funk, Juergen; Ebeling, Martin; Singer, Thomas; Landes, Christian

2017-10-01

The goal of this in situ hybridization and image analysis technique is to study the effects of new pharmacological/chemical entities on the thyroid and pituitary gland in rats, reveal the pathogenesis of thyroid follicular cell hypertrophy and to retrospectively exclude the risk of thyroid tumor development in humans. In the present study, we describe the increase of thyroid-stimulating hormone- (TSH-) beta subunit mRNA in the pars distalis of the pituitary gland and the quantitative measurement of TSH mRNA positive cells from rats of three 4-week toxicity studies treated with three different test compounds inducing thyroid follicular cell and hepatocellular hypertrophy in rats. Compared to immunohistochemistry (IHC), in situ hybridization (ISH) for TSH was found to be more sensitive. With this technique we are able to exclude a direct effect of the test compound on the thyroid gland by showing the activation of thyrotrope cells from the pituitary gland and therefore this technique retrospectively enables us to exclude a possible risk for humans at an early stage of drug development. Also in case blood serum samples for evaluation of TSH are not available anymore or hepatocellular hypertrophy is not present (close metabolic relationship between thyroid gland and liver in rodents), the described method allows retrospective investigations on thyroid follicular cell hypertrophy or hyperplasia. This can be of high relevance in human safety assessment for certain drugs in order to exclude a primary effect on the thyroid gland especially when it comes to thyroid neoplasia in rodents as previously described. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

PubMed Central

Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler

2014-01-01

Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient mice. Genetically engineered models of papillary and undifferentiated (anaplastic) thyroid carcinoma (PTC and ATC) are immunocompetent; however, slow and stochastic tumor development hinders high-throughput testing. Novel models of PTC and ATC in which tumors arise rapidly and synchronously in immunocompetent mice would facilitate the investigation of novel therapeutics and approaches. Methods: We characterized and utilized mouse cell lines derived from PTC and ATC tumors arising in genetically engineered mice with thyroid-specific expression of endogenous BrafV600E/WT and deletion of either Trp53 (p53) or Pten. These murine thyroid cancer cells were transduced with luciferase- and GFP-expressing lentivirus and implanted into the thyroid glands of immunocompetent syngeneic B6129SF1/J mice in which the growth characteristics were assessed. Results: Large locally aggressive thyroid tumors form within one week of implantation. Tumors recapitulate their histologic subtype, including well-differentiated PTC and ATC, and exhibit CD3+, CD8+, B220+, and CD163+ immune cell infiltration. Tumor progression can be followed in vivo using luciferase and ex vivo using GFP. Metastatic spread is not detected at early time points. Conclusions: We describe the development of the next generation of murine orthotopic thyroid cancer models. The implantation of genetically defined murine BRAF-mutated PTC and ATC cell lines into syngeneic mice results in rapid and synchronous tumor formation. This model allows for preclinical investigation of novel therapeutics and/or therapeutic combinations in the context of a functional immune system. PMID:24295207

Cerebral Cortex Hyperthyroidism of Newborn Mct8-Deficient Mice Transiently Suppressed by Lat2 Inactivation

PubMed Central

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M.; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2 -/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3′-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3′-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development. PMID:24819605

Cerebral cortex hyperthyroidism of newborn mct8-deficient mice transiently suppressed by lat2 inactivation.

PubMed

Núñez, Bárbara; Martínez de Mena, Raquel; Obregon, Maria Jesus; Font-Llitjós, Mariona; Nunes, Virginia; Palacín, Manuel; Dumitrescu, Alexandra M; Morte, Beatriz; Bernal, Juan

2014-01-01

Thyroid hormone entry into cells is facilitated by transmembrane transporters. Mutations of the specific thyroid hormone transporter, MCT8 (Monocarboxylate Transporter 8, SLC16A2) cause an X-linked syndrome of profound neurological impairment and altered thyroid function known as the Allan-Herndon-Dudley syndrome. MCT8 deficiency presumably results in failure of thyroid hormone to reach the neural target cells in adequate amounts to sustain normal brain development. However during the perinatal period the absence of Mct8 in mice induces a state of cerebral cortex hyperthyroidism, indicating increased brain access and/or retention of thyroid hormone. The contribution of other transporters to thyroid hormone metabolism and action, especially in the context of MCT8 deficiency is not clear. We have analyzed the role of the heterodimeric aminoacid transporter Lat2 (Slc7a8), in the presence or absence of Mct8, on thyroid hormone concentrations and on expression of thyroid hormone-dependent cerebral cortex genes. To this end we generated Lat2-/-, and Mct8-/yLat2-/- mice, to compare with wild type and Mct8-/y mice during postnatal development. As described previously the single Mct8 KO neonates had a transient increase of 3,5,3'-triiodothyronine concentration and expression of thyroid hormone target genes in the cerebral cortex. Strikingly the absence of Lat2 in the double Mct8Lat2 KO prevented the effect of Mct8 inactivation in newborns. The Lat2 effect was not observed from postnatal day 5 onwards. On postnatal day 21 the Mct8 KO displayed the typical pattern of thyroid hormone concentrations in plasma, decreased cortex 3,5,3'-triiodothyronine concentration and Hr expression, and concomitant Lat2 inactivation produced little to no modifications. As Lat2 is expressed in neurons and in the choroid plexus, the results support a role for Lat2 in the supply of thyroid hormone to the cerebral cortex during early postnatal development.

Gestational hypothyroidism: development of mild hypothyroidism in early pregnancy in previously euthyroid women.

PubMed

Hammond, Karen R; Cataldo, Nicholas A; Hubbard, Janice A; Malizia, Beth A; Steinkampf, Michael P

2015-06-01

To determine the proportion of euthyroid women attending a fertility practice who develop hypothyroidism in very early pregnancy (gestational hypothyroidism [GHT]), and to examine the association of GHT with exogenous gonadotropin treatment. Retrospective cohort study. A private reproductive medicine practice. All healthy women (N = 94) with infertility or recurrent pregnancy loss, TSH level <2.5 mIU/L, negative thyroid peroxidase antibodies at initial evaluation, and not taking thyroid medication, who conceived during an 18-month period. Usual fertility care; 30 women who had received exogenous gonadotropins. Serum TSH level at the time of pregnancy detection. Gestational hypothyroidism (TSH ≥ 2.5 mIU/L) developed in 23 of 94 women (24%). The mean increase in serum TSH level from initial evaluation to early pregnancy was 0.45 ± 0.08 [SE] mIU/L. There was a trend toward the association of GHT with use of exogenous gonadotropins. Gestational hypothyroidism was positively associated with initial prepregnancy TSH level. Euthyroid women may develop mild hypothyroidism in early pregnancy, especially after exogenous gonadotropin treatment. Appropriate vigilance will allow for timely levothyroxine treatment. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Clinical Features of Early and Late Postoperative Hypothyroidism After Lobectomy.

PubMed

Park, Suyeon; Jeon, Min Ji; Song, Eyun; Oh, Hye-Seon; Kim, Mijin; Kwon, Hyemi; Kim, Tae Yong; Hong, Suck Joon; Shong, Young Kee; Kim, Won Bae; Sung, Tae-Yon; Kim, Won Gu

2017-04-01

Lobectomy is preferred in thyroid cancer to decrease surgical complications and avoid lifelong thyroid-hormone replacement. However, postoperative hypothyroidism, requiring thyroid-hormone replacement, may occur. We aimed to identify the incidence and risk factors of postoperative hypothyroidism to develop a surveillance strategy after lobectomy for papillary thyroid microcarcinoma (PTMC). This historical cohort study involved 335 patients with PTMC treated by lobectomy. Postoperative thyroid functions were measured regularly, and patients were prescribed levothyroxine according to specific criteria. Patients not satisfying hormone-replacement criteria were closely followed up. Postoperative hypothyroidism occurred in 215 patients (64.2%) including 5 (1.5%) with overt hypothyroidism and 210 (62.7%) with subclinical hypothyroidism. Forty patients (11.9%) were required thyroid hormone replacement. One hundred nineteen patients (33.5%) experienced temporary hypothyroidism and spontaneously recovered to euthyroid state. High preoperative thyroid-stimulating hormone (TSH) was the most important factor predicting postoperative hypothyroidism and failure of recover from hypothyroidism (odds ratio [OR], 2.82 and 1.77; 95% confidence interval [CI], 2.07 to 3.95 and 1.22 to 2.63; P < 0.001 and 0.002, respectively). Of the 215 patients eventually developing postoperative hypothyroidism, 70 (32.6%) developed hypothyroidism after the first postoperative year. Postoperative 1-year TSH levels were able to differentiate patients developing late hypothyroidism or euthyroidism (OR, 2.29; 95% CI, 1.68 to 3.26; P < 0.001). Preoperative and postoperative TSH levels might be predictive for patients who develop postlobectomy hypothyroidism and identify those requiring long-term surveillance for hypothyroidism. Additionally, mild postoperative hypothyroidism cases should be followed up without immediate levothyroxine replacement with the expectation of spontaneous recovery. Copyright © 2017 by the Endocrine Society

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.

Thyroid storm associated with Graves' disease covered by diabetic ketoacidosis: A case report

PubMed Central

2011-01-01

Background Thyroid storm is a condition in which multiple organ dysfunction results from failure of the compensatory mechanisms of the body owing to excessive thyroid hormone activity induced by some factors in patients with thyrotoxicosis. While diabetic ketoacidosis (DKA) is an important trigger for thyroid storm, simultaneous development of DKA and thyroid storm is rare. Case presentation A 59-year-old woman with no history of either diabetes mellitus or thyroid disease presented to our hospital because of developing nausea, vomiting and diarrhea for 2 days. Physical examination showed mild disturbance of consciousness, fever, and tachycardia. There were no other signs of thyrotoxicosis. Laboratory studies revealed elevation of random blood glucose and glycosylated hemoglobin, strongly positive of urine acetone, and metabolic acidosis. Since DKA was diagnosed, we initiated the patient on treatment with administration of insulin and adequate fluid replacement. Although the hyperglycemia and acidosis were immediately relieved, the disturbance of consciousness and tachycardia remained persistent. Levels of FT3 and FT4 were extremely high and TSH was below the detectable limit. TRAb was positive. The thyroid storm score of Burch & Wartofsky was 75/140, and the thyroid storm diagnostic criteria of the Japan Thyroid Association were satisfied. Oral administration of thiamazole, potassium iodide and propranolol resulted in immediate relief of the tachycardia. Discussion We encountered a case of thyroid storm associated with Graves' disease covered by DKA. Thyroid storm and DKA are both potentially fatal, and the prognosis varies depending on whether or not these conditions are detected and treated sufficiently early. The thyroid storm diagnostic criteria prepared in 2008 by the Japan Thyroid Association are very simple as compared to the Burch & Wartofsky scoring system for thyroid storm. The Japanese criteria may be useful in the diagnosis of this condition since they enable clinicians to identify a broad range of cases with thyroid storm. When dealing with cases of DKA or thyroid storm, it seems essential to bear in mind the possibility of the coexistence of these two diseases. PMID:21492449

Fetal and Neonatal Iron Deficiency Exacerbates Mild Thyroid Hormone Insufficiency Effects on Male Thyroid Hormone Levels and Brain Thyroid Hormone-Responsive Gene Expression

PubMed Central

Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.

2014-01-01

Fetal/neonatal iron (Fe) and iodine/TH deficiencies lead to similar brain developmental abnormalities and often coexist in developing countries. We recently demonstrated that fetal/neonatal Fe deficiency results in a mild neonatal thyroidal impairment, suggesting that TH insufficiency contributes to the neurodevelopmental abnormalities associated with Fe deficiency. We hypothesized that combining Fe deficiency with an additional mild thyroidal perturbation (6-propyl-2-thiouracil [PTU]) during development would more severely impair neonatal thyroidal status and brain TH-responsive gene expression than either deficiency alone. Early gestation pregnant rats were assigned to 7 different treatment groups: control, Fe deficient (FeD), mild TH deficient (1 ppm PTU), moderate TH deficient (3 ppm PTU), severe TH deficient (10 ppm PTU), FeD/1 ppm PTU, or FeD/3 ppm PTU. FeD or 1 ppm PTU treatment alone reduced postnatal day 15 serum total T4 concentrations by 64% and 74%, respectively, without significantly altering serum total T3 concentrations. Neither treatment alone significantly altered postnatal day 16 cortical or hippocampal T3 concentrations. FeD combined with 1 ppm PTU treatment produced a more severe effect, reducing serum total T4 by 95%, and lowering hippocampal and cortical T3 concentrations by 24% and 31%, respectively. Combined FeD/PTU had a more severe effect on brain TH-responsive gene expression than either treatment alone, significantly altering Pvalb, Dio2, Mbp, and Hairless hippocampal and/or cortical mRNA levels. FeD/PTU treatment more severely impacted cortical and hippocampal parvalbumin protein expression compared with either individual treatment. These data suggest that combining 2 mild thyroidal insults during development significantly disrupts thyroid function and impairs TH-regulated brain gene expression. PMID:24424046

Relationship between delayed embryonic development and metabolic factors and fat deposition in fruit bat Cynopterus sphinx.

PubMed

Banerjee, Arnab; Meenakumari, K J; Krishna, Amitabh

2007-01-01

The present study was undertaken in the fruit bat Cynopterus sphinx, which breeds twice in quick succession at Varanasi, India. Its gestation period varies significantly in the two successive pregnancies of the year owing to delayed embryonic development during the first (winter) pregnancy. The primary aim of the present study was to determine the role of metabolic factors in delayed embryonic development in the fruit bat C. sphinx. Variation in bodyweight, fat deposition, oxygen (O(2)) consumption rate, basal metabolic rate (BMR), body temperature (Tb) and hepatic succinate dehydrogenase (SDH) activity, along with circulating levels of thyroid hormones (tri-iodothyronine and thyroxine), were examined as metabolic factors during the two successive pregnancies in C. sphinx. The increase in bodyweight observed in November was due to accumulation of white adipose tissue in the posterior abdominal region. A significant decline in O(2) consumption rate, BMR, Tb and SDH activity was found in early winter in November-December, which coincides closely with the period of fat accumulation and with the period of delayed embryonic development in C. sphinx. A significantly higher O(2) consumption rate, BMR, Tb and SDH activity was noted during the second pregnancy in, when embryonic development was relatively faster. Thyroid hormone levels were high during the period of embryonic delay compared with levels during the remaining months. The results of the present study suggest that the delayed embryonic development in C. sphinx during early winter may be due to a low O(2) consumption rate, BMR, Tb and SDH activity in November-December. The energy saved by suppressing embryonic development in this species may be advantageous for fat accumulation. Increased thyroid hormone levels during the early winter period might facilitate fat accumulation in C. sphinx.

Health effects models for nuclear power plant accident consequence analysis: Low LET radiation

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

Evans, J.S.

1990-01-01

This report describes dose-response models intended to be used in estimating the radiological health effects of nuclear power plant accidents. Models of early and continuing effects, cancers and thyroid nodules, and genetic effects are provided. Weibull dose-response functions are recommended for evaluating the risks of early and continuing health effects. Three potentially lethal early effects -- the hematopoietic, pulmonary, and gastrointestinal syndromes -- are considered. In addition, models are included for assessing the risks of several nonlethal early and continuing effects -- including prodromal vomiting and diarrhea, hypothyroidism and radiation thyroiditis, skin burns, reproductive effects, and pregnancy losses. Linear andmore » linear-quadratic models are recommended for estimating cancer risks. Parameters are given for analyzing the risks of seven types of cancer in adults -- leukemia, bone, lung, breast, gastrointestinal, thyroid, and other.'' The category, other'' cancers, is intended to reflect the combined risks of multiple myeloma, lymphoma, and cancers of the bladder, kidney, brain, ovary, uterus and cervix. Models of childhood cancers due to in utero exposure are also developed. For most cancers, both incidence and mortality are addressed. The models of cancer risk are derived largely from information summarized in BEIR III -- with some adjustment to reflect more recent studies. 64 refs., 18 figs., 46 tabs.« less

Oncogenesis of Thyroid Cancer

PubMed Central

Younis, Enas

2017-01-01

Thyroid neoplasms encompass a variety of lesions that range from benign adenomas to malignancies. These latter can be well-differentiated, poorly differentiated or undifferentiated (anaplastic) carcinomas. More than 95% of thyroid cancers are derived from thyroid follicular cells, while 2-3% (medullary thyroid cancers, MTC) originate from calcitonin producing C-cells. Over the last decade, investigators have developed a clearer understanding of genetic alterations underlying thyroid carcinogenesis. A number of point mutations and translocations are involved, not only in its tumorigenesis, but also as have potential use as diagnostic and prognostic indicators and therapeutic targets. Many occur in genes for several important signaling pathways, in particular the mitogen-activated protein kinase (MAPK) pathway. Sporadic (isolated) lesions account for 75% of MTC cases, while inherited MTC, often in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, constitute the remainder. However, non-MEN familial MTC may also occur. Advances in genetic testing have revolutionized the management of MTC, with prospects of genetic screening, testing and early prophylactic thyroidectomy. Ethical concerns of these advances are addressed. PMID:28610401

Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development.

PubMed

Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa; Babu, Satish; Pal, Amit; Khare, Drirh; Godbole, Madan M

2010-07-02

Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1alpha, NRF-1alpha and Tfam. Also, we for the first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development. Copyright 2010 Elsevier Inc. All rights reserved.

Evidence of a bigenomic regulation of mitochondrial gene expression by thyroid hormone during rat brain development

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

Sinha, Rohit Anthony; Pathak, Amrita; Mohan, Vishwa

Hypothyroidism during early mammalian brain development is associated with decreased expression of various mitochondrial encoded genes along with evidence for mitochondrial dysfunction. However, in-spite of the similarities between neurological disorders caused by perinatal hypothyroidism and those caused by various genetic mitochondrial defects we still do not know as to how thyroid hormone (TH) regulates mitochondrial transcription during development and whether this regulation by TH is nuclear mediated or through mitochondrial TH receptors? We here in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1{alpha}, NRF-1{alpha} and Tfam. Also, we for themore » first time demonstrate a mitochondrial localization of thyroid hormone receptor (mTR) isoform in developing brain capable of binding a TH response element (DR2) present in D-loop region of mitochondrial DNA. These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.« less

Thyroid hormone deiodinase type 2 mRNA levels in sea lamprey (Petromyzon marinus) are regulated during metamorphosis and in response to a thyroid challenge.

PubMed

Stilborn, S Salina M; Manzon, Lori A; Schauenberg, Jennifer D; Manzon, Richard G

2013-03-01

Thyroid hormones (THs) are crucial for normal vertebrate development and are the one obligate morphogen that drives amphibian metamorphosis. However, contrary to other metamorphosing vertebrates, lampreys exhibit a sharp drop in serum TH early in metamorphosis, and anti-thyroid agents such as potassium perchlorate (KClO(4)) induce metamorphosis. The type 2 deiodinase (D2) enzyme is a key regulator of TH availability during amphibian metamorphosis. We set out to determine how D2 may be involved in the regulation of lamprey metamorphosis and thyroid homeostasis. We cloned a 1.8Kb Petromyzon marinus D2 cDNA that includes the entire protein coding region and a selenocysteine (Sec) codon. Northern blotting indicated that the lamprey D2 mRNA is the longest reported to date (>9Kb). Using real-time PCR, we showed that intestinal and hepatic D2 mRNA levels were elevated prior to and during the early stages of metamorphosis and then declined dramatically to low levels that were sustained for the remainder of metamorphosis. These data are consistent with previously reported changes in serum TH levels and deiodinase activity. Treatment of larvae with either TH or KClO(4) significantly affected D2 mRNA levels in the intestine and liver. These D2 mRNA levels during metamorphosis and in response to thyroid challenges suggest that D2 may function in the regulation of TH levels during lamprey metamorphosis and the maintenance of TH homeostasis. Copyright © 2013 Elsevier Inc. All rights reserved.

Notch3 as a novel therapeutic target in metastatic medullary thyroid cancer.

PubMed

Lou, Irene; Odorico, Scott; Yu, Xiao-Min; Harrison, April; Jaskula-Sztul, Renata; Chen, Herbert

2018-01-01

Medullary thyroid cancer portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in medullary thyroid cancer liver metastasis will decrease proliferation and growth of the tumor. TT cells were modified genetically to overexpress Notch3 in the presence of doxycycline, creating the TT-Notch3 cell line. Mice were injected intrasplenically with either TT-Notch3 or control vector TT-TRE cells. Each cell line had 3 treatment groups: control with 12 weeks of standard chow, early DOX with doxycycline chow at day 0 and for 70 days thereafter, and late DOX with doxycycline chow at 8 weeks. Each animal underwent micro-computed tomography to evaluate for tumor formation and tumor quantification was performed. Animals were killed at 12 weeks, and the harvested liver was stained with Ki-67, hematoxylin and eosin, and Notch3. Induction of Notch3 did not prevent formation of medullary thyroid cancer liver metastases as all mice in the early DOX group developed tumors. However, induction of Notch after medullary thyroid cancer liver tumor formation decreased tumor size, as seen on micro-computed tomography scans (late DOX group). This translated to a 37-fold decrease in tumor volume (P = .001). Notch3 overexpression also resulted in decreased Ki-67 index (P = .038). Moreover, Notch3 induction led to increased areas of neutrophil infiltration and necrosis on hematoxylin and eosin staining of the tumors CONCLUSION: Notch3 overexpression demonstrates an antiproliferative effect on established metastatic medullary thyroid cancer liver tumors and is a potential therapeutic target in treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Fallout sup 131 I in western Nevada cattle thyroid glands: 1962-early 1969

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

Blincoe, C.; Bohman, V.R.

1991-10-01

There has been continuing interest in historical fallout data. The authors have previously published data concerning the concentrations of fallout radioactive {sup 131}I in the thyroid glands of cattle from the Nevada Test Site and from commercial slaughter cattle. These data showed that bovine thyroid {sup 131}I was an effective monitor of both local and worldwide fresh nuclear fallout. This paper extends the data on commercial slaughter cattle from western Nevada through early 1969.

Hypothyroidism following treatment for head and neck cancer

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

Vrabec, D.P.; Heffron, T.J.

One hundred ninety-six head and neck patients were studied to determine the effects of radiation therapy and surgery on thyroid function. Serum thyroid-stimulating hormone (TSH) levels were obtained as a screening test for primary hypothyroidism. Elevated TSH levels were found in 57 of the 196 patients (29.1%). The highest incidence of abnormal TSH values (66%) occurred in the group treated with combination radiation therapy and surgery, including partial thyroidectomy. TSH levels rose early in the posttreatment period with 60% of the abnormal values occurring within the first three posttreatment years. Posttreatment thyroid dysfunction was twice as common in women (48.6%)more » as in men (25.4%). When serum thyroxine levels by radioimmunoassay (T4RIA) were correlated with the elevated serum TSH levels, a similar pattern was seen with 65% of the patients in Group 3 having a decreased T4RIA level indicating overt hypothyroidism. Pretreatment levels of thyroid function including thyroid antibody studies should be established for all patients. Serial TSH levels should be done every three months during the first three posttreatment years and semiannually thereafter as long as the patient will return for follow-up care. All patients treated with combination radiation therapy and surgery who develop elevated TSH levels should be treated with thyroid replacement therapy. Patients receiving radiation therapy alone should receive replacement thyroid therapy if they develop a depressed T4RIA value or a pattern of gradually increasing TSH levels.« less

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution.

PubMed

Guaraldi, F; La Selva, R; Samà, M T; D'Angelo, V; Gori, D; Fava, P; Fierro, M T; Savoia, P; Arvat, E

2018-05-01

Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors. 52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment. During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment. Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Hypothyroidism and wound healing: occurrence after head and neck radiation and surgery

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

Alexander, M.V.; Zajtchuk, J.T.; Henderson, R.L.

1982-05-01

A retrospective five-year review of patients treated for cancer of the larynx disclosed a high prevalence of hypothyroidism after combined therapy. A total of 29 patients were studied. Seven (24%) of the 29 patients had hypothyroidism develop in the posttreatment period (zero to two years). Two (22%) of the nine patients treated with a combination of surgery and radiation had hypothyroidism develop. An additional ten patients treated with radiation alone remained clinically euthyroid, and no thyroid function tests were performed. Of the five patients who became hypothyroid after treatment with a combination of surgery and radiation, two had fistulae developmore » that were resistant to intensive local care. They closed promptly after treatment of the hypothyroidism. Of the two patients who had hypothyroidism develop after surgery alone, one had fistulae develop that were resistant to local cae, but responsive to thyroid hormone. These patients should have thyroid function tests done in the early postoperative period, and those found to be hypothyroid should be treated promptly.« less

Changes in the role of the thyroid axis during metamorphosis of the Japanese eel, Anguilla japonica.

PubMed

Sudo, Ryusuke; Okamura, Akihiro; Kuroki, Mari; Tsukamoto, Katsumi

2014-08-01

To clarify the role of thyroid function during metamorphosis from leptocephalus to glass eel in the Japanese eel, we examined the histology of the thyroid gland and measured whole-body concentrations of thyroid hormones, thyroxine (T4) and triiodothyronine (T3), and thyroid stimulating hormone β-subunit TSH (TSHβ) mRNA expression levels in five stages of artificially hatched eels (leptocephalus, early-metamorphosis, late-metamorphosis, glass eel, and elver). During metamorphosis, the inner colloid of thyroid follicles showed positive immunoreactivity for T4, and both T4 and T3 levels were significantly increased, whereas a small peak of TSHβ mRNA level was observed at the early-metamorphosis stage. Similarly, TSHβ mRNA levels were highest in the glass eel stage, and then decreased markedly in the elver stage. In contrast to TSHβ mRNA expression, thyroid hormones (both T4 and T3) increased further from the glass eel to elver stages. These results indicated that thyroid function in the Japanese eel was active both during and after metamorphosis. Therefore, the thyrotropic axis may play important roles not only in metamorphosis but also in subsequent inshore or upstream migrations. © 2014 Wiley Periodicals, Inc.

Thromboembolic complications of thyroid storm.

PubMed

Min, T; Benjamin, S; Cozma, L

2014-01-01

Thyroid storm is a rare but potentially life-threatening complication of hyperthyroidism. Early recognition and prompt treatment are essential. Atrial fibrillation can occur in up to 40% of patients with thyroid storm. Studies have shown that hyperthyroidism increases the risk of thromboembolic events. There is no consensus with regard to the initiation of anticoagulation for atrial fibrillation in severe thyrotoxicosis. Anticoagulation is not routinely initiated if the risk is low on a CHADS2 score; however, this should be considered in patients with thyroid storm or severe thyrotoxicosis with impending storm irrespective of the CHADS2 risk, as it appears to increase the risk of thromboembolic episodes. Herein, we describe a case of thyroid storm complicated by massive pulmonary embolism. Diagnosis of thyroid storm is based on clinical findings. Early recognition and prompt treatment could lead to a favourable outcome.Hypercoagulable state is a recognised complication of thyrotoxicosis.Atrial fibrillation is strongly associated with hyperthyroidism and thyroid storm.Anticoagulation should be considered for patients with severe thyrotoxicosis and atrial fibrillation irrespective of the CHADS2 score.Patients with severe thyrotoxicosis and clinical evidence of thrombosis should be immediately anticoagulated until hyperthyroidism is under control.

2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition).

PubMed

Satoh, Tetsurou; Isozaki, Osamu; Suzuki, Atsushi; Wakino, Shu; Iburi, Tadao; Tsuboi, Kumiko; Kanamoto, Naotetsu; Otani, Hajime; Furukawa, Yasushi; Teramukai, Satoshi; Akamizu, Takashi

2016-12-30

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

What Conditions or Disorders are Commonly Associated with Down Syndrome?

MedlinePlus

... Society Hib Vaccine PKU and Newborn Screening Congenital Hypothyroidism Annual NICHD Research Advances Snapshot of Early Development ... do infants without Down syndrome, for example. 2 Hypothyroidism . The thyroid is a gland that makes hormones ...

Maternal hypothyroxinaemia in early pregnancy and problem behavior in 5-year-old offspring.

PubMed

Oostenbroek, Maurits H W; Kersten, Remco H J; Tros, Benjamin; Kunst, Anton E; Vrijkotte, Tanja G M; Finken, Martijn J J

2017-07-01

There is evidence, though not consistent, that offspring born to mothers with subtle decreases in thyroid function early in their pregnancies may be at risk of cognitive impairments and attention problems. However, other types of problem behavior have not been addressed thus far. We tested whether maternal thyroid function in early pregnancy is associated with several types of problem behavior in offspring at age 5-6 years. This was a longitudinal study that included the data of 2000 mother-child pairs from the Amsterdam Born Children and their Development study. At a median gestational age of 12.9 (interquartile range: 11.9-14.1) weeks, maternal blood was sampled for assessment of free T4 and TSH. Overall problem behavior, hyperactivity/inattention, conduct problems, emotional problems, peer relationship problems and prosocial behavior were measured at age 5-6 years using the Strengths and Difficulties Questionnaire, which was filled out by both parents and teachers. Maternal hypothyroxinaemia <5th percentile was associated with a 1.70 (95% confidence interval (CI): 1.01-2.86) increased odds of teacher-reported hyperactivity/inattention after adjustment for confounders. By increasing the cut-off level to <10th percentile, the odds ratio became 1.47 (95% CI: 0.99-2.20). There were no associations between maternal thyroid function parameters and hyperactivity/inattention as reported by parents, nor with teacher or parent reports of other types of problem behavior. Our results partially confirm previous observations, showing that early disruptions in the maternal thyroid hormone supply may be associated with ADHD symptoms in offspring. Our study adds that there is no evidence for an effect on other types of problem behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cutaneous consequences of accelerated thyroid function.

PubMed

Mullin, G E; Eastern, J S

1986-02-01

General and specific cutaneous findings associated with hyperthyroidism are reviewed. Familiarity with these findings may aid the practitioner in the early diagnosis of thyroid diseases. Several normally idiopathic cutaneous diseases can occasionally be controlled if underlying thyroid disease is considered as a cause, and appropriate testing performed.

Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study.

PubMed

Wesseloo, Richard; Kamperman, Astrid M; Bergink, Veerle; Pop, Victor J M

2018-01-01

During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression. Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13. The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3-11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group. Depression was defined with a self-rating questionnaire (EDS). Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Painless thyroiditis complicating with hypercalcemic encephalopathy.

PubMed

Thewjitcharoen, Yotsapon; Lumlertgul, Nuttha

2012-01-01

Severe hypercalcemia has rarely been reported in patients with hyperthyroidism. Although the pathogenesis is not clear; it is believed to be due to activation of osteoclasts resulting in excessive bone resorption. To recognize the unusual cause of hypercalcemia from painless thyroiditis, which could manifest with transient hyperthyroidism in the early stage. A 70-year-old woman presented with watery diarrhea, nausea and vomiting and significant weight loss for two months. Initially, she was misdiagnosed as having Graves'disease from her clinical presentation and thyroid function tests. Oral propylthiouracil was given to treat hyperthyroidism. However two weeks after discharge, she developed altered consciousness due to severe hypercalcemia. After combined treatment of hypercalcemia and severe hyperthyroidism, her symptoms resolved quickly. Later on, her thyroid function tests switched to subclinical hypothyroid at two months after initial presentation. No concurrent pathological conditions could be found to explain the other causes of hypercalcemia. Therefore, painless thyroiditis complicated with severe hypercalcemia was subsequently diagnosed based on her clinical course. Hypercalcemic encephalopathy is an uncommon manifestation of hyperthyroidism that should be kept in mind in patients who demonstrated clinical pictures of hyperthyroidism and alteration of consciousness. Moreover the present case emphasizes the consideration of painless thyroiditis as a differential diagnosis of hyperthyroidism because anti-thyroid medications were not indicated in this condition.

Thyroid function, Alzheimer's disease and postoperative cognitive dysfunction: a tale of dangerous liaisons?

PubMed

Mafrica, Federica; Fodale, Vincenzo

2008-05-01

Hypothyroidism and hyperthyroidism are commonly present conditions in adults, leading to neurological symptoms, affecting the central and peripheral nervous system, and to neurocognitive impairment. Several studies investigated a possible association between Alzheimer's disease (AD) and thyroid dysfunctions. Increasing evidence supports an extensive interrelationship between thyroid hormones and the cholinergic system, which is selectively and early affected in AD. Moreover, thyroid hormones negatively regulate expression of the amyloid-beta protein precursor (AbetaPP), which plays a key role in the development of AD. A condition, the so called euthyroid sick syndrome (ESS), characterized by reduced serum T_{3} and T_{4} concentrations without increased serum thyroid stimulation hormone secretion, occurs within hours after major surgery. After surgery, elderly patients often exhibit a transient, reversible state of cognitive alterations. Delirium occurs in 10-26% of general medical patients over 65, and it is associated with a significant increase in morbidity and mortality. Modifications in thyroid hormone functioning may take place as a consequence of psycho-physical stress caused by surgery, and probably as a consequence of reduced conversion of T4 into T3 by the liver engaged in metabolizing anesthetic drugs. Therefore, modifications of thyroid hormones post-surgery, might play a role in the pathogenesis of postoperative cognitive dysfunction.

Amphibian (Xenopus sp.) iodothyronine deiodinase ...

EPA Pesticide Factsheets

The U.S. EPA-MED amphibian thyroid group is currently screening chemicals for inhibition of human iodothyronine deiodinase activity as components of the thyroid system important in human development. Amphibians are a bellwether taxonomic group to gauge toxicity of chemicals in the environment. Amphibian thyroid function is not only important in development but also metamorphosis. Xenopus sp. have been used extensively as model organisms and are well characterized genetically. We propose to screen a list of chemicals (selected from the human DIO screening results) to test for inhibition of Xenopus deiodinases. Large quantities of the enzymes will be produced using an adenovirus system. Our preliminary results show that there may be catalytic differences between human and Xenopus deiodinases. The Twin Ports Early Career Scientists is a new group formed within the Duluth-Superior scientific community. This presentation will provide a basic introduction to my research and our mission at EPA, and help to establish networking and collaboration relationships across disciplines and institutions.

Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-Mercaptobenzothiazole Part I: Fathead minnow

EPA Science Inventory

Development of adverse outcome pathways linking specific chemical-induced pathway perturbations to adverse outcomes relevant to regulatory decision-making has potential to support the development of alternatives to traditional whole organism toxicity tests, such as the fish early...

Synaptogenesis in the rat cerebellum: effects of early hypo- and hyperthyroidism.

PubMed

Nicholson, J L; Altman, J

1972-05-05

The number of synapses in the molecular layer of the rat cerebellum is reduced by early hypo-and hyperthyroidism within 30 days. Hypothyroidism retards synaptogenesis after 10 days, while hyperthyroidism accelerates synaptogenesis initially, but by 21 days the number of synapses is reduced. The sensitivity of developing synapses to thyroid hormone may permit analysis of the events triggering synaptogenesis.

Analysis of iodine-131-induced early thyroid hormone variations in Graves' disease.

PubMed

Xu, Feng; Gu, Aichun; Pan, Yifan; Yang, Liwen; Ma, Yubo

2016-11-01

This prospective study aimed to assess iodine-131 (I)-induced early thyroid hormone variations in Graves' disease (GD) and determine the associated factors. One hundred and seventy-one GD patients treated with I were evaluated (47 men, 124 women). I was administered at 9.0±4.9 mCi on average. Serum free triiodothyronine and free thyroxin were measured within 24 h before treatment and 8 (3-14) days after treatment. Patients were divided into increase, no change, and decrease groups, respectively, on the basis of hormone variations after treatment. χ-Test, analysis of variance, and the Kruskal-Wallis test were used to compare groups in terms of sex, age, course of disease, thyroid stimulating hormone receptor antibodies, antithyroid drug (ATD) pretreatment time, time of ATD discontinuation before I treatment, 24 h thyroid I uptake, thyroid weight, I activity, and I activity/thyroid weight (μCi/g). The Spearman method was used for correlation analyses. Twenty-seven, 20, and 124 cases were assigned to increase, no change, and decrease groups, respectively. Significant differences were found among groups in the time of ATD discontinuation before I treatment [the median duration for methimazole was 11 (5-26), 16 (10-30), and 21 (1-30) days, P=0.000, the median duration for propylthiouracil was 12.5 (5-24), 22 (11-26), and 26 (21-30) days, P=0.000], thyroid weight (93.5±33.6, 90.3±48.8, and 74.1±26.0 g, P=0.003), and μCi/g (84.8±11.8, 100.4±24.9, and 121.1±44.0 μCi/g, P=0.000). Interestingly, μCi/g was negatively and positively correlated to the possibility of hormone increase and decrease, respectively. No significant differences were found in the other parameters assessed. At the early stage of I treatment for GD, few patients showed increased thyroid hormone levels. Key factors may include time of ATD discontinuation before I treatment and μCi/g. High μCi/g might decrease thyroid hormone levels in early treatment, making it safe.

Using whole mount in situ hybridization to examine thyroid hormone deiodinase expression in embryonic and larval zebrafish: a tool for examining OH-BDE toxicity to early life stages.

PubMed

Dong, Wu; Macaulay, Laura J; Kwok, Kevin W H; Hinton, David E; Stapleton, Heather M

2013-05-15

Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages. Copyright © 2013 Elsevier B.V. All rights reserved.

Using Whole mount In Situ Hybridization to Examine Thyroid Hormone Deiodinase Expression in Embryonic and Larval Zebrafish: a Tool for examining OH-BDE toxicity to early life stages

PubMed Central

Dong, Wu; Macaulay, Laura; Kwok, Kevin WH; Hinton, David E; Stapleton, Heather M.

2013-01-01

Polybrominated diphenyl ethers (PBDEs) and their oxidative metabolites (hydroxylated PBDEs; OH-BDEs) are known endocrine disrupting contaminants that have been shown to disrupt thyroid hormone regulation both in mammals and in fish. The purpose of this study was to determine the precise organ and tissue locations that express genes critical to thyroid hormone regulation in developing zebrafish (Danio rerio), and to determine the effects of an OH-BDE on their expression. While RT-PCR can provide quantitative data on gene expression, it lacks spatial sensitivity to examine localized gene expression; and, isolation of organs from zebrafish embryos is technically difficult, if not impossible. For this reason, the present study used whole mount in situ hybridization to simultaneously localize and quantify gene expression in vivo. While PBDEs and OH-BDEs have been shown to inhibit the activity and expression of deiodionases, a family of enzymes that regulate thyroid hormone concentrations intracellularly, it is unclear whether or not they can affect regional expression of the different isoforms during early development. In this study we investigated deiodinase 1 (Dio1), deiodinase 2 (Dio2), and deiodinase 3 (Dio3) mRNA expression at the following life stages (2, 8, and 1k-cells; 50%-epiboly, 6 and 18-somites, 22, 24, 48, 72 hpf and/or 10 dpf) in zebrafish and found life stage specific expression of these genes that were highly localized. To demonstrate the use of this technique for investigating potential endocrine disrupting effects, zebrafish embryos were exposed to 1, 10 and 100 nM 6-OH-BDE-47. Significant increases in mean intensity of Dio1 and Dio3 expression in the periventricular zone of brain and pronephric duct, respectively (quantified by measuring intensity of coloration using ImageJ analysis software) were observed, suggesting localized response at the HPT axis with the possibility of impacting neurodevelopment. Our results demonstrate effects of OH-BDEs on thyroid regulating gene expression and provide more insight into potential sites of injury during early life stages. PMID:23531416

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.

Maternal thyroid hormones are essential for neural development in zebrafish.

PubMed

Campinho, Marco A; Saraiva, João; Florindo, Claudia; Power, Deborah M

2014-07-01

Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition.

Maternal Thyroid Hormones Are Essential for Neural Development in Zebrafish

PubMed Central

Saraiva, João; Florindo, Claudia; Power, Deborah M.

2014-01-01

Teleost eggs contain an abundant store of maternal thyroid hormones (THs), and early in zebrafish embryonic development, all the genes necessary for TH signaling are expressed. Nonetheless the function of THs in embryonic development remains elusive. To test the hypothesis that THs are fundamental for zebrafish embryonic development, an monocarboxilic transporter 8 (Mct8) knockdown strategy was deployed to prevent maternal TH uptake. Absence of maternal THs did not affect early specification of the neural epithelia but profoundly modified later dorsal specification of the brain and spinal cord as well as specific neuron differentiation. Maternal THs acted upstream of pax2a, pax7, and pax8 genes but downstream of shha and fgf8a signaling. The lack of inhibitory spinal cord interneurons and increased motoneurons in the mct8 morphants is consistent with their stiff axial body and impaired mobility. The mct8 mutations are associated with X-linked mental retardation in humans, and the cellular and molecular consequences of MCT8 knockdown during embryonic development in zebrafish provides new insight into the potential role of THs in this condition. PMID:24877564

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

Preconception management of thyroid dysfunction.

PubMed

Okosieme, Onyebuchi E; Khan, Ishrat; Taylor, Peter N

2018-04-29

Uncorrected thyroid dysfunction in pregnancy has well-recognized deleterious effects on foetal and maternal health. The early gestation period is one of the critical foetal vulnerability during which maternal thyroid dysfunction may have lasting repercussions. Accordingly, a pragmatic preconception strategy is key for ensuring optimal thyroid disease outcomes in pregnancy. Preconception planning in women with hypothyroidism should pre-empt and mirror the adaptive changes in the thyroid gland by careful levothyroxine dose adjustments to ensure adequate foetal thyroid hormone delivery in pregnancy. In hyperthyroidism, the goal of preconception therapy is to control hyperthyroidism while curtailing the unwanted side effects of foetal and maternal exposure to antithyroid drugs. Thus, pregnancy should be deferred until a stable euthyroid state is achieved, and definitive therapy with radioiodine or surgery should be considered in women with Graves' disease planning future pregnancy. Women with active disease who are imminently trying to conceive should be switched to propylthiouracil either preconception or at conception in order to minimize the risk of birth defects from carbimazole or methimazole exposure. Optimal strategies for women with borderline states of thyroid dysfunction namely subclinical hypothyroidism, isolated hypothyroxinaemia and thyroid autoimmunity remain uncertain due to the dearth of controlled interventional trials. Future trial designs should aspire to recruit and initiate therapy before conception or as early as possible in pregnancy. © 2018 John Wiley & Sons Ltd.

Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis.

PubMed

Kim, Eun Seok; Yeo, Seung-Gu

2014-06-01

Previous studies on advanced radiotherapy (RT) techniques for early stage glottic cancer have focused on sparing the carotid artery. However, the aim of the present study was to evaluate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in terms of sparing the thyroid gland in early-stage glottic cancer patients. In total, 15 cT1N0M0 glottic cancer patients treated with definitive RT using VMAT were selected, and for dosimetric comparison, a conventional RT plan comprising opposed-lateral wedged fields was generated for each patient. The carotid artery, thyroid gland and spinal cord were considered organs at risk. The prescription dose was 63 Gy at 2.25 Gy per fraction. For the thyroid gland and carotid artery, all compared parameters were significantly lower with VMAT compared with conventional RT. For the thyroid gland, the median reduction rates of the mean dose (D mean ), the volume receiving ≥30% of the prescription dose (V 30 ) and the V 50 were 32.6, 40.9 and 46.0%, respectively. The D mean was 14.7±2.6 Gy when using VMAT compared with 22.2±3.9 Gy when using conventional RT. The differences between the techniques in terms of planning target volume coverage and dose homogeneity were not significant. When considering a recent normal tissue complication probability model, which indicated the mean thyroid gland dose as the most significant predictor of radiation-induced hypothyroidism, the dosimetric advantage shown in this study may be valuable in reducing hypothyroidism following RT for early stage glottic cancer patients.

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

PubMed

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

1999-01-15

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

Serum miRNAs as Biomarkers for the Diagnosis and Prognosis of Thyroid Cancer: A Comprehensive Review of the Literature.

PubMed

Mahmoudian-Sani, Mohammad-Reza; Mehri-Ghahfarrokhi, Ameneh; Asadi-Samani, Majid; Mobini, Gholam-Reza

2017-07-01

Thyroid cancer is the most common endocrine malignancy and accounts for 1% of cancers. In recent years, there has been much interest in the feasibility of using miRNAs or miRNA panels as biomarkers for the diagnosis of thyroid cancer. miRNAs are noncoding RNAs with 21-23 nucleotides that are highly conserved during evolution. They have been proposed as regulators of gene expression, apoptosis, cancer, and cell growth and differentiation. The Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO), and Web of Science were searched. The serum level of miRNAs (miRNA-375, 34a, 145b, 221, 222, 155, Let-7, 181b) can be used as molecular markers for the diagnosis and prognosis of thyroid cancer in the serum samples of patients with thyroid glands. Given that most common methods for the screening of thyroid cancer cannot detect the disease in its early stages, identifying miRNAs that are released in the bloodstream during the gradual progression of the disease is considered a key method in the early diagnosis of thyroid cancers.

Multifactorial determinants of cognition — Thyroid function is not the only one

PubMed Central

Moncayo, Roy; Ortner, Karina

2015-01-01

Background Since the 1960s hypothyroidism together with iodine deficiency have been considered to be a principal determinant of cognition development. Following iodine supplementation programs and improved treatment options for hypothyroidism this relation might not be valid in 2015. On the other hand neurosciences have added different inputs also related to cognition. Scope of review We will examine the characteristics of the original and current publications on thyroid function and cognition and also add some general determinants of intelligence and cognition. One central issue for us is the relation of stress to cognition knowing that both physical and psychological stress, are frequent elements in subjects with thyroid dysfunction. We have considered a special type of stress called pre-natal stress which can influence cognitive functions. Fear and anxiety can be intermingled requiring mechanisms of fear extinction. Major conclusions Recent studies have failed to show an influence of thyroid medication during pregnancy on intellectual development. Neuroscience offers a better explanation of cognition than hypothyroidism and iodine deficiency. Additional factors relevant to cognition are nutrition, infection, prenatal stress, and early life stress. In turn stress is related to low magnesium levels. Magnesium supplementation can correct both latent hypothyroidism and acquired mild cognitive deficits. General significance Cognition is a complex process that depends on many determinants and not only on thyroid function. Magnesium deficiency appears to be a basic mechanism for changes in thyroid function as well as of cognition. PMID:26672993

[Severe hyperlipidemia, secondary to hypothyroidism due to atrophic thyroiditis in a girl].

PubMed

Pacín, Mirta

2009-02-01

We present a 5 years 8 months old girl with severe hyperlipidemia (high total cholesterol, and low density lipoprotein values, and also, ectopic fat pericardial deposit). She was treated with diet and cholestyramine, without diagnosis of her disease etiology. Growth detention, weight loss, retarded bone age and clinical signs of hypometabolism were recorded. Thyroid profile confirms hypothyroidism diagnosis. Based on positive anti-thyroid antibodies and clearly reduced thyroid volume, a diagnosis of autoimmune atrophic thyroiditis was made, a very unusual pathology in early infancy. Linear growth was affected by late diagnosis.

[Thyroid hormones in the early postnatal development of the CNS: effect of hyperthyroidism on proliferative activity of white matter cells of rat cerebellum].

PubMed

Moskovkin, G N

1976-01-01

The effect of triiodothyronin on the proliferative activity of the white matter cells has been studied by means of radioautography in the cerebellum vermis and hemisphere of developing rats. The index of labelled nuclei and the mitotic index of the white matter glial elements in both the cerebellum regions of 7 and 10 days old hyperthyroid animals are markedly reduced. Besides, the general tendency was found towards the increase of the mitotic cycle duration in the white matter cells due to the lengthening of S and G2 + 1/2 M periods. The data obtained are discussed with respect to the importance of thyroid hormones for the CNS development.

Ventricular fibrillation associated with early repolarization in a patient with thyroid storm.

PubMed

Ueno, Akira; Yamamoto, Takeshi; Sato, Naoki; Tanaka, Keiji

2010-11-01

We present a case of a 69-year-old male who was hospitalized for the treatment of thyroid storm due to Grave's disease, who presented with unexpected ventricular fibrillation (VF). The possible etiology was early repolarization (ER), characterized by J-point elevation in inferior and posterolateral leads, unmasked by the attenuation of beta-adrenergic effect with normalization of thyroid hormones and following the administration of a beta-blocker. Our case focuses attention on the occurrence of VF in a patient with ER during the treatment of hyperthyroidism, which to our knowledge is the first such report.

Presentations and Outcome of Thyroiditis from a Tertiary Care Hospital of Karachi.

PubMed

Mahar, Saeed Ahmed; Shahid, Muhammad; Sarfaraz, Aqiba; Shaikh, Zuhaib-u-Ddin; Shaikh, Shiraz; Shahid, Nadia

2015-10-01

To assess the clinical presentations and short-term outcomes of patients with thyroiditis presenting to a tertiary care hospital in Karachi, Pakistan. Case series. Department of Endocrinology, Liaquat National Hospital, Karachi, from June 2014 to February 2015. Patients between 18 and 70 years of age with acute onset of thyroiditis confirmed on thyroid scan or clinical judgment presenting to the outpatient services were included in the study. Pregnant females, psychiatric patients and patients having other chronic illnesses were excluded from the study. A total of 26 patients with thyroiditis attended the endocrine clinic. Mean age of patients was 41.2 ± 11.12 years. There were 18 (69.2%) females. Clinical presentations were fever (65.4%), tender neck (23.1%), goiter (19.2%), localized tenderness in neck and palpable lymph nodes (26.9%). Major symptoms reported were: sore throat (69.2%), weight loss (38.5%), upper respiratory tract infection, thyroid pain, tremor, sweating and fever of unknown origin in 26.9% cases. All the patients had raised Erythrocyte Sedimentation Rate (ESR). Low Thyroid Stimulating Hormone (TSH) < 0.4 mlU/L was seen in 88.5% and 57.7% had raised Free T4 > 1.8 ng/dL. Complete recovery was seen in 88.5% patients while 11.5% had early hypothyroidism. Fever and sore throat were the main presenting features of thyroiditis patients. ESR was raised in all patients. A majority of patients had complete recovery with appropriate management; however, few cases developed hypothyroidism.

AmphiFoxE4, an amphioxus winged helix/forkhead gene encoding a protein closely related to vertebrate thyroid transcription factor-2: expression during pharyngeal development

NASA Technical Reports Server (NTRS)

Yu, Jr-Kai; Holland, Linda Z.; Jamrich, Milan; Blitz, Ira L.; Hollan, Nicholas D.

2002-01-01

The full-length sequence and developmental expression of amphioxus AmphiFoxE4 are described. Transcripts of the gene are first detected in the pharyngeal endoderm, where the club-shaped gland is forming and subsequently in the definitive gland itself. AmphiFoxE4 is closely related to vertebrate genes encoding the thyroid-specific transcription factor-2 (TTF2), which plays an early developmental role in the morphogenesis of the thyroid gland and a later role in hormone-mediated control of thyroid function. In amphioxus, AmphiFoxE4 expression is not thyroid specific because the club-shaped gland, the only structure expressing the gene, is not homologous to the vertebrate thyroid; instead, the thyroid homologue of amphioxus is a specialized region of the pharyngeal endoderm called the endostyle. We propose that (a) the pharynx of an amphioxus-like ancestor of the vertebrates included a club-shaped gland that expressed FoxE4 as well as an endostyle that did not, and (b) the club-shaped gland soon disappeared in the vertebrate line of descent but (c) not before there was a homeogenetic transfer of FoxE4 expression from the club-shaped gland to the nearby endostyle. Such a transfer could have provided part of the genetic program enabling the endostyle to separate from the pharyngeal endoderm and migrate away as the rudiment of the thyroid gland.

Characteristics of young adults of Belarus with post-Chernobyl papillary thyroid carcinoma: a long-term follow-up of patients with early exposure to radiation at the 30th anniversary of the accident.

PubMed

Fridman, Mikhail; Lam, Alfred King-Yin; Krasko, Olga

2016-12-01

Studies of thyroid cancer related to the Chernobyl accident have focused on children as they are the most vulnerable group with the highest risk of developing radiation-associated cancer. In contrast, our research aimed to look at the clinical and pathological features of patients with post-Chernobyl papillary thyroid carcinoma that were 2 years old or less at the time of the Chernobyl accident. The study subjects were patients (n = 359) aged 0 to 2 at the time of the Chernobyl accident and aged ≥19 years at presentation/surgery who were treated in Belarus for papillary thyroid carcinoma during the period 2003-2013. In conventional or oncocytic variant of papillary thyroid carcinoma, the prevalence of extra-thyroidal extension, nodal disease, infiltrative growth or lymphatic vessel invasion was above 50%. These features were less pronounced when compared to tall cell or diffuse sclerosing variants of papillary thyroid carcinoma. The highest frequency of central lymph node metastases was found in patients aged 1-2 years at exposure (P = 0·004). Subjects exposed in utero were characterized by absent/insignificant lymphocytic infiltration around the carcinoma (P = 0·025), predominance of conventional papillary architecture and an association with lymphocytic thyroiditis. A number of features were associated with this group of patients that were very young at the time of radiation exposure. In addition, the incidence and basic characteristics of adult papillary thyroid carcinoma varied depending on the types of exposure conditions. © 2016 John Wiley & Sons Ltd.

Developmental neurotoxicity of Propylthiouracil (PTU) in rats: Relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes

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

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation daymore » (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T{sub 4}) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T{sub 4} during development. This supports the hypothesis that decreased T{sub 4} may be a relevant predictor for long-lasting developmental neurotoxicity.« less

Developmental neurotoxicity of propylthiouracil (PTU) in rats: relationship between transient hypothyroxinemia during development and long-lasting behavioural and functional changes.

PubMed

Axelstad, Marta; Hansen, Pernille Reimar; Boberg, Julie; Bonnichsen, Mia; Nellemann, Christine; Lund, Søren Peter; Hougaard, Karin Sørig; Hass, Ulla

2008-10-01

Markedly lowered thyroid hormone levels during development may influence a child's behaviour, intellect, and auditory function. Recent studies, indicating that even small changes in the mother's thyroid hormone status early in pregnancy may cause adverse effects on her child, have lead to increased concern for thyroid hormone disrupting chemicals in the environment. The overall aim of the study was therefore to provide a detailed knowledge on the relationship between thyroid hormone levels during development and long-lasting effects on behaviour and hearing. Groups of 16-17 pregnant rats (HanTac:WH) were dosed with PTU (0, 0.8, 1.6 or 2.4 mg/kg/day) from gestation day (GD) 7 to postnatal day (PND) 17, and the physiological and behavioural development of rat offspring was assessed. Both dams and pups in the higher dose groups had markedly decreased thyroxine (T(4)) levels during the dosing period, and the weight and histology of the thyroid glands were severely affected. PTU exposure caused motor activity levels to decrease on PND 14, and to increase on PND 23 and in adulthood. In the adult offspring, learning and memory was impaired in the two highest dose groups when tested in the radial arm maze, and auditory function was impaired in the highest dose group. Generally, the results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development. This supports the hypothesis that decreased T(4) may be a relevant predictor for long-lasting developmental neurotoxicity.

Effects of the soya isoflavone genistein in early life stages of the Senegalese sole, Solea senegalensis: Thyroid, estrogenic and metabolic biomarkers.

PubMed

Sarasquete, Carmen; Úbeda-Manzanaro, Maria; Ortiz-Delgado, Juan Bosco

2017-09-01

This study examines the effects induced by environmentally relevant concentrations of the isoflavone genistein (3mg/L and 10mg/L) during early life stages of the Senegalese sole. Throughout the hypothalamus-pituitary-thyroid (HPT) axis, several neurohormonal regulatory thyroid signalling patterns (thyroglobulin/Tg, thyroid peroxidase/TPO, transthyretin/TTR, thyroid receptors/TRβ, and iodothrynonine deiodinases, Dio2 and Dio3) were analysed. Furthermore, the expression patterns of estrogen receptor ERβ and haemoprotein Cyp1a were also evaluated. In the control larvae, progressive increases of constitutive hormonal signalling pathways have been evidenced from the pre-metamorphosis phase onwards, reaching the highest expression basal levels at the metamorphosis (Tg, TPO, Dio2) and/or during post-metamorphosis (TTR, TRβ, ERβ). When the early larvae were exposed to both genistein concentrations (3mg/L and 10mg/L), a statistically significant down-regulation of TPO, TTR and Tg mRNA levels was clearly detected at the metamorphic stages. In addition, the Dio2 and Dio3 transcript expression levels were also down and up-regulated when exposed to both genistein concentrations. In the larvae exposed to genistein, no statistically significant responses were recorded for the TRβ expression patterns. Nevertheless, the ERβ and Cyp1a transcript levels were up-regulated at the middle metamorphic stage (S2, at 16 dph) in the larvae exposed to high genistein concentrations and, only the ERβ was down-regulated (S1, at 12dph) at the lower doses. Finally, all these pointed out imbalances were only temporarily disrupted by exposure to genistein, since most of the modulated transcriptional signals (i.e. up or down-regulation) were quickly restored to the baseline levels. Additionally, the control and genistein-exposed Senegalese sole specimens showed characteristic ontogenetic patterns and completely suitable for an optimal development, metamorphosis, and growth. Copyright © 2017. Published by Elsevier Inc.

Effects of perinatal hypo- and hyperthyroidism on the levels of nerve growth factor and its low-affinity receptor in cerebellum.

PubMed

Figueiredo, B C; Otten, U; Strauss, S; Volk, B; Maysinger, D

1993-04-16

Deficits or excesses of thyroid hormones during critical periods of mammalian cerebellar development can lead to profound biochemical and morphological abnormalities in this system. The goal of this study was to investigate the effects of perinatal hypo- and hyperthyroidism on the ontogeny of nerve growth factor (NGF) and its low-affinity receptor (p75NGFR) in the rat cerebellum. The concentration of NGF and of p75NGFR immunoreactivity (IR) were measured, several days after birth, in cerebella of rats which had received propylthiouracil (PTU) or thyroxine. NGF concentration was markedly enhanced only on postnatal day 2 (P2) in hyperthyroid rats, whereas in hypothyroid (PTU-treated) rats NGF values were similar to age-matched controls. These observations suggest that thyroid hormone affects NGF synthesis during early periods of cerebellar development. In Purkinje cells of control animals, p75NGFR IR peaked at P10. In hypothyroid rats, the expression of p75NGFR was retarded, peaking at P15, whereas in hyperthyroid rats it was advanced, peaking at P8. The increased p75NGFR IR found in Purkinje cell bodies and the delayed disappearance of p75NGFR IR from the external granular layer of hypothyroid rats suggest different roles for thyroid hormone in the developing cerebellum. We conclude that p75NGFR and NGF are independently regulated by thyroid hormone during critical periods of cerebellar development. The effect of thyroid hormone deficiency on p75NGFR content in Purkinje cells may involve complex mechanisms such as impaired efficiency of axonal transport.

Myxedema coma: a new look into an old crisis.

PubMed

Mathew, Vivek; Misgar, Raiz Ahmad; Ghosh, Sujoy; Mukhopadhyay, Pradip; Roychowdhury, Pradip; Pandit, Kaushik; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2011-01-01

Myxedema crisis is a severe life threatening form of decompensated hypothyroidism which is associated with a high mortality rate. Infections and discontinuation of thyroid supplements are the major precipitating factors while hypothermia may not play a major role in tropical countries. Low intracellular T3 leads to cardiogenic shock, respiratory depression, hypothermia and coma. Patients are identified on the basis of a low index of suspicion with a careful history and examination focused on features of hypothyroidism and precipitating factors. Arrythmias and coagulation disorders are increasingly being identified in myxedema crisis. Thyroid replacement should be initiated as early as possible with careful attention to hypotension, fluid replacement and steroid replacement in an intensive care facility. Studies have shown that replacement of thyroid hormone through ryles tube with a loading dose and maintenance therapy is as efficacious as intravenous therapy. In many countries T3 is not available and oral therapy with T4 can be used effectively without major significant difference in outcomes. Hypotension, bradycardia at presentation, need for mechanical ventilation, hypothermia unresponsive to treatment, sepsis, intake of sedative drugs, lower GCS and high APACHE II scores and Sequential Organ Failure Assessment (SOFA) scores more than 6 are significant predictors of mortality in myxedema crisis. Early intervention in hypothyroid patients developing sepsis and other precipitating factors and ensuring continued intake of thyroid supplements may prevent mortality and morbidity associated with myxedema crisis.

Myxedema Coma: A New Look into an Old Crisis

PubMed Central

Mathew, Vivek; Misgar, Raiz Ahmad; Ghosh, Sujoy; Mukhopadhyay, Pradip; Roychowdhury, Pradip; Pandit, Kaushik; Mukhopadhyay, Satinath; Chowdhury, Subhankar

2011-01-01

Myxedema crisis is a severe life threatening form of decompensated hypothyroidism which is associated with a high mortality rate. Infections and discontinuation of thyroid supplements are the major precipitating factors while hypothermia may not play a major role in tropical countries. Low intracellular T3 leads to cardiogenic shock, respiratory depression, hypothermia and coma. Patients are identified on the basis of a low index of suspicion with a careful history and examination focused on features of hypothyroidism and precipitating factors. Arrythmias and coagulation disorders are increasingly being identified in myxedema crisis. Thyroid replacement should be initiated as early as possible with careful attention to hypotension, fluid replacement and steroid replacement in an intensive care facility. Studies have shown that replacement of thyroid hormone through ryles tube with a loading dose and maintenance therapy is as efficacious as intravenous therapy. In many countries T3 is not available and oral therapy with T4 can be used effectively without major significant difference in outcomes. Hypotension, bradycardia at presentation, need for mechanical ventilation, hypothermia unresponsive to treatment, sepsis, intake of sedative drugs, lower GCS and high APACHE II scores and Sequential Organ Failure Assessment (SOFA) scores more than 6 are significant predictors of mortality in myxedema crisis. Early intervention in hypothyroid patients developing sepsis and other precipitating factors and ensuring continued intake of thyroid supplements may prevent mortality and morbidity associated with myxedema crisis. PMID:21941682

The Thyroid Status of Children and Adolescents in Fukushima Prefecture Examined during 20–30 Months after the Fukushima Nuclear Power Plant Disaster: A Cross-Sectional, Observational Study

PubMed Central

Watanobe, Hajime; Furutani, Tomoyuki; Nihei, Masahiko; Sakuma, Yu; Yanai, Rie; Takahashi, Miyuki; Sato, Hideo; Sagawa, Fumihiko

2014-01-01

Background A possible increase in thyroid cancer in the young represents the most critical health problem to be considered after the nuclear accident in Fukushima, Japan (March 2011), which is an important lesson from the Chernobyl disaster (April 1986). Although it was reported that childhood thyroid cancer had started to increase 3–5 yr after the Chernobyl accident, we speculate that the actual period of latency might have been shorter than reported, considering the delay in initiating thyroid surveillance in the then Soviet Union and also the lower quality of ultrasonographic testing in the 1980s. Our primary objectives in the present study were to identify any possible thyroid abnormality in young Fukushima citizens at a relatively early timepoint (20–30 months) after the accident, and also to strive to find a possible relationship among thyroid ultrasonographic findings, thyroid-relevant biochemical markers, and iodine-131 ground deposition in the locations of residence where they stayed during very early days after the accident. Methods and Findings This is a cross-sectional study. We targeted the Fukushima residents who were 18 yr old or younger (including fetuses) at the time of the accident. Our examinations comprised a questionnaire, thyroid ultrasonography, thyroid-related blood tests, and urinary iodine measurement. We analyzed a possible relationship among thyroid ultrasonographic findings (1,137 subjects), serum hormonal data (731 subjects), urinary iodine concentrations (770 subjects), and iodine-131 ground deposition (1,137 subjects). We did not find any significant relationship among these indicators, and no participant was diagnosed to contract thyroid cancer. Conclusions At the timepoint of 20–30 months after the accident, we did not confirm any discernible deleterious effects of the emitted radioactivity on the thyroid of young Fukushima residents. This is the first report in English detailing the thyroid status of young Fukushima residents after the nuclear disaster. PMID:25474311

Managing hyperthyroidism in pregnancy: current perspectives

PubMed Central

Andersen, Stine Linding; Laurberg, Peter

2016-01-01

Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves’ disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6–10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy. PMID:27698567

Managing hyperthyroidism in pregnancy: current perspectives.

PubMed

Andersen, Stine Linding; Laurberg, Peter

2016-01-01

Hyperthyroidism in women who are of childbearing age is predominantly of autoimmune origin and caused by Graves' disease. The physiological changes in the maternal immune system during a pregnancy may influence the development of this and other autoimmune diseases. Furthermore, pregnancy-associated physiological changes influence the synthesis and metabolism of thyroid hormones and challenge the interpretation of thyroid function tests in pregnancy. Thyroid hormones are crucial regulators of early development and play an important role in the maintenance of a normal pregnancy and in the development of the fetus, particularly the fetal brain. Untreated or inadequately treated hyperthyroidism is associated with pregnancy complications and may even program the fetus to long-term development of disease. Thus, hyperthyroidism in pregnant women should be carefully managed and controlled, and proper management involves different medical specialties. The treatment of choice in pregnancy is antithyroid drugs (ATDs). These drugs are effective in the control of maternal hyperthyroidism, but they all cross the placenta, and so need careful management and control during the second half of pregnancy considering the risk of fetal hyper- or hypothyroidism. An important aspect in the early pregnancy is that the predominant side effect to the use of ATDs in weeks 6-10 of pregnancy is birth defects that may develop after exposure to available types of ATDs and may be severe. This review focuses on four current perspectives in the management of overt hyperthyroidism in pregnancy, including the etiology and incidence of the disease, how the diagnosis is made, the consequences of untreated or inadequately treated disease, and finally how to treat overt hyperthyroidism in pregnancy.

Thyroid endocrine disruption and external body morphology of Zebrafish

USGS Publications Warehouse

Sharma, Prakash; Grabowski, Timothy B.; Patino, Reynaldo

2016-01-01

This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15 mM)], combination of MZ (0.15 mM) and thyroxine (T4, 2 nM), T4 (2 nM), or control (reconstituted water) treatments until 33 dpf and subsequently maintained in reconstituted water until 45 dpf. Samples were taken at 33 and 45 dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45 dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45 dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45 dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45 dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45 dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects.

Thyroid endocrine disruption and external body morphology of Zebrafish.

PubMed

Sharma, Prakash; Grabowski, Timothy B; Patiño, Reynaldo

2016-01-15

This study examined the effects thyroid-active compounds during early development on body morphology of Zebrafish (Danio rerio). Three-day postfertilization (dpf) larvae were exposed to goitrogen [methimazole (MZ, 0.15mM)], combination of MZ (0.15mM) and thyroxine (T4, 2nM), T4 (2nM), or control (reconstituted water) treatments until 33dpf and subsequently maintained in reconstituted water until 45dpf. Samples were taken at 33 and 45dpf for multivariate analysis of geometric distances between selected homologous landmarks placed on digital images of fish, and for histological assessment of thyrocytes. Body mass, standard length, and pectoral fin length were separately measured on remaining fish at 45dpf. Histological analysis confirmed the hypothyroid effect (increased thyrocyte height) of MZ and rescue effect of T4 co-administration. Geometric distance analysis showed that pectoral and pelvic fins shifted backward along the rostrocaudal axis under hypothyroid conditions at 45dpf and that T4 co-treatment prevented this shift. Pectoral fin length at 45dpf was reduced by exposure to MZ and rescued by co-administration of T4, but it was not associated with standard length. Methimazole caused a reduction in body mass and length at 45dpf that could not be rescued by T4 co-administration, and non-thyroidal effects of MZ on body shape were also recognized at 33 and 45dpf. Alterations in the length and position of paired fins caused by exposure to thyroid-disrupting chemicals during early development, as shown here for Zebrafish, could affect physical aspects of locomotion and consequently other important organismal functions such as foraging, predator avoidance, and ultimately survival and recruitment into the adult population. Results of this study also suggest the need to include rescue treatments in endocrine disruption studies that rely on goitrogens as reference for thyroid-mediated effects. Published by Elsevier Inc.

Hashimoto thyroiditis associated with ataxia telangiectasia.

PubMed

Patiroglu, Turkan; Gungor, Hatice Eke; Unal, Ekrem; Kurtoglu, Selim; Yikilmaz, Ali; Patiroglu, Tahir

2012-01-01

Ataxia telangiectasia is a rare genetic disease characterized by neurological manifestations, infections, and cancers. In addition to these cardinal features, different autoimmune diseases can be seen in patients with ataxia telangiectasia. Although there were reports of positive autoimmune thyroid antibodies associated with ataxia telangiectasia, to our knowledge, we report the first cases of nodular Hashimoto thyroiditis in two patients with ataxia telangiectasia in the English medical literature. These cases illustrate that despite the rarity of nodular Hashimoto thyroiditis associated with ataxia telangiectasia, physicians should be aware of this possibility. Furthermore, thyroid examination of patient with ataxia telangiectasia is recommended for early diagnosis.

Biochemical Testing in Thyroid Disorders.

PubMed

Esfandiari, Nazanene H; Papaleontiou, Maria

2017-09-01

This article summarizes the main principles for the appropriate use of laboratory testing in the diagnosis and management of thyroid disorders, as well as controversies that have arisen in association with some of these biochemical tests. To place a test in perspective, its sensitivity and accuracy should be taken into account. Ordering the correct laboratory tests facilitates the early diagnosis of a thyroid disorder and allows for timely and appropriate treatment. This article focuses on a comprehensive update regarding thyroid-stimulating hormone, thyroxine/triiodothyronine, thyroid autoantibodies, thyroglobulin, and calcitonin. Clinical uses of these biochemical tests are outlined. Copyright © 2017 Elsevier Inc. All rights reserved.

Light-Regulated Thyroid Hormone Signaling Is Required for Rod Photoreceptor Development in the Mouse Retina.

PubMed

Sawant, Onkar; Horton, Amanda M; Shukla, Meenal; Rayborn, Mary E; Peachey, Neal S; Hollyfield, Joe G; Rao, Sujata

2015-12-01

Ambient light is both a stimulus for visual function and a regulator of photoreceptor physiology. However, it is not known if light can regulate any aspect of photoreceptor development. The purpose of this study was to investigate whether ambient light is required for the development of mouse rod photoreceptors. Newborn mouse pups (C57BL/6) were reared in either cyclic light (LD) or constant dark (DD). Pups were collected at postnatal day (P)5, P10, P17, or P24. We performed retinal morphometric and cell death analysis at P5, P10, and P17. Rhodopsin expression was assessed using immunofluorescence, Western blot, and quantitative RT-PCR analysis. Electroretinograms were performed at P17 and P24. Radioimmunoassay and ELISA were used to follow changes in thyroid hormone levels in the serum and vitreous. In the DD pups, the outer nuclear layer was significantly thinner at P10 and there were higher numbers of apoptotic cells at P5 compared to the LD pups. Rhodopsin expression was lower at P10 and P17 in DD pups. Electroretinogram a-waves were reduced in amplitude at P17 in the DD pups. The DD animals had lower levels of circulating thyroid hormones at P10. Light-mediated changes in thyroid hormones occur as early as P5, as we detected lower levels of total triiodothyronine in the vitreous from the DD animals. Drug-induced developmental hypothyroidism resulted in lower rhodopsin expression at P10. Our data demonstrate that light exposure during postnatal development is required for rod photoreceptor development and that this effect could be mediated by thyroid hormone signaling.

The association of maternal thyroid function with placental hemodynamics.

PubMed

Barjaktarovic, M; Korevaar, T I M; Chaker, L; Jaddoe, V W V; de Rijke, Y B; Visser, T J; Steegers, E A P; Peeters, R P

2017-03-01

What is the clinical association of maternal thyroid function with placental hemodynamic function? A higher free thyroxine (FT4) concentration in early pregnancy is associated with higher placental vascular resistance. Suboptimal placental function is associated with preeclampsia (which, in turn, further deteriorates placental hemodynamics and impairs the fetal blood supply), fetal growth restriction and premature delivery. Studies have suggested that thyroid hormone (TH) has a role in placental development through effects on trophoblast proliferation and invasion. This study was embedded in The Generation R cohort, a population-based prospective study from early fetal life onwards in Rotterdam, the Netherlands. In total, 7069 mothers with expected delivery date between April 2002 and January 2006 were enrolled during early pregnancy. Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations were measured during early pregnancy (median 13.4 weeks, 95% range 9.7-17.6 weeks). Placental function was assessed by Doppler ultrasound via measurement of arterial vascular resistance, i.e. umbilical artery pulsatility index (PI) and uterine artery resistance index (RI) (both measured twice, between 18-25th and after 25th gestational weeks) and the presence of uterine artery notching (once after the 25th gestational week) in 5184 pregnant women. FT4 was positively linearly associated with umbilical artery PI in the second and third trimesters as well as with uterine artery RI in the second trimester and the risk of uterine artery notching in the third trimester (P < 0.05 for all). The association of thyroid function with preeclampsia and birth weight was partially mediated through changes in placental function, with the percentages of mediated effects being 10.4% and 12.5%, respectively. A potential limitation is the availability of only a single time point for TH measurements and different numbers of missing placental ultrasound measurements for the adverse outcomes. A higher FT4 concentration in early pregnancy is associated with higher vascular resistance in the second and third trimesters in both the maternal and fetal placental compartment. These effects on placental function might explain the association of FT4 with adverse pregnancy outcomes, including preeclampsia and fetal growth restriction. This work was supported by a fellowship from ERAWEB, a project funded by the European Commission (to M.B.) and by clinical fellowship from The Netherlands Organization for Health Research and Development (ZonMw), Project 90700412 (to R.P.P.). The authors have no conflict of interest. N/A. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Evaluation and Management of the Child with Hypothyroidism.

PubMed

Leung, Alexander K C; Leung, Alexander A C

2018-05-08

Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is therefore of utmost importance to optimize physical and neurodevelopmental outcomes. To review in depth the evaluation, diagnosis, and treatment of hypothyroidism in children. A PubMed search was completed in Clinical Queries using the key term "hypothyroidism". Patents were searched using the key term "hypothyroidism" from www.freepatentsonline.com. Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment. Recent patents related to the management of childhood hypothyroidism are discussed. To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first two weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH <5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.

PubMed

Desouza, Lynette A; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E; Kottmann, Andreas H; Tole, Shubha; Vaidya, Vidita A

2011-05-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T₃ administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh(+/LacZ) mice. Further, acute T₃ treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T₃ administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.

Thyroid gland development in Rachycentron canadum during early life stages.

PubMed

Otero, Adriana P S; Rodrigues, Ricardo V; Sampaio, Luís A; Romano, Luis A; Tesser, Marcelo B

2014-09-01

The aim of this study was to describe the ontogeny of thyroid follicles in cobia Rachycentron canadum. Larvae were sampled daily (n=15 - 20) from hatching until 15 dah (days after hatching). Following, larvae were sampled every two days by 28 dah; a new sample was taken at 53 dah. The samples were dehydrated, embedded in Paraplast, and sections of 3 µm were dewaxed, rehydrated and stained with HE and PAS. A single follicle was already present 1 dah and three follicles were found 8 dah. The number of follicles increased up to 19 on 53 dah. The diameter of follicles and follicular cell height were lower 1 dah (6.83 ± 1.00 and 4.6 ± 0.01 µm), but increased from 8 dah (24.03 ± 0.46 µm e 6.43 ± 0.46 µm). From 8 dah, the presence of reabsorption vesicles was observed in the colloid and from the 19 dah some follicles did not present colloid. The early thyroid follicle appearance in cobia larvae as well as the high quantity of follicles without colloid and/or with vesicles even after the metamorphosis, might be the explanation of the fast growth of the cobia.

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.

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.

Vascular smooth muscle cell apoptosis is an early trigger for hypothyroid atherosclerosis.

PubMed

Wang, Pei; Xu, Tian-Ying; Guan, Yun-Feng; Zhao, Yan; Li, Zhi-Yong; Lan, Xiao-Hong; Wang, Xia; Yang, Peng-Yuan; Kang, Zhi-Min; Vanhoutte, Paul M; Miao, Chao-Yu

2014-06-01

Endothelial dysfunction is an initial and vascular smooth muscle cell (VSMC) apoptosis, a later step of atherosclerosis. Hypothyroidism accelerates atherosclerosis. However, the early events responsible for this pro-atherosclerotic effect are unclear. Rats were resistant to induction of atherosclerosis by high cholesterol diet alone, but became susceptible in hypothyroid state achieved by administration of propylthiouracil (PTU) for 6 weeks. VSMC dysfunction and apoptosis were obvious within 1 week after PTU treatment, without signs of endothelial dysfunction. This early VSMC damage was caused by hypothyroidism but not the high cholesterol diet. In ApoE knockout mice, PTU-induced hypothyroidism triggered early VSMC apoptosis, increased oxidative stress, and accelerated atherosclerosis development. Thyroid hormone supplementation (T4, 10, or 50 μg/kg) prevented atherogenic phenotypes in hypothyroid rats and mice. In rats, thyroidectomy caused severe hypothyroidism 5 days after operation, which also led to rapid VSMC dysfunction and apoptosis. In vitro studies did not show a direct toxic effect of PTU on VSMCs. In contrast, thyroid hormone (T3, 0.75 μg/L plus T4, 50 nmol/L) exerted a direct protection against VSMC apoptosis, which was reduced by knockdown of TRα1, rather than TRβ1 and TRβ2 receptors. TRα1-mediated inhibition of apoptotic signalling of JNKs and caspase-3 contributed to the anti-apoptotic action of thyroid hormone. These findings provide an in vivo example for VSMC apoptosis as an early trigger of hypothyroidism-associated atherosclerosis, and reveal activation of TRα1 receptors to prevent VSMC apoptosis as a therapeutic strategy in this disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

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.

Excess Iodide Induces an Acute Inhibition of the Sodium/Iodide Symporter in Thyroid Male Rat Cells by Increasing Reactive Oxygen Species

PubMed Central

Arriagada, Alejandro A.; Albornoz, Eduardo; Opazo, Ma. Cecilia; Becerra, Alvaro; Vidal, Gonzalo; Fardella, Carlos; Michea, Luis; Carrasco, Nancy; Simon, Felipe; Elorza, Alvaro A.; Bueno, Susan M.; Kalergis, Alexis M.

2015-01-01

Na+/I− symporter (NIS) mediates iodide (I−) uptake in the thyroid gland, the first and rate-limiting step in the biosynthesis of the thyroid hormones. The expression and function of NIS in thyroid cells is mainly regulated by TSH and by the intracellular concentration of I−. High doses of I− for 1 or 2 days inhibit the synthesis of thyroid hormones, a process known as the Wolff-Chaikoff effect. The cellular mechanisms responsible for this physiological response are mediated in part by the inhibition of I− uptake through a reduction of NIS expression. Here we show that inhibition of I− uptake occurs as early as 2 hours or 5 hours after exposure to excess I− in FRTL-5 cells and the rat thyroid gland, respectively. Inhibition of I− uptake was not due to reduced NIS expression or altered localization in thyroid cells. We observed that incubation of FRTL-5 cells with excess I− for 2 hours increased H2O2 generation. Furthermore, the inhibitory effect of excess I− on NIS-mediated I− transport could be recapitulated by H2O2 and reverted by reactive derived oxygen species scavengers. The data shown here support the notion that excess I− inhibits NIS at the cell surface at early times by means of a posttranslational mechanism that involves reactive derived oxygen species. PMID:25594695

Progesterone and norgestrel alter transcriptional expression of genes along the hypothalamic-pituitary-thyroid axis in zebrafish embryos-larvae.

PubMed

Liang, Yan-Qiu; Huang, Guo-Yong; Ying, Guang-Guo; Liu, Shuang-Shuang; Jiang, Yu-Xia; Liu, Shan

2015-01-01

The aim of this study was to investigate the effects of progestins on the hypothalamic-pituitary-thyroid (HPT) axis in the early stage of zebrafish. Zebrafish embryos were exposed to progesterone (P4) or norgestrel (NGT) at 5, 50 and 100 ng L(-1) for 144 h post fertilization (hpf), and the transcriptional levels of target genes along the hypothalamic-pituitary-thyroid axis were determined daily. The results showed that P4 had only minor effects on the mRNA expression of thyroglobulin (Tg), iodothyronine deiodinase type Ι (Dio1) and thyroid hormone receptor β (Thrb) genes. Similarly, the effects of NGT on transcripts of thyrotropin-releasing hormone (Trh), Dio1, iodothyronine deiodinase type II (Dio2) and thyroid hormone receptor α (Thra) genes were generally low. In addition, NGT resulted in some alterations of Tg and Thrb transcripts at different time points. However, a strong induction of Nis mRNA by P4 and NGT was observed in zebrafish embryos-larvae. The overall results showed that besides Nis no effects on the hypothalamic-pituitary-thyroid (HPT) axis are observed following exposure to P4 and NGT, which imply that both P4 and NGT have potential effects on the thyroid endocrine system by inducing transcript of Nis gene during the early stage of zebrafish. Copyright © 2014 Elsevier Inc. All rights reserved.

Incidence of Subclinical Hypothyroidism and Hypothyroidism in Early Pregnancy.

PubMed

Akram, Frida Hosseini; Johansson, Bengt; Möllerström, Gunnar; Landgren, Britt-Marie; Stavreus-Evers, Anneli; Skjöldebrand-Sparre, Lottie

2017-11-01

Untreated and subclinical hypothyroidism (SCH) has been associated with adverse pregnancy complications such as increased risk of miscarriage, hypertension, preeclampsia, and preterm delivery. However, in Sweden, screening for thyroid dysfunction during pregnancy is only recommended for women with a high risk of thyroid disease. Therefore, the aim of this study was to determine the incidence of clinical and SCH in women in the first trimester of pregnancy. In this prospective study, 1298 pregnant women were divided into three groups: one unselected general screening group (n = 611), one low-risk group comprising women without risk factors for thyroid disorder (n = 511), and one high-risk group comprising women with an inheritance or suspicion of thyroid disease or undergoing treatment for thyroid disease (n = 88). Serum was obtained up to gestational week 13, and thyrotropin (TSH) was analyzed. The incidences of thyroid dysfunction in the three screening groups were 9.8% in the general screening group, 9.6% in the low-risk group, and 10.2%, p = 0.948, in the high-risk group. In the women with known hypothyroidism on levothyroxine treatment, 50.6% had serum TSH levels above 2.0 mIU/L. High-risk screening is not useful in predicting which women are at risk of thyroid disease in early pregnancy since ∼10% of women with SCH or hypothyroidism could not be diagnosed in this way.

Changes of thyroid hormone levels and related gene expression in zebrafish on early life stage exposure to triadimefon.

PubMed

Liu, Shaoying; Chang, Juhua; Zhao, Ying; Zhu, Guonian

2011-11-01

In this study, zebrafish was exposed to triadimefon. Thyroid hormones levels and the expression of related genes in the hypothalamic-pituitary-thyroid (HPT) axis, including thyroid-stimulating hormone (TSH-beta), deiodinases (dio1 and dio2) and the thyroid hormone receptor (thraa and thrb) were evaluated. After triadimefon exposure, increased T4 can be explained by increased thyroid-stimulating hormone (TSH-beta). The conversion of T4 to T3 (deiodinase type I-dio1) was decreased, which reduced the T3 level. Thyroid hormone receptor beta (thrb) mRNA levels were significantly down-regulated, possibly as a response to the decreased T3 levels. The overall results indicated that triadimefon exposure could alter gene expression in the HPT axis and that mechanisms of disruption of thyroid status by triadimefon could occur at several steps in the synthesis, regulation, and action of thyroid hormones. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

The role of magnesium and thyroid function in early pregnancy after in-vitro fertilization (IVF): New aspects in endocrine physiology.

PubMed

Stuefer, Sibilla; Moncayo, Helga; Moncayo, Roy

2015-06-01

The initiation of a pregnancy is a process that requires adequate energetic support. Recent observations at our Institution suggest a central role of magnesium in this situation. The aim of this study was to evaluate magnesium, zinc, selenium and thyroid function as well as anti-Müllerian hormone in early pregnancy following in-vitro fertilization as compared to spontaneous successful pregnancies. A successful outcome of pregnancy after IVF treatment was associated with 2 parameters: higher levels of anti-Müllerian hormone as well as higher levels of magnesium in the pre-stimulation blood sample. These two parameters, however, showed no correlation. Spontaneous pregnancies as well as pregnancies after IVF show a fall of magnesium levels at 2-3 weeks of gestation. This drop of magnesium concentration is larger following IVF as compared to spontaneous pregnancies. Parallel to these changes TSH levels showed an increase in early IVF-pregnancy. At this time point we also observed a positive correlation between fT4 and TSH. This was not observed in spontaneous pregnancies. Thyroid antibodies showed no correlation to outcomes. In connection with the initiation of pregnancy following ovarian stimulation dynamic changes of magnesium and TSH levels can be observed. A positive correlation was found between fT4 and TSH in IVF pregnancies. In spontaneous pregnancies smaller increases of TSH levels are related to higher magnesium levels. We propose that magnesium plays a role in early pregnancy as well as in pregnancy success independently from anti-Müllerian hormone. Neither thyroid hormones nor thyroid antibodies were related to outcome.

Thyrotropin receptor autoantibodies and early miscarriages in patients with Hashimoto thyroiditis: a case-control study.

PubMed

Toulis, Konstantinos A; Goulis, Dimitrios G; Tsolakidou, Konstantina; Hilidis, Ilias; Fragkos, Marios; Polyzos, Stergios A; Gerofotis, Antonios; Kita, Marina; Bili, Helen; Vavilis, Dimitrios; Daniilidis, Michail; Tarlatzis, Basil C; Papadimas, Ioannis

2013-08-01

We have previously hypothesized that early miscarriage in women with Hashimoto thyroiditis might be the result of a cross-reactivity process, in which blocking autoantibodies against thyrotropin receptor (TSHr-Ab) antagonize hCG action on its receptor on the corpus luteum. To test this hypothesis from the clinical perspective, we investigated the presence of TSHr-Ab in Hashimoto thyroiditis patients with apparently unexplained, first-trimester recurrent miscarriages compared to that in Hashimoto thyroiditis patients with documented normal fertility. A total of 86 subjects (43 cases and 43 age-matched controls) were finally included in a case-control study. No difference in the prevalence of TSHr-Ab positivity was detected between cases and controls (Fisher's exact test, p value = 1.00). In patients with recurrent miscarriages, TSHr-Ab concentrations did not predict the number of miscarriages (univariate linear regression, p value = 0.08). These results were robust in sensitivity analyses, including only cases with full investigation or those with three or more miscarriages. We conclude that no role could be advocated for TSHr-Ab in the aetiology of recurrent miscarriages in women with Hashimoto thyroiditis.

Association of transient hyperthyroidism and severity of hyperemesis gravidarum.

PubMed

Malek, Nor Zila Hassan; Kalok, Aida; Hanafiah, Zainal Abidin; Shah, Shamsul Azhar; Ismail, Nor Azlin Mohamed

2017-03-23

Background Transient non-immune hyperthyroidism in early pregnancy is hyperthyroidism diagnosed for the first time in early pregnancy, without evidence of thyroid autoimmunity or clinical findings of Grave's disease and resolved spontaneously as the pregnancy progressed. Hyperemesis gravidarum (HG) is the commonest cause with 66%-73% of women with severe HG were found to have elevated thyroid function. Materials and methods We conducted a cross sectional study to determine the prevalence of transient hyperthyroidism in patients with hyperemesis gravidarum and its relation to the severity of nausea and vomiting. Severity of nausea and vomiting in pregnancy was assessed using the modified pregnancy-unique quantification of emesis (PUQE) scoring system. Each patient had urine and blood investigations which also included a full blood count and thyroid and renal function tests. Patients with abnormal thyroid function were retested at 20 weeks of gestation. The patients' demographic data, electrolyte levels, thyroid function and their respective PUQE score were analyzed. Results The prevalence of transient hyperthyroidism in women with hyperemesis gravidarum was 4.8%. Although there was a significant association between the severity of the PUQE score and hypokalemia (p = 0.001), there was no significant association with transient hyperthyroidism in early pregnancy (p = 0.072). Free T4 and TSH values of all women with transient hyperthyroidism were normalized by 20 weeks of gestation. Conclusion Transient hyperthyroidism in pregnancy is not significantly associated with the severity of the PUQE score. Women with transient hyperthyroidism in pregnancy are normally clinically euthyroid, hence a routine thyroid function test is unnecessary unless they exhibit clinical signs or symptoms of hyperthyroidism.

Developmental exposure to methimazole increases anxiety behavior in zebrafish.

PubMed

Reider, Masha; Connaughton, Victoria P

2015-10-01

The role of thyroid hormones in vertebrate development has been well documented for several decades. As hypothyroidism during critical periods of development can cause defects to the development of every major organ system, including brain, eye, and general morphology, we hypothesized that hypothyroidism would affect specific behaviors. To assess this, we treated zebrafish with the hypothyroid drug methimazole (MMI) and examined changes in anxiety, shoaling, vision, and locomotion. Following low-dose MMI exposure for the first 10 days of life, a time of rapid and significant development, larvae were removed from treatment and allowed to develop until 1 month of age. Comparisons between treated and controls took place between 10 and 30 days postfertilization to examine times both during and after treatment. Using the novel tank and startle response tests, we found that anxiety behaviors are significantly increased following MMI treatment. These effects persisted for several days following removal from treatment and indicate a prolonged effect of early hypothyroidism. However, permanent MMI effects on anxiety were not observed, as anxiety behaviors of early treated zebrafish recovered to control levels following 10 days out of treatment. In contrast to the strong link between MMI treatment and anxiety, shoaling and visual behaviors were not significantly affected within our experimental parameters. This indicates that disruption of thyroid system functioning early in life can differentially affect behavior by specifically altering anxiety responses without producing indiscriminate changes to overall behavioral development. (c) 2015 APA, all rights reserved).

Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules

PubMed Central

Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

2017-01-01

[99mTc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained. PMID:29212258

Diagnostic accuracy of [99mTc]Tc-Sestamibi in the assessment of thyroid nodules.

PubMed

Yordanova, Anna; Mahjoob, Soha; Lingohr, Philipp; Kalff, Jörg; Türler, Andreas; Palmedo, Holger; Biersack, Hans-Jürgen; Kristiansen, Glen; Farahati, Jamshid; Essler, Markus; Ahmadzadehfar, Hojjat

2017-11-07

[ 99m Tc]Tc-Sestamibi (MIBI) is an increasingly used tool for evaluation of thyroid nodules. However, there is a lack of evidence about the accuracy of this method in the European population. The aim of this study was to assess the utility of MIBI for the differentiation of thyroid nodules in a large cohort. 161 patients underwent MIBI, followed by a thyroidectomy. We used a dual phase MIBI protocol. Interpretation of the images included a scoring system from 0 (absent) to 3 (increased); this was to provide a scale for the uptake of the thyroid nodule in comparison to the paranodular tissue. Additionally, we evaluated the tracer uptake trend in late images compared to early images. We used the final histopathology as the reference standard. Scores 0-1 in early images, scores 0-2 in late images, and an absence of increasing uptake in the thyroid nodule in late images, showed the best predictive values to exclude malignancy, respectively (negative predictive value (NPV) 89%). Highest sensitivity (91%) for malignant nodules was evident in early images with a score 1-3. Highest specificity (91%) was obtained when the negative was defined as an absence of uptake-increase, in the late images. This study confirms that the most valuable feature of MIBI is the high NPV. Thus, with the appropriate interpretation method, high sensitivity and specificity, and moderate PPV can be obtained.

A Case of a TSH-secreting Pituitary Adenoma Associated with Evans' Syndrome.

PubMed

Yasuda, Atsushi; Seki, Toshiro; Oki, Masayuki; Takagi, Atsushi; Inomoto, Chie; Nakamura, Naoya; Atsumi, Hideki; Baba, Tanefumi; Matsumae, Mitsunori; Sasaki, Noriko; Suzuki, Yasuo; Fukagawa, Masafumi

2015-06-20

We present a case of a TSH-secreting pituitary adenoma (TSHoma) associated with Evans' syndrome. A 30-year-old woman was referred to our hospital due to purpura and ecchymoses on her limb and body and epistaxis. Evans' syndrome was diagnosed based on idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia. She had a history of malocclusion and thyroid gland enlargement 4 years prior to admission. Endocrinological tests and magnetic resonance imaging also revealed that this patient had hyperthyroidism due to the TSHoma and that this adenoma concomitantly secreted GH. Recently, several cases of Evans' syndrome were associated with hyperthyroidism caused by autoimmune thyroid disease, such as Graves' disease, suggesting that these 2 conditions may have a common immunological basis. To the best of our knowledge, there is no case report of Evans' syndrome associated with hyperthyroidism due to TSHoma. Our report suggests that the excess of thyroid hormone itself promotes autoimmunity in Evans' syndrome. Thus, early treatment for hyperthyroidism is necessary in TSHomas because of the possibility that thyroid hormone normalization may prevent the development of Evans' syndrome.

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

The surgical management of benign and malignant thyroid neoplasms in Marshall Islanders exposed to hydrogen bomb fallout.

PubMed

Dobyns, B M; Hyrmer, B A

1992-01-01

On March 1, 1954, a serious fallout accident occurred during the United States atomic testing program at Bikini in the Trust Territory of the Pacific Islands. Following the detonation of a large thermonuclear device (known as Bravo) an unexpected shift in winds resulted in deposition of radioactive debris on several inhabited atolls in the Marshall Islands. During the early post-detonation period military, sea, and air surveys traced the hottest portion of the parabolic cloud as it drifted in an ever widening pattern of diminishing concentration eastward and southeast of Bikini. The center of the cloud passed North of the Rongelap Atoll, which was the nearest inhabited atoll. This report concerns the development of thyroid lesions, the special circumstances encountered during thyroid surgery, and the results of the surgical management of benign and malignant lesions that were subsequently encountered in this population.

[Surgical treatments in recurrent Graves' disease].

PubMed

Velikov, M; Mendizov, I; Dashev, G

1998-01-01

Seventy-six patients with clinical diagnosis Graves' disease, reoperated in the Clinic of Endocrine Surgery over the period 1985 through 1996, are analyzed. Distribution by gender and age: 3 men with mean age 55.33 y (range 49-60), and 73 women at mean age 39.67 years (range 19-69). The scope of secondary operation includes: thyroidectomy--3 cases, subtotal thyroid resection--55, lobectomy with contralateral subtotal resection--2, and unilateral predominantly subtotal resection--16 cases. It is the purpose of the study to assay the underlying causes of surgical relapse in Graves' disease, its relationship to the radicalism of the intervention, thyrostatic therapy duration, and early and late postoperative complications associated with its removal. In 16 cases (21.05%) secondary operative intervention is done against the background of enhanced production of thyroid hormones. A short 3 to 6-month thyrostatic course precedes the reoperation in eleven patients (14.47%). Unilateral thyroid resection is resorted to in 16 patients (21.05%). Postoperative hypothyroidism is observed in 6 cases (7.89%). A relapse of Graves' disease after reoperation is noted in 3 instances (3.94%). Six patients of the series reviewed (7.89%) develop postoperative hypoparathyroidism: transitory in four (5.26%) and permanent in two (2.63%). In the early postoperative period, paresis of n recurrents (n laryngeus inferior) develops in 2 patients (2.63%): left- and rightside, one each respectively. In terms of morphological patterns, the ensuing relapses after surgery in Graves' disease patients portray the initial pathological process: some cases show a tendency of nodular adenomatous hyperplasia development, sporadic cases form follicular adenomas, and in 14 cases (18.42%) lymphoid infiltrates predominate with a tendency to be converted into Hashimoto's thyroiditis. The presence of enhanced proliferative response induced by a variety of factors, therapeutic ones inclusive, is the basic morphological factor of the recurrent conditions described.

Longitudinal evaluation of thyroid autoimmunity and function in pregnant Korean women.

PubMed

Han, Seong-Min; Han, Jeong Hee; Park, Jina A; Quinn, Frank A; Park, Joonseok; Oh, Eunsuk

2013-12-01

Maternal thyroid dysfunction during pregnancy has been associated with adverse outcomes for both the mother and child. For this reason, it is important to understand thyroid status in pregnant women. However, there are relatively few published studies that examine thyroid function tests (TFT) and thyroid autoimmunity in non-Western pregnant women. Serum samples were longitudinally collected throughout pregnancy from 108 Korean women. TFT, thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) testing was performed. The impact of gestational age on TPO-Ab and Tg-Ab levels was evaluated and gestational age-specific reference intervals for TFT were established in antibody negative women. In the first trimester, TPO-Ab and Tg-Ab were positive in 13.9% and 16.7% of women, respectively. For antibody positive women, median autoantibody levels for TPO-Ab and Tg-Ab dropped from first trimester to near term (133.7-10.5 IU/mL, and 162.1-21.9 IU/mL, respectively). Antibody status influenced thyroid stimulating hormone (TSH) during the first trimester, and TSH, free T4 (FT4) and total T4 (TT4) in the early second trimester. Later in gestation, no significant differences in TFT were found based on antibody status. Gestational age-specific reference intervals for TFT were calculated in antibody negative women. Laboratory evidence of autoimmune thyroid disease (AITD) is common in this population of pregnant Korean women. Antibody status influences TFT values in the first and early second trimester. Thyroid autoantibody status and titer change in an individual-specific manner throughout pregnancy. Gestational age-specific reference intervals should be utilized for interpretation of TFT results in pregnant women.

Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

PubMed Central

Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha

2011-01-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T3 administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh+/LacZ mice. Further, acute T3 treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T3 administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone. PMID:21363934

[Treatment of difficult endocrine orbitopathy cases].

PubMed

Breuer, T; Ammann-Rauch, D; Tasman, A J

2007-05-01

There can be many differences between the clinical presentation and disease development of endocrine orbitopathy. Uncommon clinical expressions of the disease may lead to misinterpretations causing difficulties in treatment. Misdiagnosed forms of the disease can end with irreversible vision loss. A 79-year old female with severe bilateral thyroid eye disease, progressive almost blinding visual loss, with the absence of exophthalmos is described. Second, a 39 year old female with a unilateral thyroid eye disease and relapsing episodes of the disease is reported. Exophthalmos, as a symptom, occurs in about 60 % of the patients diagnosed with thyroid eye disease. The absence of exophthalmos may be due to a reduced volume (atrophy ) of retrobulbar fat tissue. Progressive visual loss can be related to direct compression of the optic nerve by thickened eye muscles in the orbital apex. Thyroid eye disease presents itself unilaterally in 5-11 % of all cases and involvement of the contra lateral orbit may occur years later. A relapse of the disease may be triggered by episodes of hypo- or hyperthyroidism. Smoking is a significant risk factor for orbitopathy relapse. Physicians treating thyroid eye disease should be aware of atypical clinical presentations in order for early satisfactory treatment. An interdisciplinary approach including ophthalmologists, endocrinologists and oto-rhino-laryngologists is necessary for optimal management.

Impaired swim bladder inflation in early-life stage fathead minnows exposed to a deiodinase inhibitor, iopanoic acid

EPA Science Inventory

The thyroid axis plays a critical role in teleost fish development. The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4), to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posteri...

IMPAIRMENT IN SHORT-TERM BUT ENHANCED LONG-TERM SYNAPTIC POTENTIATION AND ERK ACTIVATION IN ADULT HIPPOCAMPAL AREA CA1 FOLLOWING DEVELOPMENTAL HYPOTHYROIDISM.

EPA Science Inventory

The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt thyroid hormone homeostasis. The existing literature identifies morphological and neurochemical indices of severe neonatal hypothyroidism in the early postnatal period i...

Pharmacology of bovine and human thyrotropin: an historical perspective.

PubMed

Robbins, J

1999-05-01

Before the induction of a brief period of hypothyroidism became the standard method for inducing 131I uptake in thyroid cancer diagnosis and therapy, several other methods were explored and used. At the dawn of this new era of recombinant human thyrotropin (TSH) it is of interest to reflect briefly on some of this work. Partially purified bovine TSH (bTSH) was supplied for many years by the Armour Company as Thytropar for intramuscular injection and was first used in thyroid cancer 50 years ago at the Montefiore Hospital and at the Memorial Sloan Kettering Cancer Center in New York City. Most of the patients were already hypothyroid and bTSH induced further 131I uptake in only a few. Experience over the next 30 years revealed frequent allergic reactions, occasionally serious ones, and in 1961 it was shown that prolonged use could result in resistance to both bTSH and human TSH. bTSH was, therefore, reserved for thyroid cancer patients unable to increase endogenous TSH when hypothyroid. bTSH also was used widely as a test to distinguish between hypothyroidism caused by thyroid or pituitary failure until it was replaced by thyrotropin-releasing hormone (TRH). In a few studies, TRH was also tested as an adjuvant to increase endogenous TSH and thus help to stimulate function in thyroid cancer, but this attracted little interest. Prolonged hypothyroidism, enhanced by antithyroid drugs, was used early on, but this very effective stimulant of thyroid cancer function was, for multiple reasons, discarded. Beginning interest 15 to 25 years ago in obtaining TSH from human pituitary glands, a byproduct of growth hormone production, was interrupted when this product was found to risk development of Creutzfeld-Jakob disease. Recombinant human TSH, a safe and effective substitute, is now ready for widespread use and development in thyroid cancer management.

The implications of iodine and its supplementation during pregnancy in fetal brain development.

PubMed

Puig-Domingo, Manel; Vila, Lluis

2013-05-01

Iodine is an essential trace element for life. Its biological effects are a consequence of its incorporation to the thyroid hormones, which play a crucial role in fetal organogenesis, and in particular in brain development. This takes place during early gestation and involves delicate targeting throughout the central nervous system, including adequate neuronal growth, migration and myelinization at different sites, such as the cerebral cortex and neocortex, visual and auditory cortex, hippocampus and cerebellum. Pregnancy is characterized by an increased demand of thyroid hormones by the feto-placental unit in order to fulfill the necessary requirements of thyroid hormone action for normal fetal development. Up until week 20, the fetal thyroid is not fully active and therefore is completely dependent on the maternal thyroxine supply. Thus, the maternal thyroid has to adapt to this situation by producing about 1.5 fold more thyroxine. This requires that enzymatic gland machinery works normally as well as an adequate iodine intake, the principal substrate for thyroid hormone synthesis. Biological consequences of iodine related maternal hypothyroxinemia are currently very well known, by both experimental models and by clinical and epidemiological evidences. The associated disturbances parallel the degree of maternal thyroxine deficiency, ranging from increased neonatal morbi-mortality and severe mental dysfunction, to hyperactivity, attention disorders and a substantial decrease of IQ of an irreversible nature in the progeny of mothers suffering a deprivation of iodine during pregnancy. As a consequence, iodine deficiency is the leading preventable cause of mental impaired function in the world, affecting as many as 2 billion people (35.2% of the entire population). Prevention of fetal iodine deficiency - a problem of pandemic proportions- is feasible, provided that an iodine supply of 200-300 μg/day to the mother is ensured, before and throughout gestation as well as during the lactating period.

Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

PubMed Central

Molehin, Deborah

2016-01-01

Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

Identification of Hürthle cell tumor by single-injection, double-phase scintigraphy with technetium-99m-sestamibi.

PubMed

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

1995-05-01

Early and late (double-phase) scintigraphy with 99mTc-MIBI was used in a comparative study of the scintigraphic aspects of Hürthle cell tumors and other thyroid tumors. Single-injection, dual-phase (15-30 min and 3-4 hr) thyroid scintigraphy with 99mTc-sestamibi (MIBI) was performed on 41 patients who displayed a cold nodule on previous 99mTc scintigraphy. Visual scoring of nodular uptake was done to compare thyroidal and background tracer uptake. In addition, the nodular-to-thyroid (N/T) uptake ratio in the early and late images and the washout rate from the nodule (WON) and thyroidal tissue (WOT) were measured. Cytologic results were obtained for all patients; histopathologic results were obtained for the 20 patients who had surgery. In eight patients (Group A), the nodule displayed intense and persistent uptake of MIBI (N/T = 1.77 +/- 0.46 and 3.20 +/- 1.37; WON = 17.2% +/- 6.3%; WOT = 24.6% +/- 7.5%); histopathology revealed Hürthle cell tumors (two carcinomas and three adenomas) in five surgical patients. In 15 patients (Group B), the nodule displayed intense uptake in the early image with fading activity in the late image (N/T = 1.45 +/- 0.54 and 0.84 +/- 0.30; WON = 30.0% +/- 7.3%; WOT = 24.5% +/- 6.8%); histopathology revealed a colloid nodule (n = 1), papillary carcinoma (n = 4) and follicular carcinoma (n = 5) in 10 surgical patients. In the remaining 18 patients (Group C), the nodule was cold and late images were not acquired. Histopathology revealed colloid nodules (n = 2) and follicular adenoma (n = 3) in five surgical patients. Single-injection, dual-phase MIBI scintigraphy of the thyroid can identify Hürthle cell tumors because these tumors have intense, persistent tracer uptake in contrast to other thyroid tumors.

The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery.

PubMed

Eid, Issam; Miller, Frank R; Rowan, Stephanie; Otto, Randal A

2013-10-01

To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. 2b. Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

[Reference interval in preliminary investigation of maternal thyroid function during pregnancy in Shenzhen China].

PubMed

Yu, Lian; Yue, Huakui; Lin, Haoyun; Wu, Wenyuan

2014-11-04

To explore the thyroid function distribution of different trimesters among normal pregnant women and establish the reference interval for maternal thyroid function during pregnancy in Shenzhen, China. A prospective study was conducted for healthy pregnant women in first trimester (n = 334), second trimester (n = 272), third trimester (n = 271) and non-pregnant controls (n = 77) from December 2012 to June 2013 at our hospital. Free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), triiodothyronine (TT3) and thyroxine (T4) of four groups were measured and analyzed. And the reference intervals for different trimesters were established. TSH declined in the first trimester and then rose in the second trimester. The reference ranges of TSH for early, middle and late pregnancy were 0.08-4.39, 0.41-4.16 and 0.30-5.46 mIU/L respectively. FT4 and healthy control groups showed no significant difference in the first trimester. But it declined in the second trimester. The reference ranges of FT4 for early, middle and late pregnancy were 7.74-14.58, 6.81-12.00 and 6.36-10.99 pmol/L respectively. FT3 rose slightly in the first trimester and then gradually decreased. The reference ranges of FT3 for early, middle and late pregnancy were 3.59-5.59, 3.34-4.91 and 3.09-4.58 pmol/L respectively. As compared with healthy control women in Shenzhen, thyroid function indicators of pregnant women show statistically significant differences. And the establishment of indicators of women's thyroid function reference intervals for different trimesters has important clinical significance in Shenzhen.

PROPOSED DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

EPA Science Inventory

Distinguishing hyperplastic lesions from neoplasia in the thyroid of bony fishes has been debated by scientists for about one hundred years. As early as the first decade of the last century, the histological interpretation of some of the striking proliferative lesions observed in...

Amiodarone induced myxedema coma: Two case reports and literature review.

PubMed

Hawatmeh, Amer; Thawabi, Mohammad; Abuarqoub, Ahmad; Shamoon, Fayez

2018-05-21

Amiodarone is a benzofuran derivative that contains 37% iodine by weight and is structurally similar to the thyroid hormones. Amiodarone has a complex effect on the thyroid gland, ranging from abnormalities of thyroid function tests to overt thyroid dysfunction, with either thyrotoxicosis or hypothyroidism. Myxedema coma secondary to amiodarone use has been rarely reported in the literature. Our two case reports are an add on to the literature, and illustrate that amiodarone is an important cause of thyroid dysfunction including hypothyroidism and myxedema coma. Hence, healthcare providers should have a high index of suspicion for these conditions while treating patients who are taking amiodarone therapy as early recognition and management are essential to optimize outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of Ammonium Perchlorate on Thyroid Function in Developing Fathead Minnows, Pimephales promelas

PubMed Central

Crane, Helen M.; Pickford, Daniel B.; Hutchinson, Thomas H.; Brown, J. Anne

2005-01-01

Perchlorate is a known environmental contaminant, largely due to widespread military use as a propellant. Perchlorate acts pharmacologically as a competitive inhibitor of thyroidal iodide uptake in mammals, but the impacts of perchlorate contamination in aquatic ecosystems and, in particular, the effects on fish are unclear. Our studies aimed to investigate the effects of concentrations of ammonium perchlorate that can occur in the environment (1, 10, and 100 mg/L) on the development of fathead minnows, Pimephales promelas. For these studies, exposures started with embryos of < 24-hr postfertilization and were terminated after 28 days. Serial sectioning of thyroid follicles showed thyroid hyperplasia with increased follicular epithelial cell height and reduced colloid in all groups of fish that had been exposed to perchlorate for 28 days, compared with control fish. Whole-body thyroxine (T4) content (a measure of total circulating T4) in fish exposed to 100 mg/L perchlorate was elevated compared with the T4 content of control fish, but 3,5,3′-triiodothyronine (T3) content was not significantly affected in any exposure group. Despite the apparent regulation of T3, after 28 days of exposure to ammonium perchlorate, fish exposed to the two higher levels (10 and 100 mg/L) were developmentally retarded, with a lack of scales and poor pigmentation, and significantly lower wet weight and standard length than were control fish. Our study indicates that environmental levels of ammonium perchlorate affect thyroid function in fish and that in the early life stages these effects may be associated with developmental retardation. PMID:15811828

Thyroid hormone regulates vitellogenin by inducing estrogen receptor alpha in the goldfish liver.

PubMed

Nelson, Erik R; Habibi, Hamid R

2016-11-15

Vitellogenin (Vtg) is an egg-yolk precursor protein that is synthesized in the liver of oviparous species and taken up from the circulation by the ovary. It is well known that Vtg is induced by circulating estrogens. However, other endocrine factors that regulate the expression of Vtg are less well characterized; factors that might play significant roles, especially in seasonal spawners such as the goldfish which require increased quantities of Vtg for the development of hundreds of follicles. In this regard, thyroid hormones have been shown to cycle with the reproductive season. Therefore, we hypothesized that the thyroid hormones might influence the synthesis of Vtg. Treatment of female goldfish with triiodothyronine (T3) resulted in increased Vtg, an observation that was absent in males. Furthermore, T3 failed to induce Vtg in cultured hepatocytes of either sex. Interestingly however, T3 consistently up-regulated the expression of the estrogen receptor alpha (ERα). The T3 mediated upregulation of ERα requires the presence of both thyroid receptor (TR) α-1 and TRβ. When goldfish or cultured hepatocytes were treated with T3 followed by estradiol, there was a synergistic increase in Vtg, a response which is dependent on the presence of ERα. Therefore, by upregulating ERα, T3 serves to prime the liver to subsequent stimuli from estradiol. This cross-talk likely reveals an important physiologic mechanism by which thyroid hormones, whose circulating levels are high during early gonadal recrudescence, facilitate the production of large amounts of Vtg required for egg development. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Urinary iodine in early pregnancy is associated with subclinical hypothyroidism in Tianjin, China: an observational study.

PubMed

Wang, Kunling; Zhang, Jie; Li, Fengao; Zhang, Wanqi; Wang, Hao; Ding, Li; Liu, Yaxin; Lin, Laixiang; Zhang, Shuang; Zhu, Mei

2017-02-17

Subclinical hypothyroidism (SH) is associated with adverse obstetric outcomes and neurodevelopment disorders. Both iodine deficiency and excess are associated with SH; however, few data regarding iodine nutrition status of pregnant women with SH are available. This study aimed to clarify whether iodine deficiency or excess is associated with SH, especially, when test results for anti-thyroid autoantibodies are negative. A total of 115 women with SH and 104 women with euthyroidism (EH) in early pregnancy in Tianjin, China were investigated, and their serum thyroid-stimulating hormone, free thyroxine, free triiodothyronine, anti-thyroid peroxidase antibody (TPOAb), anti-thyroid globulin antibody (TGAb), urinary iodine (UIC), and urinary creatinine (UCr) concentrations were measured. Thyroid ultrasonography was performed to determine thyroid echogenicity and volume. The UIC, UIC/UCr ratio, prevalence of TPOAb and TGAb positivity, and thyroid gland volume were compared between the EH and SH groups. UIC and ultrasonographic features were analysed in subjects in the SH group who were negative for TPOAb and TGAb. Median UIC of SH (154.0 μg/L) and EH (150.1 μg/L) met the World Health Organization criterion for iodine sufficiency in pregnant women. Neither UIC nor the UIC/UCr ratio differed significantly between groups. The prevalence of TPOAb and TGAb positivity in the SH group was significantly higher than that in the EH group (P < 0.01). The percentage of subjects with UIC ≥ 250 μg/L in the SH group was significantly higher than that in the EH group (p = 0.004). The percentage of subjects negative for autoantibodies and UIC ≥ 250 μg/L in the SH group tended to be higher than that in subjects in the EH group negative for autoantibodies, but the difference was not statistically significant (p = 0.025, adjusted test level α = 0.0167). Eight of 18 subjects in the SH group with negative results for TPOAb and TGAb were diagnosed with Hashimoto thyroiditis by means of thyroid ultrasonography. Women in early pregnancy with SH in Tianjin were iodine sufficient, but still at risk of iodine deficiency as pregnancy progressed. UIC ≥ 250 μg/L was associated with increased risk of SH. Serological negative autoimmune thyroiditis and UIC ≥ 250 μg/L may play a role in pathogenesis of SH cases with negative results for autoantibodies.

Smoking and Early Pregnancy Thyroid Hormone and Anti-Thyroid Antibody Levels in Euthyroid Mothers of the Northern Finland Birth Cohort 1986

PubMed Central

Männistö, Tuija; Hartikainen, Anna-Liisa; Vääräsmäki, Marja; Bloigu, Aini; Surcel, Heljä-Marja; Pouta, Anneli; Järvelin, Marjo-Riitta; Ruokonen, Aimo

2012-01-01

Background Smokers in the general population have lower thyrotropin (TSH) and higher free triiodothyronine (fT3) and free thyroxine (fT4) concentrations, but the results in pregnant population vary from no effect to a decrease in TSH and fT4 concentrations and an increase in fT3 levels. Our objective was to further evaluate the question of whether there is an association between smoking, before and during pregnancy, with maternal thyroid function during pregnancy and with the risk for subsequent hypothyroidism. Methods Our study population was a prospective population-based cohort (N=9362), the Northern Finland Birth Cohort 1986, with extensive data throughout gestation. The mothers underwent serum sampling in early pregnancy. The samples were assayed for TSH, fT3, fT4, thyroid-peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Abs) (n=5805). Mothers with thyroid dysfunction diagnosed before or during pregnancy were excluded, leaving 4837 euthyroid mothers. The smoking status of mothers and fathers were requested by questionnaires during pregnancy. Subsequent maternal morbidity relating to hypothyroidism 20 years after the index pregnancy was evaluated using national registers. Results Euthyroid mothers who smoked before, or continued smoking during first trimester of pregnancy, had higher serum fT3 (p<0.001) and lower fT4 (p=0.023) concentrations than nonsmokers. Smoking in the second trimester was associated with higher fT3 (p<0.001) concentrations, but no difference in fT4 concentrations compared with nonsmokers. TG-Abs were less common among smoking than nonsmoking mothers (2.5% vs. 4.7%, p<0.001), but the prevalence of TPO-Ab was similar. Paternal smoking had no independent effect on maternal early pregnancy thyroid hormone or antibody concentrations. The risk of subsequent maternal hypothyroidism after follow-up of 20 years was similar among prepregnancy smokers and nonsmokers. Conclusions In euthyroid women, smoking during pregnancy was associated with higher fT3 levels and lower fT4 levels; possibly reflecting smoking-induced changes in peripheral metabolism of thyroid hormones. No differences were found in TSH concentrations between smokers and nonsmokers. Our results differ from those of the general population, which usually have shown smoking-induced thyroidal stimulation. This is possibly due to pregnancy-induced changes in thyroid function. Decreases in fT4 levels among smokers might predispose to hypothyroidism or hypothyroxinemia during pregnancy. Despite these changes in thyroid function, smoking did not increase the woman's risk of subsequent hypothyroidism. PMID:22873201

[Screening of benign and malignant thyroid nodules in 5 196 physical examination population].

PubMed

Li, M H; Liu, J T

2018-02-23

Objective: To investigate the distribution characteristics of thyroid nodules and thyroid cancer in physical examination population in Tianjin, and report the outcome of ultrasonography in detection of thyroid nodules. Methods: Enrolled all of physical examination population in our hospital from Jan 1, 2014 to Dec 31, 2014 as our study subjects then the thyroid gland lesions were screened by ultrasound diagnostic technique. The risk assessment of benign and malignant thyroid nodules was assessed by ultrasonography and thyroid imaging reporting and data system (TI-RADS), and the individuals were followed up for 1 year. Results: Among the 5 196 cases, the patients with thyroid nodules was 2 068 cases (39.80%). The thyroid nodules was 35.04% in male and 44.78% in female subjects, lower in females than in male cases ( P <0.001). 18 cases of thyroid cancer patients were detected (0.35%). The thyroid cancer rate were 0.34% and 0.36% in male and female respectively ( P >0.05). Thyroid nodules increased with age, but the thyroid cancer patients were mainly concentrated in the 30 to 39 years old group and 50 to 59 years old group. All of the thyroid cancer patients underwent surgical treatment, better differentiation thyroid papillary carcinoma (17 cases) in major, most were early stage cancer and micro-cancer, possessing relatively low risk of recurrence. The sensitivity, specificity and accuracy of ultrasonography and TI-RADS diagnosis of thyroid cancer was 72.22%, 98.94% and 98.85%. Conclusions: The detection rate of thyroid nodules in our population is close to 40%, and there are differences between sexes and ages. Ultrasonography and TI-RADS association is an efficient method to detect the nodules in thyroid.

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

PubMed

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

2014-07-01

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

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

Development of the thyroid gland.

PubMed

Nilsson, Mikael; Fagman, Henrik

2017-06-15

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

Alpha-Hydroxylation of lignoceric and nervonic acids in the brain. Effects of altered thyroid function on postnatal development of the hydroxylase activity.

PubMed

Murad, S; Strycharz, G D; Kishimoto, Y

1976-09-10

Rat brain postnuclear preparations catalyzed the alpha-hydroxylation of nervonic acid with an apparent Km of 3 muM. Evidence has been presented which suggests that nervonic acid in the brain is hydroxylated by the same enzyme system which hydroxylates lignoceric acid. The hydroxylase activity in brains of normal (euthyroid) rats increased rapidly from a low in the period immediately following birth to a maximum at the 23rd day and then declined to a low level characteristic of the mature brain. Neonatal hypothyroidism retarded the development of the activity and shifted its peak to the 39th day after birth. Conversely, neonatal hyperthyroidism accelerated the entire developmental pattern and shifted the peak to the 16th day after birth. The hydroxylase activity in mouse brain was also increased by thyroid hormone administration from the 13th through the 18th day after birth. Unlike normal mice, the low activity in jimpy mice was not affected by this treatment. It is concluded that thyroid hormones play an important role in the control of brain fatty acid alpha-hydroxylation. The stimulation of alpha-hydroxy fatty acid synthesis in response to hyperthyroidism during the early postnatal period may be one of the major effects of thyroid hormones in accelerating myelination of the central nervous system.

Accuracy of episodic autobiographical memory in children with early thyroid hormone deficiency using a staged event.

PubMed

Willoughby, Karen A; McAndrews, Mary Pat; Rovet, Joanne F

2014-07-01

Autobiographical memory (AM) is a highly constructive cognitive process that often contains memory errors. No study has specifically examined AM accuracy in children with abnormal development of the hippocampus, a crucial brain region for AM retrieval. Thus, the present study investigated AM accuracy in 68 typically and atypically developing children using a staged autobiographical event, the Children's Autobiographical Interview, and structural magnetic resonance imaging. The atypically developing group consisted of 17 children (HYPO) exposed during gestation to insufficient maternal thyroid hormone (TH), a critical substrate for hippocampal development, and 25 children with congenital hypothyroidism (CH), who were compared to 26 controls. Groups differed significantly in the number of accurate episodic details recalled and proportion accuracy scores, with controls having more accurate recollections of the staged event than both TH-deficient groups. Total hippocampal volumes and anterior hippocampal volumes were positively correlated with proportion accuracy scores, but not total accurate episodic details, in HYPO and CH. In addition, greater severity of TH deficiency predicted lower proportion accuracy scores in both HYPO and CH. Overall, these results indicate that children with early TH deficiency have deficits in AM accuracy and that the anterior hippocampus may play a particularly important role in accurate AM retrieval. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Endogenous Thyrotropin and Triiodothyronine Concentrations in Individuals with Thyroid Cancer

PubMed Central

Nsouli-Maktabi, Hala; Soldin, Steven J.

2008-01-01

Background Thyroid hormone suppression therapy is associated with decreased recurrence rates and improved survival in patients with differentiated thyroid cancer. Recently higher baseline thyrotropin (TSH) levels have been found to be associated with a postoperative diagnosis of differentiated thyroid cancer. Our objective was to confirm whether preoperative TSH levels were higher in patients who were diagnosed with differentiated thyroid cancer after undergoing thyroidectomy, compared with patients who were found to have benign disease. We also sought to determine whether thyroid hormone levels were lower in the patients with malignancy. Methods The study was a retrospective analysis of a prospective study. The study setting was the General Clinical Research Center of an Academic Medical Center. Participants were 50 euthyroid patients undergoing thyroidectomy. Thyroxine, triiodothyronine (T3), and TSH levels were documented in patients prior to their scheduled thyroidectomy. Following thyroidectomy, patients were divided into those with a histologic diagnosis of either differentiated thyroid cancer or benign disease. Preoperative thyroid profiles were correlated with patients' postoperative diagnoses. Results All patients had a normal serum TSH concentration preoperatively. One-third of the group was diagnosed with thyroid cancer as a result of their thyroidectomy. These patients had a higher serum TSH level (mean = 1.50 mIU/L, CI 1.22–1.78 mIU/L) than patients with benign disease (mean = 1.01 mIU/mL, CI 0.84–1.18 mIU/L). There was a greater risk of having thyroid cancer in patients with TSH levels in the upper three quartiles of TSH values, compared with patients with TSH concentrations in the lowest quartile of TSH values (odd ratio = 8.7, CI 2.2–33.7). Patients with a thyroid cancer diagnosis also had lower T3 concentrations measured by liquid chromatography tandem mass spectrometry (mean = 112.6 ng/dL, CI 103.8–121.4 ng/dL) than did patients with a benign diagnosis (mean 129.9 ng/dL, CI 121.4–138.4 ng/dL). Conclusion These data confirm that higher TSH concentrations, even within the normal range, are associated with a subsequent diagnosis of thyroid cancer in individuals with thyroid abnormalities. This further supports the hypothesis that TSH stimulates the growth or development of thyroid malignancy during its early or preclinical phase. We also show for the first time that patients with thyroid cancer also have lower T3 levels than patients with benign disease. PMID:18788918

Thyroid storm complicated by bicytopenia and disseminated intravascular coagulation.

PubMed

Tokushima, Yoshinori; Sakanishi, Yuta; Nagae, Kou; Tokushima, Midori; Tago, Masaki; Tomonaga, Motosuke; Yoshioka, Tsuneaki; Hyakutake, Masaki; Sugioka, Takashi; Yamashita, Shu-ichi

2014-07-24

Male, 23. Thyroid storm. Delirium • diarrhea • fever • hypertension • hyperventilation • tachycardia • weight loss. -. -. Endocrinology and Metabolic. Unusual clinical course. The clinical presentation of thyroid storm includes fever, tachycardia, hypertension, and neurological abnormalities. It is a serious condition with a high mortality rate. Furthermore, some other complications affect the clinical course of thyroid storm. Although it is reported that prognosis is poor when thyroid storm is complicated by disseminated intravascular coagulation syndrome (DIC) and leukopenia, reports of such cases are rare. A 23-year-old man presented with delirium, high pyrexia, diarrhea, and weight loss of 18 kg over 2 months. According to the criteria of Burch and Wartofsky, he was diagnosed with thyroid storm on the basis of his symptom-complex and laboratory data that confirmed the presence of hyperthyroidism. Investigations also found leukopenia, thrombocytopenia, and disseminated intravascular coagulation, all of which are very rare complications of thyroid storm. We successfully treated him with combined therapy including anti-thyroid medication, despite leukopenia. Early diagnosis and treatment are essential in ensuring a good outcome for patients with this rare combination of medical problems.

Ammonium Perchlorate Induces Thyroid Hormone Insufficiency and a Cortical Heterotopia in the Rat Brain

EPA Science Inventory

A morphological defect, a cortical heterotopia, has been observed in the brains of rat pups exposed in utero to moderate doses of the thyroid hormone (TH) synthesis inhibitor propylthioruracil (PTU). TH insufficiency during late gestation/early postnatal period is required to ind...

Thyroid Hormone Insufficiency in the Pregnant Rat Induces Cortical Heterotopia in Offspring: PTU vs Perchlorate

EPA Science Inventory

We have previously reported the presence of a structural defect, a heterotopia in the brains of rat pups exposed in utero to the thyroid hormone (TH) synthesis inhibitor propylthioruracil (PTU). TH insufficiency during late gestation/early postnatal period is required to induce ...

Diagnosis and Treatment of Patients with Thyroid Cancer

PubMed Central

Nguyen, Quang T.; Lee, Eun Joo; Huang, Melinda Gingman; Park, Young In; Khullar, Aashish; Plodkowski, Raymond A.

2015-01-01

Background Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease. Objective To review the current approach to the diagnosis and treatment of patients with thyroid cancer. Discussion Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored. Conclusion The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality. PMID:25964831

Aspergillus thyroiditis: first antemortem case diagnosed by fine-needle aspiration culture in a pediatric stem cell transplant patient.

PubMed

Badawy, S M; Becktell, K D; Muller, W J; Schneiderman, J

2015-12-01

Aspergillus thyroiditis (AT) has historically been considered a postmortem diagnosis in immunocompromised patients; most have disseminated disease. This report summarizes the clinical challenge of diagnosing AT. It also highlights the value of the early use of thyroid fine-needle aspiration culture and the need for a high index of suspicion to reach the final diagnosis before disease dissemination. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Genetics of Autoimmune Thyroiditis: the first decade

PubMed Central

Rose, Noel R.

2011-01-01

Most of our current understanding of the genetic predisposition to autoimmune disease can be traced to experiments performed in the decade from 1971 to 1981. Chella David was a key contributor to this research. Many of these early steps came from studies of experimental autoimmune thyroiditis. This model has been especially valuable because essentially the same disease can occur spontaneously in selected strains of animals or can be induced by deliberate immunization. From a genetic point of view, the disease has been investigated in three different species: mice, rats and chickens. The same antigen, thyroglobulin, initiates the disease in all three species. Among the main discoveries were the relationship of autoimmune disease to the major histocompatibility complex (MHC), the interplay of different subregions within the MHC in promoting or retarding development of disease, the differing roles of MHC class II and MHC I class genes in induction and effector phases, respectively, and the cumulative effect of non-MHC genes, each of which represents a small addition to overall susceptibility. Other experiments revealed that genetic differences in thyroglobulin allotypes influence susceptibility to thyroiditis. Thyroid glands differed in different strains in vulnerability to passive transfer of antibody. The first evidence of modulatory genes on the sex-related X chromosome emerged. All of these genetic findings were concurrently translated to the human disease, Hashimoto’s thyroiditis, where thyroglobulin is also the initiating antigen. PMID:21683550

Expression of thyroid hormone regulator genes in the yolk sac membrane of the developing chicken embryo

PubMed Central

TOO, Hanny Cho; SHIBATA, Mitsuhiro; YAYOTA, Masato; DARRAS, Veerle M.; IWASAWA, Atsushi

2017-01-01

Thyroid hormones (THs) are essential for the correct development of nearly every structure in the body from the very early stages of development, yet the embryonic thyroid gland is not functional at these stages. To clarify the roles of the egg yolk as a source of THs, the TH content in the yolk and the expression of TH regulator genes in the yolk sac membrane were evaluated throughout the 21-day incubation period of chicken embryos. The yolk TH content (22.3 ng triiodothyronine and 654.7 ng thyroxine per total yolk on day 4 of incubation) decreased almost linearly along with development. Real-time PCR revealed gene expression of transthyretin, a principal TH distributor in the chicken, and of a TH-inactivating iodothyronine deiodinase (DIO3), until the second week of incubation when the embryonic pituitary-thyroid axis is generally thought to start functioning. The TH-activating deiodinase (DIO2) and transmembrane transporter of thyroxine (SLCO1C1) genes were expressed in the last week of incubation, which coincided with a marked increase of circulating thyroxine and a reduction in the yolk sac weight. DIO1, which can remove iodine from inactive THs, was expressed throughout the incubation period. It is assumed that the chicken yolk sac inactivates THs contained abundantly in the yolk and supplies the hormones to the developing embryo in appropriate concentrations until the second week of incubation, while THs may be activated in the yolk sac membrane in the last week of incubation. Additionally, the yolk sac could serve as a source of iodine for the embryo. PMID:28652559

COUP-TF1 Modulates Thyroid Hormone Action in an Embryonic Stem-Cell Model of Cortical Pyramidal Neuronal Differentiation.

PubMed

Teng, Xiaochun; Liu, Yan-Yun; Teng, Weiping; Brent, Gregory A

2018-05-01

Thyroid hormone is critical for normal brain development and acts in a spatial and temporal specific pattern. Thyroid hormone excess, or deficiency, can lead to irreversible impairment of brain and sensory development. Chicken ovalbumin upstream-transcription factor 1 (COUP-TF1), expressed early in neuronal development, is essential to achieve normal brain structure. Thyroid hormone stimulation of gene expression is inversely correlated with the level of COUP-TF1 expression. An in vitro method of differentiating mouse embryonic stem (mES) cells into cortical neurons was utilized to study the influence of COUP-TF1 on thyroid hormone signaling in brain development. mES cells were cultured and differentiated in specific conditioned media, and a high percentage of nestin-positive progenitor neurons in the first stage, and cortical neurons in the second stage, was obtained with characteristic neuronal firing. The number of nestin-positive progenitors, as determined by fluorescence-activated cell sorting analysis, was significantly greater with triiodothyronine (T3) treatment compared to control (p < 0.05). T3 enhanced the expression of cortical neuron marker (Tbr1 and Rc3) mRNAs. After COUP-TF1 knockdown, the number of nestin-positive progenitors was reduced compared to control (p < 0.05), but the number increased with T3 treatment. The mRNA of cortical neuronal gene markers was measured after COUP-TF1 knockdown. In the presence of T3, the peak expression of neuron markers Emx1, Tbr1, Camkiv, and Rc3 mRNA was earlier, at day 18 of differentiation, compared to control cells, at day 22. Furthermore, after COUP-TF1 knockdown, T3 induction of Rc3 and Tbr1 mRNA was significantly enhanced compared to cells expressing COUP-TF1. These results indicate that COUP-TF1 plays an important role in modulating the timing and magnitude of T3-stimulated gene expression required for normal corticogenesis.

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

PubMed

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

2014-03-01

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

18F-FDG PET/CT Can Predict Development of Thyroiditis due to Immunotherapy for Lung Cancer.

PubMed

Eshghi, Naghmehossadat; Garland, Linda; Nia, Emily Saghar; Betancourt, Robert; Krupinski, Elizabeth; Kuo, Phillip H

2018-03-29

Objective: For patients undergoing immunotherapy with nivolumab for lung cancer, determine if increased 18 F-FDG uptake in the thyroid gland predicts development of thyroiditis with subsequent hypothyroidism. Secondarily, determine if 18 F-FDG uptake in the thyroid gland correlates with administered cycles of nivolumab. Materials and Methods: Retrospective chart review over 2 years found 18 lung cancer patients treated with nivolumab and with 18 F-FDG PET/CT scans pre- and during therapy. Standardized uptake value (SUV) mean and maximum and total lesion glycolysis (TLG) of the thyroid gland were measured. SUVs were also measured for the pituitary gland, liver and spleen. Patients obtained monthly thyroid testing. PET/CT parameters were analyzed by unpaired t-test for differences between two groups (patients who developed hypothyroidism and those who did not). Correlation between development of thyroiditis and number of cycles of nivolumab received was also tested. Results: Six of eighteen patients developed hypothyroidism. T-test comparing the two groups (patients who developed hypothyroidism and those who did not) demonstrated significant differences in SUVmean ( P = 0.04), SUV max ( P = 0.04) and TLG ( P = 0.02) of the thyroid gland. Two of four patients who developed thyroiditis and had increased 18 F-FDG uptake in the thyroid gland, had normal TSH at time of follow-up 18 F-FDG PET/CT. Patients who developed thyroiditis with subsequent hypothyroidism stayed longer on therapy (10.6 cycles) compared to patients without thyroiditis (7.6 cycles), but the trend was not statistically significant. No significant difference in PET/CT parameters was observed for pituitary gland, liver or spleen. Conclusion: 18 F-FDG PET/CT can predict the development of thyroiditis with subsequent hypothyroidism before laboratory testing. Further study is required to confirm the positive trend between thyroiditis and duration of therapy. Copyright © 2018 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The Role of Radiopharmaceuticals in Amiodarone-Induced Thyroid Pathology.

PubMed

Irimie, Alexandru; Piciu, Doina

2017-11-10

The use of amiodarone for the treatment of ventricular and supraventricular dysrhythmias brings in organism an increased amount of iodine, interfering with thyroid function. If the treatment needs to be interrupted, iodine remains at abnormal levels for months or even years. The aim of the study was to review the literature regarding the optimal tests for early diagnostic and to analyze the role of nuclear medicine tests in the differential and correct assessment of the amiodarone-induced thyroid pathology. We made a review of available publications in PUBMED referring the amiodaroneinduced thyroid pathology, focusing on the differential diagnosis, made by nuclear medicine tests, of hypothyroidism (AIH) and hyperthyroidism expressed as: type I amiodarone induced thyrotoxicosis (AIT I), type II amiodarone induced thyrotoxicosis (AIT II), and less frequently as a mixt form, type III amiodarone induced thyrotoxicosis (AIT III). We presented cases from the database of a tertiary center in Cluj-Napoca, Romania. Despite the frequent complication of thyroid function, this pathology is underestimated and diagnosed. There is a limited number of studies and clear protocols, especially in the mixed forms cases. This increase in iodine uptake interferes seriously with thyroid hormone production and release. The nuclear medicine tests are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The destruction of the follicular cells can result in the release of excessive thyroid hormone into the circulation, with potential development of atrial fibrillation, worsening the cardiac disease, so any benefic therapeutic procedure should be known; the use of radioiodine as therapy alternative, despite the known limitations induced by blockade was clear benefic in the case presented. A special attention needs to be addressed to those patients with differentiated thyroid cancer, which will be submitted to radioiodine therapy and are under chronic therapy with amiodarone. The nuclear medicine procedures are essential in the correct assessment and differential diagnosis of different forms of induced thyroid dysfunction. The radioiodine is not recommended in AIT, due to stunning effect induced by iodine excess, but in some special, lifethreatening condition, radioiodine I-131 might be a treatment option. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Heavy metals in the volcanic environment and thyroid cancer.

PubMed

Vigneri, R; Malandrino, P; Gianì, F; Russo, M; Vigneri, P

2017-12-05

In the last two decades thyroid cancer incidence has increased worldwide more than any other cancer. Overdiagnosis of subclinical microcarcinomas has certainly contributed to this increase but many evidences indicate that a true increase, possibly due to environmental factors, has also occurred. Thyroid cancer incidence is markedly increased in volcanic areas. Thus, the volcanic environment is a good model to investigate the possible factors favoring thyroid cancer. In the volcanic area of Mt. Etna in Sicily, as well as in other volcanic areas, a non-anthropogenic pollution with heavy metals has been documented, a consequence of gas, ash and lava emission. Soil, water and atmosphere contamination, via the food chain, biocontaminate the residents as documented by high levels in the urines and the scalp hair compared to individuals living in adjacent non-volcanic areas. Trace amounts of metals are essential nutrients but, at higher concentrations, can be toxic for living cells. Metals can behave both as endocrine disruptors, perturbing the hormonal system, and as carcinogens, promoting malignant transformation. Similarly to other carcinogens, the transforming effect of heavy metals is higher in developing organisms as the fetus (contaminated via the mother) and individuals in early childhood. In the last decades environment metal pollution has greatly increased in industrialized countries. Although still within the "normal" limits for each single metal the hormesis effect (heavy metal activity at very low concentration because of biphasic, non linear cell response) and the possible potentiation effect resulting from the mixture of different metals acting synergistically can explain cell damage at very low concentrations. The effect of metals on the human thyroid is poorly studied: for some heavy metals no data are available. The scarce studies that have been performed mainly focus on metal effect as thyroid endocrine disruptors. The metal concentration in tissues has been rarely measured in the thyroid. Heavy metal accumulation and metabolism in the thyroid or the carcinogenic activity of different doses and different speciation of metals has not been investigated. These studies are now warranted to better understand thyroid biology and heavy metal role in human thyroid carcinogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Very early onset of autoimmune thyroiditis in a toddler with severe hypothyroidism presentation: a case report.

PubMed

Marzuillo, Pierluigi; Grandone, Anna; Perrotta, Silverio; Ruggiero, Laura; Capristo, Carlo; Luongo, Caterina; Miraglia Del Giudice, Emanuele; Perrone, Laura

2016-06-18

In infants under 3 years of age acquired primary hypothyroidism caused by autoimmune thyroiditis is very rare. Hypothyroidism can manifest with different signs and symptoms and has a wide range of presentations from subclinical hypothyroidism to overt form. We describe a child with acquired autoimmune thyroiditis during a very early period of life and with a severe hypothyroidism presentation. A 22-month-old white male patient with normal neonatal screening presented with a six-month history of asthenia and cutaneous pallor. At general clinical and biochemical exams he showed weight gain, statural growth deceleration, poor movements, sleepy expression, instability while walking, myxoedema, bradycardia, open anterior fontanelle, changes in the face habitus, macrocytic anaemia, ascites, and high CPK, creatinine and cholesterol levels. Acquired autoimmune thyroiditis was the final diagnosis. The thyroxine replacement therapy normalized all the clinical and biochemical abnormalities but at the age of 30 months his mental age showed a delay of 6 months. Our case could give useful learning points: i) although the screening for congenital hypothyroidism is routinely performed, a severe hypothyroidism (for example due to autoimmune thyroiditis) can anyway occur early in life and the clinicians should consider this possibility; ii) hypothyroidism can have a misleading and multi-face clinical presentation; iii) anemia, rhabdomyolysis and high creatinine levels should always include the hypothyroidism in the differential diagnosis; iv) thyroxine replacement therapy is able to revert all the clinical manifestations related to the hypothyroidism; v) evaluating the patient's previous pictures could play an important role in resolving a diagnostic conundrum.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study.

PubMed

Duyff, R F; Van den Bosch, J; Laman, D M; van Loon, B J; Linssen, W H

2000-06-01

To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism. A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment. In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6 months). Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

Hypothyroxinemia During Gestation and Offspring Schizophrenia in a National Birth Cohort

PubMed Central

Gyllenberg, David; Sourander, Andre; Surcel, Heljä-Marja; Hinkka-Yli-Salomäki, Susanna; McKeague, Ian W.; Brown, Alan S.

2015-01-01

Background Evidence from animal and human studies indicates that thyroid hormone deficiency during early gestation alters brain development. As schizophrenia is associated with prenatal brain insults and premorbid cognitive deficits, we tested the a priori hypothesis that serologically defined maternal thyroid deficiency during early to mid-gestation is associated with offspring schizophrenia. Methods The investigation is based on the Finnish Prenatal Study of Schizophrenia (FiPS-S), a nested case-control study that included archived maternal sera from virtually all pregnancies since 1983 (total N over 1 million). We identified all offspring in the cohort diagnosed with schizophrenia based on the national inpatient and outpatient register and matched them to comparison subjects (1:1) from the cohort on sex, date of birth, and residence in Finland at time of onset of the case. Maternal sera on 1010 case-control pairs were assessed for free thyroxine (fT4) and 948 for thyroid stimulating hormone (TSH). Results Maternal hypothyroxinemia (fT4≤10th percentile, normal TSH) was associated with an increased odds of schizophrenia (OR=1.75, 95% CI=1.22 – 2.50; p=0.002). When adjusted for maternal psychiatric history, province of birth and maternal smoking during pregnancy, the association remained significant (OR=1.70, 95%CI 1.13 – 2.55; p=0.010). Conclusions In a large, national birth cohort, prospectively documented early to mid-gestational hypothyroxinemia was associated with increased odds of schizophrenia in offspring. This can inform translational studies of maternal hypothyroxinemia examining molecular and cellular deviations relevant to schizophrenia. PMID:26194598

Iodine deficiency and thyroid disorders.

PubMed

Zimmermann, Michael B; Boelaert, Kristien

2015-04-01

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

Increased prevalence of hyperthyroidism as an early and transient side-effect of implementing iodine prophylaxis.

PubMed

Gołkowski, Filip; Buziak-Bereza, Monika; Trofimiuk, Małgorzata; Bałdys-Waligórska, Agata; Szybiński, Zbigniew; Huszno, Bohdan

2007-08-01

To assess the prevalence of hyperthyroidism just after implementation of iodine prophylaxis among adults from an area with iodine deficiency. A total of 1648 adults (age 16 years and older) were sampled from an area of southern Poland during two nationwide epidemiological surveys. Of these, 1424 adults with negative medical history for thyroid disorders qualified for final analysis. The authors compared thyroid dysfunction in participants prior to (1989-1990) and after implementation of iodine prophylaxis (1997-1999). The southern part of Poland. We found an increase in the serum concentration of anti-thyroid microsomal antibodies from 4.9% in the years 1989-1990 to 12.1% after introduction of iodised household salt (P < 0.0001). The prevalence of hyperthyroidism (defined as thyroid-stimulating hormone < 0.4 microU ml- 1) significantly increased in the equivalent period from 4.8 to 6.5% (P = 0.009). We concluded that a sudden rise in iodine intake after implementation of iodine prophylaxis among adults from the area with iodine deficiency may lead to an increase in thyroid autoimmunity and prevalence of hyperthyroidism. Those possible early side-effects appear to be only temporary and are acceptable when compared with the evident benefits of adequate iodine intake.

Effects of thyroid hormones on the heart.

PubMed

Vargas-Uricoechea, Hernando; Bonelo-Perdomo, Anilsa; Sierra-Torres, Carlos Hernán

2014-01-01

Thyroid hormones have a significant impact on heart function, mediated by genomic and non-genomic effects. Consequently, thyroid hormone deficiencies, as well as excesses, are expected to result in profound changes in cardiac function regulation and cardiovascular hemodynamics. Thyroid hormones upregulate the expression of the sarcoplasmic reticulum calcium-activated ATPase and downregulate the expression of phospholamban. Overall, hyperthyroidism is characterized by an increase in resting heart rate, blood volume, stroke volume, myocardial contractility, and ejection fraction. The development of "high-output heart failure" in hyperthyroidism may be due to "tachycardia-mediated cardiomyopathy". On the other hand, in a hypothyroid state, thyroid hormone deficiency results in lower heart rate and weakening of myocardial contraction and relaxation, with prolonged systolic and early diastolic times. Cardiac preload is decreased due to impaired diastolic function. Cardiac afterload is increased, and chronotropic and inotropic functions are reduced. Subclinical thyroid dysfunction is relatively common in patients over 65 years of age. In general, subclinical hypothyroidism increases the risk of coronary heart disease (CHD) mortality and CHD events, but not of total mortality. The risk of CHD mortality and atrial fibrillation (but not other outcomes) in subclinical hyperthyroidism is higher among patients with very low levels of thyrotropin. Finally, medications such as amiodarone may induce hypothyroidism (mediated by the Wolff-Chaikoff), as well as hyperthyroidism (mediated by the Jod-Basedow effect). In both instances, the underlying cause is the high concentration of iodine in this medication. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

SPORADIC GOITROUS CRETINISM

PubMed Central

Mosier, H. David

1959-01-01

Five to 10 per cent of cretinism in the United States is due to some congenital enzymatic defect in thyroid hormone synthesis. The clinical signs of hypothyroidism appear in early infancy. Differentiation from athyreotic cretinism is important because the metabolic defect tends to be familial and its presence in the patient's infant relatives should be diagnosed as early as possible. The differentiation is easily made if a goiter is discernible, but if it is not, radioiodine uptake should be measured, for in this condition the uptake is normal or greater. Thyroid replacement is the treatment in either the athyreotic state or the metabolic deficiency. The three known defects in thyroid hormone synthesis are (1) failure to oxidize iodine to elemental iodine resulting in failure of all subsequent processes; (2) failure to deiodinate free iodotyrosine, and (3) failure to form iodothyronine although the previous steps are accomplished. PMID:13618742

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.

Thyroid hormones: Possible roles in epilepsy pathology.

PubMed

Tamijani, Seyedeh Masoumeh Seyedhoseini; Karimi, Benyamin; Amini, Elham; Golpich, Mojtaba; Dargahi, Leila; Ali, Raymond Azman; Ibrahim, Norlinah Mohamed; Mohamed, Zahurin; Ghasemi, Rasoul; Ahmadiani, Abolhassan

2015-09-01

Thyroid hormones (THs) L-thyroxine and L-triiodothyronine, primarily known as metabolism regulators, are tyrosine-derived hormones produced by the thyroid gland. They play an essential role in normal central nervous system development and physiological function. By binding to nuclear receptors and modulating gene expression, THs influence neuronal migration, differentiation, myelination, synaptogenesis and neurogenesis in developing and adult brains. Any uncorrected THs supply deficiency in early life may result in irreversible neurological and motor deficits. The development and function of GABAergic neurons as well as glutamatergic transmission are also affected by THs. Though the underlying molecular mechanisms still remain unknown, the effects of THs on inhibitory and excitatory neurons may affect brain seizure activity. The enduring predisposition of the brain to generate epileptic seizures leads to a complex chronic brain disorder known as epilepsy. Pathologically, epilepsy may be accompanied by mitochondrial dysfunction, oxidative stress and eventually dysregulation of excitatory glutamatergic and inhibitory GABAergic neurotransmission. Based on the latest evidence on the association between THs and epilepsy, we hypothesize that THs abnormalities may contribute to the pathogenesis of epilepsy. We also review gender differences and the presumed underlying mechanisms through which TH abnormalities may affect epilepsy here. Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

The role of iodine in human growth and development.

PubMed

Zimmermann, Michael B

2011-08-01

Iodine is an essential component of the hormones produced by the thyroid gland. Thyroid hormones, and therefore iodine, are essential for mammalian life. Iodine deficiency is a major public health problem; globally, it is estimated that two billion individuals have an insufficient iodine intake. Although goiter is the most visible sequelae of iodine deficiency, the major impact of hypothyroidism due to iodine deficiency is impaired neurodevelopment, particularly early in life. In the fetal brain, inadequate thyroid hormone impairs myelination, cell migration, differentiation and maturation. Moderate-to-severe iodine deficiency during pregnancy increases rates of spontaneous abortion, reduces birth weight, and increases infant mortality. Offspring of deficient mothers are at high risk for cognitive disability, with cretinism being the most severe manifestation. It remains unclear if development of the offspring is affected by mild maternal iodine deficiency. Moderate-to-severe iodine deficiency during childhood reduces somatic growth. Correction of mild-to-moderate iodine deficiency in primary school aged children improves cognitive and motor function. Iodine prophylaxis of deficient populations with periodic monitoring is an extremely cost effective approach to reduce the substantial adverse effects of iodine deficiency throughout the life cycle. Copyright © 2011 Elsevier Ltd. All rights reserved.

Zebrafish bcl2l is a survival factor in thyroid development.

PubMed

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

2012-06-15

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

Early weaning PCB 95 exposure alters the neonatal endocrine system: thyroid adipokine dysfunction.

PubMed

Ahmed, R G

2013-12-01

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that can severely disrupt the endocrine system. In the present study, early-weaned male rats were administered a single dose of 2,3,6-2',5'-pentachlorinated biphenyl (PCB 95; 32 mg/kg per day, by i.p. injection) for two consecutive days (postnatal days (PNDs) 15 and 16) and killed 24 and 48 h after the administration of the last dose. Compared with the control group, administration of PCB 95 induced a reduction (P<0.01) in serum concentrations of thyroxine, triiodothyronine, and GH and an increase (P<0.01) in the serum concentration of TSH at PNDs 17 and 18. These conspicuous perturbations led to some histopathological deterioration in the thyroid gland characterized by follicular degeneration, edema, fibrosis, hemorrhage, luminal obliteration, and hypertrophy with reduced colloidal contents at PND 18. The dyshormonogenesis and thyroid dysgenesis may be attributed to the elevation of DNA fragmentation at PNDs 17 and 18. Furthermore, this hypothyroid state revealed higher (P<0.01) serum concentrations of leptin, adiponectin, and tumor necrosis factor and lower (P<0.01) serum concentrations of IGF1 and insulin at both PNDs compared with the control group. Interestingly, the body weight of the neonates in the PCB 95 group exhibited severe decreases throughout the experimental period in relation to that of the control group. These results imply that PCB 95 may act as a disruptor of the developmental hypothalamic-pituitary-thyroid axis. Hypothyroidism caused by PCB 95 may impair the adipokine axis, fat metabolism, and in general postnatal development. Thus, further studies need to be carried out to understand this concept.

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

Leonard, C.M.; Hauser, P.; Weintraub, B.D.

Resistance to thyroid hormone (RTH) is an autosomal dominant disease caused by mutations in the human thyroid receptor beta gene on chromosome 3. Individuals with RTH have an increased incidence of attention deficit hyperactivity disorder (ADHD). The purpose of this study was to search for developmental brain malformations associated with RTH. Forty-three subjects (20 affected males [AM], 23 affected females [AF]) with resistance to thyroid hormone and 32 unaffected first degree relatives (18 unaffected males [UM], 14 unaffected females [UF]) underwent MRI brain scans with a volumetric acquisition that provided 90 contiguous 2 mm thick sagittal images. Films of sixmore » contiguous images beginning at a standard sagittal position lateral to the insula were analyzed by an investigator who was blind with respect to subject characteristics. The presence of extra or missing gyri in the parietal bank of the Sylvian fissure (multimodal association cortex) and multiple Heschl`s transverse gyri (primary auditory cortex) were noted. There was a significantly increased frequency of anomalous Sylvian fissures in the left hemisphere in males with RTH (AM: 70%; AF: 30%; UM: 28% UF: 28%). Also, there was an increased frequency of anomalous Sylvian fissures on the left combined with multiple Heschl`s gyri in either hemisphere in males with RTH (AM: 50%; AF: 9%; UM: 6%; UF: 0%). However, RTH subjects with anomalies did not have an increased frequency of ADHD as compared with RTH subjects with no anomalies. Abnormal thyroid hormone action in the male fetus early during brain development may be associated with grossly observable cerebral anomalies of the left hemisphere. The effects of mutations in the thyroid receptor beta gene provide a model system for studying the complex interaction of genetic and non-genetic factors on brain and behavioral development. 19 refs., 2 figs., 2 tabs.« less

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.

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

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

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

1959-04-01

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

Polybrominated diphenyl ether (PBDE) exposures and thyroid hormones in children at age 3 years.

PubMed

Vuong, Ann M; Braun, Joseph M; Webster, Glenys M; Thomas Zoeller, R; Hoofnagle, Andrew N; Sjödin, Andreas; Yolton, Kimberly; Lanphear, Bruce P; Chen, Aimin

2018-08-01

Polybrominated diphenyl ethers (PBDEs) reduce serum thyroid hormone concentrations in animal studies, but few studies have examined the impact of early-life PBDE exposures on thyroid hormone disruption in childhood. We used data from 162 mother-child pairs from the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, OH). We measured PBDEs in maternal serum at 16 ± 3 weeks gestation and in child serum at 1-3 years. Thyroid hormones were measured in serum at 3 years. We used multiple informant models to investigate associations between prenatal and early-life PBDE exposures and thyroid hormone levels at age 3 years. Prenatal PBDEs were associated with decreased thyroid stimulating hormone (TSH) levels at age 3 years. A 10-fold increase in prenatal ∑PBDEs (BDE-28, -47, -99, -100, and -153) was associated with a 27.6% decrease (95% CI -40.8%, -11.3%) in TSH. A ten-fold increase in prenatal ∑PBDEs was associated with a 0.25 pg/mL (0.07, 0.43) increase in free triiodothyronine (FT 3 ). Child sex modified associations between prenatal PBDEs and thyroid hormones, with significant decrements in TSH among females and decreased free T 4 (FT 4 ) in males. Prenatal ∑PBDEs were not associated with TT 4 , FT 4 , or total T 3 . These findings suggest an inverse relationship between prenatal ∑PBDEs and TSH at 3 years. Associations may be sexually dimorphic, with an inverse relationship between prenatal BDE-47 and -99 and TSH in females and null associations among males. Copyright © 2018 Elsevier Ltd. All rights reserved.

Novel Application of Quantitative Single-Photon Emission Computed Tomography/Computed Tomography to Predict Early Response to Methimazole in Graves' Disease

PubMed Central

Kim, Hyun Joo; Bang, Ji-In; Kim, Ji-Young; Moon, Jae Hoon; So, Young

2017-01-01

Objective Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. Materials and Methods A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of 99mTc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. Results GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006). Conclusion A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients. PMID:28458607

Thyroid hormones and fetal brain development.

PubMed

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

2005-08-01

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

Role of maternal thyroid hormones in the developing neocortex and during human evolution

PubMed Central

Stenzel, Denise; Huttner, Wieland B.

2013-01-01

The importance of thyroid hormones during brain development has been appreciated for many decades. In humans, low levels of circulating maternal thyroid hormones, e.g., caused by maternal hypothyroidism or lack of iodine in diet, results in a wide spectrum of severe neurological defects, including neurological cretinism characterized by profound neurologic impairment and mental retardation, underlining the importance of the maternal thyroid hormone contribution. In fact, iodine intake, which is essential for thyroid hormone production in the thyroid gland, has been related to the expansion of the brain, associated with the increased cognitive capacities during human evolution. Because thyroid hormones regulate transcriptional activity of target genes via their nuclear thyroid hormone receptors (THRs), even mild and transient changes in maternal thyroid hormone levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Here we summarize how thyroid hormones may have influenced human brain evolution through the adaptation to new habitats, concomitant with changes in diet and, therefore, iodine intake. Further, we review the current picture we gained from experimental studies in rodents on the function of maternal thyroid hormones during developmental neurogenesis. We aim to evaluate the effects of maternal thyroid hormone deficiency as well as lack of THRs and transporters on brain development and function, shedding light on the cellular behavior conducted by thyroid hormones. PMID:23882187

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.

[Age characteristics of the cardiovascular system, depending on the thyroid function in type 2 diabetes mellitus].

PubMed

Ignateva, P A; Ballyuzek, M F; Shpakov, A O

To study the features of cardiovascular system in patients with diabetes mellitus type 2 considering the thyroid pathology and age, 264 patients were examined. They were divided into three groups: 1st - patients with diffuse-nodular changes in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a control group of patients without thyroid disease. The patients of different ages were examined in each of these groups. All patients were in euthyroid state. It was established that identified in diabetes mellitus type 2 thyroid pathology and the thyroid disease contribute special features to the clinical picture for combined diabetic and cardiovascular pathology even in a euthyroid state including the age features. The laboratory and instrumental researches showed that the patients with combined diabetes and thyroid pathology have a higher incidence of atrial fibrillation, ischemic heart disease, and ventricular arrhythmias of high grades. They also were noticed to have a more adverse form of the left ventricle remodeling, also the combination of diastolic and systolic dysfunctions were found to be more frequent. It was concluded about the necessity of early diagnosis and correction of the cardiovascular disorders and thyroid systems in type 2 diabetes mellitus patients, including euthyroid patients.

Hashimoto's Thyroiditis: Celebrating the Centennial Through the Lens of the Johns Hopkins Hospital Surgical Pathology Records

PubMed Central

De Remigis, Alessandra; Chuang, Kelly; Dembele, Marieme; Iwama, Akiko; Iwama, Shintaro

2013-01-01

Hashimoto's thyroiditis is now considered the most prevalent autoimmune disease, as well as the most common endocrine disorder. It was initially described in 1912, but only rarely reported until the early 1950s. To celebrate this centennial, we reviewed the surgical pathology archives of the Johns Hopkins hospital for cases of Hashimoto's thyroiditis, spanning the period from May 1889 to October 2012. Approximately 15,000 thyroidectomies were performed at this hospital over 124 years. The first surgical case was reported in 1942, 30 years after the original description. Then, 867 cases of Hashimoto's thyroiditis were seen from 1942 to 2012, representing 6% of all thyroidectomies. Hashimoto's thyroiditis was the sole pathological finding in 462 cases; it accompanied other thyroid pathologies in the remaining 405 cases. The most commonly associated pathology was papillary thyroid cancer, an association that increased significantly during the last two decades. The most common indication for thyroidectomy was a thyroid nodule that was cytologically suspicious for malignancy. Hashimoto's thyroiditis remains a widespread, intriguing, and multifaceted disease of unknown etiology one century after its description. Advances in the understanding of its pathogenesis and preoperative diagnosis will improve recognition and treatment of this disorder, and may one day lead to its prevention. PMID:23151083

Natural history of thyroid cancer [Review].

PubMed

Takano, Toru

2017-03-31

Thyroid cancers have long been considered to arise in middle age and, after their repeated proliferation, resulting in further damage to the genome, they progress to more aggressive and lethal cancers. However, in 2014, some studies were reported that might lead to a marked change in our understanding of the natural history of thyroid cancer. A high prevalence of papillary carcinoma in the young suggested that the first initiation of thyroid cancer is likely to occur in the infantile period. Such a conclusion was also supported by a very slow growth rate of papillary microcarcinomas (PMCs) in an observation trial. The proliferation rate of PMCs was negatively correlated with the age, and surgery to remove PMCs did not contribute to reduce mortality from thyroid cancer. These findings strongly suggested the existence of self-limiting cancers, which are truly malignant but do not progress to lethal cancers, for the first time in human history. The early detection of self-limiting cancers results in overdiagnosis. Ultrasonographic screening of the thyroid in the young should be avoided. Lethal thyroid cancers, whose origin is still unknown, appear suddenly after middle age. In the elderly, thyroid cancers are a mixture of self-limiting and lethal cancers; thus, when thyroid cancer is detected, careful follow-up with examination of its growth rate is required.

Original Research: Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient.

PubMed

Darcy, Justin; Fang, Yimin; Hill, Cristal M; McFadden, Sam; Sun, Liou Y; Bartke, Andrzej

2016-10-01

Ames dwarf mice are exceptionally long-lived due to a Prop1 loss of function mutation resulting in deficiency of growth hormone, thyroid-stimulating hormone and prolactin. Deficiency in thyroid-stimulating hormone and growth hormone leads to greatly reduced levels of circulating thyroid hormones and insulin-like growth factor 1, as well as a reduction in insulin secretion. Early life growth hormone replacement therapy in Ames dwarf mice significantly shortens their longevity, while early life thyroxine (T4) replacement therapy does not. Possible mechanisms by which early life growth hormone replacement therapy shortens longevity include deleterious effects on glucose homeostasis and energy metabolism, which are long lasting. A mechanism explaining why early life T4 replacement therapy does not shorten longevity remains elusive. Here, we look for a possible explanation as to why early life T4 replacement therapy does not impact longevity of Ames dwarf mice. We found that early life T4 replacement therapy increased body weight and advanced the age of sexual maturation. We also find that early life T4 replacement therapy does not impact glucose tolerance or insulin sensitivity, and any deleterious effects on oxygen consumption, respiratory quotient and heat production are transient. Lastly, we find that early life T4 replacement therapy has long-lasting effects on bone mineral density and bone mineral content. We suggest that the transient effects on energy metabolism and lack of effects on glucose homeostasis are the reasons why there is no shortening of longevity after early life T4 replacement therapy in Ames dwarf mice. © 2016 by the Society for Experimental Biology and Medicine.

Expression of thyroid hormone transporters and deiodinases at the brain barriers in the embryonic chicken: Insights into the regulation of thyroid hormone availability during neurodevelopment.

PubMed

Van Herck, Stijn L J; Delbaere, Joke; Bourgeois, Nele M A; McAllan, Bronwyn M; Richardson, Samantha J; Darras, Veerle M

2015-04-01

Thyroid hormones (THs) are key regulators in the development of the vertebrate brain. Therefore, TH access to the developing brain needs to be strictly regulated. The brain barriers separate the central nervous system from the rest of the body and impose specific transport mechanisms on the exchange of molecules between the general circulation and the nervous system. As such they form ideal structures for regulating TH exchange between the blood and the brain. To investigate the mechanism by which the developing brain regulates TH availability, we investigated the ontogenetic expression profiles of TH transporters, deiodinases and the TH distributor protein transthyretin (TTR) at the brain barriers during embryonic and early postnatal development using the chicken as a model. In situ hybridisation revealed expression of the TH transporters monocarboxylate transporter 8 (MCT8) and 10 (MCT10), organic anion transporting polypeptide 1C1 (OATP1C1) and L-type amino acid transporter 1 (LAT1) and the inactivating type 3 deiodinase (D3) in the choroid plexus which forms the blood-cerebrospinal fluid barrier. This was confirmed by quantitative PCR which additionally indicated strongly increasing expression of TTR as well as detectable expression of the activating type 2 deiodinase (D2) and the (in)activating type 1 deiodinase (D1). In the brain capillaries forming the blood-brain barrier in situ hybridisation showed exclusive expression of LAT1 and D2. The combined presence of LAT1 and D2 in brain capillaries suggests that the blood-brain barrier forms the main route for receptor-active T3 uptake into the embryonic chicken brain. Expression of multiple transporters, deiodinases and TTR in the choroid plexus indicates that the blood-cerebrospinal fluid barrier is also important in regulating early TH availability. The impact of these barrier systems can be deduced from the clear difference in T3 and T4 levels as well as the T3/T4 ratio between the developing brain and the general circulation. We conclude that the tight regulation of TH exchange at the brain barriers from early embryonic stages is one of the factors needed to allow the brain to develop within a relative microenvironment. Copyright © 2015 Elsevier Inc. All rights reserved.

Calcitonin estimation in patients with nodular goiter and its significance for early detection of MTC: european comments to the guidelines of the American Thyroid Association.

PubMed

Elisei, Rossella; Romei, Cristina

2013-03-14

One of the most discussed and controversial issue in the management of thyroid nodules is the need to perform a routine measurement of serum Calcitonin (Ct) in all cases. The American Thyroid Association guidelines do not recommend in favor or against this procedure since they retain that there are not enough evidences that it can determine an advantage to the health outcomes of these patients. This is not the view of many European experts who met in Lisbon in 2009 at the European Thyroid Association-Cancer Research Network meeting to discuss all the still open controversial issues on the management of medullary thyroid cancer patients.This paper is focused on the routine measurement of serum Ct in all patients with thyroid nodule(s): the evidences, the rational and the benefits of this procedure are deeply analysed following the discussion that was done in Lisbon. The conclusions reached at that time are reported in detail.

Using fractal analysis of thermal signatures for thyroid disease evaluation

NASA Astrophysics Data System (ADS)

Gavriloaia, Gheorghe; Sofron, Emil; Gavriloaia, Mariuca-Roxana; Ghemigean, Adina-Mariana

2010-11-01

The skin is the largest organ of the body and it protects against heat, light, injury and infection. Skin temperature is an important parameter for diagnosing diseases. Thermal analysis is non-invasive, painless, and relatively inexpensive, showing a great potential research. Since the thyroid regulates metabolic rate it is intimately connected to body temperature, more than, any modification of its function generates a specific thermal image on the neck skin. The shapes of thermal signatures are often irregular in size and shape. Euclidean geometry is not able to evaluate their shape for different thyroid diseases, and fractal geometry is used in this paper. Different thyroid diseases generate different shapes, and their complexity are evaluated by specific mathematical approaches, fractal analysis, in order to the evaluate selfsimilarity and lacunarity. Two kinds of thyroid diseases, hyperthyroidism and papillary cancer are analyzed in this paper. The results are encouraging and show the ability to continue research for thermal signature to be used in early diagnosis of thyroid diseases.

Thyroid consequences of the Chernobyl nuclear accident.

PubMed

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

1999-12-01

It is well recognized that the use of external irradiation of the head and neck to treat patients with various non-thyroid disorders increases their risk of developing papillary thyroid carcinoma years after radiation exposure. An increased risk of thyroid cancer has also been reported in survivors of the atomic bombs in Japan, as well as in Marshall Island residents exposed to radiation during the testing of hydrogen bombs. More recently, exposure to radioactive fallout as a result of the Chernobyl nuclear reactor accident has clearly caused an enormous increase in the incidence of childhood thyroid carcinoma in Belarus, Ukraine, and, to a lesser extent, in the Russian Federation, starting in 1990. When clinical and epidemiological features of thyroid carcinomas diagnosed in Belarus after the Chernobyl accident are compared with those of naturally occurring thyroid carcinomas in patients of the same age group in Italy and France, it becomes apparent that the post-Chernobyl thyroid carcinomas were much less influenced by gender, virtually always papillary (solid and follicular variants), more aggressive at presentation and more frequently associated with thyroid autoimmunity. Gene mutations involving the RET proto-oncogene, and less frequently TRK, have been shown to be causative events specific for papillary cancer. RET activation was found in nearly 70% of the patients who developed papillary thyroid carcinomas following the Chernobyl accident. In addition to thyroid cancer, radiation-induced thyroid diseases include benign thyroid nodules, hypothyroidism and autoimmune thyroiditis, with or without thyroid insufficiency, as observed in populations after environmental exposure to radioisotopes of iodine and in the survivors of atomic bomb explosions. On this basis, the authors evaluated thyroid autoimmune phenomena in normal children exposed to radiation after the Chernobyl accident. The results demonstrated an increased prevalence of circulating thyroid antibodies not associated with significant thyroid dysfunction. This finding is consistent with the short period of follow-up, but it is highly likely that these children will develop clinical thyroid autoimmune diseases in the future. Therefore, screening programmes for this at-risk population should focus, not only on the detection of thyroid nodules and cancer, but also on the development of thyroid autoimmune diseases.

MODEST THYROID HORMONE INSUFFICIENCY DURING DEVELOPMENT INDUCES A CELLULAR MALFORMATION IN THE CORPUS CALLOSUM: A MODEL OF CORTICAL DYSPLASIA.

EPA Science Inventory

There is a growing body of evidence that subtle decreases in maternal thyroid hormone during gestation can impact fetal brain development. The present study examined the impact of graded levels of thyroid hormone insufficiency on brain development in rodents. Maternal thyroid ho...

THE EFFECTS OF ATRAZINE METABOLITES ON PUBERTY AND THYROID FUNCTION IN THE MALE WISTAR RAT

EPA Science Inventory

The Effects of Atrazine Metabolites on Puberty and Thyroid Function in the Male Wistar Rat. Stoker, T.E1., Guidici, D.L.2, Laws, S.C.2 and Cooper, R.L.2 Gamete and Early Embryo Biology Branch and 2 Endocrinology Branch, Reproductive Toxicology Division, National Health and Envir...

Thyroid Function in Early Pregnancy, Child IQ, and Autistic Traits: a Meta-analysis of Individual-participant Data.

PubMed

Levie, Deborah; Korevaar, Tim I M; Bath, Sarah C; Dalmau-Bueno, Albert; Murcia, Mario; Espada, Mercedes; Dineva, Mariana; Ibarluzea, Jesús M; Sunyer, Jordi; Tiemeier, Henning; Rebagliato, Marisa; Rayman, Margaret P; Peeters, Robin P; Guxens, Mònica

2018-05-10

Low maternal free thyroxine (FT4) has been associated with poor child neurodevelopment in some single-centre studies. Evidence remains scarce for potential adverse effects of high FT4 and whether associations differ in countries with a different iodine status. To assess the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status. Meta-analysis of individual-participant data compromising 9,036 mother-child pairs from three prospective population-based birth cohorts: INMA (Spain), Generation R (The Netherlands) and ALSPAC (United Kingdom). Exclusion criteria were multiple pregnancies, fertility treatments, thyroid interfering medication usage, and known thyroid disease. Child non-verbal IQ at 5-8 years of age, verbal IQ at 1.5-8 years of age, and autistic traits within the clinical range at 5-8 years of age. FT4 <2.5th percentile was associated with a 3.9 [95% confidence interval -5.7 to -2.2)] point lower non-verbal IQ and a 2.1 (-4.0 to -0.1) point lower verbal IQ. A suggestive association of hypothyroxinemia with a higher risk of autistic traits was observed. FT4 >97.5th percentile was associated with a 1.9 (1.0 to 3.4) fold higher risk of autistic traits. No independent associations were found with thyrotropin. Low maternal FT4 was consistently associated with lower IQ across cohorts. Further studies should replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay.

Early results of an in vivo trial of ESS in thyroid cancer

NASA Astrophysics Data System (ADS)

Rosen, Jennifer E.; Goukassian, Ilona D.; A'Amar, Ousama M.; Bigio, Irving J.; Lee, Stephanie L.

2012-02-01

Introduction: Thyroid cancer is the most common endocrine malignancy. The current gold standard for diagnosis, fine-needle aspiration (FNA) biopsy, yields 10-25% of indeterminate cytology results, leading to patients undergoing thyroidectomy for diagnosis. We assessed the technical potential of a miniaturized in vivo ESS (elastic light scattering spectroscopy) probe, built into an FNA needle assembly, to differentiate benign from malignant thyroid nodules. Methods: Under IRB approval, 15 patients in the endocrine clinic undergoing FNAB of a thyroid nodule had collection of ESS data using our novel miniaturized FNA probe. Using final surgical pathology as our gold standard, data post processing and visual inspection was completed. Results: 225 spectra were grouped and analyzed (120 benign, 30 malignant and 75 from indeterminate cytology). ESS probes demonstrated excellent reproducibility in use. Initial analysis of these preliminary data is promising, indicating distinction of spectral ESS features between malignant and benign conditions. Conclusion(s): An in vivo trial of an invasive miniaturized integrated ESS biopsy probe is acceptable to patients, and collection of ESS data is feasible and reliable. With development of a disease-specific algorithm, ESS could potentially be used as an in-situ real time intra-operative diagnostic tool or as a minimally invasive adjunct to conventional FNA cytology.

Fall in thyroid stimulating hormone (TSH) may be an early marker of ipilimumab-induced hypophysitis.

PubMed

De Sousa, Sunita M C; Sheriff, Nisa; Tran, Chau H; Menzies, Alexander M; Tsang, Venessa H M; Long, Georgina V; Tonks, Katherine T T

2018-06-01

Hypophysitis develops in up to 19% of melanoma patients treated with ipilimumab, a cytotoxic T-lymphocyte antigen-4 antibody. Early detection may avert life-threatening hypopituitarism. We aimed to assess the incidence of ipilimumab-induced hypophysitis (IH) at a quaternary melanoma referral centre, and to determine whether cortisol or thyroid stimulating hormone (TSH) monitoring could predict IH onset. We performed a retrospective cohort study of ipilimumab-treated patients at a quaternary melanoma referral centre in Australia. The inclusion criteria were patients with metastatic or unresectable melanoma treated with ipilimumab monotherapy, and cortisol and TSH measurements prior to ≥ 2 infusions. The main outcomes were IH incidence and TSH and cortisol patterns in patients who did and did not develop IH. Of 78 ipilimumab-treated patients, 46 met the study criteria and 9/46 (20%) developed IH at a median duration of 13.0 weeks (range 7.7-18.1) following ipilimumab initiation. All patients whose TSH fell ≥ 80% compared to baseline developed IH, and, in 5/9 patients with IH, TSH fell prior to cortisol fall and IH diagnosis. Pre-cycle-4 TSH was significantly lower in those who developed IH (0.31 vs. 1.73 mIU/L, P = 0.006). TSH fall was detected at a median time of 9.2 (range 7.7-16.4) weeks after commencing ipilimumab, and a median of 3.6 (range of - 1.4 to 9.7) weeks before IH diagnosis. There was no difference in TSH between the groups before cycles 1-3 or in cortisol before cycles 1-4. TSH fall ≥ 80% may be an early marker of IH. Serial TSH measurement during ipilimumab therapy may be an inexpensive tool to expedite IH diagnosis.

Thyroid storm masked by hemodialysis and glucocorticoid therapy in a patient with rheumatoid arthritis.

PubMed

Sasaki, Yohei; Shimizu, Yoshio; Nakata, Junichiro; Kameda, Toshiaki; Muto, Masahiro; Ohsawa, Isao; Io, Hiroaki; Hamada, Chieko; Horikoshi, Satoshi; Tomino, Yasuhiko

2012-01-01

Thyroid function test values are generally at low levels in patients with end-stage kidney disease. Life-threatening thyrotoxicosis or thyroid storm is rare, especially in hemodialysis (HD) patients, and is characterized by multisystem involvement and a high mortality rate if not immediately recognized and treated. Here, we report a female patient with severe symptomatic thyroid storm, receiving long-term HD and glucocorticoid therapy. Methimazole at a dose of 15 mg per day, β-adrenergic blockade and HD succeeded in controlling the patient's condition by gradually adjusting the target dry weight for hyperthyroidism-induced weight loss. When she was discharged from the hospital, her dry weight was reduced from 47.2 to 39.2 kg. The management of patients with severe symptomatic thyroid storm on HD represents a rare scenario. It is essential to initiate the available treatments as early as possible to reduce its mortality.

Thyrotoxicosis in patients with hypothyroidism is not just overtreatment.

PubMed

Kempegowda, Punith; Nayak, Ananth U

2017-07-14

A 62-year-old Caucasian woman presented with hypothyroid symptoms and biochemical thyrotoxic picture. Previously, she underwent right-sided subtotal thyroidectomy and left partial thyroid lobectomy for thyroid lumps, and treated with thyroxine replacement for hypothyroidism. Although there were no significant findings on clinical examination, investigations confirmed thyrotoxicosis with positive autoimmunity against thyroid glandâ€"all in line with a diagnosis of Graves’ hyperthyroidism. We would like to highlight atypical presentations of thyroid dysfunction and conversion of underactive to overactive thyroid status with this case. Early recognition, diagnosis and intervention are essential to prevent and/or reduce associated morbidity and mortality. When encountered with such clinical conundrums, we recommend seeking opinion from an experienced endocrinologist while interpreting such situation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Studies of the morphology of the thyroid gland and thyroid hormone levels in the blood of rats in experiments on "Kosmos-1667" and "Kosmos-1887"].

PubMed

Plakhuta-Plakutina, G I; Kabitskiĭ, E N; Dmitrieva, N P; Amirkhanian, E A

1990-01-01

Using histological, electron microscopic, and biochemical (measurement of total thyroxine, free thyroxine and triiodothyronine in plasma) method, thyroid glands of 17 male rats of the Wistar SPF strain flown for 7 days on Cosmos-1667 and for 13 days on Cosmos-1887 were investigated. It was found that a longer exposure to space flight effects (for 13 days) led to a thyroid activity decline (significant reduction of thyrocyte size and nuclear area, accumulation of colloid drops in the cytoplasm, decrease of iodinated thyroglobulins in the colloid, etc.) together with a substantial decrease of T4 and T3 in plasma. The above structural and functional changes in the thyroid gland and hormonal status are characteristic of a moderate stress-reaction and reflect variations of the early and intermediate stages of adaptation to microgravity during 7- and 13-day space flights.

Differentiated and Medullary Thyroid Cancer: Surgical Management of Cervical Lymph Nodes

PubMed Central

Asimakopoulos, P.; Nixon, I.J.; Shaha, A.R.

2017-01-01

Thyroid cancer metastasises to the central and lateral compartments of the neck frequently and early. The impact of nodal metastases on outcome is affected by the histological subtype of the primary tumour and the patient’s age, as well as the size, number and location of those metastases. The impact of extranodal extension has recently been highlighted as an important prognosticating factor. Although clinically evident nodal disease in the lateral neck compartments has a significant impact on both survival and recurrence, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. Here we discuss the surgical management of neck metastases in well-differentiated and medullary thyroid carcinoma. PMID:28094086

May the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and sporadic Parkinson's disease?

PubMed

Fernández, Emilio; García-Moreno, José-Manuel; Martín de Pablos, Angel; Chacón, José

2014-11-20

The research group has detected nitrosative stress and a singular version of nitrosylated serum α-synuclein in serum of Parkinson's disease (PD) patients. Dysfunction of the thyroid gland has been proposed to be linked to this disease. The aim of the study was to know if the thyroid gland is involved in idiopathic PD and nitrosative stress. We studied 50 patients (early and advanced disease patients), 35 controls, and 6 subjects with thyroidectomy. Clinical characteristics, serum thyroperoxidase levels, and 3-nitrotyrosine proteins were analyzed. Enzyme-linked immunosorbent assay and immunoblotting methods were employed. The findings indicated that the prevalence of two thyroid dysfunctions (hyper- or hypothyroidism) was not found to be different in patients relative to controls. However, the levels of the enzyme thyroperoxidase were found to be elevated in early disease patients (p<0.006), not in advanced disease subjects, and these levels were negatively correlated with serum 3-nitrotyrosine proteins (p<0.05), the indicators of nitrosative stress. The thyroidectomized subjects showed very low levels of serum 3-nitrotyrosine proteins (78% reduction vs. controls) and, among these proteins, the nitrosylated serum α-synuclein was nearly absent. These observations lead to the hypothesis that the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and they could influence Parkinsonian nitrosative stress as well as nitrosylation of serum α-synuclein, a potentially pathogenic factor.

Cabozantinib-induced thyroid dysfunction: a review of two ongoing trials for metastatic bladder cancer and sarcoma.

PubMed

Yavuz, Sahzene; Apolo, Andrea B; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A; Shawker, Thomas; Reynolds, James; Celi, Francesco S

2014-08-01

Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event.

Cabozantinib-Induced Thyroid Dysfunction: A Review of Two Ongoing Trials for Metastatic Bladder Cancer and Sarcoma

PubMed Central

Yavuz, Sahzene; Apolo, Andrea B.; Kummar, Shivaani; del Rivero, Jaydira; Madan, Ravi A.; Shawker, Thomas; Reynolds, James

2014-01-01

Background: Thyroid dysfunction is a common adverse event associated with tyrosine kinase inhibitors (TKI), but its underlying pathophysiology is unclear. Cabozantinib is a novel TKI currently Food and Drug Administration approved for advanced medullary thyroid cancer and tested in clinical trials on solid tumors including prostate, liver, bladder, breast, and ovarian cancer. Methods: We analyzed the thyroid function of patients enrolled in two phase 2 clinical trials using cabozantinib at the National Institutes of Health Clinical Center. Two cases of thyroiditis associated with cabozantinib therapy are presented in detail, and a systematic review of the literature on TKI-associated thyroid dysfunction is also discussed. Results: Between September 2012 and September 2013, 33 patients were treated with cabozantinib, and follow-up thyroid function tests were available for 31 (20 males, 11 females; age 59±1 years). Thyroid dysfunction was recorded in the majority of patients (93.1%), with a predominance of subclinical hypothyroidism. Two cases showed a biphasic pattern of thyroid dysfunction characterized by a transient thyrotoxicosis followed by hypothyroidism. Color Doppler demonstrated an increase in vascularization during the thyrotoxic phase, but no uptake was visualized on nuclear medicine imaging. A systematic review of the literature resulted in the identification of 40 original manuscripts, of which 13 were case series and 6 were case reports describing TKI-associated thyroid dysfunction. Conclusion: TKI therapy often results in clinically significant thyroid dysfunction. Cabozantinib treatment commonly results in thyroid dysfunction varying from subclinical hypothyroidism to symptomatic thyrotoxicosis. Early detection and characterization of cabozantinib-associated thyroid dysfunction and close follow-up are essential to provide adequate management of this common adverse event. PMID:24724719

Thyroiditis: a Clinico-cytomorphological Study with a Reference to the Ethnic Groups of Northeast Regions of India.

PubMed

Kalita, Abhijit; Baruah, Ronica

2015-12-01

Definite clinico-cytological criterion is outlined for thyroid lesions. Fine needle aspiration cytology (FNAC) makes it easier to segregate cases of thyroiditis (Chronic lymphocytic thyroiditis/Hashimoto's thyroiditis-CLT/HT, and subacute thyroiditis-SAT) from other benign and malignant lesions of thyroid. The study was done for a period of 5½ years at a diagnostic centre in Guwahati. Patients underwent FNAC and smears were studied for cytomorphology. A correlation with clinical features and thyroid function, including antithyroid antibody estimation, was done, wherever possible. 792 thyroid lesions were encountered during the study, of which 213 (26.89 %) were cases of thyroiditis (70.43 % CLT/HT, 24.9 % SAT and 3.76 % having overlapping features of CLT/HT and SAT); 2 cases (0.9 %) of CLT showed suspicion of Non-Hodgkin's Lymphoma (NHL), which was confirmed on histopathology. 24 cases (11.26 %) belonged to different ethnic tribal groups of Northeast India. CLT/HT presented predominantly with diffuse thyroid enlargement, but 12 cases (8 % of CLT/HT cases) had nodular enlargement. Patients presented with predominantly hypothyroidism; however occasional hyperthyroid cases were also seen. SAT showed signs of inflammation and presented with hyperthyroidism. Overlap cases of CLT/HT and SAT showed combined clinico-cytomorphological features of both lesions. 37.5 % cases with overlapping features belonged to tribal communities. A rise in incidence of thyroiditis, particularly CLT/HT, was seen. Overlap features of CLT/HT and SAT was noticed in significant percentage. No bias was noticed amongst any specific tribal community. FNAC, coupled with clinico-serological study, helps to diagnose thyroiditis at early stage.

Neuromuscular findings in thyroid dysfunction: a prospective clinical and electrodiagnostic study

PubMed Central

Duyff, R.; Van den Bosch, J.; Laman, D; van Loon, B.-J. P.; Linssen, W.

2000-01-01

OBJECTIVES—To evaluate neuromuscular signs and symptoms in patients with newly diagnosed hypothyroidism and hyperthyroidism.
METHODS—A prospective cohort study was performed in adult patients with newly diagnosed thyroid dysfunction. Patients were evaluated clinically with hand held dynamometry and with electrodiagnosis. The clinical features of weakness and sensory signs and the biochemical data were evaluated during treatment.
RESULTS—In hypothyroid patients 79% had neuromuscular complaints, 38% had clinical weakness (manual muscle strength testing) in one or more muscle groups, 42% had signs of sensorimotor axonal neuropathy, and 29% had carpal tunnel syndrome. Serum creatine kinase did not correlate with weakness. After 1 year of treatment 13% of the patients still had weakness. In hyperthyroid patients 67% had neuromuscular symptoms, 62% had clinical weakness in at least one muscle group that correlated with FT4 concentrations, but not with serum CK. Nineteen per cent of the patients had sensory-motor axonal neuropathy and 0% had carpal tunnel syndrome. The neuromuscular signs developed rapidly, early in the course of the disorder and were severe, but resolved rapidly and completely during treatment (average time 3.6months).
CONCLUSIONS—Neuromuscular symptoms and signs were present in most patients. About 40% of the hypothyroid patients and 20% of the hyperthyroid patients had predominantly sensory signs of a sensorimotor axonal neuropathy early in the course of thyroid disease. Weakness in hyperthyroidism evolved rapidly at an early stage of the disorder and resolved completely during treatment, suggesting a functional muscle disorder. Hand held dynamometry is sensitive for the detection of weakness and for the clinical evaluation of treatment effects. Weakness in hypothyroidism is more difficult to treat, suggesting myopathy.

 PMID:10811699

Antenatal/early postnatal hypothyroidism alters arterial tone regulation in 2-week-old rats.

PubMed

Sofronova, Svetlana I; Gaynullina, Dina K; Shvetsova, Anastasia A; Borzykh, Anna A; Selivanova, Ekaterina K; Kostyunina, Daria S; Sharova, Anna P; Martyanov, Andrey A; Tarasova, Olga S

2017-11-01

The mechanisms of vascular alterations resulting from early thyroid hormones deficiency are poorly understood. We tested the hypothesis that antenatal/early postnatal hypothyroidism would alter the activity of endothelial NO pathway and Rho-kinase pathway, which are specific for developing vasculature. Dams were treated with propylthiouracil (PTU, 7 ppm) in drinking water during gestation and 2 weeks after delivery, and their progeny had normal body weight but markedly reduced blood levels of thyroid hormones (ELISA). Small arteries from 2-week-old male pups were studied using wire myography, qPCR and Western blotting. Mesenteric arteries of PTU pups, compared to controls, demonstrated smaller maximum response to α 1 -adrenergic agonist methoxamine and reduced mRNA contents of smooth muscle differentiation markers α-actin and SERCA2A. Inhibition of basal NO synthesis by l-NNA led to tonic contraction of mesenteric arteries and augmented their contractile responses to methoxamine; both l-NNA effects were impaired in PTU pups. PTU pups demonstrated lower blood level of NO metabolites compared to control group (Griess reaction). Rho-kinase inhibitor Y27632 strongly reduced mesenteric arteries responses to methoxamine in PTU pups, that was accompanied by elevated Rho-kinase content in their arteries in comparison to control ones. Unlike mesenteric, saphenous arteries of PTU pups, compared to controls, had no changes in α-actin and SERCA2A contents and in responses to l-NNA and Y27632. In conclusion, thyroid hormones deficiency suppresses the anticontractile effect of NO and potentiates the procontractile Rho-kinase effects in mesenteric arteries of 2-week-old pups. Such alterations disturb perinatal cardiovascular homeostasis and might lead to cardiovascular pathologies in adulthood. © 2017 Society for Endocrinology.

Acute exposure to synthetic pyrethroids causes bioconcentration and disruption of the hypothalamus-pituitary-thyroid axis in zebrafish embryos.

PubMed

Tu, Wenqing; Xu, Chao; Lu, Bin; Lin, Chunmian; Wu, Yongming; Liu, Weiping

2016-01-15

Synthetic pyrethroids (SPs) have the potential to disrupt the thyroid endocrine system in mammals; however, little is known of the effects of SPs and underlying mechanisms in fish. In the current study, embryonic zebrafish were exposed to various concentrations (1, 3 and 10 μg/L) of bifenthrin (BF) or λ-cyhalothrin (λ-CH) until 72 h post fertilization, and body condition, bioaccumulation, thyroid hormone levels and transcription of related genes along the hypothalamus-pituitary-thyroid (HPT) axis examined. Body weight was significantly decreased in the λ-CH exposure groups, but not the BF exposure groups. BF and λ-CH markedly accumulated in the larvae, with concentrations ranging from 90.7 to 596.8 ng/g. In both exposure groups, alterations were observed in thyroxine (T4) and triiodothyronine (T3) levels. In addition, the majority of the HPT axis-related genes examined, including CRH, TSHβ, TTR, UGT1ab, Pax8, Dio2 and TRα, were significantly upregulated in the presence of BF. Compared to BF, λ-CH induced different transcriptional regulation patterns of the tested genes, in particular, significant stimulation of TTR, Pax8, Dio2 and TRα levels along with concomitant downregulation of Dio1. Molecular docking analyses revealed that at the atomic level, BF binds to thyroid hormone receptor (TRα) protein more potently than λ-CH, consequently affecting HPT axis signal transduction. In vitro and in silico experiments disclosed that during the early stages of zebrafish development, BF and λ-CH have the potential to disrupt thyroid endocrine system. Copyright © 2015 Elsevier B.V. All rights reserved.

Prevention and treatment of recurrent laryngeal nerve injury in thyroid surgery

PubMed Central

Jiang, Yan; Gao, Bo; Zhang, Xiaohua; Zhao, Jianjie; Chen, Jinping; Zhang, Shu; Luo, Donglin

2014-01-01

Aim: To summary the experience for prevention and treatment of recurrent laryngeal nerve (RLN) injury in thyroid surgery. Methods: Clinical features of 623 patients who received thyroid surgery from January 2010 to December 2012 were analyzed retrospectively, and the features of RLN injury and intraoperative as well as postoperative treatments were reviewed. Results: RLN injury occurred in 31 patients (4.98%), in which, unilateral RLN injury occurred in 27 patients and bilateral RLN injuries occurred in 4 patients (temporary injury in 28 patients and permanent injury in 3 patients). 6 patients underwent RLN anastomosis during surgery and exhibited transient hoarseness after surgery. RLN exploration and decompression was given in 1 patient and the patient got normal vocal cord motion 2 months after surgery. 1 patient with bilateral injuries received tracheotomy and CO2 laser resection of arytenoid cartilage and achieved recovery 1 year later. Conclusions: In order to prevent RLN injury, the anatomic variations of RLN should be mastered. Routine exposure of RLN can effectively prevent the injury in patients receiving the second or multiple surgeries. Early interventions for RLN injury include mainly early discovery, early exploration and early anastomosis, and the function of RLN in some patients can recover completely. Subsequent treatments mainly focus on the improvement of the voice, expansion of glottis and melioration of dyspnea. PMID:24482694

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...

Evaluation of uric acid levels, thyroid function, and anthropometric parameters in Japanese children with Down syndrome.

PubMed

Niegawa, Tomomi; Takitani, Kimitaka; Takaya, Ryuzo; Ishiro, Manabu; Kuroyanagi, Yuichi; Okasora, Keisuke; Minami, Yukako; Matsuda, Takuya; Tamai, Hiroshi

2017-09-01

Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort.

Embryonic epithelial Pten deletion through Nkx2.1-cre leads to thyroid tumorigenesis in a strain-dependent manner

PubMed Central

Tiozzo, Caterina; Danopoulos, Soula; Lavarreda-Pearce, Maria; Baptista, Sheryl; Varimezova, Radka; Al Alam, Denise; Warburton, David; Virender, Rehan; De Langhe, Stijn; Di Cristofano, Antonio

2014-01-01

Even though the role of the tyrosine phosphatase Pten as a tumor suppressor gene has been well established in thyroid cancer, its role during thyroid development is still elusive. We therefore targeted Pten deletion in the thyroid epithelium by crossing Ptenflox/flox with a newly developed Nkx2.1-cre driver line in the BALB/c and C57BL/6 genetic backgrounds. C57BL/6 homozygous Pten mutant mice died around 2 weeks of age due to tracheal and esophageal compression by a hyperplasic thyroid. By contrast, BALB/c homozygous Pten mutant mice survived up to 2 years, but with a slightly increased thyroid volume. Characterization of the thyroid glands from C57BL/6 homozygous Pten mutant mice at postnatal day 14 (PN14) showed abnormally enlarged tissue with areas of cellular hyperplasia, disruption of the normal architecture, and follicular degeneration. In addition, differing degrees of hypothyroidism, thyroxine (T4) decrease, and thyroid-stimulating hormone elevation between the strains in the mutants and the heterozygous mutant were detected at PN14. Finally, C57BL/6 heterozygous Pten mutant mice developed thyroid tumors after 2 years of age. Our results indicate that Pten has a pivotal role in thyroid development and its deletion results in thyroid tumor formation, with the timing and severity of the tumor depending on the particular genetic background. PMID:22167068

Regulation of fish growth hormone transcription.

PubMed

Farchi-Pisanty, O; Hackett, P B; Moav, B

1995-09-01

Regulation of endogenous fish growth hormone transcription was studied using carp pituitaries in vitro. It was demonstrated that thyroid hormone (T3) and 9-cis retinoic acid have increased the steady state levels of growth hormone messenger RNA in pituitary cells, as compared with beta-actin messenger RNA levels. In contrast, estrogen failed to increase growth hormone mRNA levels. The possible involvement of thyroid hormone receptor in pituitary gene expression was demonstrated by in situ localization of both growth hormone mRNA and thyroid hormone receptor mRNA in the pituitaries as early as 4 days after fertilization.

The effects of gestational transient thyrotoxicosis on the perinatal outcomes: a case-control study.

PubMed

Kinomoto-Kondo, Satoko; Umehara, Nagayoshi; Sato, Shiori; Ogawa, Kohei; Fujiwara, Takeo; Arata, Naoko; Sago, Haruhiko

2017-01-01

To study the effects of gestational transient thyrotoxicosis (GTT) on pregnancy outcomes. This case-control study retrospectively analyzed 7976 women with singleton pregnancies whose thyroid function was measured before 16 weeks of gestation and who delivered at ≥22 weeks of pregnancy. GTT was defined as hyperthyroidism (free thyroxine [FT4] level: ≥95th percentile) in the early pregnancy, which normalized in mid-pregnancy without thyroid-stimulating hormone receptor antibodies. Using data extracted from electronic records, we examined the association between GTT and the pregnancy outcomes (preterm delivery, gestational age at delivery, pregnancy induced hypertension (PIH), preeclampsia, placental abruption, caesarian section, birth weight, low birth weight, Apgar score, cord pH, stillbirth at gestational week ≥22, and neonatal death). We classified the cases into quartiles according to their FT4 values during the early pregnancy and investigated the association with the gestational age at delivery. Two hundred and eight cases of GTT and 6317 cases with normal thyroid assessments were reviewed. GTT was associated with hyperemesis gravidarum, but not with stillbirth, preterm delivery, PIH, preeclampsia, placental abruption, or low birth weight. The gestation period was shorter in patients with GTT than in those with a normal thyroid function (38.69 ± 1.79 vs. 39.07 ± 1.64 weeks, p < 0.01). Higher FT4 levels during the early pregnancy were associated with earlier delivery (p = 0.02). GTT was associated with a lower gestational age at delivery but not with adverse pregnancy outcomes. There was a negative correlation between the FT4 values in the early pregnancy and the gestational period.

Establishment and validation of the scoring system for preoperative prediction of central lymph node metastasis in papillary thyroid carcinoma.

PubMed

Liu, Wen; Cheng, Ruochuan; Ma, Yunhai; Wang, Dan; Su, Yanjun; Diao, Chang; Zhang, Jianming; Qian, Jun; Liu, Jin

2018-05-03

Early preoperative diagnosis of central lymph node metastasis (CNM) is crucial to improve survival rates among patients with papillary thyroid carcinoma (PTC). Here, we analyzed clinical data from 2862 PTC patients and developed a scoring system using multivariable logistic regression and testified by the validation group. The predictive diagnostic effectiveness of the scoring system was evaluated based on consistency, discrimination ability, and accuracy. The scoring system considered seven variables: gender, age, tumor size, microcalcification, resistance index >0.7, multiple nodular lesions, and extrathyroid extension. The area under the receiver operating characteristic curve (AUC) was 0.742, indicating a good discrimination. Using 5 points as a diagnostic threshold, the validation results for validation group had an AUC of 0.758, indicating good discrimination and consistency in the scoring system. The sensitivity of this predictive model for preoperative diagnosis of CNM was 4 times higher than a direct ultrasound diagnosis. These data indicate that the CNM prediction model would improve preoperative diagnostic sensitivity for CNM in patients with papillary thyroid carcinoma.

Thyroid Hormones Concentrations during the Mid-Dry Period: An Early Indicator of Fatty Liver in Holstein-Friesian Dairy Cows

PubMed Central

Šamanc, Horea; Stojić, Velibor; Kirovski, Danijela; Jovanović, Milijan; Cernescu, Horia; Vujanac, Ivan

2010-01-01

Relationship between postpartal fatty liver and thyroid gland activity during the peripartal and mid dry periods was studied. Twenty one dry cows were chosen. Blood samples were obtained on days −30, −2, and +12 related to calving and analized for thyroxine (T4) and triiodothyronine (T3). A T3/T4 ratio was calculated. Liver tissue samples were taken 12 d after calving and tested for the lipid content. Cows were divided into three groups: mild (<20% fat), moderate (20 to 30%), or severe fatty liver (>30%). Cows, that were affected with severe fatty liver, were hypothyroid prior to development of the condition due to lower T4 concentrations, and had significantly lower concentration of T3 and higher T3/T4 ratios than cows with mild and moderate fatty liver. Thus, hypothyroid state during mid-dry period may be an early indicator of postpartal fatty liver and may provoke T3/T4 ratio increase in this group of cows. PMID:21048844

Primary mucinous carcinoma with rhabdoid cells of the thyroid gland: a case report.

PubMed

Matsuo, Mioko; Tuneyoshi, Masazumi; Mine, Mari

2016-06-10

Primary mucinous carcinoma of the thyroid gland is a rare disease; only 6 cases of primary mucinous carcinoma of the thyroid have been previously reported. Primary mucinous carcinoma of the thyroid gland with incomplete tumor resection tends to be associated with a poor prognosis, resulting in death within a few months. An early and appropriate diagnosis may contribute to improvement in patient prognosis; however, it is extremely difficult to diagnose primary mucinous carcinoma of the thyroid. We present the seventh reported case of primary mucinous carcinoma in the thyroid gland; moreover, rhabdoid cells were detected, which, to our knowledge, is a novel finding. An 81-year-old Japanese woman was initially diagnosed with a poorly differentiated thyroid carcinoma, and she underwent a hemithyroidectomy. Pathological examination revealed the presence of abundant mucus and agglomeration of large atypical cells. Rhabdoid cells were also seen scattered among the tumor cells. Immunostaining was performed for various markers, and on the basis of these results, we diagnosed the lesion as primary mucinous carcinoma with rhabdoid cells in the thyroid gland. Ten months after surgery, recurrence was noted in the paratracheal lymph nodes; therefore, total resection of the residual thyroid gland and paratracheal lymphadenectomy with thyroid-stimulating hormone suppression were performed. The patient is currently alive and disease-free. The current case is of interest not only because of the rare histological findings, but also because the patient achieved long-term survival following diagnosis of a mucinous carcinoma. We believe this report will be helpful for diagnosing future cases of mucinous carcinoma of the thyroid.

Trends of Thyroid Cancer in Israel: 1980–2012

PubMed Central

Keinan-Boker, Lital; Silverman, Barbara G.

2016-01-01

Objectives: Thyroid cancer incidence is increasing worldwide, while mortality from thyroid cancer is stable or decreasing. Consequently, survival rates are rising. We describe time trends in the incidence, mortality, and 5-year survival of thyroid cancer in Israel in 1980–2012, in light of the global trends. Methods: Israel National Cancer Registry database provided information regarding thyroid cancer incidence and vital status, which enabled computation of survival rates. The Central Bureau of Statistics database provided information on thyroid cancer mortality. Incidence and mortality rates were age-adjusted and presented by population group (Jews/Arabs) and gender. Relative 5-year survival rates which account for the general population survival in the corresponding time period were presented by population group and gender. Joinpoint analyses were used to assess incidence trends over time. Results: In 1980–2012 significant increases in the incidence of thyroid cancer were observed, with an annual percent change (APC) range of 3.98–6.93, driven almost entirely by papillary carcinoma (APCs 5.75–8.86), while rates of other types of thyroid cancer remained stable or decreased. Furthermore, higher rates of early detection were noted. In 1980–2012, a modest reduction in thyroid cancer mortality was observed in Jewish women (APC −1.07) with no substantial change in Jewish men. The 5-year relative survival after thyroid cancer diagnosis has increased to ≥90% in both population groups and both genders. Conclusions: The Israeli secular trends of thyroid cancer incidence (increasing), mortality (mostly stable), and survival (modestly increasing) closely follow reported global trends. PMID:26886958

Ultrasonography of Various Thyroid Diseases in Children and Adolescents: A Pictorial Essay

PubMed Central

Lee, Eun Hye; Jeong, Sun Hye; Park, Jisang; Lee, Heon

2015-01-01

Thyroid imaging is indicated to evaluate congenital hypothyroidism during newborn screening or in cases of a palpable thyroid mass in children and adolescents. This pictorial essay reviews the ultrasonography (US) of thyroid diseases in children and adolescents, including normal thyroid gland development, imaging features of congenital thyroid disorders (dysgenesis, [aplasia, ectopy, hypoplasia], dyshormonogenesis, transient hypothyroidism, thyroglossal duct cyst), diffuse thyroid disease (Grave's disease, Hashimoto's thyroiditis, and suppurative thyroiditis), and thyroid nodules. The primary imaging modalities for evaluating thyroid diseases are US and radionuclide scintigraphy. Additionally, US can be used to guide aspiration of detected nodules. PMID:25741204

Thyroid hypofunction after exposure to fallout from a hydrogen bomb explosion.

PubMed

Larsen, P R; Conard, R A; Knudsen, K D; Robbins, J; Wolff, J; Rall, J E; Nicoloff, J T; Dobyns, B M

1982-03-19

Thyroid function was evaluated in the Marshallese who were accidentally exposed to fallout-containing radioiodine isotopes in 1954. Measurements of thyrotrophin (TSH, thyroid-stimulating hormone) levels and free thyroxine (T4) index (FT4I) have revealed that, among 86 persons exposed on Rongelap and Ailingnae atolls, 14 have shown evidence of thyroid hypofunction. This was first noted in some individuals about ten years after exposure. Only two of these showed clinical evidence of hypothyroidism. The most marked TSH elevations were noted in nine persons exposed when younger than 6 years, with estimated doses to the thyroid from 390 to 2,100 rad. Most of this group subsequently had surgery for removal of thyroid nodules. The remaining five cases have been noted more recently among 36 surviving adults exposed at an older age who showed no other detectable thyroid abnormalities. This group had received estimated thyroid doses ranging from 135 to 335 rad and showed modest elevation of serum TSH levels (6 to 9 microU/mL) and a slightly subnormal FT4I. No abnormalities were found in persons on Utirik who received substantially less radiation, and hypothyroidism was present in less than 1% of the control, unexposed Marshallese. The high prevalence of a thyroid hypofunction in these persons indicates that this condition, as well as thyroid nodularity, can be a delayed complication of exposure to early fallout from a nuclear explosion. The fact that a significant fraction of the radiation to the thyroid was from short-lived radioiodine isotopes (132I, 133I, 135I), as opposed to 131I, may account for the severity of the thyroid damage.

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

PubMed

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

2011-01-01

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

[Atypical subacute thyroiditis in combination with Grave's disease:Diagnostic difficulties in a case report].

PubMed

Koutouridou, Emmanouela; Planck, Tereza; Uddman, Erik; Lantz, Mikael

2018-04-13

Subacute thyroiditis is a common inflammatory disorder of the thyroid gland, possibly of viral etiology, that typically presents with neck pain, fever and tenderness on palpation of the thyroid gland. Graves' disease is an autoimmune thyroid disorder caused by stimulation of the thyroid gland by thyrotropin receptor antibodies (TRAb). The development of Graves´ disease and subacute thyroiditis simultaneously is an uncommon condition and only a few cases have been reported. In this article we present a case of a 46-year old woman diagnosed with Graves´ disease who was started on thiamazole and weeks later developed high fever. Several differential diagnoses were considered such as infection, lymphoma and vasculitis due to thiamazole. Finally, the fine needle aspiration of the thyroid gland displayed histopathological features of subacute thyroiditis. Remarkably, our patient did not have neck pain or tenderness on palpation of the thyroid gland and overall the clinical presentation of subacute thyroiditis was atypical. Thus, subacute thyroiditis may be considered as a potential cause of fever of unknown origin.

Update on subclinical hyperthyroidism.

PubMed

Donangelo, Ines; Braunstein, Glenn D

2011-04-15

Subclinical hyperthyroidism is defined by low or undetectable serum thyroid-stimulating hormone levels, with normal free thyroxine and total or free triiodothyronine levels. It can be caused by increased endogenous production of thyroid hormone (as in Graves disease or toxic nodular goiter), administration of thyroid hormone for treatment of malignant thyroid disease, or unintentional excessive thyroid hormone therapy. The rate of progression to overt hyperthyroidism is higher in persons who have suppressed thyroid-stimulating hormone levels compared with those who have low but detectable levels. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation in older adults, and with decreased bone mineral density in postmenopausal women; however, the effectiveness of treatment in preventing these conditions is unknown. There is lesser-quality evidence suggesting an association between subclinical hyperthyroidism and other cardiovascular effects, including increased heart rate and left ventricular mass, and increased bone turnover markers. Possible associations between subclinical hyperthyroidism and quality of life parameters, cognition, and increased mortality rates are controversial. Prospective randomized controlled trials are needed to address the effects of early treatment on potential morbidities to help determine whether screening should be recommended in the asymptomatic general population.

Inherited hypothyroidism.

PubMed

Jackson, I M

1976-03-01

Familial hypothyroidism results from both thyroidal and extrathyroidal dysfunction. Specific intrathyroidal abnormalities in thyroid hormone synthesis causing goitrous hypothyroidism are iodide trap defect, organification defect, "coupling" defect, iodoprotein defect, and dehalogenase defect. The diagnostic studies for each are outlined utilizing radioiodine(131I) studies. Other causes of cretinism include failure of the thyroid gland to respond to TSH and lack of pituitary TSH (or hypothalamic TRH). The syndrome of peripheral resistance to thyroid hormone is discussed. The diagnosis of inherited hypothyrodism rests on an adequate family history and measurement of both T4 and TSH levels which can be determined in cord blood or peripheral blood from the infant. The importance of early treatment of hypothyroidism in the neonatal period to prevent brain damage is emphasized. The rec:nt discovery of the importance of reverse T3 (RT3) in fetal thyroid metabolism is described, and the possibility of amniocentesis as an aid in prenatal diagnosis is considered. The place of intrauterine administration of thyroid hormone to the fetus at risk from hypothyroidism is uncertain at this time and requires carefully controlled studies and long-term follow-up.

Ventricular Fibrillation Associated With Dynamic Changes in J-Point Elevation in a Patient With Silent Thyroiditis.

PubMed

Karashima, Shigehiro; Tsuda, Toyonobu; Wakabayashi, Yusuke; Kometani, Mitsuhiro; Demura, Masashi; Ichise, Taro; Kawashiri, Masa-Aki; Takeda, Yoshiyu; Hayashi, Kenshi; Yoneda, Takashi

2018-02-01

A J wave is a common electrocardiographic finding in the general population. Individuals with prominent J waves in multiple electrocardiogram (ECG) leads have a higher risk of lethal arrhythmias than those with low-amplitude J waves. There are few reports about the relationship between thyroid function and J-wave amplitude. We report the case of a 45-year-old man who had unexpected ventricular fibrillation (VF). He had dynamic J-point elevation in multiple ECG leads. Possible early repolarization syndrome was diagnosed. He also had thyrotoxicosis caused by silent thyroiditis, and his J-wave amplitude decreased according to changes in thyroid function because of spontaneous remission of silent thyroiditis. There was a positive correlation between serum triiodothyronine levels and J-wave amplitudes. The findings in case suggested silent thyroiditis may contribute to the occurrence of VF in a patient with dynamic changes in J-point elevation in multiple ECG leads. Thyrotoxicosis is a relatively common endocrine disease; therefore, clinicians should pay attention to J-wave amplitude in the ECG of patients with thyrotoxicosis.

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.

Molecular genetic markers for thyroid FNAB. Established assays and future perspective.

PubMed

Musholt, Thomas J; Musholt, P B

2015-01-01

Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18-65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

PubMed Central

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Marui, Suemi

2011-01-01

OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up. PMID:22012048

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin.

PubMed

Danilovic, Debora Lucia Seguro; Mendes-Correa, Maria Cassia; Chammas, Maria Cristina; Zambrini, Heverton; Marui, Suemi

2011-01-01

To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. Of the patients in our study, 54% had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19% of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16% had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11% remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up.

Development and validation of a patient symptom questionnaire to facilitate early diagnosis of thyroid-associated orbitopathy in graves' disease.

PubMed

Mohaseb, Kam; Linder, Mark; Rootman, Jack; Wilkins, G E; Schechter, Martin T; Dolman, Peter J; Singer, Joel

2008-01-01

To construct a patient-based symptom questionnaire to facilitate early referral of thyroid-associated orbitopathy (TAO) in Graves' hyperthyroidism (GH). Phase I of our study involved developing a symptomatology-based questionnaire for the self-reporting of TAO symptoms in patients recently diagnosed with GH. Phase II involved administering the questionnaire along with a standard ophthalmic examination to a screening cohort of patients newly diagnosed with GH. Symptoms highly associated with the clinical diagnosis of TAO were used to construct a tool with the highest possible sensitivity. Phase III involved validation of this tool in a new cohort of patients recently diagnosed with GH. For each patient, the diagnosis of TAO was made by both a standardized orbital ophthalmic exam and the questionnaire. Results from the questionnaire were then compared to the clinical examination. The questionnaire was compared to the standardized examination and found to have a sensitivity of 0.76 and a specificity of 0.82 in the validation phase of the study. This questionnaire may be a useful tool in clinical practice to allow identification of patients with TAO secondary to GH. Future studies using this questionnaire are needed to determine whether earlier identification and management of these patients is associated with reduced morbidity from TAO.

Revising the embryonic origin of thyroid C cells in mice and humans

PubMed Central

Johansson, Ellen; Andersson, Louise; Örnros, Jessica; Carlsson, Therese; Ingeson-Carlsson, Camilla; Liang, Shawn; Dahlberg, Jakob; Jansson, Svante; Parrillo, Luca; Zoppoli, Pietro; Barila, Guillermo O.; Altschuler, Daniel L.; Padula, Daniela; Lickert, Heiko; Fagman, Henrik; Nilsson, Mikael

2015-01-01

Current understanding infers a neural crest origin of thyroid C cells, the major source of calcitonin in mammals and ancestors to neuroendocrine thyroid tumors. The concept is primarily based on investigations in quail–chick chimeras involving fate mapping of neural crest cells to the ultimobranchial glands that regulate Ca2+ homeostasis in birds, reptiles, amphibians and fishes, but whether mammalian C cell development involves a homologous ontogenetic trajectory has not been experimentally verified. With lineage tracing, we now provide direct evidence that Sox17+ anterior endoderm is the only source of differentiated C cells and their progenitors in mice. Like many gut endoderm derivatives, embryonic C cells were found to coexpress pioneer factors forkhead box (Fox) a1 and Foxa2 before neuroendocrine differentiation takes place. In the ultimobranchial body epithelium emerging from pharyngeal pouch endoderm in early organogenesis, differential Foxa1/Foxa2 expression distinguished two spatially separated pools of C cell precursors with different growth properties. A similar expression pattern was recapitulated in medullary thyroid carcinoma cells in vivo, consistent with a growth-promoting role of Foxa1. In contrast to embryonic precursor cells, C cell-derived tumor cells invading the stromal compartment downregulated Foxa2, foregoing epithelial-to-mesenchymal transition designated by loss of E-cadherin; both Foxa2 and E-cadherin were re-expressed at metastatic sites. These findings revise mammalian C cell ontogeny, expand the neuroendocrine repertoire of endoderm and redefine the boundaries of neural crest diversification. The data further underpin distinct functions of Foxa1 and Foxa2 in both embryonic and tumor development. PMID:26395490

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

PubMed Central

2014-01-01

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

[Thyroiditis].

PubMed

Buffet, Camille; Groussin, Lionel

2013-02-01

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

Progress in molecular-based management of differentiated thyroid cancer

PubMed Central

Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

2014-01-01

Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

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

Differentiated thyroid cancer associated with intestinal polyposis syndromes: a review.

PubMed

Harb, William J; Sturgis, Erich M

2009-11-01

Intestinal polyposis syndromes, such as familial adenomatous polyposis (FAP) and Cowden's syndrome, are often associated with extraintestinal manifestations, and while many of these manifestations are benign, malignant extraintestinal manifestations, such as differentiated thyroid cancers, do occur. Although differentiated thyroid cancers (ie, papillary and follicular thyroid carcinomas) are associated with multiple syndromes, they are most commonly associated with intestinal polyposis syndromes. In the general population, the probability of developing thyroid cancer by age 65 years is only .5%. However, 1% to 2% of patients with FAP develop papillary thyroid carcinoma, the most common extraintestinal malignancy in patients with FAP. Also, up to 10% of patients with Cowden's syndrome will develop follicular thyroid carcinoma. The purpose of this review was to provide an overview of FAP, Cowden's syndrome, and Peutz-Jeghers syndrome, to discuss in detail the associations between intestinal polyposis syndromes and differentiated thyroid cancers, and to provide suggestions for screening and managing these diseases. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009.

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.

May the Thyroid Gland and Thyroperoxidase Participate in Nitrosylation of Serum Proteins and Sporadic Parkinson's Disease?

PubMed Central

García-Moreno, José-Manuel; Martín de Pablos, Angel; Chacón, José

2014-01-01

Abstract The research group has detected nitrosative stress and a singular version of nitrosylated serum α-synuclein in serum of Parkinson's disease (PD) patients. Dysfunction of the thyroid gland has been proposed to be linked to this disease. The aim of the study was to know if the thyroid gland is involved in idiopathic PD and nitrosative stress. We studied 50 patients (early and advanced disease patients), 35 controls, and 6 subjects with thyroidectomy. Clinical characteristics, serum thyroperoxidase levels, and 3-nitrotyrosine proteins were analyzed. Enzyme-linked immunosorbent assay and immunoblotting methods were employed. The findings indicated that the prevalence of two thyroid dysfunctions (hyper- or hypothyroidism) was not found to be different in patients relative to controls. However, the levels of the enzyme thyroperoxidase were found to be elevated in early disease patients (p<0.006), not in advanced disease subjects, and these levels were negatively correlated with serum 3-nitrotyrosine proteins (p<0.05), the indicators of nitrosative stress. The thyroidectomized subjects showed very low levels of serum 3-nitrotyrosine proteins (78% reduction vs. controls) and, among these proteins, the nitrosylated serum α-synuclein was nearly absent. These observations lead to the hypothesis that the thyroid gland and thyroperoxidase participate in nitrosylation of serum proteins and they could influence Parkinsonian nitrosative stress as well as nitrosylation of serum α-synuclein, a potentially pathogenic factor. Antioxid. Redox Signal. 21, 2143–2148. PMID:25125346

Thyroid hormone elevations during acute psychiatric illness: relationship to severity and distinction from hyperthyroidism.

PubMed

Roca, R P; Blackman, M R; Ackerley, M B; Harman, S M; Gregerman, R I

1990-01-01

Acute psychiatric illness may be accompanied by transient hyperthyroxinemia. The mechanism of this phenomenon was examined by determining the role of thyrotropin (TSH) in the genesis of this state. Serial measurements of TSH, thyroxine (T4), free T4 index (FT4I), triiodothyronine (T3), and free T3 index (FT3I) were performed in 45 acutely hospitalized patients with major psychiatric disorders. Twenty-two (49%) patients exhibited significant elevations (greater than or equal to 2 SD above mean value of controls) of one or more thyroid hormone (or index) levels. Among depressed patients with elevated FT4I, TSH was higher (p less than .05) on the day of the peak FT4I than on the day of the FT4I nadir. There were significant positive correlations between psychiatric symptom severity and levels of FT4I among both depressed (p less than .01) and schizophrenic (p less than .025) patients. These data show that elevations of T4, FT4I, T3, and FT3I are common among psychiatric inpatients, especially early in their hospitalization, and that levels of thyroid hormones are correlated with severity of psychiatric symptomatology. TSH is higher early in the acute phase of illness and is not suppressed in the face of elevated thyroid hormone levels, a finding that distinguishes this phenomenon from ordinary hyperthyroidism. Elevations of peripheral thyroid hormone levels, particularly among depressed patients, may result from a centrally-mediated hypersecretion of TSH.

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

Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents.

PubMed

Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey

2018-04-01

In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows' milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper.

Comparative analysis of the countermeasures taken to mitigate exposure of the public to radioiodine following the Chernobyl and Fukushima accidents: lessons from both accidents

PubMed Central

Uyba, Vladimir; Samoylov, Alexander; Shinkarev, Sergey

2018-01-01

Abstract In the case of a severe radiation accident at a nuclear power station, the most important radiation hazard for the public is internal exposure of the thyroid to radioiodine. The purposes of this paper were (i) to compare countermeasures conducted (following the Chernobyl and Fukushima accidents) aimed at mitigation of exposure to the thyroid for the public, (ii) to present comparative estimates of doses to the thyroid and (iii) to derive lessons from the two accidents. The scale and time of countermeasures applied in the early phase of the accidents (sheltering, evacuation, and intake of stable iodine to block the thyroid) and at a later time (control of 131I concentration in foodstuffs) have been described. After the Chernobyl accident, the estimation of the thyroid doses for the public was mainly based on direct thyroid measurements of ~400 000 residents carried out within the first 2 months. The highest estimates of thyroid doses to children reached 50 Gy. After the Fukushima accident, the estimation of thyroid doses was based on radioecological models due to a lack of direct thyroid measurements (only slightly more than 1000 residents were measured). The highest estimates of thyroid doses to children were a few hundred mGy. Following the Chernobyl accident, ingestion of 131I through cows’ milk was the dominant pathway. Following the Fukushima accident, it appears that inhalation of contaminated air was the dominant pathway. Some lessons learned following the Chernobyl and Fukushima accidents have been presented in this paper. PMID:29415268

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

Distinct Disease and Functional Characteristics of Thyroid Surgery-Related Vocal Fold Palsy.

PubMed

Tseng, Wen-Chun; Pei, Yu-Cheng; Wong, Alice M K; Li, Hsueh-Yu; Fang, Tuan-Jen

2016-07-01

Iatrogenic trauma induced by thyroid surgery is the most common etiology of unilateral vocal fold paralysis (UVFP). UVFP after thyroid surgery may lead to profound physical and psychosocial distress. This study comprehensively evaluated UVFP caused by thyroid surgery, and compared the results with those caused by other surgical trauma. Patients with surgery-related UVFP were evaluated using quantitative laryngeal electromyography, videolaryngostroboscopy, voice acoustic analysis, the Voice Outcome Survey, and the Short Form-36 Health Survey quality-of-life questionnaire. Patients with thyroid surgery and other surgeries were compared. A total of 105 patients were recruited, of whom 52 and 53 were assigned to the thyroid surgery and the other surgery group, respectively. Patients in the thyroid surgery group had a higher proportion of external branch of superior laryngeal nerve (eSLN) involvement, longer duration from disease onset to the first laryngeal electromyography examination, lower jitter, higher harmonic-to-noise ratio, and better quality of life compared with the other surgery group. Specifically for patients in the thyroid surgery group, those with eSLN involvement tended to have more pronounced impairment in jitter and shimmer compared with patients without eSLN involvement. UVFP caused by thyroid surgery has a distinct clinical presentation with relatively high involvement in the eSLN, better voice acoustics, longer waiting time before asking for evaluation, and less impact on quality of life. The involvement of eSLN in these patients further impaired their voice. Early referral is suggested for these patients, especially with suspected eSLN injury.

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.

Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area.

PubMed

Huszno, B; Szybiński, Z; Przybylik-Mazurek, E; Stachura, J; Trofimiuk, M; Buziak-Bereza, M; Gołkowski, F; Pantoflinski, J

2003-01-01

The aim of the study was to evaluate the correlation between thyroid cancer histotype and incidence rate (IR) and iodine nutrition level in two endemic goiter areas: the districts of Krakow and Nowy Sacz. The suspension of iodine prophylaxis in Poland in 1980 resulted in increased goiter prevalence in schoolchildren and adults and elevated TSH levels in newborns in the early 1990s. Since 1992 a rise in thyroid cancer IR was observed. Thyroid cancer IR in the Krakow population was 2.22 in 1986; 3.62 in 1995 and 6.02 in 2001; in Nowy Sacz: 1.52; 2.59 and 3.88 respectively. In 1986 papillary/follicular cancer ratio in both areas was about 1.0--the value typical of iodine deficient areas. After restoring the obligatory iodine prophylaxis in 1997, a significant decrease in elevated TSH concentration in newborns and urinary iodine concentration increase in schoolchildren were observed. A relative rise in the incidence of papillary thyroid cancer and decrease in follicular cancer, resulting in rise in papillary/follicular thyroid cancer ratio up to 5.9 in 2001 was also observed. Since 1999 no further thyroid cancer IR increase was noted. In conclusion, a significant increase in differentiated thyroid cancer IR was observed in association with the iodine prophylaxis suspension. Changes in thyroid cancer histotypes in 1986-2001 and a significant decrease in incremental rate of differentiated thyroid cancer probably reflect the influence of effective iodine prophylaxis. The significant difference between IR of thyroid cancer incidence in the districts of Krakow and Nowy Sacz may be related to differences in the exposure to radiation after the Chernobyl accident.

Back so soon? – Is early recurrence of Papillary Thyroid Cancer really just persistent disease?

PubMed Central

Bates, Maria F; Lamas, Marcos R; Randle, Reese W; Long, Kristin L; Pitt, Susan C; Schneider, David F; Sippel, Rebecca S

2017-01-01

Background Papillary thyroid carcinoma (PTC) has excellent survival, yet recurrence remains a challenge. We sought to determine the proportion of re-operations performed for persistent, rather than truly recurrent disease. Methods We conducted a retrospective review of a prospectively maintained database. Patients with PTC that had re-operation for disease from 2000–2016 were included. We defined recurrence as disease that developed after a patient had an undetectable thyroglobulin and negative ultrasound within one year of surgery. Results A total of 69 patients underwent 92 re-operations. On initial pathology: mean tumor size was 2.6cm; 50.7% were multifocal; and 42% had extra-thyroidal extension. Half (46%) of the patients underwent a central/lateral neck dissection at initial surgery and 76.8% were treated with post-operative radioactive iodine. The median time to first re-operation was 21 months (range, 1–292), and 41.8% occurred within 1 year. Only three operations met criteria for true “recurrence”, while 71 operations were categorized as persistence. Conclusion Many re-operations for PTC are for management of persistent disease. Over half of the patients required re-operation within the first two years, which strongly suggests that improvements in the pre-operative assessment and adequacy of initial surgery need to be made to improve the care of patients with thyroid cancer. PMID:29128176

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...

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.

Thyrotoxicosis-induced acute myocardial infarction due to painless thyroiditis.

PubMed

Kim, Hee Jin; Jung, Tae Sik; Hahm, Jong Ryeal; Hwang, Seok-Jae; Lee, Sang Min; Jung, Jung Hwa; Kim, Soo Kyoung; Chung, Soon Il

2011-10-01

Thyrotoxicosis influences cardiovascular hemodynamics and can induce coronary vasospasm. Patients with thyrotoxicosis-induced acute myocardial infarction (AMI) are unusual and almost all reported cases have been associated with Graves' disease. Patients with painless thyroiditis show a thyrotoxic phase during the early stages. Here we describe a very rare case of thyrotoxicosis with painless thyroiditis-induced AMI. A 35-year-old Korean man visited the emergency room for a 2-hour duration of typical AMI chest pain. The patient did not have any coronary artery disease (CAD) risk factors. The electrocardiogram showed 3 mm of ST-segment elevation in leads II, III, and aVF, which is consistent with inferior AMI. We immediately treated the patient with aspirin, clopidogrel, and nitroglycerine and performed emergent coronary angiography. Coronary angiography showed normal coronary arteries without any stenotic lesions. Consistent with AMI, cardiac enzyme levels of serum creatine kinase (CK), CK-MB, and troponin-I were also elevated. Laboratory findings showed thyrotoxicosis without any thyroid autoantibodies. A 99m-technetium scintigraphy showed markedly decreased thyroid uptake compatible with thyroiditis. We treated the patient with calcium channel blockers and nitrates. The patient spontaneously recovered normal thyroid function after 6 weeks of observation and did not complain of chest pain. Thyrotoxicosis due to painless thyroiditis provoked AMI in a young man who had no atherosclerotic coronary lesions and no CAD risk factors.

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

PubMed

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

2010-12-01

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

Thyroid Cancer Risk Assessment Tool

Cancer.gov

The R package thyroid implements a risk prediction model developed by NCI researchers to calculate the absolute risk of developing a second primary thyroid cancer (SPTC) in individuals who were diagnosed with a cancer during their childhood.

Histopathologic study of the so called 'palpation thyroiditis'.

PubMed Central

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

1988-01-01

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

[Core principles of treatment of corneal damage in patients with thyroid eye disease].

PubMed

Grusha, Y O; Ismailova, D S; Sherstneva, L V

To develop a therapeutic approach and to estimate the efficiency of complex treatment of corneal damage in patients with thyroid eye disease (TED). The study enrolled 44 patients (52 eyes) divided into 2 groups depending on the severity of corneal damage. Treatment of those with severe involvement included pathogenetic measures (pulse steroid therapy and/or radiation therapy) and surgery (orbital decompression, eyelid and corneal surgery). As the result of the treatment, orbital inflammation decreased and the state of the cornea improved in all patients. The treatment of corneal damage in patients with TED may differ depending on numerous factors, such as the severity of corneal damage and activity of orbital inflammation. Taking into account the potential danger of corneal involvement, one should make efforts to early detection and management of the risk factors.

NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

PubMed Central

Schneider, David F.; Chen, Herbert

2013-01-01

Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834

Thyroidectomy: post-operative care and common complications.

PubMed

Furtado, L

Any surgical procedure involves risks. Thyroid surgery can cause potentially fatal complications during the early post-operative phase. It is essential that nurses have the knowledge and skills to detect early signs and symptoms of potential complications and take appropriate action. Early detection and rapid response are key to maintaining patient safety and minimising harm.

Modeling mixtures of thyroid gland function disruptors in a vertebrate alternative model, the zebrafish eleutheroembryo

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

Thienpont, Benedicte; Barata, Carlos; Raldúa, Demetrio, E-mail: drpqam@cid.csic.es

2013-06-01

Maternal thyroxine (T4) plays an essential role in fetal brain development, and even mild and transitory deficits in free-T4 in pregnant women can produce irreversible neurological effects in their offspring. Women of childbearing age are daily exposed to mixtures of chemicals disrupting the thyroid gland function (TGFDs) through the diet, drinking water, air and pharmaceuticals, which has raised the highest concern for the potential additive or synergic effects on the development of mild hypothyroxinemia during early pregnancy. Recently we demonstrated that zebrafish eleutheroembryos provide a suitable alternative model for screening chemicals impairing the thyroid hormone synthesis. The present study usedmore » the intrafollicular T4-content (IT4C) of zebrafish eleutheroembryos as integrative endpoint for testing the hypotheses that the effect of mixtures of TGFDs with a similar mode of action [inhibition of thyroid peroxidase (TPO)] was well predicted by a concentration addition concept (CA) model, whereas the response addition concept (RA) model predicted better the effect of dissimilarly acting binary mixtures of TGFDs [TPO-inhibitors and sodium-iodide symporter (NIS)-inhibitors]. However, CA model provided better prediction of joint effects than RA in five out of the six tested mixtures. The exception being the mixture MMI (TPO-inhibitor)-KClO{sub 4} (NIS-inhibitor) dosed at a fixed ratio of EC{sub 10} that provided similar CA and RA predictions and hence it was difficult to get any conclusive result. There results support the phenomenological similarity criterion stating that the concept of concentration addition could be extended to mixture constituents having common apical endpoints or common adverse outcomes. - Highlights: • Potential synergic or additive effect of mixtures of chemicals on thyroid function. • Zebrafish as alternative model for testing the effect of mixtures of goitrogens. • Concentration addition seems to predict better the effect of mixtures of goitrogens.« less

Computer assisted detection and analysis of tall cell variant papillary thyroid carcinoma in histological images

NASA Astrophysics Data System (ADS)

Kim, Edward; Baloch, Zubair; Kim, Caroline

2015-03-01

The number of new cases of thyroid cancer are dramatically increasing as incidences of this cancer have more than doubled since the early 1970s. Tall cell variant (TCV-PTC) papillary thyroid carcinoma is one type of thyroid cancer that is more aggressive and usually associated with higher local recurrence and distant metastasis. This variant can be identified through visual characteristics of cells in histological images. Thus, we created a fully automatic algorithm that is able to segment cells using a multi-stage approach. Our method learns the statistical characteristics of nuclei and cells during the segmentation process and utilizes this information for a more accurate result. Furthermore, we are able to analyze the detected regions and extract characteristic cell data that can be used to assist in clinical diagnosis.

Thyrotoxic periodic paralysis associated with transient thyrotoxicosis due to painless thyroiditis.

PubMed

Oh, Sang Bo; Ahn, Jinhee; Oh, Min Young; Choi, Bo Gwang; Kang, Ji Hyun; Jeon, Yun Kyung; Kim, Sang Soo; Kim, Bo Hyun; Kim, Yong Ki; Kim, In Joo

2012-07-01

Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. All ethnicities can be affected, but TPP typically presents in men of Asian descent. The most common cause of TPP in thyrotoxicosis is Graves' disease. However, TPP can occur with any form of thyrotoxicosis. Up to our knowledge, very few cases ever reported the relationship between TPP and painless thyroiditis. We herein report a 25-yr-old Korean man who suffered from flaccid paralysis of the lower extremities and numbness of hands. The patient was subsequently diagnosed as having TPP associated with transient thyrotoxicosis due to painless thyroiditis. The paralytic attack did not recur after improving the thyroid function. Therefore, it is necessary that early diagnosis of TPP due to transient thyrotoxicosis is made to administer definite treatment and prevent recurrent paralysis.

Thyrotoxic Periodic Paralysis Associated with Transient Thyrotoxicosis Due to Painless Thyroiditis

PubMed Central

Oh, Sang Bo; Ahn, Jinhee; Oh, Min Young; Choi, Bo Gwang; Kang, Ji Hyun; Jeon, Yun Kyung; Kim, Sang Soo; Kim, Yong Ki; Kim, In Joo

2012-01-01

Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. All ethnicities can be affected, but TPP typically presents in men of Asian descent. The most common cause of TPP in thyrotoxicosis is Graves' disease. However, TPP can occur with any form of thyrotoxicosis. Up to our knowledge, very few cases ever reported the relationship between TPP and painless thyroiditis. We herein report a 25-yr-old Korean man who suffered from flaccid paralysis of the lower extremities and numbness of hands. The patient was subsequently diagnosed as having TPP associated with transient thyrotoxicosis due to painless thyroiditis. The paralytic attack did not recur after improving the thyroid function. Therefore, it is necessary that early diagnosis of TPP due to transient thyrotoxicosis is made to administer definite treatment and prevent recurrent paralysis. PMID:22787383

Evaluation of uric acid levels, thyroid function, and anthropometric parameters in Japanese children with Down syndrome

PubMed Central

Niegawa, Tomomi; Takitani, Kimitaka; Takaya, Ryuzo; Ishiro, Manabu; Kuroyanagi, Yuichi; Okasora, Keisuke; Minami, Yukako; Matsuda, Takuya; Tamai, Hiroshi

2017-01-01

Down syndrome, caused by trisomy 21, is characterized by congenital abnormalities as well as mental retardation. From the neonatal stage through adolescence, patients with Down syndrome often have several complications. Thus, it is important to attain knowledge of the prevalence of these comorbidities in children with Down syndrome. We, therefore, evaluated the biochemical data, thyroid function, and anthropometric parameters, and analyzed the association among them in Japanese children and early adolescents with Down syndrome. There was no difference in the prevalence of obesity and overweight between boys and girls. The level of uric acid was higher in boys than in girls. Moreover, the prevalence of hyperuricemia was also higher in boys than in girls (approximately 32% and 10%, respectively). The prevalence of subclinical hypothyroidism in children with Down syndrome was approximately 20%, with no significant sex differences. The levels of uric acid and dehydroepiandrosterone-sulfate were positively associated with age, while the levels of thyroid-stimulating hormone and free thyroxine had a negative association with age. Overall, children with Down syndrome, exhibit a higher incidence of hyperuricemia. Therefore, uric acid levels, as well as thyroid function, from childhood to early adulthood should be monitored in this patient cohort. PMID:28955133

Global epidemiology of hyperthyroidism and hypothyroidism.

PubMed

Taylor, Peter N; Albrecht, Diana; Scholz, Anna; Gutierrez-Buey, Gala; Lazarus, John H; Dayan, Colin M; Okosieme, Onyebuchi E

2018-05-01

Thyroid hormones are essential for growth, neuronal development, reproduction and regulation of energy metabolism. Hypothyroidism and hyperthyroidism are common conditions with potentially devastating health consequences that affect all populations worldwide. Iodine nutrition is a key determinant of thyroid disease risk; however, other factors, such as ageing, smoking status, genetic susceptibility, ethnicity, endocrine disruptors and the advent of novel therapeutics, including immune checkpoint inhibitors, also influence thyroid disease epidemiology. In the developed world, the prevalence of undiagnosed thyroid disease is likely falling owing to widespread thyroid function testing and relatively low thresholds for treatment initiation. However, continued vigilance against iodine deficiency remains essential in developed countries, particularly in Europe. In this report, we review the global incidence and prevalence of hyperthyroidism and hypothyroidism, highlighting geographical differences and the effect of environmental factors, such as iodine supplementation, on these data. We also highlight the pressing need for detailed epidemiological surveys of thyroid dysfunction and iodine status in developing countries.

A branching morphogenesis program governs embryonic growth of the thyroid gland

PubMed Central

Liang, Shawn; Johansson, Ellen; Barila, Guillermo; Altschuler, Daniel L.; Fagman, Henrik

2018-01-01

ABSTRACT The developmental program that regulates thyroid progenitor cell proliferation is largely unknown. Here, we show that branching-like morphogenesis is a driving force to attain final size of the embryonic thyroid gland in mice. Sox9, a key factor in branching organ development, distinguishes Nkx2-1+ cells in the thyroid bud from the progenitors that originally form the thyroid placode in anterior endoderm. As lobes develop the thyroid primordial tissue branches several generations. Sox9 and Fgfr2b are co-expressed distally in the branching epithelium prior to folliculogenesis. The thyroid in Fgf10 null mutants has a normal shape but is severely hypoplastic. Absence of Fgf10 leads to defective branching and disorganized angiofollicular units although Sox9/Fgfr2b expression and the ability of cells to differentiate and form nascent follicles are not impaired. These findings demonstrate a novel mechanism of thyroid development reminiscent of the Fgf10-Sox9 program that characterizes organogenesis in classical branching organs, and provide clues to aid understanding of how the endocrine thyroid gland once evolved from an exocrine ancestor present in the invertebrate endostyle. PMID:29361553

A branching morphogenesis program governs embryonic growth of the thyroid gland.

PubMed

Liang, Shawn; Johansson, Ellen; Barila, Guillermo; Altschuler, Daniel L; Fagman, Henrik; Nilsson, Mikael

2018-01-25

The developmental program that regulates thyroid progenitor cell proliferation is largely unknown. Here, we show that branching-like morphogenesis is a driving force to attain final size of the embryonic thyroid gland in mice. Sox9, a key factor in branching organ development, distinguishes Nkx2-1 + cells in the thyroid bud from the progenitors that originally form the thyroid placode in anterior endoderm. As lobes develop the thyroid primordial tissue branches several generations. Sox9 and Fgfr2b are co-expressed distally in the branching epithelium prior to folliculogenesis. The thyroid in Fgf10 null mutants has a normal shape but is severely hypoplastic. Absence of Fgf10 leads to defective branching and disorganized angiofollicular units although Sox9/Fgfr2b expression and the ability of cells to differentiate and form nascent follicles are not impaired. These findings demonstrate a novel mechanism of thyroid development reminiscent of the Fgf10-Sox9 program that characterizes organogenesis in classical branching organs, and provide clues to aid understanding of how the endocrine thyroid gland once evolved from an exocrine ancestor present in the invertebrate endostyle. © 2018. Published by The Company of Biologists Ltd.

Thyroid gland disorder emergencies: thyroid storm and myxedema coma.

PubMed

Hampton, Jessica

2013-01-01

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

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

PubMed Central

Hard, G C

1998-01-01

This review covers new mechanistic information spanning the past 10 years relevant to normal and abnormal thyroid growth and function that may assist in the risk assessment of chemicals inducing thyroid follicular cell neoplasia. Recent studies have shown that thyroid regulation occurs via a complex interactive network mediated through several different messenger systems. Increased thyroid-stimulating hormone (TSH) levels activate the signal transduction pathways to stimulate growth and differentiation of the follicular cell. The important role of TSH in growth as well as in function helps to explain how disruptions in the thyroid-pituitary axis may influence thyroid neoplasia in rodents. New investigations that couple mechanistic studies with information from animal cancer bioassays (e. g., sulfamethazine studies) confirm the linkage between prolonged disruption of the thyroid-pituitary axis and thyroid neoplasia. New initiation/promotion studies in rodents also support the concept that chronic stimulation of the thyroid induced by goitrogens can result in thyroid tumors. Some of these studies confirm previous suggestions regarding the importance of chemically induced thyroid peroxidase inhibition and the inhibition of 3,3',5, 5'-tetraiodothyronine (T4, thyroxine) deiodinases on disruption of the thyroid-pituitary axis leading to thyroid neoplasia. Some comparative physiologic and mechanistic data highlight certain differences between rodents and humans that could be expected to confer an increased vulnerability of rodents to chronic hypersecretion of TSH. New data from epidemiologic and molecular genetic studies in humans contribute further to an understanding of thyroid neoplasia. Acute exposure to ionizing radiation, especially in childhood, remains the only verified cause of thyroid carcinogenesis in humans. Iodine deficiency studies as a whole remain inconclusive, even though several new studies in humans examine the role of dietary iodine deficiency in thyroid cancer. Specific alterations in gene expression have been identified in human thyroid neoplasia, linked to tumor phenotype, and thus oncogene activation and tumor-suppressor gene inactivation may also be factors in the development and progression of thyroid cancer in humans. An analysis by the U.S. EPA Risk Assessment Forum, prepared as a draft report in 1988 and completed in 1997, focused on the use of a threshold for risk assessment of thyroid follicular tumors. New studies, involving several chemicals, provide further support that there will be no antithyroid activity until critical intracellular concentrations are reached. Thus, for chemically induced thyroid neoplasia linked to disruptions in the thyroid-pituitary axis, a practical threshold for thyroid cancer would be expected. More information on thyroid autoregulation, the role of oncogene mutations and growth factors, and studies directly linking persistently high TSH levels with the sequential cellular development of thyroid follicular cell neoplasia would provide further confirmation. PMID:9681969

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study.

PubMed

Kobayashi, Tomoko; Iwama, Shintaro; Yasuda, Yoshinori; Okada, Norio; Tsunekawa, Taku; Onoue, Takeshi; Takagi, Hiroshi; Hagiwara, Daisuke; Ito, Yoshihiro; Morishita, Yoshiaki; Goto, Motomitsu; Suga, Hidetaka; Banno, Ryoichi; Yokota, Kenji; Hase, Tetsunari; Morise, Masahiro; Hashimoto, Naozumi; Ando, Masahiko; Kiyoi, Hitoshi; Gotoh, Momokazu; Ando, Yuichi; Akiyama, Masashi; Hasegawa, Yoshinori; Arima, Hiroshi

2018-03-01

Immune checkpoint inhibitors, including anti-programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies. This study examined the incidence of endocrine irAEs induced by nivolumab. Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks. Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti-thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions. Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.

Genetically modified mouse models to investigate thyroid development, function and growth.

PubMed

Löf, C; Patyra, K; Kero, A; Kero, J

2018-06-01

The thyroid gland produces thyroid hormones (TH), which are essential regulators for growth, development and metabolism. The thyroid is mainly controlled by the thyroid-stimulating hormone (TSH) that binds to its receptor (TSHR) on thyrocytes and mediates its action via different G protein-mediated signaling pathways. TSH primarily activates the G s -pathway, and at higher concentrations also the G q/11 -pathway, leading to an increase of intracellular cAMP and Ca 2+ , respectively. To date, the physiological importance of other G protein-mediated signaling pathways in thyrocytes is unclear. Congenital hypothyroidism (CH) is defined as the lack of TH at birth. In familial cases, high-throughput sequencing methods have facilitated the identification of novel mutations. Nevertheless, the precise etiology of CH yet remains unraveled in a proportion of cases. Genetically modified mouse models can reveal new pathophysiological mechanisms of thyroid diseases. Here, we will present an overview of genetic mouse models for thyroid diseases, which have provided crucial insights into thyroid gland development, function, and growth with a special focus on TSHR and microRNA signaling. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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

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

Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

PubMed

Elnady, Basant M; Kamal, Naglaa M; Shaker, Raneyah H M; Soliman, Amal F; Hasan, Waleed A; Alghamdi, Hamed A; Algethami, Mohammed M; Jajah, Mohamed Bilal

2016-09-01

Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001).ATD is more associated with rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus and RA, with early referral to rheumatologists for close follow-up and early diagnoses for appropriate disease management of the disease, as early disease control will allow better quality of life.

Treatment Approaches in Down's Syndrome: A Review.

ERIC Educational Resources Information Center

Foreman, Philip J.; Ward, James

1986-01-01

The paper reviews research into treatment approaches in Down's Syndrome. Pharmacological treatments reviewed include thyroid therapy, 5-hydroxytryptophan, vitamin therapy, and cell therapy. Other treatments considered are movement patterning, early intervention, and facial surgery. Early educational intervention is seen as the most effective…

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

PubMed

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

2012-01-01

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

Iodide transport: implications for health and disease

PubMed Central

2014-01-01

Disorders of the thyroid gland are among the most common conditions diagnosed and managed by pediatric endocrinologists. Thyroid hormone synthesis depends on normal iodide transport and knowledge of its regulation is fundamental to understand the etiology and management of congenital and acquired thyroid conditions such as hypothyroidism and hyperthyroidism. The ability of the thyroid to concentrate iodine is also widely used as a tool for the diagnosis of thyroid diseases and in the management and follow up of the most common type of endocrine cancers: papillary and follicular thyroid cancer. More recently, the regulation of iodide transport has also been the center of attention to improve the management of poorly differentiated thyroid cancer. Iodine deficiency disorders (goiter, impaired mental development) due to insufficient nutritional intake remain a universal public health problem. Thyroid function can also be influenced by medications that contain iodide or interfere with iodide metabolism such as iodinated contrast agents, povidone, lithium and amiodarone. In addition, some environmental pollutants such as perchlorate, thiocyanate and nitrates may affect iodide transport. Furthermore, nuclear accidents increase the risk of developing thyroid cancer and the therapy used to prevent exposure to these isotopes relies on the ability of the thyroid to concentrate iodine. The array of disorders involving iodide transport affect individuals during the whole life span and, if undiagnosed or improperly managed, they can have a profound impact on growth, metabolism, cognitive development and quality of life. PMID:25009573

[Changes of iodine nutrition status and thyroid function among pregnant women in iodine sufficient rural area of Gansu province].

PubMed

Wang, Yanling; Sun, Wei; Zhu, Xiaonan; Cao, Yongqin; Ge, Pengfei

2014-01-01

To assess the iodine nutrition and thyroid function of pregnant women during different periods of pregnancy, to provide evidence for guiding iodine supplementation for them. A cross-sectional survey was performed in 215 pregnant women in Yongjing couty from May to June 2013. Samples of blood and random urine were collected, and serum thyrotrophin (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti-thyroid peroxidase (anti-TPO), antithyroglobulin ( anti-TG)and urinary iodine were measured. The medians of urinary iodine from the three groups of pregnant women(first, second and third trimester) were 189.8 µg/L, 152.5 µg/L and 144.9 µg/L respectively. With the exception of pregnant women in the third trimester, the urinary iodine medians of pregnant women in the first and second trimesters were within the 150-249 µg/L range which was defined as optimal by WHO/UNICEF/ICCIDD. With the increase of gestational age, the level of FT3 decreased (P < 0.05), with the FT3 levels in the first trimester were higher than those in the second or third trimester (P < 0.05). The difference of TSH levels among the three groups of pregnant women was statistically significant (P < 0.01), with a U-shaped curve seen between the iodine TSH levels and the gestational age. The medians of anti-TG and anti-TPO appeared the lowest in the first trimester, and remained at a high level in women at second and third trimesters. Significant difference was seen in anti-TG, anti-TPO levels of the three groups of pregnant women (first, second and third trimester) (P < 0.01). The incidence of thyroid function disorder was 1.86%, including subclinical hypothyroidism accounted for 1.40%, and hypothyroidism accounted for 0.47%. The incidence of thyroid function disorder mainly appeared in the early pregnancy. Abnormal FT3, TSH, positive anti-TG and anti-TPO were mainly seen during early pregnancy. The changes of TSH, FT3, FT4, anti-TG and anti-TPO along with the changes of urine iodine levels were not obvious. With the increase of gestational age, the incidence of iodine deficiency also increased among pregnant women. Abnormal thyroid hormones, TSH, positive anti-TG and anti-TPO were mainly existed in the early pregnancy. Programs as monitoring urinary iodine as well as thyroid function targeting all the pregnant women should be carried out.

Endocrinological side-effects of immune checkpoint inhibitors.

PubMed

Torino, Francesco; Corsello, Salvatore M; Salvatori, Roberto

2016-07-01

Three mAbs targeting immune checkpoint proteins are available for the treatment of patients with melanoma, lung, and kidney cancer, and their use will likely expand in the future to additional tumor types. We here update the literature on the incidence and pathophysiology of endocrine toxicities induced by these agents, and discuss management guidance. Immune checkpoint inhibition may trigger autoimmune syndromes involving different organs, including several endocrine glands (pituitary, thyroid, adrenals, and endocrine pancreas). Hypophysitis is more frequently associated with ipilimumab, whereas the incidence of thyroid dysfunction is higher with nivolumab/pembrolizumab. Primary adrenal insufficiency can rarely occur with either treatment. Autoimmune diabetes is very rare. As hypophysitis and adrenalitis may be life-threatening, endocrinological evaluation is essential particularly in patients developing fatigue and other symptoms consistent with adrenal insufficiency. Corticosteroids should be promptly used when hypophysitis-induced adrenal insufficiency or adrenalitis are diagnosed, but not in thyroiditis or diabetes. No impact of corticosteroids on the efficacy/activity of immune checkpoint-inhibiting drugs is reported. Hormonal deficiencies are often permanent. In absence of predicting factors, accurate information to patients provided by the oncology care team is essential for early diagnosis and to limit the consequences of checkpoint inhibition-related endocrine toxicity.

Infrared signature analysis of the thyroid tumors

NASA Astrophysics Data System (ADS)

Gavriloaia, Gheorghe; Ghemigian, Adina-Mariana; Gavriloaia, Mariuca-Roxana

2009-07-01

Cancer is a leading cause of death worldwide, and about 30% of cancer deaths can be prevented. In the next future, the number of global cancer deaths is projected to increase 45% in the future. A general treatment has not yet been found. The best defense against cancer is early detection, when tumor dimensions are very small. The methods as mammography, ultrasounds, MRI, CT, etc., can detect anatomic or structural changes like tumors and cysts. They are anatomical imaging procedures, consequently, they have the ability to locate the area of the tumor, but they cannot detect a fast-growing cancer in the pre-invasive stage. Thermograms are looking for the physiologic changes in tissue; which may indicate a risk of developing cancer in the future. The results using a new device, operating in infrared band, are described. The paper focuses on thyroid cancer because it allows investigations on larger areas before surgery and on residual, smaller areas following surgery. The experiment results for 24 patients with thyroid nodules are described. Malign tumors have a distinct infrared signature. Only the area affected is thermal registered and that has an irregular shape and a strong nonuniform structure with rapid variations on skin temperature.

Maternal iron deficiency alters circulating thyroid hormone levels in developing neonatal rats

EPA Science Inventory

Thyroid hormone insufficiency and iron deficiency (FeD) during fetal and neonatal life are both similarly deleterious to mammalian development suggesting a possible linkage between iron and thyroid hormone insufficiencies. Recent published data from our laboratory demonstrate a r...

Metachronous solitary metastasis to the thyroid gland from squamous cell carcinoma of the lung: a case report and literature review.

PubMed

Gelsomino, Francesco; Lamberti, Giuseppe; Ambrosini, Valentina; Sperandi, Francesca; Agosti, Roberto; Morganti, Alessio G; Ardizzoni, Andrea

2017-11-15

Non-small cell lung cancer presents at an advanced stage at diagnosis in two-thirds of cases. The most frequent metastatic sites are the central nervous system, adrenal glands and bones. By contrast, the thyroid gland is an extremely rare site of dissemination. A 64-year-old Caucasian man previously treated with radiosurgery and brain metastasectomy followed by right middle lobectomy for a squamous cell lung carcinoma had a metachronous solitary metastasis to the thyroid gland, as confirmed by fine-needle aspiration cytology and open biopsy. He underwent curative radiotherapy, with an initial response. At 9 months' follow-up the tumor relapsed both in the thyroid and the lung. Review of the literature confirmed that thyroid metastasis from lung cancer is very uncommon in clinical practice. No data on the role of surgery or curative radiotherapy in thyroid metastasis are available because of the lack of prospective studies addressing the impact on survival of these treatment strategies either alone or in combination. In the case described here, radical treatment with radiotherapy allowed to obtain a modest benefit in terms of relapse-free survival. A diagnosis of metastasis to the thyroid gland should be suspected in patients who present a thyroid nodule or suggestive imaging findings when there is a history of malignancy, including lung cancer. Indeed, an early diagnosis allows to pursue radical treatment that, in selected patients, could lead to long-term survival.

Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

PubMed Central

Lee, Jung Eun

2017-01-01

Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs) are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life. PMID:28443254

Congenital hypothyroidism of dogs and cats: a review.

PubMed

Bojanic, K; Acke, E; Jones, B R

2011-05-01

Congenital hypothyroidism is a rare and underdiagnosed congenital endocrine disorder in dogs and cats and the true incidence is unknown. The disorder may cause a range of clinical signs depending on the primary defect, which affect production of thyroid hormones; some cases present when adult. Hallmark clinical signs of congenital hypothyroidism are mental impairment and skeletal developmental abnormalities, resulting in disproportionate dwarfism; goitre may or may not be present. Documented causes of congenital hypothyroidism in dogs include deficiency of, or unresponsiveness to, thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH), thyroid dysgenesis, dyshormonogenesis and iodine deficiency. In cats, TSH unresponsiveness, thyroid dysgenesis, dyshormonogenesis and iodine deficiency have been confirmed. Adequate replacement therapy results in a successful outcome in the majority of cases, especially when started early in life, as permanent developmental abnormalities can be prevented. This review describes reported cases in dogs and cats, diagnostic investigation, and recommendations for treatment.

Heritability analysis of IgG4 antibodies in autoimmune thyroid disease.

PubMed

Outschoorn, I M; Talor, M V; Burek, C L; Hoffman, W H; Rose, N R

2014-08-01

A study of IgG4 autoantibody levels in juvenile thyroid disease patients showed evidence of heritability using the ROMP screening method. These levels increased with time despite the fact that total IgG antibody decreased with time. Evidence of heritability was demonstrated only in patients with high titers of autoantibodies to both thyroglobulin (Tg) and thyroperoxidase (TPO) unlike family members who may show high titers of one or the other and be asymptomatic at the time of sampling. Since high and low IgG4 levels give different heritability plots, these findings may represent a more severe fibrotic form of thyroiditis with a distinct genetic background. Hence a simple predictive approach is offered by this screening tool for the disease in patients and family members which may be helpful in the future to identify IgG4-related thyroiditis early in the course of disease without the requirement for biopsy.

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

PubMed Central

Kobayashi, Tomoko; Iwama, Shintaro; Yasuda, Yoshinori; Okada, Norio; Tsunekawa, Taku; Onoue, Takeshi; Takagi, Hiroshi; Hagiwara, Daisuke; Ito, Yoshihiro; Morishita, Yoshiaki; Goto, Motomitsu; Suga, Hidetaka; Banno, Ryoichi; Yokota, Kenji; Hase, Tetsunari; Morise, Masahiro; Hashimoto, Naozumi; Ando, Masahiko; Kiyoi, Hitoshi; Gotoh, Momokazu; Ando, Yuichi; Akiyama, Masashi; Hasegawa, Yoshinori; Arima, Hiroshi

2018-01-01

Abstract Context Immune checkpoint inhibitors, including anti–programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies. Objective This study examined the incidence of endocrine irAEs induced by nivolumab. Patients and Main Outcome Measured Sixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks. Results Four out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti–thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions. Conclusions Our real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit. PMID:29600292

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

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.

Thyroid insufficiency in developing rat brain: A genomic analysis.

EPA Science Inventory

Thyroid Insufficiency in the Developing Rat Brain: A Genomic Analysis. JE Royland and ME Gilbert, Neurotox. Div., U.S. EPA, RTP, NC, USA. Endocrine disruption (ED) is an area of major concern in environmental neurotoxicity. Severe deficits in thyroid hormone (TH) levels have bee...

Thyroid Histopathology Assessments for the Amphibian Metamorphosis Assay to Detect Thyroid-active Substances

EPA Science Inventory

In support of an Organization for Economic Cooperation and Development (OECD) Amphibian Metamorphosis Assay (AMA) Test Guideline for the detection of substances that interact with the hypothalamic-pituitary-thyroid axis, a document was developed that provides a standardized appro...

Incidence of breast carcinoma in women with thyroid carcinoma.

PubMed

Vassilopoulou-Sellin, R; Palmer, L; Taylor, S; Cooksley, C S

1999-02-01

Breast carcinoma and differentiated thyroid carcinoma(the most common endocrine malignancy) occur predominantly in women. An association between the two tumors has been suggested by some investigators, but the potential impact of treatment of one of these diseases on the development of the other remains unclear. The authors examined the relation between the occurrence of these two tumors. There were 41,686 patients with breast carcinoma and 3662 with thyroid carcinoma who registered at The University of Texas M. D. Anderson Cancer Center between March 1944 and April 1997. Women who received both diagnoses since 1976 were identified and incidence rates and relative risks of secondary tumor development were calculated. Surveillance, Epidemiology and End Results (SEER) program data on the age-adjusted incidences of these diseases during the same time period were used for the expected incidences in the same population. Among 18,931 women with a diagnosis of breast carcinoma since 1976, 11 developed differentiated thyroid carcinoma > or = 2 years after the diagnosis of breast carcinoma. These breast carcinoma patients contributed 129,336 person-years of follow-up; the observed incidence of thyroid carcinoma in this group was not different from that in a similar age group of women in the SEER database. Among 1013 women with a diagnosis of thyroid carcinoma since 1976, 24 developed breast carcinoma > or = 2 years after the diagnosis of thyroid carcinoma. These thyroid carcinoma patients contributed 8380 person-years of follow-up; the observed incidence of breast carcinoma in women ages 40-49 years was significantly higher than the expected incidence for women in the same age group in the SEER database. Breast carcinoma developing after thyroid carcinoma was diagnosed more frequently than expected in young adult women seen at the study institution since 1976. This potential association and plausible mechanisms of breast carcinoma development after thyroid carcinoma should be evaluated in larger cohorts of patients.

Assessing the relationship between perfluoroalkyl substances, thyroid hormones and binding proteins in pregnant women; a longitudinal mixed effects approach.

PubMed

Berg, Vivian; Nøst, Therese Haugdahl; Hansen, Solrunn; Elverland, Astrid; Veyhe, Anna-Sofía; Jorde, Rolf; Odland, Jon Øyvind; Sandanger, Torkjel Manning

2015-04-01

The mechanisms involved in thyroid homeostasis are complex, and perfluoroalkyl substances (PFASs) have been indicated to interfere at several levels in this endocrine system. Disruption of the maternal thyroid homeostasis during early pregnancy is of particular concern, where subclinical changes in maternal thyroid hormones (THs) may affect embryonic and foetal development. The present study investigated associations between THs, thyroid binding proteins (TH-BPs) and PFAS concentrations in pregnant women from Northern Norway. Women participating in The Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood sample at three visits related to their pregnancy and postpartum period (during the second trimester, 3 days and 6 weeks after delivery) in the period 2007-2009. Participants were assigned to quartiles according to PFAS concentrations during the second trimester and mixed effects linear models were used to investigate potential associations between PFASs and repeated measurements of THs, TH-BPs, thyroxin binding capacity and thyroid peroxidase antibodies (anti-TPOs). Women within the highest perfluorooctane sulfonate (PFOS) quartile had 24% higher mean concentrations of thyroid stimulating hormone (TSH) compared to the first quartile at all sampling points. Women within the highest quartiles of perfluorodecanoate (PFDA) had 4% lower mean concentrations of triiodothyronine (T3) and women within the highest quartile of perfluoroundecanoate (PFUnDA) had 3% lower mean concentrations of free triiodothyronine (FT3). Further, the difference in concentrations and the changes between three time points were the same for the PFAS quartiles. Thyroxin binding capacity was associated with all the THs and TH-BPs, and was selected as a holistic adjustment for individual changes in TH homeostasis during pregnancy. Finally, adjusting for maternal iodine status did not influence the model predictions. Findings in the present study suggest modifications of TH homeostasis by PFASs in a background exposed maternal population. The variation in levels of THs between PFAS quartiles was within normal reference ranges and may not be of clinical significance in the pregnant woman. However, subtle individual changes in maternal THs may have significant consequences for foetal health. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prior irradiation and the development of coexistent differentiated thyroid cancer and hyperparathyroidism

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

Prinz, R.A.; Barbato, A.L.; Braithwaite, S.S.

1982-03-01

Twelve patients with coexistent well-differentiated thyroid carcinoma and primary hyperparathyoidism were studied to determine the frequency of previous radiation exposure. Eight were found to have received prior irradiation. External radiation was administered to the head and neck region for benign conditions such as tonsillar enlargement, acne, scrofula, and thyroid enlargement. One patient received 131I therapy for carcinoma of the thyroid. The observation that 67% of the patients in this series had previous radiation to the head and neck strongly implicates radiation exposure in the development of coexistent well-differentiated thyroid carcinoma and hyperparathyroidism.

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

PubMed

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

2007-07-01

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

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.

Neuroplastic effects of music lessons on hippocampal volume in children with congenital hypothyroidism.

PubMed

Zendel, Benjamin Rich; Willoughby, Karen A; Rovet, Joanne F

2013-12-04

Children with congenital hypothyroidism (CH) who experience a neonatal thyroid hormone deficiency have reduced hippocampal volumes compared with healthy controls. Interestingly, evidence suggests that musical training can contribute to structural plasticity in a number of brain areas, including the hippocampus. Therefore, we investigated whether taking music lessons could ameliorate the volumetric reductions of the hippocampus in children with CH. Left and right hippocampal volumes were measured in four groups of children: children with CH with and without music lessons, and healthy controls with and without music lessons. We found that the volume of the right hippocampus was comparable between children with CH who had taken music lessons and the healthy controls. Children with CH who had not taken music lessons had reduced hippocampal volumes compared with the other three groups. These results suggest that music lessons may induce structural neuroplasticity in children with atypical hippocampal development because of early thyroid hormone deficiencies.

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

PubMed Central

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

2012-01-01

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

Shear wave elastography diagnosis of the diffuse sclerosing variant of papillary thyroid carcinoma: A case report.

PubMed

Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei

2016-08-01

The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC.

Shear wave elastography diagnosis of the diffuse sclerosing variant of papillary thyroid carcinoma: A case report

PubMed Central

Xue, Nianyu; Xu, Youfeng; Huang, Pintong; Zhang, Shengmin; Wang, Hongwei; Yu, Fei

2016-01-01

The present study aimed to report the shear wave elastography (SWE) findings in a patient with the diffuse sclerosing variant of papillary thyroid carcinoma (DSVPTC). Since patients with DSVPTC may present with typical clinicopathological features and initially appear to have Hashimoto's thyroiditis, a thorough clinical evaluation and an early diagnosis are important. A 20-year-old female patient presented with a 1-month history of a neck mass and sore throat. Conventional ultrasound and SWE were performed using an AIXPLORER system with 14-5 MHz linear transducer. The patient had undergone total thyroidectomy and bilateral neck lymph node dissection, and an intraoperative pathology consultation to confirm the malignancy of lymph node metastasis. Pathological diagnosis was DSVPTC in both lobes, with lymph node metastases in the bilateral neck. The clinical presentation and serological findings were all indicative of Hashimoto's thyroiditis. Thyroid ultrasonography revealed diffuse enlargement of the both lobes, heterogenous echogenicity without mass formation, diffuse scattered microcalcifications and poor vascularization. SWE revealed stiff values of the thyroid: The mean stiffness was 99.7 kpa, the minimum stiffness was 59.1 kpa and the maximum stiffness was 180.1 kpa. The maximum stiffness of the DSVPTC (180.1 kpa) was higher compared with the diagnostic criteria of malignant thyroid nodules (65 kPa). SWE may be considered as a novel and valuable method to diagnose DSVPC. PMID:27446574

[Analysis on iodine nutritional status and thyroid function in pregnant women].

PubMed

Li, Hongbo; Wang, Yanling; Zheng, Jing; Wang, Yancai; Huang, Dahong; Liang, Liping; Ren, Xudong; Dou, Yugui; Zhu, Xiaonan

2012-07-01

To investigate the iodine nutritional status and thyroid function of pregnant women during different periods of pregnancy, to provide evidence for guiding iodine supplementation for them. A cross-sectional survey was performed in 90 pregnant women in Wuwei City from April 2009 to January 2010. The morning blood samples and random urine samples were collected, and the thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroglobulin antibodies (TGAb), thyroid microsomal antibodies (TMAb) in blood samples and iodine in urine samples were detected. The medians of urinary iodine were 231.49, 158.25 and 328.35 microg/L for women in early, middle and late period of pregnancy, The ratio of urinary iodine below 150 microg/L were 39.29%, 45.16% and 25.81%, respectively. The FT3, FT4 levels in the first trimester were higher than those in the third trimester (P < 0.05) and TSH level was increased, but no significant difference (P > 0.05). The positive rate of TGAb and TMAb antibody of pregnant women in different period of time were not significantly different (P > 0.05). The incidence of thyroid function disorder was significantly different in different gestation periods. Generally, the iodine nutritional status of these pregnant women was appropriate, but there was a tendency towards hypothyroid in some women. Monitoring urinary iodine and thyroid function in pregnant women should be carried out regularly.

Pediatric pulmonary arterial hypertension and hyperthyroidism: a potentially fatal combination.

PubMed

Trapp, Christine M; Elder, Robert W; Gerken, Adrienne T; Sopher, Aviva B; Lerner, Shulamit; Aranoff, Gaya S; Rosenzweig, Erika B

2012-07-01

Patients with pulmonary arterial hypertension (PAH) who develop hyperthyroidism are at risk for acute cardiopulmonary decompensation and death. We present a series of eight idiopathic PAH/heritable PAH pediatric patients who developed hyperthyroidism between 1999 and 2011. Institutional Review Board approval was obtained; informed consent was waived due to the retrospective nature of the series. All eight patients were receiving iv epoprostenol; five of the eight patients presented with acute cardiopulmonary decompensation in the setting of hyperthyroidism. In the remaining three patients, hyperthyroidism was detected during routine screening of thyroid function tests. The one patient who underwent emergency thyroidectomy was the only survivor of those who presented in cardiopulmonary decline. Aggressive treatment of the hyperthyroid state, including emergency total thyroidectomy and escalation of targeted PAH therapy and β-blockade when warranted, may prove lifesaving in these patients. Prompt thyroidectomy or radioactive iodine ablation should be considered for clinically stable PAH patients with early and/or mild hyperthyroidism to avoid potentially life-threatening cardiopulmonary decompensation. Although the association between hyperthyroidism and PAH remains poorly understood, the potential impact of hyperthyroidism on the cardiopulmonary status of PAH patients must not be ignored. Hyperthyroidism must be identified early in this patient population to optimize intervention before acute decompensation. Thyroid function tests should be checked routinely in patients with PAH, particularly those on iv epoprostenol, and urgently in patients with acute decompensation or symptoms of hyperthyroidism.

Thyroid Disorders Overview

MedlinePlus

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

Secondary and tertiary preventions of thyroid disease.

PubMed

Azizi, Fereidoun; Mehran, Ladan; Hosseinpanah, Farhad; Delshad, Hossein; Amouzegar, Atieh

2018-05-01

Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.

Development of thyroid anthropomorphic phantoms for use in nuclear medicine

NASA Astrophysics Data System (ADS)

Cerqueira, R. A. D.; Maia, A. F.

2014-02-01

The objective of this study was to develop thyroid anthropomorphic phantoms to be used in control tests of medical images in scintillation cameras. The main difference among the phantoms was the neck shape: in the first, called OSCT, it was geometrically shaped, while in the second, called OSAP, it was anthropomorphically shaped. In both phantoms, thyroid gland prototypes, which were made of acrylic and anthropomorphically shaped, were constructed to allow the simulation of a healthy thyroid and of thyroids with hyperthyroidism and hypothyroidism. Images of these thyroid anthropomorphic phantoms were obtained using iodine 131 with an activity of 8.695 MBq. The iodine 131 was chosen because it is widely used in studies of thyroid scintigraphy. The images obtained proved the effectiveness of the phantoms to simulate normal or abnormal thyroids function. These phantoms can be used in medical imaging quality control programs and, also in the training of professionals involved in the analysis of images in nuclear medicine centers.

Aspergillus thyroiditis in a renal transplant recipient mimicking subacute thyroiditis.

PubMed

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

2011-04-01

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

Developmental thyroid hormone insufficiency and brain development: A role for brain-derived neurotrophic factor (BDNF)?*

EPA Science Inventory

Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth. Neurotrophins have been implicated in a host of brain cellular func...

A quantitative adverse outcome pathway model for thyroid axis disruption in Xenopus laevis tadpoles

EPA Science Inventory

The development of Xenopus laevis tadpoles is tightly controlled by the thyroid hormones tetraiodothyronine (T4) and triiodothyronine (T3). Toxicity testing efforts have shown that several compounds interfere with development in X. laevis tadpoles by disrupting the thyroid axis a...

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

PubMed

Matti, Bashar; Cohen-Hallaleh, Ruben

2016-09-09

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

[Sub-acute thyroiditis in a patient on immunosuppressive treatment].

PubMed

D'Amico, Giovanna; Di Crescenzo, Vincenzo; Caleo, Alessia; Garzi, Alfredo; Vitale, Mario

2013-01-01

Sub-acute thyroiditis or De Quervain's thyroiditis is a viral, inflammatory disease which causes the serum release of thyroidal hormones and hyperthyroidism. The pathogenesis of thyroid follicle damage is unclear because the exclusive viral action or a concomitant autoimmune component, determined by the lymphoid infiltrate remain to be assessed. We describe the case of a patient under immunosuppressive treatment, who developed sub-acute thyroiditis with hormone release and hyperthyroidism. The patient, while was under immunosuppressive treatment for kidney transplant, exhibited a clinical picture and hormonal profile of hyperthyroidism. Thyroid scintiscan exhibited an extremely low uptake. Fine-needle cytologic diagnosis was granulomatous sub-acute thyroiditis (De Quervain's thyroiditis). This case suggests the primary or even exclusive role of the viral infection in hormone release and hyperthyroidism in sub-acute thyroiditis, excluding an autoimmune component.

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.

Hepatic thyroid signaling of heat-stressed late pregnant and early lactating cows

PubMed Central

Weitzel, Joachim M; Viergutz, Torsten; Albrecht, Dirk; Bruckmaier, Rupert; Schmicke, Marion; Tuchscherer, Armin; Koch, Franziska

2017-01-01

During the transition between late gestation and early lactation, dairy cows experience severe metabolic stress due to the high energy and nutrient requirements of the fetus and the mammary gland. Additional thermal stress that occurs with rising temperatures during the ongoing climate change has further adverse implications on energy intake, metabolism and welfare. The thyroid hormone (TH)-mediated cellular signaling has a pivotal role in regulation of body temperature, energy intake and metabolic adaptation to heat. To distinguish between energy intake and heat stress-related effects, Holstein cows were first kept at thermoneutrality at 15°C followed by exposure to heat stress (HS) at 28°C or pair-feeding (PF) at 15°C for 6 days, in late pregnancy and again in early lactation. Herein, we focused on hepatic metabolic changes associated with alterations in the hypothalamic–pituitary–thyroid axis in HS and PF animals. T3 and T4 levels dropped with HS or PF; however, in HS animals, this decline was more pronounced. Thyroid-stimulating hormone (TSH) levels remain unaffected, while plasma cholesterol concentrations were lower in HS than PF animals. Hepatic marker genes for TH action (THRA, DIO1 and PPARGC1) decreased after HS and were lower compared to PF cows but only post-partum. Proteomics data revealed reduced hepatic amino acid catabolism ante-partum and a shift toward activated beta-oxidation and gluconeogenesis but declined oxidative stress defense post-partum. Thus, liver metabolism of HS and PF cows adapts differently to diminished energy intake both ante-partum and post-partum, and a different TH sensitivity is involved in the regulation of catabolic processes. PMID:28500083

Successful treatment of thyroid storm presenting as recurrent cardiac arrest and subsequent multiorgan failure by continuous renal replacement therapy.

PubMed

Park, Han Soo; Kwon, Su Kyoung; Kim, Ye Na

2017-01-01

Thyroid storm is a rare and potentially life-threatening medical emergency. We experienced a case of thyroid storm associated with sepsis caused by pneumonia, which had a catastrophic course including recurrent cardiac arrest and subsequent multiple organ failure (MOF). A 22-year-old female patient with a 10-year history of Graves' disease was transferred to our emergency department (ED). She had a cardiac arrest at her home and a second cardiac arrest at the ED. Her heart recovered after 20 min of cardiac resuscitation. She was diagnosed with thyroid storm associated with hyperthyroidism complicated by pneumonia and sepsis. Although full conventional medical treatment was given, she had progressive MOF and hemodynamic instability consisting of hyperthermia, tachycardia and hypotension. Because of hepatic and renal failure with refractory hypotension, we reduced the patient's dose of beta-blocker and antithyroid drug, and she was started on continuous veno-venous renal replacement therapy (CRRT) with intravenous albumin and plasma supplementation. Subsequently, her body temperature and pulse rate began to stabilize within 1 h, and her blood pressure reached 120/60 mmHg after 6 h. We discontinued antithyroid drug 3 days after admission because of aggravated hyperbilirubinemia. The patient exhibited progressive improvement in thyroid function even after cessation of antithyroid drug, and she successfully recovered from thyroid storm and MOF. This is the first case of thyroid storm successfully treated by CRRT in a patient considered unfit for antithyroid drug treatment. The presenting manifestations of thyroid storm vary and can include cardiac arrest with multiorgan failure in rare cases.In some patients with thyroid storm, especially those with severe complications, conventional medical treatment may be ineffective or inappropriate.During thyroid storm, the initiation of CRRT can immediately lower body temperature and subsequently stabilize vital signs.Early initiation of CRRT can be life-saving in patients with thyroid storm complicated by MOF, even when used in combination with suboptimal medical treatment.

Impaired swim bladder inflation in early-life stage fathead ...

EPA Pesticide Factsheets

The thyroid axis plays a critical role in teleost fish development. The present study investigated whether inhibition of deiodinase, the enzyme which converts thyroxine (T4), to the more biologically-active form, 3,5,3'-triiodothyronine (T3), would impact inflation of the posterior and/or anterior swim bladder (SB), processes which we previously demonstrated to be thyroid-hormone regulated. Two experiments were conducted using iopanoic acid (IOP), a pharmaceutical used to treat hyperthyroidism, as a model deiodinase inhibitor. In the first study, fathead minnow (Pimephales promelas) embryos (~1 day post-fertilization [dpf]) were exposed in a flow-through system to three concentrations of IOP (0.6, 1.9, 6.0 mg/L) or control water and sampled at 4 and 6 dpf. Whole body T4 and T3 concentrations were measured using LC-MS/MS. Abundance of deiodinase 1-3 (dio1-3), thyroid-stimulating hormone (tsh), and thyroperoxidase (tpo) transcripts was examined using quantitative polymerase-chain reaction. Posterior SB inflation was assessed at 6 dpf. To examine effects on anterior SB inflation, a second study was conducted in which 6 dpf larvae, whose posterior SB had already inflated, were exposed to the same IOP concentrations. Fish were sampled at 10, 14, 18, and 21 dpf for T4/T3 measurements, gene transcription analyses, and thyroid histopathology. In the embryo study, incidence and length of inflated posterior SBs were significantly reduced in the 6.0 mg/L treatment at 6 dp

Ultrasound variants of autoimmune thyroiditis in children and adolescents and their clinical implication in relation to papillary thyroid carcinoma development.

PubMed

Januś, D; Wójcik, M; Drabik, G; Wyrobek, Ł; Starzyk, J B

2018-03-01

The prevalence of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) is rising in children and adolescents, and the coincidence of AIT and PTC is as high as 6.3-43%. To investigate the ultrasound manifestation of AIT in relation to PTC development in paediatric patients. 179 paediatric patients (133 females), mean (SD) age: 13.9 (3.03) years diagnosed with AIT and referred for ultrasound evaluation. Eight patients were diagnosed with PTC (6 females). Retrospective analysis of thyroid ultrasound scans of patients diagnosed with AIT. Thyroid and autoimmune status was assessed based on TSH, fT4, fT3 and increased aTPO and/or aTG and/or TRAB levels. In patients with PTC, total thyroidectomy was performed. Analysis of thyroid US scans revealed that the following five ultrasound variants of AIT were observed in 179 patients: the most common in 35.2%-diffuse thyroiditis with hypoechogenic background and normoechogenic parenchyma, in 30.2%-diffuse thyroiditis with irregular background, in 18.9% nodular variant with normoechogenic background, in 11.7%-micronodulations and in 3.9%-diffuse hypoechogenic background. Eight cases of PTC were diagnosed in nodular variant of AIT with normoechogenic irregular background. Patients with AIT and nodular variant with normoechogenic irregular background of the thyroid gland on US scans are in the risk group of developing PTC and should be followed up with regular neck US assessment.

[Streptococcal mediastinitis after thyroidectomy. A literature review].

PubMed

Bures, C; Zielinski, V; Klatte, T; Swietek, N; Kober, F; Tatzgern, E; Bobak-Wieser, R; Gschwandtner, E; Gilhofer, M; Wechsler-Fördös, A; Hermann, M

2015-12-01

Surgical site infections after thyroid surgery are mostly superficial and can be well treated. Streptococcal mediastinitis in contrast is a rare but life-threatening complication. A 57-year-old female patient experienced septic fever, increase of inflammation parameters and erythema 2 days after thyroid surgery for Graves' disease. This process was triggered by a three-compartment infection by group A Streptococcus (GAS) with involvement of the mediastinum. Therapy over 6 weeks including seven wound revisions with the patient under general anesthesia, pathogen-adapted antibiotic treatment and cervical negative pressure treatment managed to control the infection. A total of 21 cases have been published on this phenomenon, 11 of which had a fatal outcome. High fever and surgical site erythema in the early postoperative period after thyroid surgery can be signs of a GAS infection, which might lead to necrotizing, descending, life-threatening mediastinitis. Early diagnosis with support of computed tomography (CT) scans, immediate therapy including wound opening, lavage, intravenous antibiotic treatment with penicillin and clindamycin are vital. If treatment resistance occurs, cervical negative pressure treatment should be considered.

[Thyroid and pregnancy].

PubMed

Iwen, K A; Lehnert, H

2018-05-17

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

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

EPA Science Inventory

Thyroid hormones (TH) 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 neurological impairments associated with low level TH ...

THYROID INSUFFICIENCY AND GENE EXPRESSION IN DEVELOPING RAT BRAIN: A DOSE RESPONSE STUDY.

EPA Science Inventory

Thyroid Insufficiency and Gene Expression in Developing Rat Brain: A Dose Response Study. JE Royland and ME Gilbert, Neurotox. Div., U.S. EPA, RTP, NC, USA. Endocrine disruption is an area of major concern in environmental neurotoxicity. Deficits in thyroid hormone (TH) levels h...

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

EPA Science Inventory

Thyroid hormones (TH) 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...

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

EPA Science Inventory

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

THE THYROID HORMONE TRANSPORTER, MCT8, SELECTIVELY RESPONDS TO THYROID HORMONE INSUFFICIENCY IN THE DEVELOPMENT RAT BRAIN.

EPA Science Inventory

Thyroid hormone (TH) is essential for normal brain development. Therefore, it is not surprising that a variety of adaptive mechanisms are activated in response to TH insufficiency. However, not all brain regions respond in the same fashion to TH insufficiency. This observation...

Development of Thyroid Gland Specific Markers of Hypothalamic-pituitary-thyroid Axis Disruption in the Amphibian Model Species Xenopus laevis

EPA Science Inventory

The focus of the research presented here is the development of an in vitro thyroid gland culture system to test the effect of chemicals directly on the gland without influence of other parts of the HPT axis.

METAMORPHIC INHIBITION OF XENOPUS LAEVIS BY SODIUM PERCHLORATE: EFFECTS ON DEVELOPMENT AND THYROID HISTOLOGY

EPA Science Inventory

The perchlorate anion inhibits thyroid hormone (TH) synthesis via inhibition of the sodium-iodide symporter. It is, therefore, a good model chemical to aid in the development of a bioassay to screen chemicals for effects on thyroid function. Xenopus laevis larvae were exposed to ...

Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health.

PubMed

Minatoya, Machiko; Naka Jima, Sonomi; Sasaki, Seiko; Araki, Atsuko; Miyashita, Chihiro; Ikeno, Tamiko; Nakajima, Tamie; Goto, Yuko; Kishi, Reiko

2016-09-15

Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary. Copyright © 2016. Published by Elsevier B.V.

Interaction between perchlorate and iodine in the metamorphosis of Hyla versicolor

USGS Publications Warehouse

Sparling, D.; Harvey, G.; Nzengung, V.; ,

2003-01-01

Perchlorate (ClO4-) is a water-soluble, inorganic anion that is often combined with ammonium, potassium or other cations for use in industry and agriculture. Ammonium perchlorate, for example, is a potent oxidizer and is used in various military applications including rocket fuel. It has also been found in an historically widely used fertilizer, Chilean nitrate and in other fertilizers. It has been found in ground and surface waters of over 30 states and is considered a human health risk. Because of its similar atomic radius and volume, perchlorate competes with iodide for thyroid uptake and storage and thereby inhibits production of thyroid hormones. Amphibians may be particularly affected by perchlorate because they rely on the thyroid for metamorphosis. This study exposed early larval Hyla versicolor to concentrations of perchlorate ranging from 2.2 to 50 ppm to determine the effects of perchlorate on a native amphibian. In addition, three controls, 0 perchlorate, 0 perchlorate with 0.10 ppm iodide (C + I) and 50 ppm perchlorate + 0.10 ppm iodide (50 + I) were tested. Mortality (< 11% with all treatments) and growth appeared to be unaffected by perchlorate. Inhibition of development started with 2.2 ppm perchlorate and little or no development occurred at 22.9 ppm and above. This inhibition was particularly apparent at the latter stages of development including hindlimb formation and metamorphosis. The estimated EC50 for total inhibition of metamorphosis at 70 days of treatment was 3.63 ppm. There was no evidence of inhibition of development with the 50 + I, C + I, or controls, indicating that the presence of small concentrations of iodide could counter the effects of perchlorate. When tadpoles that had been inhibited by perchlorate were subsequently treated with iodide, development through prometamorphosis progressed but mortality was very high.

Interaction between perchlorate and iodine in the metamorphosis of Hyla versicolor

USGS Publications Warehouse

Sparling, D.W.; Harvey, G.; Nzengung, V.; Linder, Gregory L.; Krest, Sherry K.; Sparling, Donald W.; Little, Edward E.

2003-01-01

Perchlorate (ClO4-) is a water-soluble, inorganic anion that is often combined with ammonium, potassium or other cations for use in industry and agriculture. Ammonium perchlorate, for example, is a potent oxidizer and is used in various military applications including rocket fuel. It has also been found in an historically widely used fertilizer, Chilean nitrate and in other fertilizers. It has been found in ground and surface waters of over 30 states and is considered a human health risk. Because of its similar atomic radius and volume, perchlorate competes with iodide for thyroid uptake and storage and thereby inhibits production of thyroid hormones. Amphibians may be particularly affected by perchlorate because they rely on the thyroid for metamorphosis. This study exposed early larval Hyla versicolor to concentrations of perchlorate ranging from 2.2 to 50 ppm to determine the effects of perchlorate on a native amphibian. In addition, three controls, 0 perchlorate, 0 perchlorate with 0.10 ppm iodide (C + I) and 50 ppm perchlorate + 0.10 ppm iodide (50 + I) were tested. Mortality (<11% with all treatments) and growth appeared to be unaffected by perchlorate. Inhibition of development started with 2.2 ppm perchlorate and little or no development occurred at 22.9 ppm and above. This inhibition was particularly apparent at the latter stages of development including hindlimb formation and metamorphosis. The estimated EC50 for total inhibition of metamorphosis at 70 days of treatment was 3.63 ppm. There was no evidence of inhibition of development with the 50 + I, C + I, or controls, indicating that the presence of small concentrations of iodide could counter the effects of perchlorate. When tadpoles that had been inhibited by perchlorate were subsequently treated with iodide, development through prometamorphosis progressed but mortality was very high.

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

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.

Hepatitis C Virus E2 Protein Induces Upregulation of IL-8 Pathways and Production of Heat Shock Proteins in Human Thyroid Cells.

PubMed

Hammerstad, Sara Salehi; Stefan, Mihaela; Blackard, Jason; Owen, Randall P; Lee, Hanna J; Concepcion, Erlinda; Yi, Zhengzi; Zhang, Weijia; Tomer, Yaron

2017-02-01

Thyroiditis is one of the most common extrahepatic manifestations of hepatitis C virus (HCV) infection. By binding to surface cell receptor CD81, HCV envelope glycoprotein E2 mediates entry of HCV into cells. Studies have shown that different viral proteins may individually induce host responses to infection. We hypothesized that HCV E2 protein binding to CD81 expressed on thyroid cells activates a cascade of inflammatory responses that can trigger autoimmune thyroiditis in susceptible individuals. Human thyroid cell lines ML-1 and human thyrocytes in primary cell culture were treated with HCV recombinant E2 protein. The expression of major proinflammatory cytokines was measured at the messenger RNA and protein levels. Next-generation transcriptome analysis was used to identify early changes in gene expression in thyroid cells induced by E2. HCV envelope protein E2 induced strong inflammatory responses in human thyrocytes, resulting in production of interleukin (IL)-8, IL-6, and tumor necrosis factor-α. Furthermore, the E2 protein induced production of several heat shock proteins including HSP60, HSP70p12A, and HSP10, in human primary thyrocytes. In thyroid cell line ML-1, RNA sequencing identified upregulation of molecules involved in innate immune pathways with high levels of proinflammatory cytokines and chemokines and increased expression of costimulatory molecules, specifically CD40, known to be a major thyroid autoimmunity gene. Our data support a key role for HCV envelope protein E2 in triggering thyroid autoimmunity through activation of cytokine pathways by bystander mechanisms. Copyright © 2017 by the Endocrine Society

Diagnosis of Metastasis to the Thyroid Gland: Comparison of Core-Needle Biopsy and Fine-Needle Aspiration.

PubMed

Choi, Sang Hyun; Baek, Jung Hwan; Ha, Eun Ju; Choi, Young Jun; Song, Dong Eun; Kim, Jae Kyun; Chung, Ki-Wook; Kim, Tae Yong; Lee, Jeong Hyun

2016-04-01

Early detection and diagnosis of metastasis to the thyroid gland is important. This study aims to evaluate the clinical value of core-needle biopsy (CNB) by comparing the results of CNB and fine-needle aspiration (FNA) in patients with clinically suspected metastasis to the thyroid gland. Case series with chart review. Tertiary referral practice. Fifty-two thyroid nodules from 52 patients with clinically suspected metastasis to the thyroid gland (mean age, 62.8 years). Of these 52 patients, FNA was initially used in 41 patients and CNB in 20 patients (11 patients as the initial approach and 9 patients after inconclusive FNA results). Ultrasound features of metastasis to the thyroid gland were evaluated. The diagnostic performance, repeated diagnostic examination rate, and diagnostic surgery rate were evaluated for FNA and CNB. Among these 52 patients, 46 were diagnosed with thyroid metastases and 6 were diagnosed with primary thyroid cancer. Common ultrasound features were an ovoid to round shape (58.7%), ill-defined margin (56.5%), hypoechogenicity (65.2%), and no calcifications (87.0%). Core-needle biopsy achieved a significantly higher sensitivity than FNA (100.0% vs 58.6%, P = .008) without any false-negative results. Both the repeated diagnostic examination rate and the diagnostic surgery rate were significantly lower in CNB than in FNA (5.0% vs 46.3%, P = .001, and 5.0% vs 34.1%, P = .013, respectively). In cases of known rare primary malignancy, nontypical ultrasound features of primary thyroid malignancy, and need for an additional immunohistochemical analysis, CNB may be primarily considered. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

75 FR 66104 - Government-Owned Inventions; Availability for Licensing

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-27

... receptor gene exhibit impaired growth and resistance to thyroid hormone. Proc Natl Acad Sci U S A. 2000 Nov... overactivated. These mice have a knock-in dominantly negative mutant thyroid hormone receptor [beta] gene (TR... mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model...

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...

Hes1 Is Required for Appropriate Morphogenesis and Differentiation during Mouse Thyroid Gland Development

PubMed Central

Carre, Aurore; Rachdi, Latif; Tron, Elodie; Richard, Bénédicte; Castanet, Mireille; Schlumberger, Martin; Bidart, Jean-Michel

2011-01-01

Notch signalling plays an important role in endocrine development, through its target gene Hes1. Hes1, a bHLH transcriptional repressor, influences progenitor cell proliferation and differentiation. Recently, Hes1 was shown to be expressed in the thyroid and regulate expression of the sodium iodide symporter (Nis). To investigate the role of Hes1 for thyroid development, we studied thyroid morphology and function in mice lacking Hes1. During normal mouse thyroid development, Hes1 was detected from E9.5 onwards in the median anlage, and at E11.5 in the ultimobranchial bodies. Hes1 −/− mouse embryos had a significantly lower number of Nkx2-1-positive progenitor cells (p<0.05) at E9.5 and at E11.5. Moreover, Hes1 −/− mouse embryos showed a significantly smaller total thyroid surface area (−40 to −60%) compared to wild type mice at all study time points (E9.5−E16.5). In both Hes1 −/− and wild type mouse embryos, most Nkx2-1-positive thyroid cells expressed the cell cycle inhibitor p57 at E9.5 in correlation with low proliferation index. In Hes1 −/− mouse embryos, fusion of the median anlage with the ultimobranchial bodies was delayed by 3 days (E16.5 vs. E13.5 in wild type mice). After fusion of thyroid anlages, hypoplastic Hes1 −/− thyroids revealed a significantly decreased labelling area for T4 (−78%) and calcitonin (−65%) normalized to Nkx2-1 positive cells. Decreased T4-synthesis might be due to reduced Nis labelling area (−69%). These findings suggest a dual role of Hes1 during thyroid development: first, control of the number of both thyrocyte and C-cell progenitors, via a p57-independent mechanism; second, adequate differentiation and endocrine function of thyrocytes and C-cells. PMID:21364918

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.

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

PubMed

Benvenga, Salvatore; Antonelli, Alessandro; Vita, Roberto

2015-12-01

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

Environmental triggers of thyroiditis: hepatitis C and interferon-α.

PubMed

Menconi, F; Hasham, A; Tomer, Y

2011-01-01

Autoimmune thyroid diseases (AITD) are postulated to develop as a result of a complex interplay between several genetic and environmental influences. The pathogenesis of AITD is still not clearly defined. However, among the implicated triggers (e.g. iodine, infections, medications), more recent data confirmed strong associations of AITD with the hepatitis C virus (HCV) infection and interferon-α (IFNα) therapy. Moreover, it is likely that HCV and IFN act in synergism to trigger AITD in patients. Indeed, approximately 40% of HCV patients develop either clinical or subclinical disease while receiving IFNα. Interferon induced thyroiditis (IIT) can manifest as non-autoimmune thyroiditis (presenting as destructive thyroiditis, or non-autoimmune hypothyroidism), or autoimmune thyroiditis [presenting with clinical features of Graves' disease (GD) or Hashimoto's thyroiditis (HT)]. Although not yet clearly understood, it is thought that IFNα can induce thyroiditis via both immune stimulatory and direct toxic effects on the thyroid. In view of the high frequency of IIT, routine screening and surveillance of HCV patients receiving IFNα is recommended to avoid the complications, such as cardiac arrhythmias, associated with thyrotoxicosis. In summary, IIT is a common clinical problem that can be readily diagnosed with routine thyroid function screening of HCV patients receiving IFN. The treatment of IIT consists of the standard therapy for differing clinical manifestations of IIT such as GD, HT, or destructive thyroiditis. However, anti-thyroid medications are not recommended in this setting since they can potentially be hepatotoxic.

Recurrent pregnancy loss in patients with thyroid dysfunction.

PubMed

Sarkar, Debanjali

2012-12-01

Thyroid disturbances are common in women during their reproductive years. Thyroid dysfunction interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. This review highlights the gap in knowledge regarding the contribution of thyroid dysfunction in reproduction. Following implantation, the maintenance of the pregnancy is dependent on a multitude of endocrinological events that will eventually aid in the successful growth and development of the fetus. It is estimated that approximately 8-12% of all pregnancy losses are the result of endocrine factors. Autoimmune thyroid disease is present in around 4% of young females and up to 15% are at risk because they are thyroid antibody-positive. There is a strong relationship between thyroid immunity on one hand and infertility, miscarriage, and thyroid disturbances in pregnancy and postpartum, on the other hand. Even minimal hypothyroidism can increase rates of miscarriage and fetal death and may also have adverse effects on later cognitive development of the offspring. Hyperthyroidism during pregnancy may also have adverse consequences. Pregnant women with subclinical hypothyroidism or thyroid antibodies have an increased risk of complications, especially pre-eclampsia, perinatal mortality, and miscarriage. Universal screening for thyroid hormone abnormalities is not routinely recommended at present, but thyroid function must be examined in female with fetal loss or menstrual disturbances. Practitioners providing health care for women should be alert to thyroid disorders as an underlying etiology for recurrent pregnancy loss.

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.

The effects of thyrotropin-suppressing therapy on bone metabolism in patients with well-differentiated thyroid carcinoma.

PubMed

Kim, Mee Kyoung; Yun, Kyung-Jin; Kim, Min-Hee; Lim, Dong-Jun; Kwon, Hyuk-Sang; Song, Ki-Ho; Kang, Moo-Il; Baek, Ki Hyun

2015-02-01

Studies on the effects of levothyroxine (LT4) therapy on bone and bone metabolism have yielded conflicting results. This 1-year prospective study examined whether LT4 in patients with well-differentiated thyroid carcinoma (DTC) is a risk factor for bone mass loss and the subsequent development of osteoporosis. We examined 93 patients with DTC over 12months after initiating LT4 therapy (early postoperative period). We examined another 33 patients on long-term LT4 therapy for DTC (late postoperative period). Dual energy X-ray absorptiometry was performed at baseline and after 1year. The mean bone losses during the early postoperative period in the lumbar spine, femoral neck, and total hip, calculated as the percentage change between levels at baseline and 12months, were -0.88, -1.3 and -0.81%, respectively. Bone loss was more evident in postmenopausal women (lumbar spine -2.1%, femoral neck -2.2%, and hip -2.1%; all P<0.05). We compared the changes in annual bone mineral density (BMD) in postmenopausal women according to calcium/vitamin D supplementation. Bone loss tended to be higher in the postmenopausal women receiving no supplementation. There was no decrease in BMD among patients during the late postoperative period. The mean bone loss was generally greater in the early than in the late postoperative group, and this was significant at the lumbar spine (P=0.041) and femoral neck (P=0.010). TSH-suppressive levothyroxine therapy accelerates bone loss, predominantly in postmenopausal women and exclusively during the early post-thyroidectomy period. Copyright © 2014 Elsevier Inc. All rights reserved.

Intratumor heterogeneity and clonal evolution in an aggressive papillary thyroid cancer and matched metastases.

PubMed

Le Pennec, Soazig; Konopka, Tomasz; Gacquer, David; Fimereli, Danai; Tarabichi, Maxime; Tomás, Gil; Savagner, Frédérique; Decaussin-Petrucci, Myriam; Trésallet, Christophe; Andry, Guy; Larsimont, Denis; Detours, Vincent; Maenhaut, Carine

2015-04-01

The contribution of intratumor heterogeneity to thyroid metastatic cancers is still unknown. The clonal relationships between the primary thyroid tumors and lymph nodes (LN) or distant metastases are also poorly understood. The objective of this study was to determine the phylogenetic relationships between matched primary thyroid tumors and metastases. We searched for non-synonymous single-nucleotide variants (nsSNVs), gene fusions, alternative transcripts, and loss of heterozygosity (LOH) by paired-end massively parallel sequencing of cDNA (RNA-Seq) in a patient diagnosed with an aggressive papillary thyroid cancer (PTC). Seven tumor samples from a stage IVc PTC patient were analyzed by RNA-Seq: two areas from the primary tumor, four areas from two LN metastases, and one area from a pleural metastasis (PLM). A large panel of other thyroid tumors was used for Sanger sequencing screening. We identified seven new nsSNVs. Some of these were early events clonally present in both the primary PTC and the three matched metastases. Other nsSNVs were private to the primary tumor, the LN metastases and/or the PLM. Three new gene fusions were identified. A novel cancer-specific KAZN alternative transcript was detected in this aggressive PTC and in dozens of additional thyroid tumors. The PLM harbored an exclusive whole-chromosome 19 LOH. We have presented the first, to our knowledge, deep sequencing study comparing the mutational spectra in a PTC and both LN and distant metastases. This study has yielded novel findings concerning intra-tumor heterogeneity, clonal evolution and metastases dissemination in thyroid cancer. © 2015 Society for Endocrinology.

Predicted Risk of Radiation-Induced Cancers After Involved Field and Involved Node Radiotherapy With or Without Intensity Modulation for Early-Stage Hodgkin Lymphoma in Female Patients

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

Weber, Damien C., E-mail: damien.weber@unige.ch; Johanson, Safora; Peguret, Nicolas

2011-10-01

Purpose: To assess the excess relative risk (ERR) of radiation-induced cancers (RIC) in female patients with Hodgkin lymphoma (HL) female patients treated with conformal (3DCRT), intensity modulated (IMRT), or volumetric modulated arc (RA) radiation therapy. Methods and Materials: Plans for 10 early-stage HL female patients were computed for 3DCRT, IMRT, and RA with involved field RT (IFRT) and involvednode RT (INRT) radiation fields. Organs at risk dose--volume histograms were computed and inter-compared for IFRT vs. INRT and 3DCRT vs. IMRT/RA, respectively. The ERR for cancer induction in breasts, lungs, and thyroid was estimated using both linear and nonlinear models. Results:more » The mean estimated ERR for breast, lung, and thyroid were significantly lower (p < 0.01) with INRT than with IFRT planning, regardless of the radiation delivery technique used, assuming a linear dose-risk relationship. We found that using the nonlinear model, the mean ERR values were significantly (p < 0.01) increased with IMRT or RA compared to those with 3DCRT planning for the breast, lung, and thyroid, using an IFRT paradigm. After INRT planning, IMRT or RA increased the risk of RIC for lung and thyroid only. Conclusions: In this comparative planning study, using a nonlinear dose--risk model, IMRT or RA increased the estimated risk of RIC for breast, lung, and thyroid for HL female patients. This study also suggests that INRT planning, compared to IFRT planning, may reduce the ERR of RIC when risk is predicted using a linear model. Observing the opposite effect, with a nonlinear model, however, questions the validity of these biologically parameterized models.« less

Scintigraphic Profile of Thyrotoxicosis Patients and Correlation with Biochemical and Sonological Findings

PubMed Central

Mohan, Abhish; Kumar, PG; Puri, Pankaj

2017-01-01

Introduction Thyrotoxicosis is a spectrum of disorder with a rather common clinical presentation with different aetiologies. The aetiological diagnosis is important as the management differs. It is essential to accurately diagnose the cause before starting treatment. Scintigraphy of thyroid helps in differentiating accurately the various causes. USG is routinely being advocated and T3/T4 ratio has also been used. Aim This study aims to evaluate the scintigraphic profile of thyrotoxicosis patients and to correlate biochemical and USG findings with scintigraphy. Materials and Methods A total of 60 newly diagnosed thyrotoxicosis patients based on biochemical reports were included in the study. They underwent further evaluation with ultrasonography and 99mTc scintigraphy. Results Of 60 patients of thyrotoxicosis, 45 cases were of Grave’s disease, 10 cases were of thyroiditis and five cases were of Toxic Multinodular Goiter (MNG). The clinical characteristics were helpful in establishing the diagnosis in only six (10%) patients who presented with classic features of Grave’s disease with ophthalmopathy. T3/T4 ratio greater than 20 was seen only in 29 (66%) patients of Grave’s disease and also in three (33.33%) of thyroiditis patients. USG had a sensitivity and specificity of 81.82% and 93.75% in diagnosing Graves’ disease and 100% and 82.4% in diagnosing thyroiditis respectively. Conclusion Clinical findings do not help in accurately delineating aetiological diagnosis of thyrotoxicosis. Serum T3/T4 ratio when used as a criterion has marked overlap between the various conditions causing thyrotoxicosis. USG has reasonable sensitivity however, misses many cases of early Grave’s disease. Follow up scintigraphy helps in a small population with resolving thyroiditis or early Grave’s disease where the initial scintiscan is normal or inconclusive. PMID:28658823

Scintigraphic Profile of Thyrotoxicosis Patients and Correlation with Biochemical and Sonological Findings.

PubMed

Avs, Anil Kumar; Mohan, Abhish; Kumar, P G; Puri, Pankaj

2017-05-01

Thyrotoxicosis is a spectrum of disorder with a rather common clinical presentation with different aetiologies. The aetiological diagnosis is important as the management differs. It is essential to accurately diagnose the cause before starting treatment. Scintigraphy of thyroid helps in differentiating accurately the various causes. USG is routinely being advocated and T3/T4 ratio has also been used. This study aims to evaluate the scintigraphic profile of thyrotoxicosis patients and to correlate biochemical and USG findings with scintigraphy. A total of 60 newly diagnosed thyrotoxicosis patients based on biochemical reports were included in the study. They underwent further evaluation with ultrasonography and 99mTc scintigraphy. Of 60 patients of thyrotoxicosis, 45 cases were of Grave's disease, 10 cases were of thyroiditis and five cases were of Toxic Multinodular Goiter (MNG). The clinical characteristics were helpful in establishing the diagnosis in only six (10%) patients who presented with classic features of Grave's disease with ophthalmopathy. T3/T4 ratio greater than 20 was seen only in 29 (66%) patients of Grave's disease and also in three (33.33%) of thyroiditis patients. USG had a sensitivity and specificity of 81.82% and 93.75% in diagnosing Graves' disease and 100% and 82.4% in diagnosing thyroiditis respectively. Clinical findings do not help in accurately delineating aetiological diagnosis of thyrotoxicosis. Serum T3/T4 ratio when used as a criterion has marked overlap between the various conditions causing thyrotoxicosis. USG has reasonable sensitivity however, misses many cases of early Grave's disease. Follow up scintigraphy helps in a small population with resolving thyroiditis or early Grave's disease where the initial scintiscan is normal or inconclusive.

Lithium toxicity precipitated by thyrotoxicosis due to silent thyroiditis: cardiac arrest, quadriplegia, and coma.

PubMed

Sato, Yoshinori; Taki, Katsumi; Honda, Yuki; Takahashi, Shoichiro; Yoshimura, Ashio

2013-06-01

Lithium is widely used to treat bipolar disorders. Lithium toxicity is generally caused by inappropriately high doses of lithium or impaired lithium excretion. Most lithium is eliminated via the kidneys and, since thyroid hormone increases tubular reabsorption of lithium, thyrotoxicosis could contribute to the development of lithium toxicity. We report a case of severe lithium toxicity that was apparently precipitated by the onset of thyrotoxicosis resulting from silent thyroiditis and dehydration. The patient was a 64-year-old woman who was admitted for muscle weakness in the lower extremities, diarrhea, and palpitations. She had bipolar disorder and was being treated with lithium carbonate, which she discontinued one week before admission. Her circulating lithium levels had been monitored yearly. Early in her admission she was dehydrated and had febrile episodes, paroxysmal atrial fibrillation, and muscle weakness. Initially, fluid therapy was started, but she lost consciousness and had a cardiac arrest for 2 minutes due to prolonged sinus arrest. Chest compression and manual artificial ventilation were performed, and body surface pacing was started. Serum lithium was markedly elevated to 3.81 mEq/L (therapeutic range, 0.4-1.0 mEq/L), and thyroid hormone levels were increased (free triiodothyronine, 8.12 pg/mL; free thyroxine, 4.45 ng/dL), while thyrotropin (TSH) was suppressed (<0.01 μIU/mL). Hemodialysis was performed, and a temporary pacemaker was inserted for severe sinus bradycardia. The serum thyroglobulin was 4680 ng/mL (reference range, <32.7 ng/mL). A TSH receptor antibody test was negative. Glucocorticoid therapy and inorganic iodine (100 mg) were administered and continued until day 11. However, her neurological symptoms deteriorated with floppy quadriplegia and deep coma. She gradually recovered. On day 36, she was discharged without any neurological symptoms or thyrotoxicosis. A 64-year-old woman taking lithium for bipolar disorder developed lithium toxicity in the setting of what seemed likely to be a recent onset of thyrotoxicosis due to silent thyroiditis. Thyrotoxicosis may be a contributing cause of lithium toxicity, particularly if it is abrupt in onset and even with cessation of lithium therapy if renal function is compromised. Thyroid function should be assessed immediately in patients with suspected lithium toxicity.

Trends in Costs of Thyroid Disease Treatment in Denmark during 1995-2015.

PubMed

Møllehave, Line Tang; Linneberg, Allan; Skaaby, Tea; Knudsen, Nils; Ehlers, Lars; Jørgensen, Torben; Thuesen, Betina Heinsbæk

2018-03-01

Iodine fortification (IF) may contribute to changes in costs of thyroid disease treatment through changes in disease patterns. From a health economic perspective, assessment of the development in costs of thyroid disease treatment in the population is pertinent. To assess the trends in annual medicine and hospital costs of thyroid disease treatment during 1995-2015 in Denmark, i.e., before and after the introduction of mandatory IF in 2000. Information on treatments for thyroid disease (antithyroid medication, thyroid hormone therapy, thyroid surgery, and radioiodine treatment) was obtained from nationwide registers. Costs were valued at 2015 prices using sales prices for medicines and the Danish Diagnosis-Related Group (DRG) and Danish Ambulatory Grouping System (DAGS) tariffs of surgeries/radioiodine treatments. Results were adjusted for changes in population size and age and sex distribution. The total direct medicine and hospital costs of thyroid disease treatment increased from EUR ∼190,000 per 100,000 persons in 1995 to EUR ∼270,000 per 100,000 persons in 2015. This was mainly due to linearly increased costs of thyroid hormone therapy and increased costs of thyroid surgery since 2008. Costs of antithyroid medication increased slightly and transiently after IF, while costs of radioiodine treatment remained constant. Costs of thyroid hormone therapy and thyroid surgery did not follow the development in the prevalence of hypothyroidism and structural thyroid diseases observed in concurrent studies. The costs of total direct medicine and hospital costs for thyroid disease treatment in Denmark increased from 1995 to 2015. This is possibly due to several factors, e.g., changes in treatment practices, and the direct effect of IF alone remains to be estimated.

[Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus].

PubMed

Shpakov, A O

2017-05-01

Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and as a consequence, the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (TH) are used to correct functions of the thyroid system. However, they are characterized by many side effects, such as their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to disturb insulin-producing function of pancreas, exacerbating thereby diabetic pathology. Therefore, the analogues of TH, selective for certain types of TH receptors, that do not have these side effects, are being developed. The peptide and low-molecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, metformin therapy and drugs with antioxidant activity are effective for the treatment of thyroid pathology in types 1 and 2 DM. In the review, the literature data and the results of own investigations on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM are summarized and analyzed.

Computational modeling of the amphibian thyroid axis supported by targeted in vivo testing to advance quantitative adverse outcome pathway development

EPA Science Inventory

In vitro screening of chemicals for bioactivity together with computational modeling are beginning to replace animal toxicity testing in support of chemical risk assessment. To facilitate this transition, an amphibian thyroid axis model has been developed to describe thyroid home...

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.

Transient Non-Autoimmune Hyperthyroidism of Early Pregnancy

PubMed Central

Goldman, Alexander M.; Mestman, Jorge H.

2011-01-01

It is characterized by chemical and sometimes clinical hyperthyroidism, without evidence of thyroid autoimmunity that resolves spontaneously by 16 weeks gestation without significant obstetrical complications. PMID:21785688

Lymphoedema of the upper limb: a rare complication of thyroid surgery?

PubMed Central

Stephen, Christopher; Munnoch, David Alexander

2016-01-01

A 40-year-old woman underwent an elective thyroidectomy for a non-toxic, multinodular goitre. In the early postoperative period, the patient developed a significant unilateral swelling of the right upper limb, which was subsequently confirmed to be lymphoedema. This was eventually treated successfully using liposuction and compression garment therapies. We report the case due to its rarity and present a possible explanation for such an unexpected complication based on known anatomical variations of lymphatic drainage of the upper limb. PMID:27090542

Effects of GH replacement therapy on thyroid volume and nodule development in GH deficient adults: a retrospective cohort study.

PubMed

Curtò, Lorenzo; Giovinazzo, Salvatore; Alibrandi, Angela; Campennì, Alfredo; Trimarchi, Francesco; Cannavò, Salvatore; Ruggeri, Rosaria Maddalena

2015-05-01

Despite the well-known effects of GH/IGF1 signaling on the thyroid, few data are available on the risk of developing nodular goiter in hypopituitary subjects during GH replacement therapy (GHRT). We aimed to define the effects of GH therapy on thyroid volume (TV) and nodular growth. The records of 96 subjects (47 males and 49 females, median age 48 years) with GH deficit (GHD) were investigated. Seventy also had central hypothyroidism (CH). At the time of our retrospective evaluation, median treatment duration was 5 years. Pre-treatment TV was smaller in GHD patients than in healthy subjects (P=0.030). During GH treatment, TV significantly increased (P=0.016 for the entire group and P=0.014 in euthyroid GHD patients). Before starting GH therapy, 17 patients harbored thyroid nodules. During GH therapy, nodule size increased slightly in seven patients, and new thyroid nodules occurred in nine patients. Among the 79 patients without pre-existing thyroid nodules, 17 developed one or more nodules. There was no difference in the prevalence of CH in GHD patients with or without thyroid nodules (P=0.915; P=0.841, when patients with pre-therapy nodular goiter were excluded), the main predictor for nodule development being serum IGF1 (P=0.038). GHRT is associated with TV's increase in GHD patients. Thyroid nodules developed in 27% of patients, mainly in relation to pre-therapy IGF1 levels, independently of normal or impaired TSH stimulation. © 2015 European Society of Endocrinology.

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

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.

Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer.

PubMed

Yu, Hea Min; Park, Soon Hyun; Lee, Jae Min; Park, Kang Seo

2013-09-01

Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

A Concise Atlas of Thyroid Cancer Next-Generation Sequencing Panel ThyroSeq v.2

PubMed Central

Alsina, Jorge; Alsina, Raul; Gulec, Seza

2017-01-01

The next-generation sequencing technology allows high out-put genomic analysis. An innovative assay in thyroid cancer, ThyroSeq® was developed for targeted mutation detection by next generation sequencing technology in fine needle aspiration and tissue samples. ThyroSeq v.2 next generation sequencing panel offers simultaneous sequencing and detection in >1000 hotspots of 14 thyroid cancer-related genes and for 42 types of gene fusions known to occur in thyroid cancer. ThyroSeq is being increasingly used to further narrow the indeterminate category defined by cytology for thyroid nodules. From a surgical perspective, genomic profiling also provides prognostic and predictive information and closely relates to determination of surgical strategy. Both the genomic analysis technology and the informatics for the cancer genome data base are rapidly developing. In this paper, we have gathered existing information on the thyroid cancer-related genes involved in the initiation and progression of thyroid cancer. Our goal is to assemble a glossary for the current ThyroSeq genomic panel that can help elucidate the role genomics play in thyroid cancer oncogenesis. PMID:28117295

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.

Genetics Home Reference: Hashimoto thyroiditis

MedlinePlus

... is the most common cause of thyroid underactivity (hypothyroidism) in the United States. Related Information What information ... However, some people with thyroid antibodies never develop hypothyroidism or experience any related signs or symptoms. People ...

Hurthle Cell Cancer

MedlinePlus

... can be more aggressive than other types of thyroid cancer. Surgery to remove the thyroid gland is the ... factors Factors that increase the risk of developing thyroid cancer include: Being female Being older Having a history ...

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

PubMed Central

Lamos, Elizabeth M.; Munir, Kashif M.

2016-01-01

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

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

PubMed Central

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

2014-01-01

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

Clinical manifestations of postpartum thyroid disease.

PubMed

Lazarus, J H

1999-07-01

Postpartum thyroiditis (PPT) occurs in 5%-9% of unselected postpartum women; hyperthyroidism and hypothyroidism develop, the latter being permanent, in up to 25 %-30% of women. PPT is strongly associated with antithyroid peroxidase (anti-TPO) antibodies, but 50% of anti-TPO positive women do not develop thyroid dysfunction. Symptom analysis has shown that lack of energy and irritability were the most frequent hyperthyroid symptoms whereas lack of energy, aches and pains, poor memory, dry skin, and cold intolerance were the significant hypothyroid features. Some of these symptoms were more frequently observed than in antibody-negative controls even when these patients were euthyroid and in anti-TPOAb positive women who did not develop PPT at all. The diagnosis of PPT is based on the observation of abnormal thyroid function tests in a postpartum anti-TPOAb-positive woman: transient hyperthyroidism occurs at 14 weeks and hypothyroidism at 19 weeks postpartum. Diffuse or multifocal hypoechogenicity of the thyroid is seen on echography and a thyroid destructive process is evidenced by an increase in serum thyroglobulin and urinary iodine excretion. In addition to the 25%-30% of women who develop permanent hypothyroidism at 3 years, recent data indicate that 50% of women who have developed PPT will be hypothyroid 7-9 years later. The long-term risk is only 5% for those anti-TPOAb positive women not developing thyroid dysfunction postpartum. The risk of recurrent PPT is 70% if previous PPT was experienced and 25% if the patient was euthyroid after the first pregnancy.

[Assessment of thyroid function in women treated for vomiting in early pregnancy].

PubMed

Makowska, Beata; Preis, Krzysztof; Swiatkowska-Freund, Małgorzata; Leszczyńska, Katarzyna

2005-08-01

Hyperthyroidism does not influence procreation ability significantly, but very often causes complications of the course of pregnancy and increases neonatal morbidity and mortality in newborns. Nausea and vomiting in the first trimester of pregnancy are very common complaints in these patients. The aim of the study was to prove, that assessment of the thyroid hormones in every vomiting woman in the first trimester allows to start the proper treatment of hyperthyreosis as early as possible and improves the prognosis. Authors analyzed 22 pregnant women treated for vomiting during the first trimester in the Department of Obstetrics and 5 women treated in the Outpatient Clinic. In none of them hormonal dysfunction was diagnosed before pregnancy. In 21 patients free thyroxine (fT4) in serum was assessed. In 8 cases (38%) hyperthyreosis was diagnosed. Except the routine anti vomiting treatment, they received a beta-blocker 30 mg per day. It allowed to avoid hospitalization in three pregnant women treated in the outpatient clinic. Two patients, who had earlier two spontaneous abortions, delivered healthy babies. 1. The beta-blocker in treatment gives very good results and allows to avoid hospitalization in patients with hyperthyroidism and hyper emesis gravidarum. 2. In some patients vomiting may be the only symptom of sub clinical hyperthyroidism in early pregnancy. Assessment of the thyroid hormones levels and adequate treatment may give these women a chance for a healthy child.

Maternal thyroid function and child educational attainment: prospective cohort study

PubMed Central

Haig, Caroline; McConnachie, Alex; Sattar, Naveed; Ring, Susan M; Smith, George D; Lawlor, Debbie A; Lindsay, Robert S

2018-01-01

Abstract Objective To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. Design Prospective cohort study. Setting Avon Longitudinal Study of Parents and Children cohort in the UK. Participants 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). Exposures Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. Main outcome measures Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. Results No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. Conclusions Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement. PMID:29463525

Update: the status of clinical trials with kinase inhibitors in thyroid cancer.

PubMed

Wells, Samuel A; Santoro, Massimo

2014-05-01

Thyroid cancer is usually cured by timely thyroidectomy; however, the treatment of patients with advanced disease is challenging because their tumors are mostly unresponsive to conventional therapies. Recently, the malignancy has attracted much interest for two reasons: the dramatic increase in its incidence over the last three decades, and the discovery of the genetic mutations or chromosomal rearrangements causing most histological types of thyroid cancer. This update reviews the molecular genetics of thyroid cancer and the clinical trials evaluating kinase inhibitors (KIs) in patients with locally advanced or metastatic disease. The update also reviews studies in other malignancies, which have identified mechanisms of efficacy, and also resistance, to specific KIs. This information has been critical both to the development of effective second-generation drugs and to the design of combinatorial therapeutic regimens. Finally, the update addresses the major challenges facing clinicians who seek to develop more effective therapy for patients with thyroid cancer. PubMed was searched from January 2000 to November 2013 using the following terms: thyroid cancer, treatment of thyroid cancer, clinical trials in thyroid cancer, small molecule therapeutics, kinase inhibitors, and next generation sequencing. A new era in cancer therapy has emerged based on the introduction of KIs for the treatment of patients with liquid and solid organ malignancies. Patients with thyroid cancer have benefited from this advance and will continue to do so with the development of drugs having greater specificity and with the implementation of clinical trials of combined therapeutics to overcome drug resistance.

[Effects of hypophyseal Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthetic peptides on immunity, hemostasis, morphology and functions of the thyroid gland in neonatally hypophysectomized chicken and one-year-old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2010-01-01

Neonatal hypophysectomy in chicken produces enlarged follicles of the thyroid gland, accumulation of colloids, impressed follicular epithelium, increased nucleus-cytoplasm ratio in thyrocytes, atrophied inter-follicular epithelium, depressed immunity, development of hypercoagulation and depressed fibrinolysis. When hypophysectomy is performed in one-year-old birds the impairments developing in thyroid morphology, immunity and hemostasis are less pronounced. Peptides of the anterior (Lys-Glu-Asp-Gly) and posterior (Ala-Glu-Asp-Gly) thyroid lobes injected to hypophysectomized birds prevent atrophic changes of the thyroid gland, normalize immune and hemostatic parameters.

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.

Heterochronic opsin expression due to early light deprivation results in drastically shifted visual sensitivity in a cichlid fish: Possible role of thyroid hormone signaling.

PubMed

Karagic, Nidal; Härer, Andreas; Meyer, Axel; Torres-Dowdall, Julián

2018-06-14

During early ontogeny, visual opsin gene expression in cichlids is influenced by prevailing light regimen. Red light, for example, leads to an early switch from the expression of short-wavelength sensitive to long-wavelength sensitive opsins. Here, we address the influence of light deprivation on opsin expression. Individuals reared in constant darkness during the first 14 days post-hatching (dph) showed a general developmental delay compared with fish reared under a 12:12 hr light-dark cycle (control group). Several characters including pigmentation patterns and eye development, appeared later in dark-reared individuals. Quantitative real-time PCR and fluorescent in situ hybridization at six time points during the 14 days period revealed that fish from the control group expressed opsin genes from 5 dph on and maintained a short-wavelength sensitive phenotype (sws1, rh2b, and rh2a). Onset of opsin expression in dark-reared Midas cichlids was delayed by 4 days and visual sensitivity rapidly progressed toward a long-wavelength sensitive phenotype (sws2b, rh2a, and lws). Shifts in visual sensitivities toward longer wavelengths are mediated by thyroid hormone (TH) in many vertebrates. Compared to control fish, dark-reared individuals showed elevated dio3 expression levels - a validated proxy for TH concentration - suggesting higher circulating TH levels. Despite decelerated overall development, ontogeny of opsin gene expression was accelerated, resulting in retinae with long-wavelength shifted predicted sensitivities compared to light-reared individuals. Indirect evidence suggests that this was due to altered TH metabolism. © 2018 Wiley Periodicals, Inc.

Thyroid and associated polyglandular neoplasms in patients who received head and neck irradiation during childhood

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

Katz, A.D.

One hundred fifty-one patients with a history of childhood irradiation to the head, neck, and thorax had neck explorations (142 for cold thyroid nodules and 9 for hypercalcemia). Fifty-nine of the patients had thyroid carcinoma, and associated glandular tumors were found in 20 others. In addition, 6 female patients developed breast carcinoma; 4 of these women also had thyroid carcinoma. In this series, 48.6% of the patients irradiated for acne and 36.4% with tonsil and adenoid irradiation developed thyroid carcinoma, but only 10.5% with thymic irradiation did so. It is suggested that the workup on these patients include not onlymore » complete thyroid and parathyroid testing, but also a careful examination of all salivary glands, both major and minor. Women should have thorough breast examinations and should perhaps be followed as if they were in the potentially high-risk breast group. When thyroid surgery is performed, a total thyroidectomy is recommended.« less

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.

PROGRESS TOWARDS DEVELOPMENT OF AN AMPHIBIAN-BASED THYROID SCREENING ASSAY USING XENOPUS LAEVIS: ORGANISMAL AND THYROIDAL RESPONSES TO THE MODEL COMPOUNDS 6-PROPYLTHIOURACIL, METHIMAZOLE, AND THYROXINE.

EPA Science Inventory

The data presented in this manuscript specifically addresses the development and standardization needs associated with an amphibian thyroid axis screening assay. A protocol for an amphibian growth and reproduction test has been requested by the Office of Science Council and Polic...

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.

Radiation-related thyroid autoimmunity and dysfunction

PubMed Central

Nagayama, Yuji

2018-01-01

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

Detection of ATM germline variants by the p53 mitotic centrosomal localization test in BRCA1/2-negative patients with early-onset breast cancer.

PubMed

Prodosmo, Andrea; Buffone, Amelia; Mattioni, Manlio; Barnabei, Agnese; Persichetti, Agnese; De Leo, Aurora; Appetecchia, Marialuisa; Nicolussi, Arianna; Coppa, Anna; Sciacchitano, Salvatore; Giordano, Carolina; Pinnarò, Paola; Sanguineti, Giuseppe; Strigari, Lidia; Alessandrini, Gabriele; Facciolo, Francesco; Cosimelli, Maurizio; Grazi, Gian Luca; Corrado, Giacomo; Vizza, Enrico; Giannini, Giuseppe; Soddu, Silvia

2016-09-06

Variant ATM heterozygotes have an increased risk of developing cancer, cardiovascular diseases, and diabetes. Costs and time of sequencing and ATM variant complexity make large-scale, general population screenings not cost-effective yet. Recently, we developed a straightforward, rapid, and inexpensive test based on p53 mitotic centrosomal localization (p53-MCL) in peripheral blood mononuclear cells (PBMCs) that diagnoses mutant ATM zygosity and recognizes tumor-associated ATM polymorphisms. Fresh PBMCs from 496 cancer patients were analyzed by p53-MCL: 90 cases with familial BRCA1/2-positive and -negative breast and/or ovarian cancer, 337 with sporadic cancers (ovarian, lung, colon, and post-menopausal breast cancers), and 69 with breast/thyroid cancer. Variants were confirmed by ATM sequencing. A total of seven individuals with ATM variants were identified, 5/65 (7.7 %) in breast cancer cases of familial breast and/or ovarian cancer and 2/69 (2.9 %) in breast/thyroid cancer. No variant ATM carriers were found among the other cancer cases. Excluding a single case in which both BRCA1 and ATM were mutated, no p53-MCL alterations were observed in BRCA1/2-positive cases. These data validate p53-MCL as reliable and specific test for germline ATM variants, confirm ATM as breast cancer susceptibility gene, and highlight a possible association with breast/thyroid cancers.

TERT, HRAS, and EIF1AX Mutations in a Patient with Follicular Adenoma.

PubMed

Topf, Michael C; Wang, Zi-Xuan; Tuluc, Madalina; Pribitkin, Edmund A

2018-06-01

Molecular markers are increasingly used as diagnostic tools in the management of thyroid nodules. There is a paucity of studies evaluating the prevalence of molecular markers in benign lesions. A 68-year-old woman with hypothyroidism presented with a right thyroid nodule, which was atypia of undetermined significance on cytology. The fine-needle aspirate of the nodule was examined with next-generation sequencing and found to harbor a C228T mutation in the TERT gene, a Q61R mutation in the HRAS gene, and an A113_splice mutation in the EIF1AX gene. Right thyroid lobectomy was performed, with final pathology showing follicular adenoma. All three mutations detected in the original fine-needle aspirate specimen were detected in the final surgical specimen as well. A rare case of TERT, HRAS, and EIF1AX mutations is reported in a patient with follicular adenoma. TERT promoter mutations may be an early genetic event in the molecular pathogenesis of follicular thyroid carcinoma.

The Early Interventionist and the Medical Problems of the Child with Down Syndrome.

ERIC Educational Resources Information Center

Roizen, Nancy J.

2003-01-01

This article describes medical problems that occur more frequently in young children with Down syndrome. These include common cardiac, hearing, and vision problems and less common thyroid and celiac diseases. Guidelines for preventing dental and obesity problems are followed by suggestions to early interventionists for watching for leukemia, neck…

[Early recurrent miscarriage: Evaluation and management].

PubMed

Gallot, V; Nedellec, S; Capmas, P; Legendre, G; Lejeune-Saada, V; Subtil, D; Nizard, J; Levêque, J; Deffieux, X; Hervé, B; Vialard, F

2014-12-01

To establish recommendations for early recurrent miscarriages (≥3 miscarriages before 14weeks of amenorrhea). Literature review, establishing levels of evidence and recommendations for grades of clinical practice. Women evaluation includes the search for a diabetes (grade A), an antiphospholipid syndrome (APS) (grade A), a thyroid dysfunction (grade A), a hyperprolactinemia (grade B), a vitamin deficiency and a hyperhomocysteinemia (grade C), a uterine abnormality (grade C), an altered ovarian reserve (grade C), and a couple chromosome analysis (grade A). For unexplained early recurrent miscarriages, treatment includes folic acid and progesterone supplementation, and a reinsurance policy in the first quarter (grade C). It is recommended to prescribe the combination of aspirin and low-molecular-weight heparin when APS (grade A), glycemic control in diabetes (grade A), L-Thyroxine in case of hypothyroidism (grade A) or the presence of thyroid antibodies (grade B), bromocriptine if hyperprolactinemia (grade B), a substitution for vitamin deficiency or hyperhomocysteinemia (grade C), sectionning a uterine septum (grade C) and treating an uterine acquired abnormality (grade C). These recommendations should improve the management of couples faced with early recurrent miscarriages. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Thyroid and cardiovascular disorders].

PubMed

Zyśko, Dorota; Gajek, Jacek

2004-05-01

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

[Rare differential diagnosis of hyperthyroidism].

PubMed

Besemer, Britta; Müssig, Karsten

2016-06-01

A 54-year-old female patient is admitted for evaluation of her thyroid function after two cycles of ipilimumab therapy. The decision for the anti-cytotoxic-T-lymphocyte-antigen-4-therapy (anti-CTLA-4) was made two months earlier because of malignant melanoma with pulmonary metastases. The patient was euthyroid before initiation of treatment and without known thyroid disease. The laboratory reveals thyrotoxicosis with elevated anti-thyroid peroxidase and anti-thyroglobulin antibody levels. The anti-thyroid stimulating hormone receptor antibody levels are within the normal range. Thyroid ultrasound shows a normal-sized, inhomogenous, hypoechogenic thyroid gland, consistent with autoimmune thyroiditis. Diagnosis of hyperthyroidism due to ipilimumab-induced autoimmune thyroiditis is made. The patient does not receive any thyroid-specific medication, with regular control of the thyroid hormone levels. When the patient becomes euthyroid, the ipilimumab therapy is continued. Three weeks later, the patient develops hypothyroidism and a supplementation with L-thyroxine is initiated. An anti-CTLA-4 therapy may cause thyroid dysfunction. Therefore, before initiation and in the course of the treatment, regular controls of the thyroid hormone levels are required. © Georg Thieme Verlag KG Stuttgart · New York.

Mean platelet volume could be a possible biomarker for papillary thyroid carcinomas.

PubMed

Baldane, Suleyman; Ipekci, Suleyman H; Sozen, Mehmet; Kebapcilar, Levent

2015-01-01

Thyroid cancer is the most prevalent endocrine cancer and is evident in nearly 5% of thyroid nodules. The correlation between mean platelet volume (MPV) and many other cancer types has been investigated previously. However, the correlation between papillary thyroid carcinoma (PTC) and MPV has not yet been studied in detail. The aim of this study was to examine whether MPV would be a useful inflammatory marker to differentiate PTC patients from cases of benign goiter and healthy controls. Preoperative MPV levels in patients with PTC were found to be significantly higher when compared with benign goiter patients and healthy controls ((respectively, 8.05 femtoliter (fl), 7.57 fl, 7.36 fl, p=0.001). After surgical treatment of PTC patients, a significant decrease in MPV levels was seen (8.05 fl versus 7.60 fl, p=0.005). ROC analysis suggested 7.81 as the cut-off value for MPV (AUC=0.729, sensitivity 60%, specificity 80%). In conclusion, maybe changes in MPV levels can be used as an easily available biomarker for monitoring the risk of PTC in patients with thyroid nodules, enabling early diagnosis of PTC.

Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis.

PubMed

Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko

2017-02-23

BACKGROUND Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. CASE REPORT A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient's thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. CONCLUSIONS Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT.

Conversion of autoimmune hypothyroidism to hyperthyroidism.

PubMed

Furqan, Saira; Haque, Naeem-ul; Islam, Najmul

2014-08-03

Graves' disease and Hashimoto's thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone.

Conversion of autoimmune hypothyroidism to hyperthyroidism

PubMed Central

2014-01-01

Background Graves’ disease and Hashimoto’s thyroiditis are the two autoimmune spectrum of thyroid disease. Cases of conversion from hyperthyroidism to hypothyroidism have been reported but conversion from hypothyroidism to hyperthyroidism is very rare. Although such cases have been reported rarely in the past we are now seeing such conversions from hypothyroidism to hyperthyroidism more frequently in clinical practice. Case presentation We are reporting three cases of middle aged Asian females who presented with classical symptoms of hypothyroidism and the investigations showed elevated thyroid stimulating hormone with positive thyroid antibodies. Diagnosis of autoimmune hypothyroidism was made and thyroxine replacement therapy was initiated. Patients became asymptomatic with normalization of thyroid stimulating hormone level. After few years they developed symptoms of hyperthyroidism with suppressed thyroid stimulating hormone level. Over replacement of thyroxine was considered and the dose of thyroxine was decreased, but they remain symptomatic. After gradual decrease in the dose of thyroxine it was stopped finally. Even after few months of stopping thyroxine, the symptoms of hyperthyroidism did not improve and the biochemical and imaging modalities confirmed that the patients have developed hyperthyroidism. Anti-thyroid treatment was then started and the patients became symptom free. Conclusion High index of suspicion should be there for possible conversion of hypothyroidism to hyperthyroidism if a patient with primary hypothyroidism develops persistent symptoms of hyperthyroidism. Otherwise it can be missed easily considering it as an over replacement with thyroid hormone. PMID:25086829

Down syndrome--genetic and nutritional aspects of accompanying disorders.

PubMed

Mazurek, Dominika; Wyka, Joanna

2015-01-01

Down syndrome (DS) is one of the more commonly occurring genetic disorders, where mental retardation is combined with nutritional diseases. It is caused by having a third copy of chromosome 21, and there exist 3 forms; Simple Trisomy 21, Translocation Trisomy and Mosaic Trisomy. Symptoms include intellectual disability/mental retardation, early onset of Alzheimer's disease and the appearance of various phenotypic features such as narrow slanted eyes, flat nose and short stature. In addition, there are other health problems throughout the body, consisting in part of cardiac defects and thyroid function abnormalities along with nutritional disorders (ie. overweight, obesity, hypercholesterolemia and deficiencies of vitamins and minerals). Those suffering DS have widespread body frame abnormalities and impaired brain development and function; the latter leading to impaired intellectual development. Many studies indicate excessive or deficient nutrient uptakes associated with making inappropriate foodstuff choices, food intolerance, (eg. celiac disease) or malabsorption. DS persons with overweight or obesity are linked with a slow metabolic rate, abnormal blood leptin concentrations and exhibit low levels of physical activity. Vitamin B group deficiencies and abnormal blood homocysteine levels decrease the rate of intellectual development in DS cases. Zinc deficiencies result in short stature, thyroid function disorders and an increased appetite caused by excessive supplementation. Scientific advances in the research and diagnosis of DS, as well as preventing any associated conditions, have significantly increased life expectancies of those with this genetic disorder. Early dietary interventions by parents or guardians of DS children afford an opportunity for decreasing the risk or delaying some of the DS associated conditions from appearing, thus beneficially impacting on their quality of life.

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

PubMed Central

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

2016-01-01

Background: Thyroid nodules are a common clinical problem, and differentiated thyroid cancer is becoming increasingly prevalent. Since the American Thyroid Association's (ATA's) guidelines for the management of these disorders were revised in 2009, significant scientific advances have occurred in the field. The aim of these guidelines is to inform clinicians, patients, researchers, and health policy makers on published evidence relating to the diagnosis and management of thyroid nodules and differentiated thyroid cancer. Methods: The specific clinical questions addressed in these guidelines were based on prior versions of the guidelines, stakeholder input, and input of task force members. Task force panel members were educated on knowledge synthesis methods, including electronic database searching, review and selection of relevant citations, and critical appraisal of selected studies. Published English language articles on adults were eligible for inclusion. The American College of Physicians Guideline Grading System was used for critical appraisal of evidence and grading strength of recommendations for therapeutic interventions. We developed a similarly formatted system to appraise the quality of such studies and resultant recommendations. The guideline panel had complete editorial independence from the ATA. Competing interests of guideline task force members were regularly updated, managed, and communicated to the ATA and task force members. Results: The revised guidelines for the management of thyroid nodules include recommendations regarding initial evaluation, clinical and ultrasound criteria for fine-needle aspiration biopsy, interpretation of fine-needle aspiration biopsy results, use of molecular markers, and management of benign thyroid nodules. Recommendations regarding the initial management of thyroid cancer include those relating to screening for thyroid cancer, staging and risk assessment, surgical management, radioiodine remnant ablation and therapy, and thyrotropin suppression therapy using levothyroxine. Recommendations related to long-term management of differentiated thyroid cancer include those related to surveillance for recurrent disease using imaging and serum thyroglobulin, thyroid hormone therapy, management of recurrent and metastatic disease, consideration for clinical trials and targeted therapy, as well as directions for future research. Conclusions: We have developed evidence-based recommendations to inform clinical decision-making in the management of thyroid nodules and differentiated thyroid cancer. They represent, in our opinion, contemporary optimal care for patients with these disorders. PMID:26462967

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

PubMed

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

2016-01-01

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

Conditional immortalization of human thyroid epithelial cells: a tool for analysis of oncogene action.

PubMed Central

Wynford-Thomas, D; Bond, J A; Wyllie, F S; Burns, J S; Williams, E D; Jones, T; Sheer, D; Lemoine, N R

1990-01-01

To overcome the difficulty of assessing oncogene action in human epithelial cell types, such as thyroid, which have limited proliferative potential in culture, we have explored the use of temperature-sensitive (ts) mutants of simian virus 40 (SV40) early region to create conditionally immortalized epithelial cell lines. Normal primary cultures of human thyroid follicular cells were transfected with a plasmid containing the SV40 early region from mutant tsA58. Expanding epithelial colonies were observed after 2 to 3 months, all of which grew to greater than 200 population doublings without crisis. All showed tight temperature dependence for growth. After switch-up to the restrictive temperature (40.5 degrees C), no further increase in cell number was seen after 1 to 2 days. However, DNA synthesis declined much more slowly; the dissociation from cell division led to marked polyploidy. Viability was maintained for up to 2 weeks. Introduction of an inducible mutant ras gene into ts thyroid cells led, as expected, to morphological transformation at the permissive temperature when ras was induced. Interestingly, this was associated with a marked reduction in net growth rate. At the restrictive temperature, induction of mutant ras caused rapid cell death. These results demonstrate the utility of a ts SV40 mutant to permit the study of oncogene action in an otherwise nonproliferative target cell and reveal important differences in the interaction between ras and SV40 T in these epithelial cells compared with previously studied cell types. Images PMID:1697930

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.

Ultrasonography and the Ultrasound-Based Management of Thyroid Nodules: Consensus Statement and Recommendations

PubMed Central

Baek, Jung Hwan; Jung, So Lyung; Kim, Dong Wook; Kim, Eun Kyung; Kim, Ji Young; Kwak, Jin Young; Lee, Jeong Hyun; Lee, Joon Hyung; Lee, Young Hen; Na, Dong Gyu; Park, Jeong Seon; Park, Sun Won

2011-01-01

The detection of thyroid nodules has become more common with the widespread use of ultrasonography (US). US is the mainstay for detecting and making the differential diagnosis of thyroid nodules as well as for providing guidance for a biopsy. The Task Force on Thyroid Nodules of the Korean Society of Thyroid Radiology has developed recommendations for the US diagnosis and US-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature, the results of multicenter studies and from the consensus of experts. PMID:21228935

Thyroid and parathyroid tumours in patients submitted to X-ray scalp epilation during the tinea capitis eradication campaign in the North of Portugal (1950-1963).

PubMed

Boaventura, Paula; Pereira, Dina; Mendes, Adélia; Teixeira-Gomes, José; Sobrinho-Simões, Manuel; Soares, Paula

2014-10-01

Tinea capitis attained epidemical proportions in the fifth and sixth decades in Portugal, as in other countries. Before starting the utilization of griseofulvin in 1959, the best approach to treat tinea capitis infection was X-ray scalp epilation combined with topical antimycotic ointments. A long-term side effect of this therapy is thyroid disease, namely thyroid cancer; data on parathyroid lesions (hyperplasia, adenoma and carcinoma) are scarce. We observed clinically 1,375 individuals irradiated in childhood for tinea capitis treatment in the North of Portugal with the main purpose of evaluating thyroid and parathyroid tumours as possible sequelae of the irradiation treatment. For each individual, a cervical ultrasound and a serum calcium measurement were proposed. Fine needle aspiration cytology was suggested whenever ultrasound thyroid nodules presented suspicious features. We observed a 54 % frequency of thyroid nodules and a 2.8 % frequency of thyroid carcinoma (38/1,375). Nineteen of the 38 (50 %) carcinomas were diagnosed by us, whereas the remaining 19 carcinomas had been diagnosed and treated prior to our observation. The carcinomas were significantly more frequent in women than in men. Benign excised lesions were also significantly more frequent in women and in patients irradiated at younger ages. Seven women, considered asymptomatic until our clinical observation, had laboratory signs of hyperparathyroidism. The data we have obtained, namely high thyroid cancer frequency, corroborate previous data from childhood irradiated cohorts and highlight the need for the close follow-up of these populations in order to identify and treat early undiagnosed head and neck lesions. No evidence of increased parathyroid disease was found in this cohort of head and neck X-irradiated patients.

Neonatal nicotine exposure alters leptin signaling in the hypothalamus-pituitary-thyroid axis in the late postnatal period and adulthood in rats.

PubMed

Santos-Silva, A P; Moura, E G; Pinheiro, C R; Rios, A S; Abreu-Villaça, Y; Passos, M C F; Oliveira, E; Lisboa, P C

2010-07-31

Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus-pituitary-thyroid axis of suckling and adult offspring. Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p<0.05. In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (-61%, -42%, -56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (-52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (-44%, -50%, -47%) and higher pSTAT-3 expression (+80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+1.54x) and lower pSTAT-3 content (-34%). Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood. Copyright 2010 Elsevier Inc. All rights reserved.

Medullary Thyroid Carcinoma Program | Center for Cancer Research

Cancer.gov

Medullary Thyroid Carcinoma Program Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment.

Homozygous Resistance to Thyroid Hormone β: Can Combined Antithyroid Drug and Triiodothyroacetic Acid Treatment Prevent Cardiac Failure?

PubMed

Moran, Carla; Habeb, Abdelhadi M; Kahaly, George J; Kampmann, Christoph; Hughes, Marina; Marek, Jan; Rajanayagam, Odelia; Kuczynski, Adam; Vargha-Khadem, Faraneh; Morsy, Mofeed; Offiah, Amaka C; Poole, Ken; Ward, Kate; Lyons, Greta; Halsall, David; Berman, Lol; Watson, Laura; Baguley, David; Mollon, John; Moore, Anthony T; Holder, Graham E; Dattani, Mehul; Chatterjee, Krishna

2017-09-01

Resistance to thyroid hormone β (RTH β ) due to homozygous THRB defects is exceptionally rare, with only five kindreds reported worldwide. Cardiac dysfunction, which can be life-threatening, is recognized in the disorder. Here we describe the clinical, metabolic, ophthalmic, and cardiac findings in a 9-year-old boy harboring a biallelic THRB mutation (R243Q), along with biochemical, physiologic, and cardiac responses to carbimazole and triiodothyroacetic acid (TRIAC) therapy. The patient exhibits recognized features (goiter, nonsuppressed thyroid-stimulating hormone levels, upper respiratory tract infections, hyperactivity, low body mass index) of heterozygous RTH β , with additional characteristics (dysmorphic facies, winging of scapulae) and more markedly elevated thyroid hormone levels, associated with the homozygous form of the disorder. Notably, an older sibling with similar clinical features and probable homozygous RTH β had died of cardiac failure at age 13 years. Features of early dilated cardiomyopathy in our patient prompted combination treatment with carbimazole and TRIAC. Careful titration of therapy limited elevation in TSH levels and associated increase in thyroid volume. Subsequently, sustained reduction in thyroid hormones with normal TSH levels was reflected in lower basal metabolic rate, gain of lean body mass, and improved growth and cardiac function. A combination of antithyroid drug and TRIAC therapy may prevent thyrotoxic cardiomyopathy and its decompensation in homozygous or even heterozygous RTH β in which life-threatening hyperthyroid features predominate.

[Detection of thyroid dysfunction in pregnant women: universal screening is justified].

PubMed

Vila, Lluís; Velasco, Inés; González, Stella; Morales, Francisco; Sánchez, Emilia; Lailla, José Maria; Martinez-Astorquiza, Txanton; Puig-Domingo, Manel

2012-11-03

There is a controversy among different scientific societies in relation to the recommendations on whether universal screening for the detection of thyroid dysfunction during gestation should be performed or not. Although various studies have shown an association between subclinical hypothyroidism or hypothyroxinemia with obstetric problems and/or neurocognitive impairment in the offspring, no evidence on the possible positive effects of treatment of such conditions with thyroxin has been demonstrated so far. However, there is a general agreement about the need for treatment of clinical hypothyroidism during pregnancy and the risks of not doing so. Because it is a common, easily diagnosed and effectively treated disorder without special risk, the working Group of Iodine Deficiency Disorders and Thyroid Dysfunction of the Spanish Society of Endocrinology and Nutrition and Spanish Society of Gynaecology and Obstetrics recommends an early evaluation (before week 10) of thyroid function in all pregnant women. Given the complex physiology of thyroid function during pregnancy, hormone assessment should be performed according to reference values for each gestational trimester and generated locally in each reference laboratory. Thyrotropin determination would be sufficient for screening purposes and only if it is altered, free thyroxin or total thyroxin would be required. Adequate iodine nutrition is also highly recommended before and during pregnancy to contribute to a normal thyroid function in the pregnant women and fetus.

Detection of thyroid dysfunction in pregnant women: universal screening is justified.

PubMed

Vila, Lluís; Velasco, Inés; González, Stella; Morales, Francisco; Sánchez, Emilia; Lailla, José Maria; Martinez-Astorquiza, Txanton; Puig-Domingo, Manel

2012-11-01

There is a controversy among different scientific societies in relation to the recommendations on whether universal screening for the detection of thyroid dysfunction during gestation should be performed or not. Although various studies have shown an association between subclinical hypothyroidism or hypothyroxinemia with obstetric problems and/or neurocognitive impairment in the offspring, no evidence on the possible positive effects of treatment of such conditions with thyroxin has been demonstrated so far. However, there is a general agreement about the need for treatment of clinical hypothyroidism during pregnancy and the risks of not doing so. Because it is a common, easily diagnosed and effectively treated disorder without special risk, the working Group of Iodine Deficiency Disorders and Thyroid Dysfunction of the Spanish Society of Endocrinology and Nutrition and Spanish Society of Gynaecology and Obstetrics recommends an early evaluation (before week 10) of thyroid function in all pregnant women. Given the complex physiology of thyroid function during pregnancy, hormone assessment should be performed according to reference values for each gestational trimester and generated locally in each reference laboratory. Thyrotropin determination would be sufficient for screening purposes and only if it is altered, free thyroxin or total thyroxin would be required. Adequate iodine nutrition is also highly recommended before and during pregnancy to contribute to a normal thyroid function in the pregnant women and fetus. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

[Pregnancy and breastfeeding. Side effects of drugs used in the treatment of thyroid diseases, on the fetus and the newborn].

PubMed

Matos, L; Afonso, A

2003-01-01

The authors allude to the composed anti-thyroid drugs, blocking drugs, iodides, radioactive iodine, lithium carbonate and tyrosine side effects. The most common are composed anti-thyroid drugs and tyrosine. Anti-thyroid drugs risks are related to the tresspassing of the placenta barrier which can induce in goitre and hypothyroidism. Thyroid hormones are also very important for the fetus neural development during the first quarter when they cross the placenta.

Pediatric Pulmonary Arterial Hypertension and Hyperthyroidism: A Potentially Fatal Combination

PubMed Central

Trapp, Christine M.; Elder, Robert W.; Gerken, Adrienne T.; Sopher, Aviva B.; Lerner, Shulamit; Rosenzweig, Erika B.

2012-01-01

Context: Patients with pulmonary arterial hypertension (PAH) who develop hyperthyroidism are at risk for acute cardiopulmonary decompensation and death. Cases and Setting: We present a series of eight idiopathic PAH/heritable PAH pediatric patients who developed hyperthyroidism between 1999 and 2011. Institutional Review Board approval was obtained; informed consent was waived due to the retrospective nature of the series. All eight patients were receiving iv epoprostenol; five of the eight patients presented with acute cardiopulmonary decompensation in the setting of hyperthyroidism. In the remaining three patients, hyperthyroidism was detected during routine screening of thyroid function tests. The one patient who underwent emergency thyroidectomy was the only survivor of those who presented in cardiopulmonary decline. Evidence Synthesis: Aggressive treatment of the hyperthyroid state, including emergency total thyroidectomy and escalation of targeted PAH therapy and β-blockade when warranted, may prove lifesaving in these patients. Prompt thyroidectomy or radioactive iodine ablation should be considered for clinically stable PAH patients with early and/or mild hyperthyroidism to avoid potentially life-threatening cardiopulmonary decompensation. Conclusions: Although the association between hyperthyroidism and PAH remains poorly understood, the potential impact of hyperthyroidism on the cardiopulmonary status of PAH patients must not be ignored. Hyperthyroidism must be identified early in this patient population to optimize intervention before acute decompensation. Thyroid function tests should be checked routinely in patients with PAH, particularly those on iv epoprostenol, and urgently in patients with acute decompensation or symptoms of hyperthyroidism. PMID:22622024

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.

Molecular pathobiology of thyroid neoplasms.

PubMed

Tallini, Giovanni

2002-01-01

Tumors of thyroid follicular cells provide a very interesting model to understand the development of human cancer. It is becoming apparent that distinct molecular events are associated with specific stages in a multistep tumorigenic process with good genotype/ phenotype correlation. For instance, mutations of the gsp and thyroid-stimulating hormone receptor genes are associated with benign hyperfunctioning thyroid nodules and adenomas while alterations of other specific genes, such as oncogenic tyrosine kinase alterations (RET/PTC, TRK) in papillary carcinoma and the newly discovered PAX8/peroxisome proliferator-activated receptor gamma rearrangement, are distinctive features of cancer. Although activating RAS mutations occur at all stages of thyroid tumorigenesis, evidence is accumulating that they may also play an important role in tumor progression, a role that is well documented for p53. Environmental factors (iodine deficiency, ionizing radiations) have been shown to play a crucial role in promoting the development of thyroid cancer, influencing both its genotypic and phenotypic features. It is possible that the follicular thyroid cell has unique ways to respond to DNA damage. Similarly to leukemia or sarcomas (and unlike most epithelial cancers), numerous specific rearrangements are being discovered in thyroid cancer suggesting preferential activation of DNA repair instead of cell death programs after environmentally induced genetic alterations.

Clinical Value of Thyrotropin Receptor Antibodies for the Differential Diagnosis of Interferon Induced Thyroiditis.

PubMed

Benaiges, D; Garcia-Retortillo, M; Mas, A; Cañete, N; Broquetas, T; Puigvehi, M; Chillarón, J J; Flores-Le Roux, J A; Sagarra, E; Cabrero, B; Zaffalon, D; Solà, R; Pedro-Botet, J; Carrión, J A

2016-01-01

The clinical value of thyrotropin receptor antibodies for the differential diagnosis of thyrotoxicosis induced by pegylated interferon-alpha remains unknown. We analyzed the diagnostic accuracy of thyrotropin receptor antibodies in the differential diagnosis of thyrotoxicosis in patients with chronic hepatitis C (CHC) receiving pegylated interferon-alpha plus ribavirin. Retrospective analysis of 274 patients with CHC receiving pegylated interferon-alpha plus ribavirin. Interferon-induced thyrotoxicosis was classified according to clinical guidelines as Graves disease, autoimmune and non- autoimmune destructive thyroiditis. 48 (17.5%) patients developed hypothyroidism, 17 (6.2%) thyrotoxicosis (6 non- autoimmune destructive thyroiditis, 8 autoimmune destructive thyroiditis and 3 Graves disease) and 22 "de novo" thyrotropin receptor antibodies (all Graves disease, 2 of the 8 autoimmune destructive thyroiditis and 17 with normal thyroid function). The sensitivity and specificity of thyrotropin receptor antibodies for Graves disease diagnosis in patients with thyrotoxicosis were 100 and 85%, respectively. Patients with destructive thyroiditis developed hypothyroidism in 87.5% of autoimmune cases and in none of those with a non- autoimmune etiology (p<0.001). Thyrotropin receptor antibodies determination cannot replace thyroid scintigraphy for the differential diagnosis of thyrotoxicosis in CHC patients treated with pegylated interferon. © Georg Thieme Verlag KG Stuttgart · New York.

The role of Epstein-Barr virus infection in the development of autoimmune thyroid diseases.

PubMed

Janegova, Andrea; Janega, Pavol; Rychly, Boris; Kuracinova, Kristina; Babal, Pavel

2015-01-01

Autoimmune thyroid diseases, including Graves' and Hashimoto's thyroiditis, are the most frequent autoimmune disorders. Viral infection, including Epstein-Barr virus (EBV), is one of the most frequently considered environmental factors involved in autoimmunity. Its role in the development of AITD has not been confirmed so far. Surgical specimens of Graves' and Hashimoto's diseases and nodular goitres were included in the study. The expression of EBV latent membrane protein 1 (LMP1) was analysed by immunohistochemistry, with the parallel detection of virus-encoded small nuclear non-polyadenylated RNAs (EBER) by in situ hybridisation. In none of the Graves' disease specimens but in 34.5% of Hashimoto's thyroiditis cases the cytoplasmic expression of LMP1 was detected in follicular epithelial cells and in infiltrating lymphocytes. EBER nuclear expression was detected in 80.7% of Hashimoto's thyroiditis cases and 62.5% of Graves' disease cases, with positive correlation between LMP1 and EBER positivity in all Hashimoto's thyroiditis LMP1-positive cases. We assume that high prevalence of EBV infection in cases of Hashimoto's and Graves' diseases imply a potential aetiological role of EBV in autoimmune thyroiditis. The initiation of autoimmune thyroiditis could start with EBV latency type III infection of follicular epithelium characterised by LMP1 expression involving the production of inflammatory mediators leading to recruitment of lymphocytes. The EBV positivity of the infiltrating lymphocytes could be only the presentation of a carrier state, but in cases with EBER+/ LMP1+ lymphocytes (transforming latent infection) it could represent a negative prognostic marker pointing to a higher risk of primary thyroid lymphoma development.

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

PubMed Central

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

2017-01-01

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

Clark T. Sawin historical vignette: what do criminology, Harry Houdini, and King George V have in common with postpartum thyroid dysfunction?

PubMed

Smallridge, Robert C

2014-12-01

The history of postpartum thyroid dysfunction (PPTD) dates back almost two millennia, when Soranus of Ephesus, who practiced obstetrics and neonatology, observed swelling in the necks (presumably goiters) of women after pregnancy. The next reference to PPTD appeared in artwork more than 1000 years later, with many portraits illustrating women with goiter while holding infants. In the early to mid-19th century, Caleb Hillier Parry and Armand Trousseau described postpartum hyperthyroidism, while in the late 1800s, Sir Horatio Bryan Donkin reported the first patient with postpartum hypothyroidism. The modern era of PPTD began with the description in the late 1940s by H.E.W. Roberton of women after delivery reporting hypothyroid symptoms and responding to thyroid extract. The immunologic influence on PPTD was recognized initially by Parker and Beierwaltes in the early 1960s, and the clinical variability and natural history were carefully documented by numerous investigators in the 1970s-1980s. The past two decades have seen further refinements in understanding the prevalence, etiology, and treatment of PPTD. Yet to be determined is the role of screening as a cost-effective measure.

Role of Thyroid Hormones in Skeletal Development and Bone Maintenance

PubMed Central

Bassett, J. H. Duncan

2016-01-01

The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID:26862888

TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects.

PubMed

Jun, Ji Eun; Jin, Sang-Man; Jee, Jae Hwan; Bae, Ji Cheol; Hur, Kyu Yeon; Lee, Moon-Kyu; Kim, Sun Wook; Kim, Jae Hyeon

2017-03-01

Thyroid function is known to influence glucose metabolism, and thyroid-stimulating hormone is the most useful parameter in screening for thyroid dysfunction. Therefore, the aim of this study was to investigate the incidence of type 2 diabetes according to baseline thyroid-stimulating hormone level and thyroid-stimulating hormone change in euthyroid subjects. We identified and enrolled 17,061 euthyroid subjects without diabetes among participants who had undergone consecutive thyroid function tests between 2006 and 2012 as a part of yearly health check-up program. Thyroid-stimulating hormone changes were determined by subtracting baseline thyroid-stimulating hormone level from thyroid-stimulating hormone level at 1 year before diagnosis of diabetes or at the end of follow-up in subjects who did not develope diabetes. During 84,595 person-years of follow-up, there were 956 new cases of type 2 diabetes. Cox proportional hazards models showed the risk of incident type 2 diabetes was significantly increased with each 1 μIU/mL increment in TSH after adjustment for multiple confounding factors (hazard ratio = 1.13, 95% confidence interval: 1.07-1.20, P < 0.001). Compared with individuals in the lowest tertile (-4.08 to 0.34 μIU/mL), those in the highest thyroid-stimulating hormone change tertile (0.41-10.84 μIU/mL) were at greater risk for incident type 2 diabetes (hazard ratio = 1.25, 95% confidence interval: 1.05-1.48, P for trend = 0.011). However, baseline thyroid-stimulating hormone level and tertile were not associated with the risk for diabetes. Prominent increase in thyroid-stimulating hormone concentration can be an additional risk factor for the development of type 2 diabetes in euthyroid subjects.

Hormonal changes associated with the transition between nursing and natural fasting in northern elephant seals (Mirounga angustirostris)

NASA Technical Reports Server (NTRS)

Ortiz, Rudy M.; Houser, Dorian S.; Wade, Charles E.; Ortiz, C. Leo

2003-01-01

To better interpret previously described hormonal changes observed during the natural postweaning fast (2-3 months) endured by pups of the northern elephant seal (Mirounga angustirostris), we compared plasma cortisol, thyroid hormones, and leptin in pups (n=5) measured during nursing and fasting periods. Blood samples were taken at four times; early (9 days postpartum) and late (18-22 days postpartum) nursing, and early (second week postweaning) and late (eighth week postweaning) fasting. Plasma cortisol increased 39% between early and late nursing and almost 4-fold by late fasting. After the early nursing period, cortisol and body mass were negatively correlated (y=28.3-0.19 x; R=0.569; p=0.027). Total thyroxine (tT(4)), free T(4) (fT(4)), total triiodothyronine (tT3) and reverse T(3) (rT(3)) were greatest at early nursing and reduced by late nursing and remained so throughout the fast, with the exception of tT(4), which increased between late nursing (17.7+/-2.1 ng mL(-1)) and late fasting (30.1+/-2.8 ng mL(-1)) periods. Leptin remained unaltered among the four sampling periods and was not correlated with body mass. Pups appear to exhibit a shift in the relationship between cortisol and body mass suggesting a potential role for cortisol in the regulation of body fat. The higher concentrations of tT(3) and tT(4) during early nursing may reflect enhanced growth and development during this period, however the increase late in fasting is likely physiologically insignificant and an artifact of reduced metabolic clearance of these hormones. Transition of the pups from nursing to fasting states is characterized by a striking lack of change in cortisol, thyroid hormones, and leptin suggesting that any metabolic alterations associated with this transition may occur independent of these hormones.

Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956)- An Assessment of Quantities released, Off-Site Radiation Doses, and Potential Excess Risks of Thyroid Cancer, Volume 1

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

Apostoaei, A.I.; Burns, R.E.; Hoffman, F.O.

1999-07-01

In the early 1990s, concern about the Oak Ridge Reservation's past releases of contaminants to the environment prompted Tennessee's public health officials to pursue an in-depth study of potential off-site health effects at Oak Ridge. This study, the Oak Ridge dose reconstruction, was supported by an agreement between the U.S. Department of Energy (DOE) and the State of Tennessee, and was overseen by a 12-member panel appointed by Tennessee's Commissioner of Health. One of the major contaminants studied in the dose reconstruction was radioactive iodine, which was released to the air by X-10 (now called Oak Ridge National Laboratory) asmore » it processed spent nuclear reactor fuel from 1944 through 1956. The process recovered radioactive lanthanum for use in weapons development. Iodine concentrates in the thyroid gland so health concerns include various diseases of the thyroid, such as thyroid cancer. The large report, ''Iodine-131 Releases from Radioactive Lanthanum Processing at the X-10 Site in Oak Ridge, Tennessee (1944-1956) - An Assessment of Quantities Released, Off-site Radiation Doses, and Potential Excess Risks of Thyroid Cancer,'' is in two volumes. Volume 1 is the main body of the report, and Volume 1A, which has the same title, consists of 22 supporting appendices. Together, these reports serve the following purposes: (1) describe the methodologies used to estimate the amount of iodine-131 (I-131) released; (2) evaluate I-131's pathway from air to vegetation to food to humans; (3) estimate doses received by human thyroids; (4) estimate excess risk of acquiring a thyroid cancer during ones lifetime; and (5) provide equations, examples of historical documents used, and tables of calculated values. Results indicate that females born in 1952 who consumed milk from a goat pastured a few miles east of X-10 received the highest doses from I-131 and would have had the highest risks of contracting thyroid cancer. Doses from cow's milk are considerably less . Detailed dose and risk estimates, and associated uncertainties, for other contaminants studied for the Oak Ridge dose reconstruction are presented in several other technical reports. One way to easily locate them in OSTI's Information Bridge is by searching the ''report number field'' for the number DOE/OR/21981*. Be sure to place the asterisk after the base number so your search can list the complete series of reports related to Oak Ridge Dose Reconstruction.« less

Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.

PubMed

Segar, Jeffrey L; Volk, Ken A; Lipman, Michael H B; Scholz, Thomas D

2013-03-01

Thyroid hormone exerts broad effects on the adult heart, but little is known regarding the role of thyroid hormone in the regulation of cardiac growth early in development and in response to pathophysiological conditions. To address this issue, we determined the effects of fetal thyroidectomy on cardiac growth and growth-related gene expression in control and pulmonary-artery-banded fetal sheep. Fetal thyroidectomy (THX) and/or placement of a restrictive pulmonary artery band (PAB) were performed at 126 ± 1 days of gestation (term, 145 days). Four groups of animals [n = 5-6 in each group; (i) control; (ii) fetal THX; (iii) fetal PAB; and (iv) fetal PAB + THX] were monitored for 1 week prior to being killed. Fetal heart rate was significantly lower in the two THX groups compared with the non-THX groups, while mean arterial blood pressure was similar among groups. Combined left and right ventricle free wall + septum weight, expressed per kilogram of fetal weight, was significantly increased in PAB (6.27 ± 0.85 g kg(-1)) compared with control animals (4.72 ± 0.12 g kg(-1)). Thyroidectomy significantly attenuated the increase in cardiac mass associated with PAB (4.94 ± 0.13 g kg(-1)), while THX alone had no detectable effect on heart mass (4.95 ± 0.27 g kg(-1)). The percentage of binucleated cardiomyocytes was significantly decreased in THX and PAB +THX groups (∼16%) compared with the non-THX groups (∼27%). No differences in levels of activated Akt, extracellular signal-regulated kinase or c-Jun N-terminal kinase were detected among the groups. Markers of cellular proliferation but not apoptosis or expression of growth-related genes were lower in the THX and THX+ PAB groups relative to thyroid-intact animals. These findings suggest that in the late-gestation fetal heart, thyroid hormone has important cellular growth functions in both physiological and pathophysiological states. Specifically, thyroid hormone is required for adaptive fetal cardiac growth in response to pressure overload.

Genetic analysis of interferon induced thyroiditis (IIT): evidence for a key role for MHC and apoptosis related genes and pathways.

PubMed

Hasham, Alia; Zhang, Weijia; Lotay, Vaneet; Haggerty, Shannon; Stefan, Mihaela; Concepcion, Erlinda; Dieterich, Douglas T; Tomer, Yaron

2013-08-01

Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFNα) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFNα and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFNα treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFNα-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFNα. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFNα. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT. Published by Elsevier Ltd.

GENETIC ANALYSIS OF INTERFERON INDUCED THYROIDITIS (IIT): EVIDENCE FOR A KEY ROLE FOR MHC AND APOPTOSIS RELATED GENES AND PATHWAYS

PubMed Central

Hasham, Alia; Zhang, Weijia; Lotay, Vaneet; Haggerty, Shannon; Stefan, Mihaela; Concepcion, Erlinda; Dieterich, Douglas T.; Tomer, Yaron

2013-01-01

Autoimmune thyroid diseases (AITD) have become increasingly recognized as a complication of interferon-alpha (IFNα) therapy in patients with chronic Hepatitis C virus (HCV) infection. Interferon-induced thyroiditis (IIT) can manifest as clinical thyroiditis in approximately 15% of HCV patients receiving IFNα and subclinical thyroiditis in up to 40% of patients, possibly resulting in either dose reduction or discontinuation of IFNα treatment. However, the exact mechanisms that lead to the development of IIT are unknown and may include IFNα-mediated immune-recruitment as well as direct toxic effects on thyroid follicular cells. We hypothesized that IIT develops in genetically predisposed individuals whose threshold for developing thyroiditis is lowered by IFNα. Therefore, our aim was to identify the susceptibility genes for IIT. We used a genomic convergence approach combining genetic association data with transcriptome analysis of genes upregulated by IFNα. Integrating results of genetic association, transcriptome data, pathway, and haplotype analyses enabled the identification of 3 putative loci, SP100/110/140 (2q37.1), HLA (6p21.3), and TAP1 (6p21.3) that may be involved in the pathogenesis of IIT. Immune-regulation and apoptosis emerged as the predominant mechanisms underlying the etiology of IIT. PMID:23683877

DIAGNOSIS OF ENDOCRINE DISEASE: High-yield thyroid fine-needle aspiration cytology: an update focused on ancillary techniques improving its accuracy.

PubMed

Bongiovanni, M; Trimboli, P; Rossi, E D; Fadda, G; Nobile, A; Giovanella, L

2016-02-01

Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing areas is represented by molecular tests applied to cytological material. Patients that could benefit the most from these tests are those that have been diagnosed as 'indeterminate' on FNA. They could be better stratified in terms of malignancy risk and thus oriented with more confidence to the appropriate management. Taking in to consideration the need to improve and keep high the yield of thyroid FNA, professionals from various fields (i.e. molecular biologists, endocrinologists, nuclear medicine physicians and radiologists) are refining and fine-tuning their diagnostic instruments. In particular, all these developments aim at increasing the negative predictive value of FNA to improve the selection of patients for diagnostic surgery. These advances involve terminology, the application of next-generation sequencing to thyroid FNA, the use of immunocyto- and histo-chemistry, the development of new sampling techniques and the increasing use of nuclear medicine as well as molecular imaging in the management of patients with a thyroid nodule. Herein, we review the recent advances in thyroid FNA cytology that could be of interest to the 'thyroid-care' community, with particular focus on the indeterminate diagnostic category. © 2016 European Society of Endocrinology.

Mapping fundamental life elements in papillary thyroid carcinoma tissue

NASA Astrophysics Data System (ADS)

Merolle, L.; Ragazzi, M.; Gianoncelli, A.; Altissimo, M.; Ciarrocchi, A.; Bedolla, D. E.; Marraccini, C.; Baricchi, R.; Pertinhez, T. A.

2018-05-01

Well-differentiated papillary thyroid carcinomas (PTCs) are the most common type of thyroid cancer. Thyroid function depends on the presence of certain trace elements necessary for both the synthesis and the metabolism of thyroid hormones. We conducted an observational translational study on formalin fixed paraffin embedded thyroid tissue slices collected from five patients who underwent surgical resection of thyroid gland after thyroid cancer diagnosis. A synchrotron-based XRF set up was used to map the distribution of oxygen, sodium, aluminum, selenium and magnesium in PTC sections. These experiments were performed at the TwinMic beamline (Elettra—Sincrotrone Trieste, Trieste, Italy). Our results show that Mg levels in PTC tissues are significantly higher than in the control ones. The results seem to provide highly valuable information suggesting that Mg may play a role in the development and metabolic process of PTC.

Thyroid autoimmunity in bipolar disorder: A systematic review.

PubMed

Barbuti, Margherita; Carvalho, André F; Köhler, Cristiano A; Murru, Andrea; Verdolini, Norma; Guiso, Giovanni; Samalin, Ludovic; Maes, Michael; Stubbs, Brendon; Perugi, Giulio; Vieta, Eduard; Pacchiarotti, Isabella

2017-10-15

Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. The samples, study design and outcomes were heterogeneous. Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD. Copyright © 2017 Elsevier B.V. All rights reserved.

Pioglitazone Induces a Proadipogenic Antitumor Response in Mice with PAX8-PPARγ Fusion Protein Thyroid Carcinoma

PubMed Central

Dobson, Melissa E.; Diallo-Krou, Ericka; Grachtchouk, Vladimir; Yu, Jingcheng; Colby, Lesley A.; Wilkinson, John E.; Giordano, Thomas J.

2011-01-01

Approximately 35% of follicular thyroid carcinomas harbor a chromosomal translocation that results in expression of a paired box gene 8-peroxisome proliferator-activated receptor γ gene (PPARγ) fusion protein (PPFP). To better understand the oncogenic role of PPFP and its relationship to endogenous PPARγ, we generated a transgenic mouse model that combines Cre-dependent PPFP expression (PPFP;Cre) with homozygous deletion of floxed Pten (PtenFF;Cre), both thyroid specific. Although neither PPFP;Cre nor PtenFF;Cre mice develop thyroid tumors, the combined PPFP;PtenFF;Cre mice develop metastatic thyroid cancer, consistent with patient data that PPFP is occasionally found in benign thyroid adenomas and that PPFP carcinomas have increased phosphorylated AKT/protein kinase B. We then tested the effects of the PPARγ agonist pioglitazone in our mouse model. Pioglitazone had no effect on PtenFF;Cre mouse thyroids. However, the thyroids in pioglitazone-fed PPFP;PtenFF;Cre mice decreased 7-fold in size, and metastatic disease was prevented. Remarkably, pioglitazone caused an adipogenic response in the PPFP;PtenFF;Cre thyroids characterized by lipid accumulation and the induction of a broad array of adipocyte PPARγ target genes. These data indicate that, in the presence of pioglitazone, PPFP has PPARγ-like activity that results in trans-differentiation of thyroid carcinoma cells into adipocyte-like cells. Furthermore, the data predict that pioglitazone will be therapeutic in patients with PPFP-positive carcinomas. PMID:21952241

Thyroid abnormalities after therapeutic external radiation

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

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

1995-03-30

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

The Emerging Cell Biology of Thyroid Stem Cells

PubMed Central

Latif, Rauf; Minsky, Noga C.; Ma, Risheng

2011-01-01

Context: Stem cells are undifferentiated cells with the property of self-renewal and give rise to highly specialized cells under appropriate local conditions. The use of stem cells in regenerative medicine holds great promise for the treatment of many diseases, including those of the thyroid gland. Evidence Acquisition: This review focuses on the progress that has been made in thyroid stem cell research including an overview of cellular and molecular events (most of which were drawn from the period 1990–2011) and discusses the remaining problems encountered in their differentiation. Evidence Synthesis: Protocols for the in vitro differentiation of embryonic stem cells, based on normal developmental processes, have generated thyroid-like cells but without full thyrocyte function. However, agents have been identified, including activin A, insulin, and IGF-I, which are able to stimulate the generation of thyroid-like cells in vitro. In addition, thyroid stem/progenitor cells have been identified within the normal thyroid gland and within thyroid cancers. Conclusions: Advances in thyroid stem cell biology are providing not only insight into thyroid development but may offer therapeutic potential in thyroid cancer and future thyroid cell replacement therapy. PMID:21778219

Detection of autoantibodies against thyroid peroxidase in serum samples of hypothyroid dogs.

PubMed

Skopek, Evelyn; Patzl, Martina; Nachreiner, Raymond F

2006-05-01

To establish a sensitive test for the detection of autoantibodies against thyroid peroxidase (TPO) in canine serum samples. 365 serum samples from dogs with hypothyroidism as determined on the basis of serum concentrations of total and free triiodothyronine (T3), total and free thyroxine (T4), and thyroid-stimulating hormone, of which 195 (53%) had positive results for at least 1 of 3 thyroid autoantibodies (against thyroglobulin [Tg], T4, or T3) and serum samples from 28 healthy dogs (control samples). TPO was purified from canine thyroid glands by extraction with detergents, ultracentrifugation, and precipitation with ammonium sulfate. Screening for anti-TPO autoantibodies in canine sera was performed by use of an immunoblot assay. Thyroid extract containing TPO was separated electrophoretically, blotted, and probed with canine sera. Alkaline phosphatase-conjugated rabbit anti-dog IgG was used for detection of bound antibodies. TPO bands were observed at 110, 100, and 40 kd. Anti-TPO autoantibodies against the 40-kd fragment were detected in 33 (17%) sera of dogs with positive results for anti-Tg, anti-T4, or anti-T3 autoantibodies but not in sera of hypothyroid dogs without these autoantibodies or in sera of healthy dogs. The immunoblot assay was a sensitive and specific method for the detection of autoantibodies because it also provided information about the antigen. Anti-TPO autoantibodies were clearly detected in a fraction of hypothyroid dogs. The value of anti-TPO autoantibodies for use in early diagnosis of animals with thyroid gland diseases should be evaluated in additional studies.

Relational Stability in the Expression of Normality, Variation, and Control of Thyroid Function

PubMed Central

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

2016-01-01

Thyroid hormone concentrations only become sufficient to maintain a euthyroid state through appropriate stimulation by pituitary thyroid-stimulating hormone (TSH). In such a dynamic system under constant high pressure, guarding against overstimulation becomes vital. Therefore, several defensive mechanisms protect against accidental overstimulation, such as plasma protein binding, conversion of T4 into the more active T3, active transmembrane transport, counter-regulatory activities of reverse T3 and thyronamines, and negative hypothalamic–pituitary–thyroid feedback control of TSH. TSH has gained a dominant but misguided role in interpreting thyroid function testing in assuming that its exceptional sensitivity thereby translates into superior diagnostic performance. However, TSH-dependent thyroid disease classification is heavily influenced by statistical analytic techniques such as uni- or multivariate-defined normality. This demands a separation of its conjoint roles as a sensitive screening test and accurate diagnostic tool. Homeostatic equilibria (set points) in healthy subjects are less variable and do not follow a pattern of random variation, rather indicating signs of early and progressive homeostatic control across the euthyroid range. In the event of imminent thyroid failure with a reduced FT4 output per unit TSH, conversion efficiency increases in order to maintain FT3 stability. In such situations, T3 stability takes priority over set point maintenance. This suggests a concept of relational stability. These findings have important implications for both TSH reference limits and treatment targets for patients on levothyroxine. The use of archival markers is proposed to facilitate the homeostatic interpretation of all parameters. PMID:27872610

Hashimoto's encephalitis associated with AMPAR2 antibodies: a case report.

PubMed

Zhu, Mingqin; Yu, Xuefan; Liu, Caiyun; Duan, Chenchen; Li, Chunxiao; Zhu, Jie; Zhang, Ying

2017-02-21

Hashimoto's encephalitis (HE) is a rare neurological complication of Hashimoto's thyroiditis (HT), while limbic encephalitis (LE) is an autoimmune inflammatory disorder frequently associated with anti-neuronal antibodies. The glutamate receptor α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) is important for synaptic transmission, memory, and learning. The etiology of HE remains unclear. We present a case of HE with antibodies to AMPAR2 both in the serum and cerebrospinal fluid. The patient presented with progressive memory loss and subsequently went into a coma. Magnetic resonance imaging revealed temporal lobe and hippocampal lesions, while the electrocardiogram showed paroxysmal delta waves. Elevated serum levels of antibodies against thyroid globulin, thyroid peroxidase, and thyroid stimulating receptor were also noted. Ultrasonography showed enlargement of the thyroid gland. Therefore, the diagnosis was established as HE. Both the CSF and serum samples of the patient tested positive for antibodies to the cell-surface antigen AMPAR2. Intravenous injection of immunoglobulin followed by dexamethasone treatment resulted in recovery from the coma. Follow-up examination three months later showed some improvement of memory. To our knowledge, this is the first report on the detection of AMPAR2 antibodies in HE. Our findings suggest that antibodies to AMPAR2 may be involved in the pathogenesis of HE. Elevated levels of thyroid antibodies possibly cause immune dysfunction, leading to the production of anti-AMPAR2 antibodies that are detrimental to the neurons. We believe that encephalitis patients with thyroid abnormalities should undergo screening for anti-neuronal antibodies, and early immune therapy may improve prognosis.

[Hyperthyroid and acute tonsillitis in a 23-year-old woman].

PubMed

Beyer, G; Küster, I; Budde, C; Wilhelm, E; Hoene, A; Evert, K; Stracke, S; Friesecke, S; Mayerle, J; Steveling, A

2016-07-01

A 23-year-old woman with preexisting Graves' disease who received thiamazole treatment presented with fever, dysphagia, hyperthyroidism and leukopenia. With suspicion of thyreotoxicosis accompanied by drug-induced agranulocytosis she was successfully managed by plasmapheresis, G‑CSF administration and inhibition of periphereal conversion of thyroid hormones. In due course she underwent thyroidectomy. Thiamazole is frequently associated with drug-induced agranulocytosis. Long-term therapy with thiamazole requires critical evaluation and alternatives should be considered early. Plasmapheresis is an adequate treatment option to achieve normal thyroid hormonal status.

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

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

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

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

A case of thyroid storm with multiple organ failure effectively treated with plasma exchange.

PubMed

Sasaki, Kazuki; Yoshida, Akira; Nakata, Yukiko; Mizote, Isamu; Sakata, Yasushi; Komuro, Issei

2011-01-01

We describe a 48-year-old man with thyroid storm presenting with heart failure. He presented severely impaired left ventricular wall motion and a marked increase in the liver enzymes. He developed disseminated intravascular coagulation on day 2. Due to elevated serum thyroid hormone level, anti-thyroid hormone receptor antibody positivity, and his clinical symptoms, he was diagnosed as thyroid storm due to untreated Graves' disease. His condition did not improve even after 6 days of conventional therapy including steroids. After therapeutic plasma exchange was carried out, his thyroid hormone level decreased markedly. Consequently, his condition recovered gradually, and he was discharged at day 43.

[Diagnosis and treatment of thyroid storm].

PubMed

Akamizu, Takashi

2012-11-01

Thyrotoxic storm is a life-threatening condition requiring emergency treatment. Neither its epidemiological data nor diagnostic criteria have been fully established. We clarified the clinical and epidemiological characteristics of thyroid storm using nationwide surveys and then formulate diagnostic criteria for thyroid storm. To perform the nationwide survey on thyroid storm, we first developed tentative diagnostic criteria for thyroid storm, mainly based upon the literature (the first edition). We analyzed the relationship of the major features of thyroid storm to mortality and to certain other features. Finally, based upon the findings of these surveys, we revised the diagnostic criteria. Thyrotoxic storm is still a life-threatening disorder with over 10% mortality in Japan.

TPOAb and Thyroid Function Are Not Associated with Breast Cancer Outcome: Evidence from a Large-Scale Study Using Data from the Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001)

PubMed Central

Muller, Ilaria; Kilburn, Lucy S.; Taylor, Peter N.; Barrett-Lee, Peter J.; Bliss, Judith M.; Ellis, Paul; Ludgate, Marian E.; Dayan, Colin M.

2017-01-01

Background Small-scale studies correlated the presence of thyroid autoimmunity with both improved or worsened breast cancer outcome. Objectives We aimed to clarify this association in a large cohort using the phase III, randomized, controlled Taxotere as Adjuvant Chemotherapy Trial (TACT, CRUK01/001). Methods TACT women >18 years old with node-positive or high-risk node-negative early breast cancer (pT1–3a, pN0–1, M0), with stored plasma (n = 1,974), taken 15.5 (median; IQR 7.0–24.0) months after breast surgery were studied. Patients had also received chemotherapy (100%), radiotherapy (1,745/1,974; 88.4%), hormonal therapy (1,378/ 1,974; 69.8%), or trastuzumab (48/1,974; 2.4%). History of thyroid diseases and/or related treatments was not available. The prognostic significance of autoantibodies to thyroid peroxidase (TPOAb; positive ≥6 kIU/L), free-thyroxine and thyrotropin (combined: euthyroid, hypothyroid, hyperthyroid) was evaluated for disease-free survival (DFS), overall-survival (OS), and time-to-recurrence (TTR), with Cox regression models in univariate and multivariable analyses. The extended median follow-up was 97.5 months. Results No difference in DFS was found by TPOAb status (unadjusted hazard ratio [HR]: 0.97, 95%CI: 0.78–1.19; p = 0.75) and/or thyroid function (unadjusted HR [hypothyroid vs. euthyroid]: 1.15, 95% CI: 0.79–1.68; p = 0.46; unadjusted HR [hyperthyroid vs. euthyroid]: 1.14, 95% CI: 0.82–1.61; p = 0.44). Similar results were obtained for OS, TTR, multivariable analyses, when TPOAb titre by tertiles was considered, and in a subgroup of 123 patients with plasma collected before adjuvant treatments. Conclusions No evidence for a prognostic role of TPOAb and/or thyroid function in moderate-to-high-risk early breast cancer was found in the largest and longest observational study to date. PMID:28868260

Correlation of enhanced oxidative stress with altered thyroid profile: Probable role in spontaneous abortion.

PubMed

Ramandeep, Kaur; Kapil, Gupta; Harkiran, Kaur

2017-01-01

Spontaneous abortion or miscarriage is defined as the loss of a clinically recognized pregnancy that occurs before 20 weeks of gestational age. Changes in thyroid function can impact greatly on reproductive function before, during, and after conception. Oxidative stress affects both implantation and early embryo development by modifying the key of transcription. Malondialdehyde (MDA) is a major breakdown product of split off from lipid peroxidation. Superoxide dismutase (SOD) is responsible for detoxification of superoxide anion and required for normal health and reproduction. The aim of this study was to define the involvement of thyroid hormones, MDA and SOD levels and to establish MDA levels as an index of lipid peroxidation in women with spontaneous abortion by comparing the results with healthy pregnant females as controls. A cross-sectional case-control study was designed with two groups of women with 30 each in healthy pregnancy and with spontaneous abortion. Demographic characteristics such as maternal age, paternal age, gestational age, body mass index, waist-hip ratio as well as biochemical parameters such as blood pressure, hemoglobin (Hb), sugar levels were found to be similar in both the participating groups. Characteristics like gravida and parity were found to be higher in the study group and differ significantly from control group. Spontaneous abortion before 24 weeks of gestational age was found to be associated with significant increase in mean serum thyroid stimulating hormone (TSH) ( P = 0.0115) and MDA ( P = 0.0001) levels and a significant decrease in mean serum T3 ( P = 0.0003) and SOD ( P = 0.0005) levels. The linear (Pearson) correlation analysis demonstrated a significant positive correlation of TSH with MDA and negative correlation with SOD in women with spontaneous abortion. The study demonstrates that altered thyroid profile, increased lipid peroxidation in terms of increased MDA levels and decreased SOD levels might be involved in the termination of otherwise wanted pregnancy.

Correlation of enhanced oxidative stress with altered thyroid profile: Probable role in spontaneous abortion

PubMed Central

Ramandeep, Kaur; Kapil, Gupta; Harkiran, Kaur

2017-01-01

Background: Spontaneous abortion or miscarriage is defined as the loss of a clinically recognized pregnancy that occurs before 20 weeks of gestational age. Changes in thyroid function can impact greatly on reproductive function before, during, and after conception. Oxidative stress affects both implantation and early embryo development by modifying the key of transcription. Malondialdehyde (MDA) is a major breakdown product of split off from lipid peroxidation. Superoxide dismutase (SOD) is responsible for detoxification of superoxide anion and required for normal health and reproduction. Aim: The aim of this study was to define the involvement of thyroid hormones, MDA and SOD levels and to establish MDA levels as an index of lipid peroxidation in women with spontaneous abortion by comparing the results with healthy pregnant females as controls. Materials and Methods: A cross-sectional case-control study was designed with two groups of women with 30 each in healthy pregnancy and with spontaneous abortion. Results: Demographic characteristics such as maternal age, paternal age, gestational age, body mass index, waist-hip ratio as well as biochemical parameters such as blood pressure, hemoglobin (Hb), sugar levels were found to be similar in both the participating groups. Characteristics like gravida and parity were found to be higher in the study group and differ significantly from control group. Spontaneous abortion before 24 weeks of gestational age was found to be associated with significant increase in mean serum thyroid stimulating hormone (TSH) (P = 0.0115) and MDA (P = 0.0001) levels and a significant decrease in mean serum T3 (P = 0.0003) and SOD (P = 0.0005) levels. The linear (Pearson) correlation analysis demonstrated a significant positive correlation of TSH with MDA and negative correlation with SOD in women with spontaneous abortion. Conclusion: The study demonstrates that altered thyroid profile, increased lipid peroxidation in terms of increased MDA levels and decreased SOD levels might be involved in the termination of otherwise wanted pregnancy. PMID:28251103

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis.

PubMed

Brust, Ester S; Beltrao, Cristine B; Chammas, Maria C; Watanabe, Tomoco; Sapienza, Marcelo T; Marui, Suemi

2012-04-01

To precisely classify the various forms of TD, and then to screen for mutations in transcription factor genes active in thyroid development. Patients underwent ultrasound, thyroid scan, and serum thyroglobulin measurement to accurately diagnose the form of TD. DNA was extracted from peripheral leukocytes. The PAX8, and NKX2.5 genes were evaluated in all patients, and TSH receptor (TSHR) gene in those with hypoplasia. In 27 nonconsanguineous patients with TD, 13 were diagnosed with ectopia, 11 with hypoplasia, and 3 with athyreosis. No mutations were detected in any of the genes studied. Sporadic cases of TD are likely to be caused by epigenetic factors, rather than mutations in thyroid transcription factors or genes involved in thyroid development.

Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation, and Dendritic Arbor Elaboration in the Tadpole Visual System

PubMed Central

Thompson, Christopher K.

2016-01-01

Thyroid hormone (TH) regulates many cellular events underlying perinatal brain development in vertebrates. Whether and how TH regulates brain development when neural circuits are first forming is less clear. Furthermore, although the molecular mechanisms that impose spatiotemporal constraints on TH action in the brain have been described, the effects of local TH signaling are poorly understood. We determined the effects of manipulating TH signaling on development of the optic tectum in stage 46–49 Xenopus laevis tadpoles. Global TH treatment caused large-scale morphological effects in tadpoles, including changes in brain morphology and increased tectal cell proliferation. Either increasing or decreasing endogenous TH signaling in tectum, by combining targeted DIO3 knockdown and methimazole, led to corresponding changes in tectal cell proliferation. Local increases in TH, accomplished by injecting suspensions of tri-iodothyronine (T3) in coconut oil into the midbrain ventricle or into the eye, selectively increased tectal or retinal cell proliferation, respectively. In vivo time-lapse imaging demonstrated that local TH first increased tectal progenitor cell proliferation, expanding the progenitor pool, and subsequently increased neuronal differentiation. Local T3 also dramatically increased dendritic arbor growth in neurons that had already reached a growth plateau. The time-lapse data indicate that the same cells are differentially sensitive to T3 at different time points. Finally, TH increased expression of genes pertaining to proliferation and neuronal differentiation. These experiments indicate that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting cell proliferation and differentiation and by acting on neurons to increase dendritic arbor elaboration. SIGNIFICANCE STATEMENT Thyroid hormone (TH) is a critical regulator of perinatal brain development in vertebrates. Abnormal TH signaling in early pregnancy is associated with significant cognitive deficits in humans; however, it is difficult to probe the function of TH in early brain development in mammals because of the inaccessibility of the fetal brain in the uterine environment and the challenge of disambiguating maternal versus fetal contributions of TH. The external development of tadpoles allows manipulation and direct observation of the molecular and cellular mechanisms underlying TH's effects on brain development in ways not possible in mammals. We find that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting neural progenitor cell proliferation and differentiation and by acting on neurons to enhance dendritic arbor elaboration. PMID:27707971

Technological innovations in surgical approach for thyroid cancer.

PubMed

Lang, Brian Hung-Hin; Lo, Chung-Yau

2010-01-01

Over the last decade, surgeons have witnessed dramatic changes in surgical practice as a result of the introduction of new technological advancement. Some of these changes include refinement of techniques in thyroid cancer surgery. The development of various endoscopic thyroidectomy techniques, the addition of the da Vinci robot, and the use of operative adjuncts in thyroid surgery, such as intraoperative neuromonitoring and quick intraoperative parathyroid hormone, have made thyroid cancer surgery not only safer and better accepted by patients with thyroid cancer but also offer them more surgical treatment options.

SP600125 has a remarkable anticancer potential against undifferentiated thyroid cancer through selective action on ROCK and p53 pathways.

PubMed

Grassi, Elisa Stellaria; Vezzoli, Valeria; Negri, Irene; Lábadi, Árpád; Fugazzola, Laura; Vitale, Giovanni; Persani, Luca

2015-11-03

Thyroid cancer is the most common endocrine malignancy with increasing incidence worldwide.The majority of thyroid cancer cases are well differentiated with favorable outcome. However, undifferentiated thyroid cancers are one of the most lethal human malignancies because of their invasiveness, metastatization and refractoriness even to the most recently developed therapies.In this study we show for the first time a significant hyperactivation of ROCK/HDAC6 pathway in thyroid cancer tissues, and its negative correlation with p53 DNA binding ability.We demonstrate that a small compound, SP600125 (SP), is able to induce cell death selectively in undifferentiated thyroid cancer cell lines by specifically acting on the pathogenic pathways of cancer development. In detail, SP acts on the ROCK/HDAC6 pathway involved in dedifferentiation and invasiveness of undifferentiated human cancers, by restoring its physiological activity level. As main consequence, cancer cell migration is inhibited and, at the same time, cell death is induced through the mitotic catastrophe. Moreover, SP exerts a preferential action on the mutant p53 by increasing its DNA binding ability. In TP53-mutant cells that survive mitotic catastrophe this process results in p21 induction and eventually lead to premature senescence. In conclusion, SP has been proved to be able to simultaneously block cell replication and migration, the two main processes involved in cancer development and dissemination, making it an ideal candidate for developing new drugs against anaplastic thyroid cancer.

B cell-targeted therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' hyperthyroidism

PubMed Central

Ueki, I; Abiru, N; Kobayashi, M; Nakahara, M; Ichikawa, T; Eguchi, K; Nagayama, Y

2011-01-01

Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development. PMID:21235532

B cell-targeted therapy with anti-CD20 monoclonal antibody in a mouse model of Graves' hyperthyroidism.

PubMed

Ueki, I; Abiru, N; Kobayashi, M; Nakahara, M; Ichikawa, T; Eguchi, K; Nagayama, Y

2011-03-01

Graves' disease is a B cell-mediated and T cell-dependent autoimmune disease of the thyroid which is characterized by overproduction of thyroid hormones and thyroid enlargement by agonistic anti-thyrotrophin receptor (TSHR) autoantibody. In addition to antibody secretion, B cells have recently been recognized to function as antigen-presenting/immune-modulatory cells. The present study was designed to evaluate the efficacy of B cell depletion by anti-mouse (m) CD20 monoclonal antibody (mAb) on Graves' hyperthyroidism in a mouse model involving repeated injection of adenovirus expressing TSHR A-subunit (Ad-TSHR289). We observe that a single injection of 250 µg/mouse anti-mCD20 mAb eliminated B cells efficiently from the periphery and spleen and to a lesser extent from the peritoneum for more than 3 weeks. B cell depletion before immunization suppressed an increase in serum immunoglobulin (Ig)G levels, TSHR-specific splenocyte secretion of interferon (IFN)-γ, anti-TSHR antibody production and development of hyperthyroidism. B cell depletion 2 weeks after the first immunization, a time-point at which T cells were primed but antibody production was not observed, was still effective at inhibiting antibody production and disease development without inhibiting splenocyte secretion of IFN-γ. By contrast, B cell depletion in hyperthyroid mice was therapeutically ineffective. Together, these data demonstrate that B cells are critical not only as antibody-producing cells but also as antigen-presenting/immune-modulatory cells in the early phase of the induction of experimental Graves' hyperthyroidism and, although therapeutically less effective, B cell depletion is highly efficient for preventing disease development. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice

PubMed Central

Lesage, Sylvie; Collin, Roxanne; Banuelos, Bianca; Aliesky, Holly A.; Rapoport, Basil

2017-01-01

Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the major histocompatibility class (MHC) molecule I-Ak from B10.A(4R) mice to nonobese diabetic (NOD) mice. Apart from I-Ak, the genes responsible for the NOD.H2h4 phenotype are unknown. Extending serendipitous observations from crossing BALB/c to NOD.H2h4 mice, thyroid autoimmunity was investigated in both genders of the F1, F2, and the second-generation backcross of F1 to NOD.H2h4 (N2). Medium-density linkage analysis was performed on thyroid autoimmunity traits in F2 and N2 progeny. TgAb develop before TPOAb and were measured after 8 and 16 weeks of iodide exposure; TPOAb and thyroiditis were studied at 16 weeks. TgAb, TPOAb, and thyroiditis, absent in BALB/c and F1 mice, developed in most NOD.H2h4 and in more N2 than F2 progeny. No linkages were observed in F2 progeny, probably because of the small number of autoantibody-positive mice. In N2 progeny (equal numbers of males and females), a chromosome 17 locus is linked to thyroiditis and TgAb and is suggestively linked to TPOAb. This locus includes MHC region genes from B10.A(4R) mice (such as I-Ak and Tnf, the latter involved in thyrocyte apoptosis) and genes from NOD mice such as Satb1, which most likely plays a role in immune tolerance. In conclusion, MHC and non-MHC genes, encoded within the chromosome 17 locus from both B10.A(4R) and NOD strains, are most likely responsible for the Hashimoto disease–like phenotype of NOD.H2h4 mice. PMID:28323998

Accidental finding of Hashimoto-like thyroiditis in male B.U.T. 6 turkeys at slaughter.

PubMed

Plesch, P; Schade, B; Breithaupt, A; Bellof, G; Kienzle, E

2014-10-01

In the context of a study on the tolerance of rapeseed meal in B.U.T. 6 turkeys, thyroid glands were histologically and immunohistochemically examined because of potential thyreostatic effects. In all groups including the controls with no rapeseed meal in their food, there was a high incidence of lymphocytic infiltration and thyroiditis (14% of thyroids with moderate to severe lymphocytic thyroiditis). Thirty per cent of mononuclear inflammatory cells were immunohistochemically identified as T cells. There were occasional accumulations of PAX-5 labelled cells, indicating germinal centre development. These lesions resemble Hashimoto's disease in humans. The effect on thyroid function is unknown. Mild hypothyreosis might enhance productivity but also explain dispositions towards diseases seen in context with thyroid dysfunction such as skin diseases (foot pad disease?) and cardiovascular problems. Further studies on thyroid function in these turkeys are needed. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

Thyroid storm: an updated review.

PubMed

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

2015-03-01

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

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.

A Review: Radiographic Iodinated Contrast Media-Induced Thyroid Dysfunction

PubMed Central

Leung, Angela M.; Braverman, Lewis E.; Brent, Gregory A.; Pearce, Elizabeth N.

2015-01-01

Context: Thyroid hormone production is dependent on adequate iodine intake. Excess iodine is generally well-tolerated, but thyroid dysfunction can occur in susceptible individuals after excess iodine exposure. Radiological iodinated contrast media represent an increasingly common source of excess iodine. Objective: This review will discuss the thyroidal response after acute exposure to excess iodine; contrast iodine-induced thyroid dysfunction; risks of iodine-induced thyroid dysfunction in vulnerable populations, such as the fetus, neonate, and patients with impaired renal function; and recommendations for the assessment and treatment of contrast iodine-induced thyroid dysfunction. Methods: Data for this review were identified by searching PubMed, Google Scholar, and references from relevant articles from 1948 to 2014. Conclusions: With the increase in the use of computed tomography scans in the United States, there is increasing risk of contrast-induced thyroid dysfunction. Patients at risk of developing iodine-induced thyroid dysfunction should be closely monitored after receiving iodinated contrast media and should be treated as needed. PMID:25375985

Benign and malignant thyroid nodules after neck irradiation

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

Fjaelling, M.T.; Tisell, L.E.; Carlsson, S.

1986-09-15

A total of 444 persons were examined for the presence of thyroid nodules on average of 43 years after having been treated with x-rays for cervical tuberculous adenitis. Of this total, 101 subjects had undergone surgery for thyroid nodules: 25 for carcinoma (6%) and 76 for benign nodules (17%). Carcinoma occurred with the same frequency in multinodular and uninodular glands. Because of the uneven age distribution in the current series, it could not be decided whether there was a higher susceptibility of the young thyroid to the induction of thyroid carcinoma or benign nodules. The dosage range for the wholemore » series was 0.40 to 50.90 Gy (40-5090 rad). There was a positive correlation between the absorbed radiation dose and the probability of developing benign and malignant thyroid nodules, even after doses of 20 Gy or more. The risk of developing thyroid carcinoma was equal for men and women, while the female-to-male ratio for benign nodules was 2.9:1, indicating that risk factors associated with females are of less importance in irradiated than in nonirradiated populations. The median latency for carcinoma was 40 years, suggesting that the increased risk of thyroid carcinoma after irradiation remains for the rest of the patient's life.« less

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.

Emerging Therapeutics for Advanced Thyroid Malignancies: Rationale and Targeted Approaches

PubMed Central

Harris, Pamela; Bible, Keith C.

2011-01-01

Introduction Thyroid cancer is an emerging public health concern. In the U.S., its incidence has doubled in the past decade, making it the 8th most commonly diagnosed neoplasm in 2010. Despite this alarming increase, most thyroid cancer patients benefit from conventional approaches (surgery, radioiodine, radiotherapy, TSH suppression with levothyroxine) and are often cured. Nevertheless, a minority have aggressive tumors resistant to cytotoxic and other historical therapies; these patients sorely need new treatment options. Areas covered Herein the biology and molecular characteristics of the common histological types of thyroid cancer are reviewed to provide context for subsequent discussion of recent developments and emerging therapeutics for advanced thyroid cancers. Expert opinion Several kinase inhibitors, especially those targeting VEGFR and/or RET, have already demonstrated promising activity in differentiated and medullary thyroid cancers (DTC, MTC). Although of minimal benefit in DTC and MTC, cytotoxic chemotherapy with anti-microtubule agents and/or anthracyclines in combination with intensity modulated radiation therapy appears to extend survival for patients with locoregionally-confined anaplastic thyroid cancer (ATC), but to have only modest benefit in metastatic ATC. Further discovery and development of novel agents and combinations of agents will be critical to further progress in treating advanced thyroid cancers of all histotypes. PMID:21910667

[Pay attention to the standardized application of new techniques in surgical treatment of thyroid disease].

PubMed

Tian, W; Xi, H Q; Wang, B

2017-08-01

The continuous development and application of new technology in thyroid surgery has promoted the rapid improvement of thyroid surgery. New technology in the field of thyroid surgery has developed rapidly. The application of neural monitoring technology has enabled the thyroid surgery to enter an accurate era. Imtraoperative neuromonitoring and continuous intraoperative neuromonitoring have made the recurrent laryngeal nerve protection more secure. Nano-carbon parathyroid gland negative imaging technology could identify parathyroid gland more precise. However, when the nano-carbon was used, the injection time, position and dosage should be grasped so as to achieve the best effect of negative imaging. Endoscopic and robotic thyroid surgery could meet the demand of cosmetic. "Treatment first, beauty second" is still the principle to be strictly followed. Do not blindly expand indications and pursue endoscopic surgery. Energy surgical instruments' update made the operation more efficient, while the instruments have some disadvantages. Thyroid surgeon must correctly understand the working principle of new energy devices and use them rationally. Through grasping the working principle and application skills of new technology in clinical work, definiting its advantages and disadvantages, adhereing to the "reasonable choice, standard application" principle, learning the pioneers' experience, the application of new thyroid diagnosis and treatment technology could be more reasonable and safe.

Thyroid hormone accelerates the differentiation of adult hippocampal progenitors.

PubMed

Kapoor, R; Desouza, L A; Nanavaty, I N; Kernie, S G; Vaidya, V A

2012-09-01

Disrupted thyroid hormone function evokes severe physiological consequences in the immature brain. In adulthood, although clinical reports document an effect of thyroid hormone status on mood and cognition, the molecular and cellular changes underlying these behavioural effects are poorly understood. More recently, the subtle effects of thyroid hormone on structural plasticity in the mature brain, in particular on adult hippocampal neurogenesis, have come to be appreciated. However, the specific stages of adult hippocampal progenitor development that are sensitive to thyroid hormone are not defined. Using nestin-green fluorescent protein reporter mice, we demonstrate that thyroid hormone mediates its effects on hippocampal neurogenesis by influencing Type 2b and Type 3 progenitors, although it does not alter proliferation of either the Type 1 quiescent progenitor or the Type 2a amplifying neural progenitor. Thyroid hormone increases the number of doublecortin (DCX)-positive Type 3 progenitors, and accelerates neuronal differentiation into both DCX-positive immature neurones and neuronal nuclei-positive granule cell neurones. Furthermore, we show that this increase in neuronal differentiation is accompanied by a significant induction of specific transcription factors involved in hippocampal progenitor differentiation. In vitro studies using the neurosphere assay support a direct effect of thyroid hormone on progenitor development because neurospheres treated with thyroid hormone are shifted to a more differentiated state. Taken together, our results indicate that thyroid hormone mediates its neurogenic effects via targeting Type 2b and Type 3 hippocampal progenitors, and suggests a role for proneural transcription factors in contributing to the effects of thyroid hormone on neuronal differentiation of adult hippocampal progenitors. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

Thyroid cancer in a patient with Lynch syndrome - case report and literature review.

PubMed

Fazekas-Lavu, Monika; Parker, Andrew; Spigelman, Allan D; Scott, Rodney J; Epstein, Richard J; Jensen, Michael; Samaras, Katherine

2017-01-01

Lynch syndrome describes a familial cancer syndrome comprising germline mutations in one of four DNA mismatch repair genes, MLH1 , MSH2 , MSH6 , and PMS2 and is characterized by colorectal, endometrial, and other epithelial malignancies. Thyroid cancer is not usually considered to be part of the constellation of Lynch syndrome cancers nor have Lynch syndrome tumor gene mutations been reported in thyroid malignancies. This study reports a woman with Lynch syndrome (colonic cancer and a DNA mismatch repair mutation in the MSH2 gene) with a synchronous papillary thyroid cancer. Six years later, she developed metachronous breast cancer. Metastatic bone disease developed after 3 years, and the disease burden was due to both breast and thyroid diseases. Despite multiple interventions for both metastatic breast and thyroid diseases, the patient's metastatic burden progressed and she died of leptomeningeal metastatic disease. Two prior case reports suggested thyroid cancer may be an extraintestinal malignancy of the Lynch syndrome cancer group. Hence, this study examined the genetic relationship between the patient's known Lynch syndrome and her thyroid cancer. The thyroid cancer tissue showed normal expression of MSH2 , suggesting that the tumor was not due to the oncogenic mutation of Lynch syndrome, and molecular analysis confirmed BRAF V600E mutation. Although in this case the thyroid cancer was sporadic, it raises the importance of considering cancer genetics in familial cancer syndromes when other cancers do not fit the criteria of the syndrome. Careful documentation of other malignancies in patients with thyroid cancer and their families would assist in better understanding of any potential association. Appropriate genetic testing will clarify whether a common pathogenic mechanism links seemingly unrelated cancers.

[Metabolic disorders and nutritional status in autoimmune thyroid diseases].

PubMed

Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

2015-01-02

In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic disorders and nutritional status with the occurrence of ATD.

Investigation of factors influencing radioiodine (131I) biokinetics in patients with benign thyroid disease using nonlinear mixed effects approach.

PubMed

Topić Vučenović, Valentina; Rajkovača, Zvezdana; Jelić, Dijana; Stanimirović, Dragi; Vuleta, Goran; Miljković, Branislava; Vučićević, Katarina

2018-05-13

Radioiodine ( 131 I) therapy is the common treatment option for benign thyroid diseases. The objective of this study was to characterize 131 I biokinetics in patients with benign thyroid disease and to investigate and quantify the influence of patients' demographic and clinical characteristics on intra-thyroidal 131 I kinetics by developing a population model. Population pharmacokinetic analysis was performed using a nonlinear mixed effects approach. Data sets of 345 adult patients with benign thyroid disease, retrospectively collected from patients' medical records, were evaluated in the analysis. The two-compartment model of 131 I biokinetics representing the blood compartment and thyroid gland was used as the structural model. Results of the study indicate that the rate constant of the uptake of 131 I into the thyroid (k tu ) is significantly influenced by clinical diagnosis, age, functional thyroid volume, free thyroxine in plasma (fT 4 ), use of anti-thyroid drugs, and time of discontinuation of therapy before administration of the radioiodine (THDT), while the effective half-life of 131 I is affected by the age of the patients. Inclusion of the covariates in the base model resulted in a decrease of the between subject variability for k tu from 91 (3.9) to 53.9 (4.5)%. This is the first population model that accounts for the influence of fT 4 and THDT on radioiodine kinetics. The model could be used for further investigations into the correlation between thyroidal exposure to 131 I and the outcome of radioiodine therapy of benign thyroid disease as well as the development of dosing recommendations.

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

PubMed

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

2011-06-01

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

Endocrinology Update: Thyroid Disorders.

PubMed

Kelley, Scott

2016-12-01

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

Maternal thyroid function and child educational attainment: prospective cohort study.

PubMed

Nelson, Scott M; Haig, Caroline; McConnachie, Alex; Sattar, Naveed; Ring, Susan M; Smith, George D; Lawlor, Debbie A; Lindsay, Robert S

2018-02-20

To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. Prospective cohort study. Avon Longitudinal Study of Parents and Children cohort in the UK. 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

PubMed

Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

2017-10-01

Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC = differentiated thyroid cancer; LASA = linear analog self-assessment; PR = partial response; QOL = quality of life; RAI = radioactive iodine; RAIR = RAI-resistant; RECIST = Response Evaluation Criteria In Solid Tumors; Tg = thyroglobulin; VEGFR = vascular endothelial growth factor receptor.

Histologic Findings and Cytological Alterations in Thyroid Nodules After Radioactive Iodine Treatment for Graves' Disease: A Diagnostic Dilemma.

PubMed

El Hussein, Siba; Omarzai, Yumna

2017-06-01

Unlike the well-documented relation between radiation to the neck and development of papillary thyroid carcinoma, a causal association between radioactive iodine treatment for Graves' disease and development of thyroid malignancy is less defined. However, patients with a background of thyroid dysfunction presenting with clinically palpable thyroid nodules are followed more closely than the average population, and fine needle aspiration is recommended in such circumstances. Cytological examination of aspirates, and histologic examination of tissue provided from patients with a known history of Graves' disease, managed by radioactive iodine therapy can create a diagnostic dilemma, as the distinction between radiation effect and a malignant primary thyroid neoplasm can be very challenging. Thus, pathologists should be aware of the existence of these changes in the setting of radiation therapy for Graves' disease. Providing pathologists with appropriate clinical history of Graves' disease treated with radioactive iodine is of paramount importance in order to prevent an overdiagnosis of malignancy.

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2012-01-01

Transgenic mice with the human thyrotropin-receptor (TSHR) A-subunit targeted to the thyroid are tolerant of the transgene. In transgenics that express low A-subunit levels (Lo-expressors), regulatory T cell (Treg) depletion using anti-CD25 before immunization with adenovirus encoding the A-subunit (A-sub-Ad) breaks tolerance, inducing extensive thyroid lymphocytic infiltration, thyroid damage and antibody spreading to other thyroid proteins. In contrast, no thyroiditis develops in Hi-expressor transgenics or wild-type mice. Our present goal was to determine if thyroiditis could be induced in Hi-expressor transgenics using a more potent immunization protocol: Treg depletion, priming with Complete Freund's Adjuvant (CFA) + A-subunit protein and further Treg depletions before two boosts with A-sub-Ad. As controls, anti-CD25 treated Hi- and Lo-expressors and wild-type mice were primed with CFA+ mouse thyroglobulin (Tg) or CFA alone before A-sub-Ad boosting. Thyroiditis developed after CFA+A-subunit protein or Tg and A-sub-Ad boosting in Lo-expressor transgenics but Hi- expressors (and wild-type mice) were resistant to thyroiditis induction. Importantly, in Lo-expressors, thyroiditis was associated with the development of antibodies to the mouse TSHR downstream of the A-subunit. Unexpectedly, we observed that the effect of bacterial products on the immune system is a “double-edged sword”. On the one hand, priming with CFA (mycobacteria emulsified in oil) plus A-subunit protein broke tolerance to the A-subunit in Hi-expressor transgenics leading to high TSHR antibody levels. On the other hand, prior treatment with CFA in the absence of A-subunit protein inhibited responses to subsequent immunization with A-sub-Ad. Consequently, adjuvant activity arising in vivo after bacterial infections combined with a protein autoantigen can break self-tolerance but in the absence of the autoantigen, adjuvant activity can inhibit the induction of immunity to autoantigens (like the TSHR) displaying strong self-tolerance. PMID:22970131

Thyroid storm causing placental abruption: Cardiovascular and management complications for the Intensivist.

PubMed

Lane, Andrew S; Tarvade, Sanjay

2015-08-01

Thyroid storm is a rare and serious complication of pregnancy which can lead to spontaneous abortion, preterm delivery, preeclampsia and cardiac failure. It is also associated with high maternal and foetal mortality if not diagnosed and managed promptly. The diagnosis of thyroid storm in pregnancy can pose significant challenges due to its presentation being similar to other pregnancy-related complications. We present a patient who developed thyroid storm at 29 weeks of pregnancy, which resulted in pre-term delivery, cardiac failure and thyroidectomy. We discuss the treatment of thyroid storm in pregnancy, the decision making involved in proceeding to thyroidectomy or to use radio-iodine, and foetal thyroid status in thyrotoxicosis.

Prospective Observation of 5-Year Clinical Course of Subclinical Hypothyroidism in Korean Population

PubMed Central

Park, Woo Ri; Oh, Tae Keun

2013-01-01

Subclinical hypothyroidism (SCH) is a common clinical condition, whereas it's natural course has not been identified distinctly. We evaluated the natural history of 169 SCH patients over 5-yr and the prognostic factors including thyroid autoantibodies and thyroid ultrasonographic (USG) findings related to develop overt hypothyroidism. After 5 yr, 47.3% of patients showed normalization of TSH, while 36.7% of patients remained persistence of high level of TSH, and overt hypothyroidism developed in 11.2% of patients. There were painless thyroiditis (2.9%) and hyperthyroidism (1.7%) during 5 yr follow-up. The thyroid nodule was seen in 48.6% of patients. Most of patients had 1 to 2 nodules whereas only 3% of patients with thyroid nodule had more than 6 nodules. Overt hypothyroidism patients had more heterogenous echogenecity in USG compared to patients with normalization or persistent SCH (76.5% vs 50.0% vs 35.0%, P = 0.048) and higher prevalence positive anti-thyroid peroxidase (anti-TPO Ab) and anti-thyroglobulin antibody (anti-Tg Ab) and titer of anti-TPO Ab than other two groups. The cut off values for prediction of overt hypothyroidism were TSH > 7.45 µIU/mL, free T4 < 1.09 ng/dL and Anti-TPO Ab > 560 IU/mL. SCH has various courses and initial TSH, free T4, presence of thyroid autoantibody, titer of thyroid autoantibody; and thyroid USG findings can serve as a prognostic factor for progression of overt hypothyroidism. These parameters suggest consideration to initiate thyroid hormone treatment in SCH. PMID:24265525

Thyroid Storm Precipitated by Diabetic Ketoacidosis and Influenza A: A Case Report and Literature Review.

PubMed

Ikeoka, Toshiyuki; Otsuka, Hiroaki; Fujita, Naruhiro; Masuda, Yukiko; Maeda, Shigeto; Horie, Ichiro; Ando, Takao; Abiru, Norio; Kawakami, Atsushi

2017-01-01

A 46-year-old woman with a history of Graves' disease presented with the chief complaints of appetite loss, weight loss, fatigue, nausea, and sweating. She was diagnosed with diabetic ketoacidosis (DKA), thyroid storm, and influenza A. She was treated with an intravenous insulin drip, intravenous fluid therapy, intravenous hydrocortisone, oral potassium iodine, and oral methimazole. As methimazole-induced neutropenia was suspected, the patient underwent thyroidectomy. It is important to maintain awareness that thyroid storm and DKA can coexist. Furthermore, even patients who have relatively preserved insulin secretion can develop DKA if thyroid storm and infection develop simultaneously.

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.

Differentiation of postpartum Graves' thyrotoxicosis from postpartum destructive thyrotoxicosis using antithyrotropin receptor antibodies and thyroid blood flow.

PubMed

Ide, Akane; Amino, Nobuyuki; Kang, Shino; Yoshioka, Waka; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Nakamura, Hirotoshi; Miyauchi, Akira

2014-06-01

Postpartum thyroid dysfunction occurs in approximately 5-10% of women in the general population within one year of delivery. Differentiation of postpartum Graves' thyrotoxicosis (PPGr) from postpartum destructive thyrotoxicosis (PPDT) is essential because of the difference in treatment measures between the two. However, it is sometimes difficult because radioactive iodine uptake is contraindicated when patients are lactating. We examined the usefulness of determining the time of onset postpartum and measurement of antithyrotropin (anti-TSH) receptor antibodies and thyroid blood flow. Forty-two patients with newly developed thyrotoxicosis after delivery were examined: 18 had Graves' disease and 24 had destructive thyrotoxicosis. Serum free thyroxine (fT4), free triiodothyronine (fT3), and TSH were measured by chemiluminescent immunoassays. Anti-TSH receptor antibodies (TRAb), antithyroglobulin antibodies (TgAb), and antithyroid peroxidase antibodies (TPOAb) were measured by the Elecsys electrochemiluminescence immunoassay. Thyroid volume and blood flow (TBF) were measured quantitatively by color flow Doppler ultrasonography. Onset of thyrotoxicosis was distributed from 2 to 12 months postpartum. Twelve (85.7%) of 14 patients who developed thyrotoxicosis at three months or earlier after delivery had PPDT. On the other hand, all 11 patients who developed thyrotoxicosis at 6.5 months or later had PPGr. All patients with PPGr had positive TRAb (14.9±14.9 IU/L, mean±standard deviation (SD)) and all patients with PPDT had negative TRAb (0.1±0.3 IU/L, p<0.0001). Fifteen (83.3%) of 18 PPGr patients had high TBF of more than 4.0% (8.9±4.4), and all PPDT patients had low TBF of <4.0% (1.6±1.0, p<0.0001). The fT3/fT4 ratio was higher in PPGr (64.0±23.9) than in PPDT (38.9±13.1, p<0.0002), but absolute values overlapped between the two. Early onset of thyrotoxicosis postpartum was associated mainly with PPDT, and a late onset was suggestive of PPGr. Positive TRAb and high TBF >4.0% are indicators of postpartum onset of Graves' disease.

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

PubMed Central

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

2011-01-01

Background We have shown that thyroid-stimulating hormone (TSH) has a direct inhibitory effect on osteoclastic bone resorption and that TSH receptor (TSHR) null mice display osteoporosis. To determine the stage of osteoclast development at which TSH may exert its effect, we examined the influence of TSH and agonist TSHR antibodies (TSHR-Ab) on osteoclast differentiation from murine embryonic stem (ES) cells to gain insight into bone remodeling in hyperthyroid Graves' disease. Methods Osteoclast differentiation was initiated in murine ES cell cultures through exposure to macrophage colony stimulation factor, receptor activator of nuclear factor кB ligand, vitamin D, and dexamethasone. Results Tartrate resistant acid phosphatase (TRAP)-positive osteoclasts formed in ∼12 days. This coincided with the expected downregulation of known markers of self renewal and pluripotency (including Oct4, Sox2, and REX1). Both TSH and TSHR-Abs inhibited osteoclastogenesis as evidenced by decreased development of TRAP-positive cells (∼40%–50% reduction, p = 0.0047), and by decreased expression, in a concentration-dependent manner, of osteoclast differentiation markers (including the calcitonin receptor, TRAP, cathepsin K, matrix metallo-proteinase-9, and carbonic anhydrase II). Similar data were obtained using serum immunoglobulin-Gs (IgGs) from patients with hyperthyroid Graves' disease and known TSHR-Abs. TSHR stimulators inhibited tumor necrosis factor-alpha mRNA and protein expression, but increased the expression of osteoprotegerin (OPG), an antiosteoclastogenic human soluble receptor activator of nuclear factor кB ligand receptor. Neutralizing antibody to OPG reversed the inhibitory effect of TSH on osteoclast differentiation evidencing that the TSH effect was at least in part mediated by increased OPG. Conclusion These data establish ES-derived osteoclastogenesis as an effective model system to study the regulation of osteoclast differentiation in early development. The results support the observations that TSH has a bone protective action by negatively regulating osteoclastogenesis. Further, our results implicate TSHR-Abs in offering skeletal protection in hyperthyroid Graves' disease, even in the face of high thyroid hormone and low TSH levels. PMID:21745106

Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.

PubMed

Alhusseini, M; Samantray, J

2017-04-01

Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent. © Georg Thieme Verlag KG Stuttgart · New York.

Histological Changes in the Thyroid Gland in Cases of Infant and Early Childhood Asphyxia-A Preliminary Study.

PubMed

Byard, Roger W; Bellis, Maria

2016-05-01

A retrospective blinded study of thyroid gland histology was undertaken in 50 infants and young children aged from 1 to 24 months. Deaths were due to (i) suffocation (N = 7), hanging (4), wedging (3), and chest and/or neck compression (4), and (ii) SIDS (20), noncervical trauma (7), organic disease, (4) and drug toxicity (1). In the asphyxia group (N = 18), thyroid gland congestion ranged from 0 to 3+ with 39% of cases (7/18) having moderate/marked congestion. In three cases, focal aggregates of red blood cells (blood islands) were observed within the intrafollicular colloid. These deaths involved chest compression, chest and/or neck compression, and crush asphyxia in a vehicle accident, and all had facial petechiae. Only 22% of the 32 control cases (7/32) had moderate/marked congestion with no blood islands being identified (p < 0.05). Blood islands within the thyroid gland may be caused by congestion associated with crushing or compression and may provide supportive evidence for this diagnosis. © 2016 American Academy of Forensic Sciences.

Evaluation of Xerostomia and salivary flow rate in Hashimoto’s Thyroiditis

PubMed Central

Shirzad, Nooshin; Moosavi, Mahdieh-Sadat

2016-01-01

Background One of the most common causes of hypothyroidism is Hashimoto´s Thyroiditis (HT). Early detection of dry mouth is critical in preserving and promoting systemic and oral health. In this study we have assessed, for the first time, salivary function and xerostomia in HT patients who have not been involved with Sjögren´s syndrome. Material and Methods HT was diagnosed in 40 patients based on clinical findings and positive anti-thyroid peroxidase antibodies (anti-TPO). Controls, matched by sex, age and body mass index (BMI), and with no history of thyroid disease, were selected. A questionnaire was used for diagnosis of xerostomia. Saliva samples were taken between 8 a.m. and 9 a.m., and at least 2 hours after the last intake of food or drink. The flow rate was calculated in milliliters per minute. Results Xerostomia was significantly higher in patients with HT. Unstimulated salivary flow rate was significantly lower in the HT group. Stimulated salivary flow rate was lower in HT group, but the difference was not significant. Conclusions The patients with HT experienced xerostomia, and their salivary flow rate was diminished. Spitting the saliva then assessing salivary flow rate based on milliliter per minute is non-invasive, fast, and simple for chair-side diagnosis of dry mouth. Autoimmune diseases can be accompanied by salivary gland dysfunction. This may be due to the effect of cytokines in the autoimmune process or because of thyroid hormone dysfunctions. Key words:Thyroid, salivary gland, xerostomia. PMID:26595829

A mutation screening of oncogenes, tumor suppressor gene TP53 and nuclear encoded mitochondrial complex I genes in oncocytic thyroid tumors.

PubMed

Evangelisti, Cecilia; de Biase, Dario; Kurelac, Ivana; Ceccarelli, Claudio; Prokisch, Holger; Meitinger, Thomas; Caria, Paola; Vanni, Roberta; Romeo, Giovanni; Tallini, Giovanni; Gasparre, Giuseppe; Bonora, Elena

2015-03-21

Thyroid neoplasias with oncocytic features represent a specific phenotype in non-medullary thyroid cancer, reflecting the unique biological phenomenon of mitochondrial hyperplasia in the cytoplasm. Oncocytic thyroid cells are characterized by a prominent eosinophilia (or oxyphilia) caused by mitochondrial abundance. Although disruptive mutations in the mitochondrial DNA (mtDNA) are the most significant hallmark of such tumors, oncocytomas may be envisioned as heterogeneous neoplasms, characterized by multiple nuclear and mitochondrial gene lesions. We investigated the nuclear mutational profile of oncocytic tumors to pinpoint the mutations that may trigger the early oncogenic hit. Total DNA was extracted from paraffin-embedded tissues from 45 biopsies of oncocytic tumors. High-resolution melting was used for mutation screening of mitochondrial complex I subunits genes. Specific nuclear rearrangements were investigated by RT-PCR (RET/PTC) or on isolated nuclei by interphase FISH (PAX8/PPARγ). Recurrent point mutations were analyzed by direct sequencing. In our oncocytic tumor samples, we identified rare TP53 mutations. The series of analyzed cases did not include poorly- or undifferentiated thyroid carcinomas, and none of the TP53 mutated cases had significant mitotic activity or high-grade features. Thus, the presence of disruptive TP53 mutations was completely unexpected. In addition, novel mutations in nuclear-encoded complex I genes were identified. These findings suggest that nuclear genetic lesions altering the bioenergetics competence of thyroid cells may give rise to an aberrant mitochondria-centered compensatory mechanism and ultimately to the oncocytic phenotype.

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

EPA Science Inventory

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

Analysis of thyroid hormones in gland and serum using liquid chromatography-tandem mass spectrometry

EPA Science Inventory

Thyroid hormones (THs), which are critical for growth and development in all vertebrates, can be impacted through chemical perturbation of the hypothalamic-pituitary-thyroid (HPT)-axis. Amphibian and mammalian models are being used to address this research priority within US EPA...

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

EPA Science Inventory

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

A 46-Year-Old Woman With Dyspnea From an Inhalational Exposure, Triggering Thyroid Storm and Subsequent Multi-Organ System Failure.

PubMed

Moraco, Andrew H; Banauch, Gisela; Kopec, Scott

2015-12-01

Thyroid storm is a rare, life-threatening condition which arises in patients with thyrotoxicosis, with an annual incidence of 2 patients per 1,000,000 and a mortality rate of 11%. We present the case of a 46-year-old-female with a medical history of controlled mild intermittent asthma, who presented with a severe asthma exacerbation, that triggered thyroid storm after exposure to polyurethane fumes. This patient represents, to the best of our knowledge, the first patient in whom the stress related to a severe asthma attack triggered the development of thyroid storm. She also is the first patient with no indication of cardiac dysfunction who developed fatal cardiac arrest after initiation of b-blockade for treatment of thyroid storm. © The Author(s) 2015.

Hyperthyroidism After Allogeneic Hematopoietic Stem Cell Transplantation: A Report of Four Cases

PubMed Central

Sağ, Erdal; Gönç, Nazlı; Alikaşifoğlu, Ayfer; Kuşkonmaz, Barış; Uçkan, Duygu; Özön, Alev; Kandemir, Nurgün

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves’ disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation. PMID:26777050

Quality of life, clinical outcomes and safety of early prophylactic levothyroxine administration in patients with Graves' hyperthyroidism undergoing radioiodine therapy: a randomized controlled study.

PubMed

Taïeb, David; Bournaud, Claire; Eberle, Marie-Claude; Catargi, Bogdan; Schvartz, Claire; Cavarec, Marie-Béatrice; Faugeron, Isabelle; Toubert, Marie-Elisabeth; Benisvy, Danielle; Archange, Cendrine; Mundler, Olivier; Caron, Philippe; Abdullah, Ahmad Esmaeel; Baumstarck, Karine

2016-04-01

While radioiodine therapy is commonly used for treating Graves' disease, a prolonged and clinical hypothyroidism may result in disabling symptoms leading to deterioration of quality of life (QoL) of patients. Introducing levothyroxine (LT4) treatment in the early post-therapeutic period may be an interesting approach to limit this phenomenon. A multicenter, prospective, open-label randomized controlled trial enrolled 94 patients with Graves' hyperthyroidism randomly assigned to the experimental group (n=46) (group A: early prophylactic LT4 treatment) or the control group (n=48) (group B: standard follow-up). The primary endpoint was the 6-month QoL. The secondary endpoints were other QoL scores such as Graves' ophthalmopathy (GO) outcomes, thyroid function tests and safety. The primary endpoint at 6 months was achieved: the mental composite score (MCS) of Short Form 36 (SF-36) was significantly higher in group A compared to group B (P=0.009). Four other dimension scores of the SF-36 and four dimension scores of the thyroid-specific patient-reported outcome (ThyPRO) significantly differed between the two groups, indicating better QoL in group A. After adjustment for variables, the early LT4 administration strategy was found as an independent factor for only two scores of SF-36: the MCS and the general health (GH) score. There were no differences in GO, final thyroid status and changes in the anti-TSH receptor antibodies (TRAbs) levels between the two groups. No adverse cardiovascular event was reported. Early LT4 administration post-radioactive iodine (RAI) could represent a safe potential benefit for patients with regard to QoL. The optimal strategy taking into account administered RAI activities and LT4 treatment dosage and timing remains to be determined. © 2016 European Society of Endocrinology.