Crafting a gene expression timeline for the thyroid in the early-life stages of fathead minnows (Pimephales promelas)

EPA Science Inventory

The hypothalamic-pituitary-thyroid (HPT) axis plays a number of critical roles in chordate physiology including regulation of metabolism, growth, and development. While the role of the HPT axis and thyroid hormone signaling in mammalian and amphibian development is well establis...

Gene transcription ontogeny of thyroid-axis development in early-life stage fathead minnows (Pimephales promelas)

EPA Science Inventory

Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in develo...

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.

Thyroid stimulating hormone and serum, plasma, and platelet brain-derived neurotrophic factor during a 3-month follow-up in patients with major depressive disorder.

PubMed

Baek, Ji Hyun; Kang, Eun-Suk; Fava, Maurizio; Mischoulon, David; Nierenberg, Andrew A; Lee, Dongsoo; Heo, Jung-Yoon; Jeon, Hong Jin

2014-12-01

Thyroid dysfunction and elevated thyroid stimulating hormone (TSH) are common in patients with depression. TSH might exert its function in the brain through blood levels of brain-derived neurotrophic factor (BDNF). BDNF decreases during depressed states and normalize after treatment. The gap is that the association between TSH and BDNF in patients with major depressive disorder (MDD) is unknown. We studied 105 subjects ≥18 years of age with MDD and measured serum, plasma, and platelet BDNF at baseline, 1 month and 3 months during antidepressant treatment. Other baseline measurements included hypothalamic-pituitary-thyroid axis hormones such as TSH, triiodothyronine (T3) and thyroxine (T4); hypothalamic-pituitary-adrenal (HPA) axis hormones and hypothalamic-pituitary-gonadal (HPG) axis hormones and prolactin. Linear mixed model effect analyses revealed that baseline TSH level was negatively associated with changes of serum BDNF from baseline to 3 months (F=7.58, p=0.007) after adjusting for age, sex, and body mass index, but was not associated with plasma and platelet BDNF. In contrast, T3 and T4, HPA axis hormones, HPG axis hormones, and prolactin were not associated with serum, plasma, or platelet BDNF levels. Patients in the highest quartile of TSH showed significantly lower serum BDNF than in the other quartiles (F=4.54, p=0.038), but no significant differences were found based on T3 and T4 levels. TSH was only measured at baseline. Higher TSH is associated with lower baseline and reduced the increase of serum BDNF levels during antidepressant treatment in patients with MDD. Copyright © 2014 Elsevier B.V. All rights reserved.

Flatfish metamorphosis: a hypothalamic independent process?

PubMed

Campinho, Marco A; Silva, Nadia; Roman-Padilla, Javier; Ponce, Marian; Manchado, Manuel; Power, Deborah M

2015-03-15

Anuran and flatfish metamorphosis are tightly regulated by thyroid hormones that are the necessary and sufficient factors that drive this developmental event. In the present study whole mount in situ hybridization (WISH) and quantitative PCR in sole are used to explore the central regulation of flatfish metamorphosis. Central regulation of the thyroid in vertebrates is mediated by the hypothalamus-pituitary-thyroid (HPT) axis. Teleosts diverge from other vertebrates as hypothalamic regulation in the HPT axis is proposed to be through hypothalamic inhibition although the regulatory factor remains enigmatic. The dynamics of the HPT axis during sole metamorphosis revealed integration between the activity of the thyrotrophes in the pituitary and the thyroid follicles. No evidence was found supporting a role for thyroid releasing hormone (trh) or corticotrophin releasing hormone (crh) in hypothalamic control of TH production during sole metamorphosis. Intriguingly the results of the present study suggest that neither hypothalamic trh nor crh expression changes during sole metamorphosis and raises questions about the role of these factors and the hypothalamus in regulation of thyrotrophs. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

EPA Science Inventory

Disruption of thyroid hormone signaling is a form of endocrine disruption that is of concern to both human health and ecosystems. Research is being conducted to define the biological targets chemicals may interact with to disrupt thyroid hormone signaling and the stages in develo...

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.

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

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

Bowyer, J.F.; Latendresse, J.R.; Delongchamp, R.R.

Acrylamide (AA) is an important industrial chemical that is neurotoxic in rodents and humans and carcinogenic in rodents. The observation of cancer in endocrine-responsive tissues in Fischer 344 rats has prompted hypotheses of hormonal dysregulation, as opposed to DNA damage, as the mechanism for tumor induction by AA. The current investigation examines possible evidence for disruption of the hypothalamic-pituitary-thyroid axis from 14 days of repeated exposure of male Fischer 344 rats to doses of AA that range from one that is carcinogenic after lifetime exposure (2.5 mg/kg/d), an intermediate dose (10 mg/kg/d), and a high dose (50 mg/kg/d) that ismore » neurotoxic for this exposure time. The endpoints selected include: serum levels of thyroid and pituitary hormones; target tissue expression of genes involved in hormone synthesis, release, and receptors; neurotransmitters in the CNS that affect hormone homeostasis; and histopathological evaluation of target tissues. These studies showed virtually no evidence for systematic alteration of the hypothalamic-pituitary-thyroid axis and do not support hormone dysregulation as a plausible mechanism for AA-induced thyroid cancer in the Fischer 344 rat. Specifically, there were no significant changes in: 1) mRNA levels in hypothalamus or pituitary for TRH, TSH, thyroid hormone receptor {alpha} and {beta}, as well 10 other hormones or releasing factors; 2) mRNA levels in thyroid for thyroglobulin, thyroid peroxidase, sodium iodide symporter, or type I deiodinases; 3) serum TSH or T3 levels (T4 was decreased at high dose only); 4) dopaminergic tone in the hypothalamus and pituitary or importantly 5) increased cell proliferation (Mki67 mRNA and Ki-67 protein levels were not increased) in thyroid or pituitary. These negative findings are consistent with a genotoxic mechanism of AA carcinogenicity based on metabolism to glycidamide and DNA adduct formation. Clarification of this mechanistic dichotomy may be useful in human cancer risk assessments for AA.« less

Exposure to PFDoA causes disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae.

PubMed

Zhang, Shengnan; Guo, Xiaochun; Lu, Shaoyong; Sang, Nan; Li, Guangyu; Xie, Ping; Liu, Chunsheng; Zhang, Liguo; Xing, Yi

2018-04-01

Perfluorododecanoic acid (PFDoA), a kind of perfluorinated carboxylic acid (PFCA) with 12 carbon atoms, has an extensive industrial utilization and is widespread in both wildlife and the water environment, and was reported to have the potential to cause a disruption in the thyroid hormone system homeostasis. In this study, zebrafish embryos/larvae were exposed to different concentrations of PFDoA (0, 0.24, 1.2, 6 mg/L) for 96 h post-fertilization (hpf). PFDoA exposure caused obvious growth restriction connected with the reduced thyroid hormones (THs) contents in zebrafish larvae, strengthening the interference effect on the growth of fish larvae. The transcriptional level of genes within the hypothalamic-pituitary-thyroid (HPT) axis was analyzed. The gene expression levels of thyrotropin-releasing hormone (trh) and corticotrophin-releasing hormone (crh) were upregulated upon exposure to 6 mg/L of PFDoA, and iodothyronine deiodinases (dio2) was upregulated in the 1.2 mg/L PFDoA group. The transcription of thyroglobulin (tg) and thyroid receptor (trβ) were significantly downregulated upon exposure to 1.2 mg/L and 6 mg/L of PFDoA. PFDoA could also decrease the levels of sodium/iodide symporter (nis) and transthyretin (ttr) gene expression in a concentration-dependent manner after exposure. A significant decrease in thyroid-stimulating hormoneβ (tshβ), uridinediphosphate-glucuronosyltransferase (ugt1ab) and thyroid receptor (trα) gene expression were observed at 6 mg/L PFDoA exposure. Upregulation and downregulation of iodothyronine deiodinases (dio1) gene expression were observed upon the treatment of 1.2 mg/L and 6 mg/L PFDoA, respectively. All the data demonstrated that gene expression in the HPT axis altered after different PFDoA treatment and the potential mechanisms of the disruption of thyroid status could occur at several steps in the process of synthesis, regulation, and action of thyroid hormones. Copyright © 2018 Elsevier Ltd. All rights reserved.

The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.

PubMed

Astapova, Inna; Vella, Kristen R; Ramadoss, Preeti; Holtz, Kaila A; Rodwin, Benjamin A; Liao, Xiao-Hui; Weiss, Roy E; Rosenberg, Michael A; Rosenzweig, Anthony; Hollenberg, Anthony N

2011-02-01

The role of nuclear receptor corepressor (NCoR) in thyroid hormone (TH) action has been difficult to discern because global deletion of NCoR is embryonic lethal. To circumvent this, we developed mice that globally express a modified NCoR protein (NCoRΔID) that cannot be recruited to the thyroid hormone receptor (TR). These mice present with low serum T(4) and T(3) concentrations accompanied by normal TSH levels, suggesting central hypothyroidism. However, they grow normally and have increased energy expenditure and normal or elevated TR-target gene expression across multiple tissues, which is not consistent with hypothyroidism. Although these findings imply an increased peripheral sensitivity to TH, the hypothalamic-pituitary-thyroid axis is not more sensitive to acute changes in TH concentrations but appears to be reset to recognize the reduced TH levels as normal. Furthermore, the thyroid gland itself, although normal in size, has reduced levels of nonthyroglobulin-bound T(4) and T(3) and demonstrates decreased responsiveness to TSH. Thus, the TR-NCoR interaction controls systemic TH sensitivity as well as the set point at all levels of the hypothalamic-pituitary-thyroid axis. These findings suggest that NCoR levels could alter cell-specific TH action that would not be reflected by the serum TSH.

The environmental contaminant tributyltin leads to abnormalities in different levels of the hypothalamus-pituitary-thyroid axis in female rats.

PubMed

Andrade, Marcelle Novaes; Santos-Silva, Ana Paula; Rodrigues-Pereira, Paula; Paiva-Melo, Francisca Diana; de Lima Junior, Niedson Correa; Teixeira, Mariana Pires; Soares, Paula; Dias, Glaecir Roseni Munstock; Graceli, Jones Bernardes; de Carvalho, Denise Pires; Ferreira, Andrea Claudia Freitas; Miranda-Alves, Leandro

2018-06-11

Tributyltin is a biocide used in nautical paints, aiming to reduce fouling of barnacles in ships. Despite the fact that many effects of TBT on marine species are known, studies in mammals have been limited, especially those evaluating its effect on the function of the hypothalamus-pituitary-thyroid (HPT) axis. The aim of this study was to investigate the effects of subchronic exposure to TBT on the HPT axis in female rats. Female Wistar rats received vehicle, TBT 200 ng kg -1 BW d -1 or 1000 ng kg -1 BW d -1 orally by gavage for 40 d. Hypothalamus, pituitary, thyroid, liver and blood samples were collected. TBT200 and TBT1000 thyroids showed vacuolated follicular cells, with follicular hypertrophy and hyperplasia. An increase in epithelial height and a decrease in the thyroid follicle and colloid area were observed in TBT1000 rats. Moreover, an increase in the epithelium/colloid area ratio was observed in both TBT groups. Lower TRH mRNA expression was observed in the hypothalami of TBT200 and TBT1000 rats. An increase in Dio1 mRNA levels was observed in the hypothalamus and thyroid in TBT1000 rats only. TSH serum levels were increased in TBT200 rats. In TBT1000 rats, there was a decrease in total T4 serum levels compared to control rats, whereas T3 serum levels did not show significant alterations. We conclude that TBT exposure can promote critical abnormalities in the HPT axis, including changes in TRH mRNA expression and serum TSH and T4 levels, in addition to affecting thyroid morphology. These findings demonstrate that TBT disrupts the HPT axis. Additionally, the changes found in thyroid hormones suggest that TBT may interfere with the peripheral metabolism of these hormones, an idea corroborated by the observed changes in Dio1 mRNA levels. Therefore, TBT exposition might interfere not only with the thyroid axis but also with thyroid hormone metabolism. Copyright © 2018 Elsevier Ltd. All rights reserved.

Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

PubMed

Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

2015-10-01

Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. Published by Elsevier Ltd.

The hypothalamic-pituitary-thyroid axis and biological rhythms: The discovery of TSH's unexpected role using animal models.

PubMed

Ikegami, Keisuke; Yoshimura, Takashi

2017-10-01

Thyroid hormones (TH) are important for development, growth, and metabolism. It is also clear that the synthesis and secretion of TH are regulated by the hypothalamic-pituitary-thyroid (HPT) axis. Animal models have helped advance our understanding of the roles and regulatory mechanisms of TH. The animals' bodies develop through coordinated timing of cell division and differentiation. Studies of frog metamorphosis led to the discovery of TH and their role in development. However, to adapt to rhythmic environmental changes, animals also developed various endocrine rhythms. Studies of rodents clarified the neural and molecular mechanisms underlying the circadian regulation of the HPT axis. Moreover, birds have a sophisticated seasonal adaptation mechanism, and recent studies of quail revealed unexpected roles for thyroid-stimulating hormone (TSH) and TH in the seasonal regulation of reproduction. Interestingly, this mechanism is conserved in mammals. Thus, we review how animal studies have shaped our general understanding of the HPT axis in relation to biological rhythms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanism-based testing strategy using in vitro approaches for identification of thyroid hormone disrupting chemicals

EPA Science Inventory

The thyroid hormone (TH) system is involved in several important physiological processes, including regulation of energy metabolism, growth and differentiation, development and maintenance of brain function, thermo-regulation, osmo-regulation, and axis of regulation of other endo...

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

PubMed

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

2016-02-01

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

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.

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.

A BBDR-HPT Axis Model for the Lactating Rat and Nursing Pup: Evaluation of Iodide Deficiency

EPA Science Inventory

A biologically based dose response (BBDR) model for the lactating rat and pup hypothalamic-pituitary-thyroid (HPT) axis is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the lactating rat and pup quanti...

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.

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.

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

EPA Science Inventory

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

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2015-09-30

ranging individuals support the existence of these same stress response pathways in marine mammals. 2 While the HPA axis and physiological processes...relying upon methods which include capture-release health assessments. Stress and reproductive hormones (cortisol, aldosterone , thyroid, testosterone...Analyses Hormone concentrations (cortisol, aldosterone , reproductive and thyroid hormones) in serum samples were analyzed by Cornell’s Animal Health

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2014-09-30

axis and physiological processes driven by the GCs are essential for an individual’s ability to respond and adapt to stress, prolonged elevation of...health assessments. Stress and reproductive hormones (cortisol, aldosterone , thyroid, testosterone, progesterone) have been routinely measured in blood...in South Carolina. Laboratory Analyses Hormone concentrations (cortisol, aldosterone , reproductive and thyroid hormones) in serum samples have

Stereoselective degradation and thyroid endocrine disruption of lambda-cyhalothrin in lizards (Eremias argus) following oral exposure.

PubMed

Chang, Jing; Hao, Weiyu; Xu, Yuanyuan; Xu, Peng; Li, Wei; Li, Jianzhong; Wang, Huili

2018-01-01

The disturbance of the thyroid system and elimination of chiral pyrethroid pesticides with respect to enantioselectivity in reptiles have so far received limited attention by research. In this study, bioaccumulation, thyroid gland lesions, thyroid hormone levels, and hypothalamus-pituitary-thyroid axis-related gene expression in male Eremias argus were investigated after three weeks oral administration of lambda-cyhalothrin (LCT) enantiomers. In the lizard liver, the concentration of LCT was negatively correlated with the metabolite-3-phenoxybenzoic acid (PBA) level during 21 days of exposure. (+)-LCT exposure induced a higher thyroid follicular epithelium height than (-)-LCT exposure. The thyroxine levels were increased in both treated groups while only (+)-LCT exposure induced a significant change in the triiodothyronine (T3) level. In addition, the expressions of hypothalamus-pituitary-thyroid axis-related genes including thyroid hormone receptors (trs), deiodinases (dios), uridinediphosphate glucuronosyltransferase (udp), and sulfotransferase (sult) were up-regulated after exposure to the two enantiomers. (+)-LCT treatment resulted in higher expression of trs and (-)-LCT exposure led to greater stimulation of dios in the liver, which indicated PBA-induced antagonism on thyroid hormone receptors and LCT-induced disruption of thyroxine (T4) deiodination. The results suggest the (-)-LCT exposure causes higher residual level in lizard liver while induces less disruption on lizard thyroid activity than (+)-LCT. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2009-01-01

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

Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System.

PubMed

Rachdaoui, Nadia; Sarkar, Dipak K

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body's most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic-pituitary-adrenal axis, the hypothalamic-pituitary-gonadal axis, the hypothalamic-pituitary-thyroid axis, the hypothalamic-pituitary-growth hormone/insulin-like growth factor-1 axis, and the hypothalamic-posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol's effects on various components of the endocrine system and their consequences.

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.

Mathematical model describing the thyroids-pituitary axis with distributed time delays in hormone transportation

NASA Astrophysics Data System (ADS)

Neamţu, Mihaela; Stoian, Dana; Navolan, Dan Bogdan

2014-12-01

In the present paper we provide a mathematical model that describe the hypothalamus-pituitary-thyroid axis in autoimmune (Hashimoto's) thyroiditis. Since there is a spatial separation between thyroid and pituitary gland in the body, time is needed for transportation of thyrotropin and thyroxine between the glands. Thus, the distributed time delays are considered as both weak and Dirac kernels. The delayed model is analyzed regarding the stability and bifurcation behavior. The last part contains some numerical simulations to illustrate the effectiveness of our results and conclusions.

Regulation of Thyroid-stimulating Hormone Release from the Pituitary by Thyroxine during Metamorphosis in Xenopus laevis

EPA Science Inventory

Environmentally-relevant chemicals such as perchlorate have the ability to disrupt the hypothalamo-pituitary-thyroid (HPT) axis of exposed individuals. Larval anurans are a particularly suitable model species for studying the effects of thyroid-disrupting chemicals (TDCs) becaus...

Thyroid hormone receptor beta2 is strongly up-regulated at all levels of the hypothalamo-pituitary-thyroidal axis during late embryogenesis in chicken.

PubMed

Grommen, Sylvia V H; Arckens, Lutgarde; Theuwissen, Tim; Darras, Veerle M; De Groef, Bert

2008-03-01

In this study, we tried to elucidate the changes in thyroid hormone (TH) receptor beta2 (TRbeta2) expression at the different levels of the hypothalamo-pituitary-thyroidal (HPT) axis during the last week of chicken embryonic development and hatching, a period characterized by an augmented activity of the HPT axis. We quantified TRbeta2 mRNA in retina, pineal gland, and the major control levels of the HPT axis - brain, pituitary, and thyroid gland - at day 18 of incubation, and found the most abundant mRNA content in retina and pituitary. Thyroidal TRbeta2 mRNA content increased dramatically between embryonic day 14 and 1 day post-hatch. In pituitary and hypothalamus, TRbeta2 mRNA expression rose gradually, in parallel with increases in plasma thyroxine concentrations. Using in situ hybridization, we have demonstrated the presence of TRbeta2 mRNA throughout the diencephalon and confirmed the elevation in TRbeta2 mRNA expression in the hypophyseal thyrotropes. In vitro incubation with THs caused a down-regulation of TRbeta2 mRNA levels in embryonic but not in post-hatch pituitaries. The observed expression patterns in pituitary and diencephalon may point to substantial changes in TRbeta2-mediated TH feedback active during the perinatal period. The strong rise in thyroidal TRbeta2 mRNA content could be indicative of an augmented modulation of thyroid development and/or function by THs toward and after hatching. Finally, THs proved to exert an age-dependent effect on pituitary TRbeta2 mRNA expression.

Relationship Between the Thyroid Axis and Alcohol Craving

PubMed Central

Aoun, Elie G.; Lee, Mary R.; Haass-Koffler, Carolina L.; Swift, Robert M.; Addolorato, Giovanni; Kenna, George A.; Leggio, Lorenzo

2015-01-01

Aims: A few studies have suggested a relationship between thyroid hormones and alcohol dependence (AD) such as a blunted increase of thyroid stimulating hormone (TSH) in response to thyrotropin-releasing hormone (TRH), lower levels of circulating free triiodothyronine (fT3) and free thyroxine (fT4) levels and down regulation of the TRH receptors. The current study aimed to explore the relationship between the hormones of the thyroid axis and alcohol-seeking behaviors in a sample of alcohol-dependent patients. Methods: Forty-two treatment-seeking alcohol-dependent individuals enrolled in a 12-week treatment study were considered. The Timeline Follow Back (TLFB) was used to assess the number of drinks consumed during the 12-week period. Blood levels of thyroid hormones (TSH, fT3 and fT4) were measured prior to and at the end of treatment. Questionnaires were administered to evaluate craving for alcohol [Penn Alcohol Craving Scale (PACS) and the Obsessive Compulsive Drinking Scale (OCDS) and its two subscales ODS for obsessions and CDS for compulsions] as well as anxiety [State and Trait Inventory (STAI)], depression [the Zung Self-Rating Depression Scale (Zung)] and aggression [the Aggressive Questionnaire (AQ)]. Results: At baseline, we found significant positive correlations between fT3 and OCDS (r = 0.358, P = 0.029) and CDS (r = 0.405, P = 0.013) and negative correlations between TSH levels and STAI (r = −0.342, P = 0.031), and AQ (r = −0.35, P = 0.027). At the end of the 12-week study period, abstinent patients had a greater change in TSH than those who relapsed (−0.4 vs. −0.25, F(1,24) = 5.4, P = 0.029). Conclusion: If confirmed in larger samples, these findings could suggest that the thyroid axis might represent a biomarker of alcohol craving and drinking. PMID:25433251

New Insights into Thyroid Hormone Action

PubMed Central

Mendoza, Arturo; Hollenberg, Anthony N.

2017-01-01

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

The Hypothalamic-Pituitary-Thyroid (HPT) Axis in Frogs and its Role in Frog Development and Reproduction

EPA Science Inventory

Metamorphosis of the amphibian tadpole is a thyroid hormone (TH)-dependent developmental process. For this reason, the tadpole is considered to be an ideal bioassay system to identify disruption of thyroid function by environmental contaminants. Here we provide an in-depth review...

The role of thyroid hormones in stress response of fish.

PubMed

Peter, M C Subhash

2011-06-01

Thyroxine (T(4)) and triiodothyronine (T(3)), the principal thyroid hormones (THs) secreted from the hypothalamic-pituitary-thyroid (HPT) axis, produce a plethora of physiologic actions in fish. The diverse actions of THs in fishes are primarily due to the sensitivity of thyroid axis to many physical, chemical and biological factors of both intrinsic and extrinsic origins. The regulation of THs homeostasis becomes more complex due to extrathyroidal deiodination pathways by which the delivery of biologically active T(3) to target cells has been controlled. As primary stress hormones and the end products of hypothalamic-pituitary-interrenal (HPI) and brain-sympathetic-chromaffin (BSC) axes, cortisol and adrenaline exert its actions on its target tissues where it promote and integrate osmotic and metabolic competence. Despite possessing specific osmoregulatory and metabolic actions at cellular and whole-body levels, THs may fine-tune these processes in accordance with the actions of hormones like cortisol and adrenaline. Evidences are presented that THs can modify the pattern and magnitude of stress response in fishes as it modifies either its own actions or the actions of stress hormones. In addition, multiple lines of evidence indicate that hypothalamic and pituitary hormones of thyroid and interrenal axes can interact with each other which in turn may regulate THs/cortisol-mediated actions. Even though it is hard to define these interactions, the magnitude of stress response in fish has been shown to be modified by the changes in the status of THs, pointing to its functional relationship with endocrine stress axes particularly with the interrenal axis. The fine-tuned mechanism that operates in fish during stressor-challenge drives the THs to play both fundamental and modulator roles in stress response by controlling osmoregulation and metabolic regulation. A major role of THs in stress response is thus evident in fish. Copyright © 2011 Elsevier Inc. All rights reserved.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

PubMed

Reindl, Martin; Feistritzer, Hans-Josef; Reinstadler, Sebastian Johannes; Mueller, Lukas; Tiller, Christina; Brenner, Christoph; Mayr, Agnes; Henninger, Benjamin; Mair, Johannes; Klug, Gert; Metzler, Bernhard

2018-04-01

Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. Patients with left ventricular remodeling ( n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.

Pathophysiology of the Effects of Alcohol Abuse on the Endocrine System

PubMed Central

Rachdaoui, Nadia; Sarkar, Dipak K.

2017-01-01

Alcohol can permeate virtually every organ and tissue in the body, resulting in tissue injury and organ dysfunction. Considerable evidence indicates that alcohol abuse results in clinical abnormalities of one of the body’s most important systems, the endocrine system. This system ensures proper communication between various organs, also interfacing with the immune and nervous systems, and is essential for maintaining a constant internal environment. The endocrine system includes the hypothalamic–pituitary–adrenal axis, the hypothalamic–pituitary–gonadal axis, the hypothalamic–pituitary–thyroid axis, the hypothalamic–pituitary–growth hormone/insulin-like growth factor-1 axis, and the hypothalamic–posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders. Studies in both humans and animal models have helped shed light on alcohol’s effects on various components of the endocrine system and their consequences. PMID:28988577

Computational modeling of the amphibian thyroid axis ...

EPA Pesticide Factsheets

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

The role of polyhalogenated aromatic hydrocarbons on thyroid hormone disruption and cognitive function: a review.

PubMed

Builee, T L; Hatherill, J R

2004-11-01

Thyroid hormones (TH) are essential to normal brain development, influencing behavior and cognitive function in both adult and children. It is suggested that conditions found in TH abnormalities such as hypothyroidism, hyperthyroidism and generalized resistance to thyroid hormone (GRTH) share symptomatic behavioral impulses found in cases of attention deficit hyperactivity disorder (ADHD) and other cognitive disorders. Disrupters of TH are various and prevalent in the environment. This paper reviews the mechanisms of TH disruption caused by the general class of polyhalogenated aromatic hydrocarbons (PHAH)'s acting as thyroid disrupters (TD). PHAHs influence the hypothalamus-pituitary-thyroid (HPT) axis, as mimicry agents affecting synthesis and secretion of TH. Exposure to PHAH induces liver microsomal enzymes UDP-glucuronosyltransferase (UGT) resulting in accelerated clearance of TH. PHAHs can compromise function of transport and receptor binding proteins such as transthyretin and aryl hydrocarbon receptors (Ahr). Glucose metabolism and catecholamine synthesis are disrupted in the brain by the presence of PHAH. Further, PHAH can alter brain growth and development by perturbing cytoskeletal formation, thereby affecting neuronal migration, elongation and branching. The complex relationships between PHAH and cognitive function are examined in regard to the disruption of T4 regulation in the hypothalamus-pituitary-thyroid axis, blood, brain, neurons, liver and pre and postnatal development.

78 FR 57859 - Draft Guidance for Industry on Endocrine Disruption Potential of Drugs: Nonclinical Evaluation...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... include the sex hormones (e.g., estrogen and androgen), the hypothalamic-pituitary-adrenal axis, the thyroid hormone, and the hormones involved in the feedback regulation of those components (e.g., gonadotropin releasing hormone and corticotropin). Changes in endocrine function can result in...

Effects of a 5-day treatment with the UV-filter octyl-methoxycinnamate (OMC) on the function of the hypothalamo-pituitary-thyroid function in rats.

PubMed

Klammer, Holger; Schlecht, Christiane; Wuttke, Wolfgang; Schmutzler, Cornelia; Gotthardt, Inka; Köhrle, Josef; Jarry, Hubertus

2007-09-05

Octyl-methoxycinnamate (OMC) is one of the most frequently used UV-filters in sunscreens to protect the skin against the noxious influence of UV radiation. Recently, OMC was suspected to act as an "endocrine active chemical" (EAC) with estrogenic actions. While EACs have been investigated thoroughly for interference with reproductive function in mammalians, surprisingly little efforts have been made to investigate an interference of EACs with the hypothalamo-pituitary-thyroid (HPT) axis despite the expression of estrogen receptors in all parts of this axis. Therefore, we conducted an in vivo study with ovariectomised rats treated for 5 days with different doses of OMC or 17beta-estradiol (E2) as a control. Determined parameters comprised serum levels of TSH, T4 and T3, hypothalamic TRH mRNA expression, protein-expression of the sodium-iodide-symporter (NIS) and the TSH receptor and the activities of thyroid peroxidase (TPO) in the thyroid and the T3-responsive hepatic type I 5'deiodinase (Dio1) in the liver. While E2 did not affect TSH-, T4- or T3-levels, OMC caused a dose-dependent decrease of serum concentrations of all of these hormones. TRH expression remained unaffected, while in the thyroid, expression of the TSH receptor but not of NIS was stimulated by OMC. TPO activity was unaltered but Dio1 activity was reduced by OMC. Thus, our results demonstrate a non-estrogenic interference of OMC within the rodent HPT axis with inadequate feedback response to impaired thyroid hormone status, indicated by decreased serum thyroid hormone and hepatic Dio1 levels.

Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae

PubMed Central

Zhang, Dan-hua; Zhou, En-xiang; Yang, Zhu-lin

2017-01-01

Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 μg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 μg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 μg/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 μg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 μg/L of BPS treatment group. Moreover, exposure to 10 μg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 μg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trβ) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption. PMID:28467477

Thyroid axis dysfunction in patients with Prader-Willi syndrome during the first 2 years of life.

PubMed

Vaiani, Elisa; Herzovich, Viviana; Chaler, Eduardo; Chertkoff, Lilien; Rivarola, Marco A; Torrado, Maria; Belgorosky, Alicia

2010-10-01

Prader-Willi syndrome (PWS) is a genetic disorder caused by the loss of expression of paternally transcribed genes in a highly imprinted region of chromosome 15q11-13. The clinical phenotype has been well characterized, mostly related to hypothalamic dysfunction. Even though central hypothyroidism has been documented in 20-30% of patients with PWS, thyroid function during the first 2 years of life has not been clearly defined. To evaluate hypothalamic-pituitary-thyroid function in infant PWS patients. Eighteen patients with PWS, aged 0.16-2 years, were included in a prospective study. PWS diagnosis was based on clinical features and molecular analysis. Serum total (T) T4, free (F) T4, T3 and thyroid-stimulating hormone (TSH) were evaluated in the patients with PWS included in the study. Serum hormone values were compared to those of a large reference population of the same age. In 13 of 18 patients with PWS (72.2%), serum TT4 and/or FT4 levels were below the 2.5th percentile of the reference population, while in only one PWS patient serum T3 was below this cut-off. The results of this study suggest that transient or definitive thyrotropin-releasing hormone (TRH)-TSH thyroid axis dysfunction may frequently be present in infant PWS patients. Paediatricians should be aware of this dysfunction in this critical period of thyroid hormone action on neurological development. © 2010 Blackwell Publishing Ltd.

SYSTEMS APPROACH TO CHARACTERIZING AND PREDICTING THYROID TOXICITY

EPA Science Inventory

A systems approach is being undertaken in which in vivo and in vitro assays are integrated to understand the mechanisms of thyroid hormone mediated pathways controlling frog metamorphosis, and more generally the regulation and control of the HPT axis.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

PubMed

Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

2017-05-01

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

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

EPA Science Inventory

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

Hormonal disturbances in visceral leishmaniasis (kala-azar).

PubMed

Verde, Frederico Araujo Lima; Verde, Francisco Agenor Araujo Lima; Neto, Augusto Saboia; Almeida, Paulo César; Verde, Emir Mendonça Lima

2011-05-01

This study presents a cross-sectional analysis of the hormonal alterations of patients with visceral leishmaniasis. The diagnosis was established by the bone marrow aspiration and polymerase chain reaction test. Primary adrenal insufficiency was observed in 45.8% of patients; low aldosterone/renin plasma ratio in 69.4%; low daily urinary aldosterone excretion in 61.1%; and low transtubular potassium gradient in 68.0%. All patients had normal plasma antidiuretic hormone (ADH) concentrations, hyponatremia, and high urinary osmolality. Plasma parathyroid hormone was low in 63%; hypomagnesemia was present in 46.4%, and increased Mg(++)(EF) in 100%. Primary thyroid insufficiency was observed in 24.6%, and secondary thyroid insufficiency in 14.1%. Normal follicle-stimulating hormone plasma levels were present in 81.4%; high luteinizing hormone and low testosterone plasma levels in 58.2% of men. There are evidences of hypothalamus-pituitary-adrenal axis abnormalities, inappropriate aldosterone and ADH secretions, and presence of hypoparathyroidism, magnesium depletion, thyroid and testicular insufficiencies.

Effects of thyroid hormone manipulation on pre-nuptial molt, luteinizing hormone and testicular growth in male white-crowned sparrows (Zonotrichia leuchophrys gambelii).

PubMed

Pérez, Jonathan H; Meddle, Simone L; Wingfield, John C; Ramenofsky, Marilyn

2018-01-01

Most seasonal species rely on the annual change in day length as the primary cue to appropriately time major spring events such as pre-nuptial molt and breeding. Thyroid hormones are thought to be involved in the regulation of both of these spring life history stages. Here we investigated the effects of chemical inhibition of thyroid hormone production using methimazole, subsequently coupled with either triiodothyronine (T3) or thyroxine (T4) replacement, on the photostimulation of pre-nuptial molt and breeding in Gambel's white-crowned sparrows (Zonotrichia leuchophrys gambelii). Suppression of thyroid hormones completely prevented pre-nuptial molt, while both T3 and T4 treatment restored normal patterns of molt in thyroid hormone-suppressed birds. Testicular recrudescence was blocked by methimazole, and restored by T4 but not T3, in contrast to previous findings demonstrating central action of T3 in the photostimulation of breeding. Methimazole and replacement treatments elevated plasma luteinizing hormone levels compared to controls. These data are partially consistent with existing theories on the role of thyroid hormones in the photostimulation of breeding, while highlighting the possibility of additional feedback pathways. Thus we suggest that regulation of the hypothalamic pituitary gonad axis that controls breeding may be more complex than previously considered. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Psychiatric Symptoms due to Thyroid Disease in a Female Adolescent

PubMed Central

Capetillo-Ventura, Nelly; Baeza, Inmaculada

2014-01-01

The hypothalamic-pituitary-thyroid axis is involved in the production of thyroid hormone which is needed to maintain the normal functioning of various organs and systems, including the central nervous system. This study reports a case of hypothyroidism in a fifteen-year-old female adolescent who was attended for psychiatric symptoms. This case reveals the importance of evaluating thyroid function in children and adolescents with neuropsychiatric symptoms. PMID:25436160

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

PubMed

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

2016-09-15

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

The Role of the Multiple Hormonal Dysregulation in the Onset of “Anemia of Aging”: Focus on Testosterone, IGF-1, and Thyroid Hormones

PubMed Central

Maggio, Marcello; De Vita, Francesca; Fisichella, Alberto; Lauretani, Fulvio; Ticinesi, Andrea; Ceresini, Graziano; Cappola, Anne; Ferrucci, Luigi; Ceda, Gian Paolo

2015-01-01

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is “unexplained.” Ageing process is also characterized by a “multiple hormonal dysregulation” with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals. PMID:26779261

The Role of the Multiple Hormonal Dysregulation in the Onset of "Anemia of Aging": Focus on Testosterone, IGF-1, and Thyroid Hormones.

PubMed

Maggio, Marcello; De Vita, Francesca; Fisichella, Alberto; Lauretani, Fulvio; Ticinesi, Andrea; Ceresini, Graziano; Cappola, Anne; Ferrucci, Luigi; Ceda, Gian Paolo

2015-01-01

Anemia is a multifactorial condition whose prevalence increases in both sexes after the fifth decade of life. It is a highly represented phenomenon in older adults and in one-third of cases is "unexplained." Ageing process is also characterized by a "multiple hormonal dysregulation" with disruption in gonadal, adrenal, and somatotropic axes. Experimental studies suggest that anabolic hormones such as testosterone, IGF-1, and thyroid hormones are able to increase erythroid mass, erythropoietin synthesis, and iron bioavailability, underlining a potential role of multiple hormonal changes in the anemia of aging. Epidemiological data more consistently support an association between lower testosterone and anemia in adult-older individuals. Low IGF-1 has been especially associated with anemia in the pediatric population and in a wide range of disorders. There is also evidence of an association between thyroid hormones and abnormalities in hematological parameters under overt thyroid and euthyroid conditions, with limited data on subclinical statuses. Although RCTs have shown beneficial effects, stronger for testosterone and the GH-IGF-1 axis and less evident for thyroid hormones, in improving different hematological parameters, there is no clear evidence for the usefulness of hormonal treatment in improving anemia in older subjects. Thus, more clinical and research efforts are needed to investigate the hormonal contribution to anemia in the older individuals.

HPT axis, CSF monoamine metabolites, suicide intent and depression severity in male suicide attempters.

PubMed

Jokinen, Jussi; Samuelsson, Mats; Nordström, Anna-Lena; Nordström, Peter

2008-11-01

A lower thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in depressed women has been associated with violent suicide attempts, suicidal intent, higher lethality and suicide risk. The cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) levels are related to suicidal behaviour. We studied the HPT axis function in twelve male suicide attempters and eight healthy volunteers submitted to lumbar puncture and to TRH test. Suicidal behaviour and depression severity were assessed. There was no association between deltamaxTSH and violent suicidality or subsequent suicide. The deltamaxTSH correlated with CSF HVA in suicide attempters. The plasma T3 showed a negative correlation with the Beck Suicide Intent Scale and the Montgomery Asberg Depression rating scale. Dopaminergic regulatory mechanisms on the thyroid hormone activity may be altered in male suicide attempters.

Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.).

PubMed

Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M

2006-12-01

The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

Application of Physiologically-Based Pharmacokinetic/Pharmacodynamic Model for Interpretation of High-throughput Screening Assay for Thyroperoxidase Inhibition

EPA Science Inventory

In vitro based assays are used to identify potential endocrine disrupting chemicals. Thyroperoxidase (TPO), an enzyme essential for thyroid hormone (TH) synthesis, is a target site for disruption of the thyroid axis for which a high-throughput screening (HTPS) assay has recently ...

Type 3 deiodinase deficiency results in functional abnormalities at multiple levels of the thyroid axis.

PubMed

Hernandez, Arturo; Martinez, M Elena; Liao, Xiao-Hui; Van Sande, Jacqueline; Refetoff, Samuel; Galton, Valerie Anne; St Germain, Donald L

2007-12-01

The type 3 deiodinase (D3) is a selenoenzyme that inactivates thyroid hormones and is highly expressed during development and in the adult central nervous system. We have recently observed that mice lacking D3 activity (D3KO mice) develop perinatal thyrotoxicosis followed in adulthood by a pattern of hormonal levels that is suggestive of central hypothyroidism. In this report we describe the results of additional studies designed to investigate the regulation of the thyroid axis in this unique animal model. Our results demonstrate that the thyroid and pituitary glands of D3KO mice do not respond appropriately to TSH and TRH stimulation, respectively. Furthermore, after induction of severe hypothyroidism by antithyroid treatment, the rise in serum TSH in D3KO mice is only 15% of that observed in wild-type mice. In addition, D3KO animals rendered severely hypothyroid fail to show the expected increase in prepro-TRH mRNA in the paraventricular nucleus of the hypothalamus. Finally, treatment with T(3) results in a serum T(3) level in D3KO mice that is much higher than that in wild-type mice. This is accompanied by significant weight loss and lethality in mutant animals. In conclusion, the absence of D3 activity results in impaired clearance of T(3) and significant defects in the mechanisms regulating the thyroid axis at all levels: hypothalamus, pituitary, and thyroid.

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.

Endocannabinoids and the Endocrine System in Health and Disease.

PubMed

Hillard, Cecilia J

2015-01-01

Some of the earliest reports of the effects of cannabis consumption on humans were related to endocrine system changes. In this review, the effects of cannabinoids and the role of the CB1 cannabinoid receptor in the regulation of the following endocrine systems are discussed: the hypothalamic-pituitary-gonadal axis, prolactin and oxytocin, thyroid hormone and growth hormone, and the hypothalamic-pituitary-adrenal axis. Preclinical and human study results are presented.

Thyroid Disruption in Zebrafish Larvae by Short-Term Exposure to Bisphenol AF

PubMed Central

Tang, Tianle; Yang, Yang; Chen, Yawen; Tang, Wenhao; Wang, Fuqiang; Diao, Xiaoping

2015-01-01

Bisphenol AF (BPAF) is extensively used as a raw material in industry, resulting in its widespread distribution in the aqueous environment. However, the effect of BPAF on the hypothalamic-pituitary-thyroidal (HPT) axis remains unknown. For elucidating the disruptive effects of BPAF on thyroid function and expression of the representative genes along the HPT axis in zebrafish (Danio rerio) embryos, whole-body total 3,3′,5-triiodothyronine (TT3), total 3,5,3′,5′-tetraiodothyronine (TT4), free 3,3′,5-triiodothyronine (FT3) and free 3,5,3′,5′-tetraiodothyronine (FT4) levels were examined following 168 h post-fertilization exposure to different BPAF concentrations (0, 5, 50 and 500 μg/L). The results showed that whole-body TT3, TT4, FT3 and FT4 contents decreased significantly with the BPAF treatment, indicating an endocrine disruption of thyroid. The expression of thyroid-stimulating hormone-β and thyroglobulin genes increased after exposing to 50 μg/L BPAF in seven-day-old larvae. The expressions of thyronine deiodinases type 1, type 2 and transthyretin mRNAs were also significantly up-regulated, which were possibly associated with a deterioration of thyroid function. However, slc5a5 gene transcription was significantly down-regulated at 50 μg/L and 500 μg/L BPAF exposure. Furthermore, trα and trβ genes were down-regulated transcriptionally after BPAF exposure. It demonstrates that BPAF exposure triggered thyroid endocrine toxicity by altering the whole-body contents of thyroid hormones and changing the transcription of the genes involved in the HPT axis in zebrafish larvae. PMID:26501309

Acute and transient activation of pituitary-thyroid axis during unforced restriction in rats: component of nonshivering thermogenesis in conscious animals?

PubMed

Langer, P; Földes, O; Macho, L; Kvetnanský, R

1983-01-01

Groups of 6-8 male Wistar Olac SPF rats weighing about 300 g were subjected to unforced restriction (UR) in small cages with a metallic bottom and a Plexiglas cover for various intervals from 2 min to 72 h. An acute activation of the pituitary-thyroid axis was found which was manifested by an increase of thyrotropin (TSH) and thyroxine (T4) levels at 2-5 min of UR. This was presumably due to the emotional effect of a rapid transfer and to the placing of the animals into restriction cages. Later, between 3 and 6 h of UR, another, and more pronounced period of activation of the pituitary-thyroid axis and of the peripheral thyroid hormone metabolism was repeatedly observed which lasted until about 36-48 h and was manifested by a highly significant increase of TSH, T4, 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine (rT3) levels. It was concluded that this phenomenon presumably may be a component of nonshivering thermogenesis resulting from a decreased muscular activity and resembling the conditions occurring under cold stress. Such a view was supported by findings of highly increased nonesterified fatty acid levels in plasma in restricted animals, by unchanged levels of TSH and thyroid hormones found in unrestricted animals kept individually in regular group cages and, finally, by a preventive effect of ambient temperature of 32 degrees C on the pituitary-thyroid activation at 6 h of UR. In some experiments, no substantial differences in hormone levels were found between the animals kept in Plexiglas or stainless wire-mesh restriction cages. Finally, a multifold increase of prolactin level in plasma was found as early as 2 min of UR, the peak being observed between 5 and 20 min and a decrease to about the initial level at about 360 min.

A BBDR-HPT Axis Model for the Pregnant Rat and Fetus: Evaluation of Iodide Deficiency

EPA Science Inventory

A biologically based dose response (BBDR) model for the hypothalamic-pituitarythyroid (HPT) axis for the pregnant rat and fetus is being developed to advance understanding of thyroid hormone disruptions and developmental neurotoxicity (DNT). The model for the pregnant rat and fet...

The −258 A/G (SNP rs12885300) polymorphism of the human type-2 deiodinase gene is associated with a shift in the pattern of secretion of thyroid hormones following a TRH-induced acute rise in TSH

PubMed Central

Peltsverger, Maya Y.; Butler, Peter W.; Alberobello, Anna Teresa; Smith, Sheila; Guevara, Yanina; Dubaz, Ornella M.; Luzon, Javier A.; Linderman, Joyce; Celi, Francesco S.

2012-01-01

Objective Type-2 deiodinase gene (DIO2) polymorphisms have been associated with changes in pituitary-thyroid axis homeostasis. The −258 A/G (SNP rs12885300) polymorphism has been associated with increased enzymatic activity, but data are conflicting. To characterize the effects of the −258 A/G polymorphism on intra-thyroidal T4 to T3 conversion and thyroid hormone secretion pattern we studied the effects of acute, TRH-mediated, TSH stimulation of the thyroid gland. Design Retrospective analysis. Methods The thyroid hormone secretion in response to 500 mcg iv TRH injection was studied in 45 healthy volunteers. Results Twenty-six subjects (16 females, 10 males, 32.8±10.4 years) were homozygous for the ancestral (−258 A/A) allele, 19 (11 females, 8 males, 31.1±10.9 years) were carrier of the (−258 G/x) variant. While no differences in the peak TSH and T3 levels were observed, carriers of the −258G/x allele showed a blunted rise in free T4 (p<0.01). The −258G/x 92Thr/Thr haplotype, compared to the other groups, had lower TSH values at 60' (p<0.03). No differences were observed between genotypes in baseline thyroid hormone levels. Conclusions The −258G/x DIO2 polymorphism variant is associated with a decreased rate of acute TSH-stimulated free T4 secretion with a normal T3 release from the thyroid consistent with a shift in the reaction equilibrium toward the product. These data indicate that the −258G DIO2 polymorphism cause changes in the pattern of hormonal secretion. These findings are a proof-of-concept that common polymorphisms in the DIO2 can subtly affect the circulating levels of thyroid hormone and might modulate the thyroid hormone homeostasis. PMID:22307573

Unraveling the different toxic effect of flufenoxuron on the thyroid endocrine system of the Mongolia racerunner (Eremias Argus) at different stages.

PubMed

Chang, Jing; Li, Wei; Guo, Baoyuan; Xu, Peng; Wang, Yinghuan; Li, Jianzhong; Wang, Huili

2017-04-01

Flufenoxuron is a widely used pesticide to inhibit the synthesis of chitin during insect development and its effect on the growth of lizards has been little addressed. The hypothalamus-pituitary-thyroid (HPT) axis plays an important role on the development of lizards. In this study, the lizards at different development stages (proliferation and resting stages) were exposed to flufenoxuron for 21 days. The plasma thyroid hormone levels, thyroid gland histopathology and expression profiles of thyroid hormone receptors (trα, trβ), deiodinases (dio1, dio2), and transthyretin (ttr) genes were measured to evaluated the toxic effect of flufenoxuron on the HPT axis at different stages. The flufenoxuron exposure showed more seriously effect on the triiodothyronine (T3) level at resting phase than that at proliferation stage. The follicle epithelium cell height in the thyroid was only significantly increased when the exposed male lizards were at proliferation stage. The alteration of HPT axis-related genes expression was gender and tissue dependent after flufenoxuron treatment. The lizards exposed to flufenoxuron showed that the trα, trβ, dio1, dio2, and ttr genes in the female liver were more sensitive at the proliferation stage than that at the resting stage. In the male brain, the expressions of trα, trβ, dio1, and dio2 gene were significant decreased at proliferation stage while significant increased at resting stage after flufenoxuron exposure. Therefore, the thyroid endocrine system of lizards could be affected by the flufenoxuron exposure and the different development stage should also be considered when study the toxic effect of contaminants on the lizards. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes of rats with mammary gland cancer induced by N-methyl nitrosourea.

PubMed

Carrera, M P; Ramírez-Expósito, M J; Valenzuela, M T; García, M J; Mayas, M D; Arias de Saavedra, J M; Sánchez, R; Pérez, M C; Martínez-Martos, J M

2005-02-01

Pyrrolidon carboxypeptidase is an omega-peptidase that hydrolyses N-terminal pyroglutamyl residues from biologically active peptides such as gonadotropin-releasing and thyrotrophin-releasing hormones. We previously described a decrease in both rat and human pyrrolidon carboxypeptidase activity with breast cancer, suggesting that gonadotropin-releasing hormone may be an important local intracrine, autocrine and/or paracrine hormonal factor in the pathogenesis of breast cancer while playing a role in the tumoral process. However, the other susceptible substrate of pyrrolidon carboxypeptidase, thyrotrophin-releasing hormone, may also be modified with breast cancer, supporting an association between breast cancer and thyroid disorders. The present work analyses soluble and membrane-bound pyrrolidon carboxypeptidase activities in the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-ovary axes in N-methyl nitrosourea-induced breast cancer in rats. Our aim was to determine the possible relationship between gonadotropin-releasing hormone and thyrotrophin-releasing hormone regulation through pyrrolidon carboxypeptidase activity. We propose that pyrrolidon carboxypeptidase activity dysregulation at various local and systemic levels may participate in the initiation, promotion and progression of breast cancer induced in rat by N-methyl nitrosourea through the increase in gonadotropin-releasing hormone. Since pyrrolidon carboxypeptidase activity also acts on thyrotrophin-releasing hormone, the dysregulation of this enzyme's activity could indirectly affect hypothalamus-pituitary-thyroid axis function, and thus potentially represent a link between the diseases of thyroid and breast cancer.

Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears

PubMed Central

TØ, Bechshøft; Sonne, C; Dietz, R; Born, EW; Muir, DCG; Letcher, RJ; Novak, MA; Henchey, E; Meyer, JS; Jenssen, BM; Villanger, GD

2012-01-01

The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p′-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis. PMID:22575327

EFFECTS OF AMMONIUM PERCHLORATE ON LIVER ENZYMES AND THE THYROID AXIS OF RATS PRETREATED WITH PCB126.

EPA Science Inventory

Ammonium perchlorate and 3,3,4,4,5-pentachlorobiphenyl (PCB126) are environmental contaminants that are known to disturb thyroid hormone (TH) homeostasis by well defined modes of action that lead to hypothyroidism in the rat. PCB126 increases phase II conjugation of T4 by induc...

Neuroendocrine Alterations in Obese Patients with Sleep Apnea Syndrome

PubMed Central

Lanfranco, Fabio; Motta, Giovanna; Minetto, Marco Alessandro; Baldi, Matteo; Balbo, Marcella; Ghigo, Ezio; Arvat, Emanuela; Maccario, Mauro

2010-01-01

Obstructive sleep apnea syndrome (OSAS) is a serious, prevalent condition that has significant morbidity and mortality when untreated. It is strongly associated with obesity and is characterized by changes in the serum levels or secretory patterns of several hormones. Obese patients with OSAS show a reduction of both spontaneous and stimulated growth hormone (GH) secretion coupled to reduced insulin-like growth factor-I (IGF-I) concentrations and impaired peripheral sensitivity to GH. Hypoxemia and chronic sleep fragmentation could affect the sleep-entrained prolactin (PRL) rhythm. A disrupted Hypothalamus-Pituitary-Adrenal (HPA) axis activity has been described in OSAS. Some derangement in Thyroid-Stimulating Hormone (TSH) secretion has been demonstrated by some authors, whereas a normal thyroid activity has been described by others. Changes of gonadal axis are common in patients with OSAS, who frequently show a hypogonadotropic hypogonadism. Altogether, hormonal abnormalities may be considered as adaptive changes which indicate how a local upper airway dysfunction induces systemic consequences. The understanding of the complex interactions between hormones and OSAS may allow a multi-disciplinary approach to obese patients with this disturbance and lead to an effective management that improves quality of life and prevents associated morbidity or death. PMID:20182553

Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

PubMed

Berga, Sarah L; Loucks, Tammy L

2006-12-01

Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that address problematic behaviors and attitudes, such as cognitive behavior therapy (CBT), have the potential to permit resumption of full ovarian function along with recovery of the adrenal, thyroidal, and other neuroendocrine aberrations. Full endocrine recovery potentially offers better individual, maternal, and child health.

EFFECTS OF LOW DOSE MIXTURES OF PCB126 AND PERCHLORATE ON THE HYPTHALAMIC-PITUITARY-THYROID (HPT) AXIS IN THE MALE RAT.

EPA Science Inventory

Perchlorate (ClO4) and 3,3',4,4',5-pentachlorobiphenyl (PCB126) are environmental contaminants known to disturb thyroid hormone homeostasis by well defined modes of action that lead to hypothyroidism in the rat. PCB126 increases phase II conjugation of T4 (T4-glucuronide) by indu...

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

PubMed

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

2005-07-01

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

Time-dependent inhibitory effects of Tris(1, 3-dichloro-2-propyl) phosphate on growth and transcription of genes involved in the GH/IGF axis, but not the HPT axis, in female zebrafish.

PubMed

Zhu, Ya; Su, Guanyong; Yang, Dandong; Zhang, Yongkang; Yu, Liqin; Li, Yufei; Giesy, John P; Letcher, Robert J; Liu, Chunsheng

2017-10-01

Growth curves were used to determine sensitive exposure windows for evaluation of developmental toxicity of chemicals to zebrafish. Dose- and time-dependent effects on body mass, body length and expression of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis were examined after exposure to environmentally relevant concentrations of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP). Based on growth curves, zebrafish grew most rapidly between 60 and 90 days post fertilization (dpf). Exposure to environmentally relevant concentrations of TDCIPP significantly decreased body mass and body length and down-regulated expression of several genes involved in the GH/IGF axis of female zebrafish, but no such effects were observed in male zebrafish. Exposure to TDCIPP did not change concentrations of thyroid hormones or expression of genes along the HPT axis in female and male zebrafish. These results suggest that growth stages of zebrafish between 60 and 90 dpf might be most appropriate for evaluation of developmental toxicity of chemicals, and down-regulation of genes involved in the GH/IGF axis, but not the HPT axis, might be responsible for the observed growth inhibition in females exposed to TDCIPP. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of amphibian and mammalian thyroperoxidase ...

EPA Pesticide Factsheets

Thyroperoxidase (TPO) catalyzes the production of thyroid hormones in the vertebrate thyroid gland by oxidizing iodide (I- ) to produce iodinated tyrosines on thyroglobulin, and further coupling of specific mono- or di-iodinated tyrosines to generate the triiodo- and tetra-iodothyronine, precursors to thyroid hormone. This enzyme is a target for thyroid disrupting chemicals. TPO-inhibition by xenobiotics is a molecular initiating event that is known to perturb the thyroid axis by preventing synthesis of thyroid hormone. Previous work on TPO-inhibition has been focused on mammalian TPO; specifically, the rat and pig. A primary objective of this experiment was to directly measure TPO activity in a non-mammalian system, in this case a thyroid gland homogenate from Xenopus laevis; as well as compare chemical inhibition from past mammalian studies to the amphibian data generated. Thyroid glands obtained from X. laevis tadpoles at NF stages 58-60, were pooled and homogenized by sonication in phosphate buffer. This homogenate was then used to test 24 chemicals for inhibition of TPO as measured by conversion of Amplex UltraRed (AUR) substrate to its fluorescent product. The test chemicals were selected based upon previous results from rat in vitro TPO assays, and X. laevis in vitro and in vivo studies for thyroid disrupting endpoints, and included both positive and negative chemicals in these assays. An initial screening of the chemicals was done at a single high con

Quantitative analysis of in-vivo responses of reproductive and thyroid endpoints in male goldfish exposed to monocrotophos pesticide.

PubMed

Zhang, Xiaona; Liu, Wei; Wang, Jun; Tian, Hua; Wang, Wei; Ru, Shaoguo

2018-09-01

Cross-regulation occurs at many points between the hypothalamic-pituitary-gonad (HPG) and hypothalamic-pituitary-thyroid (HPT) axes. Monocrotophos (MCP) pesticide could disrupt HPG and HPT axes, but its direct target within the endocrine system is still unclear. In the present study, hormone concentrations and transcriptional profiles of HPG and HPT genes were examined in male goldfish (Carassius auratus) exposed to 0, 4, 40, and 400 μg/L MCP for 2, 4, 8, and 12 d. In vivo data were analyzed by multiple linear regression and correlation analysis, quantitatively indicating that MCP-induced plasma 17β-estradiol (E 2 ) levels were most associated with alteration of cyp19a transcription, which was also a potential point indirectly modulated by the MCP-altered thyroid hormones (THs) status; disturbance of THs pathways was most related with effect of MCP on regulation of the hypothalamic-pituitary hormones involved in the thyroid system, and the increased E 2 levels might enhance the impact of MCP on HPT axis by modulating hepatic deiodinase expression. Our finding, based on these correlational data, gave a whole view of the regulations, especially on the cross-talk between sex hormone and thyroid hormone pathways upon exposure to chemicals with unknown direct target in vivo, and cautions should be exercised when developing adverse outcome pathway networks for reproductive and thyroidal endocrine disruption. Copyright © 2018 Elsevier Inc. All rights reserved.

[Genetic aspects in congenital hypothyrodism].

PubMed

Perone, Denise; Teixeira, Silvânia S; Clara, Sueli A; Santos, Daniela C dos; Nogueira, Célia R

2004-02-01

Congenital hypothyroidism (CH) affects between 1:3,000 and 1:4,000 newborns. Many genes are essential for normal development of the hypothalamus-pituitary-thyroid axis and hormone production, and are associated with CH. About 85% of primary hypothyroidism is called thyroid digenesis and evidence suggests that mutations in transcription factors (TTF2, TTF1, and PAX-8) and TSH receptor gene could be responsible for the disease. Genetic defects of hormone synthesis could be caused by mutations in the following genes: NIS (natrium-iodide symporter), pendrine, thyreoglobulin (TG), peroxidase (TPO). Recently, mutations in the THOX-2 gene have also been related to organification defects. Central hypothyroidism affects about 1:20,000 newborns and has been associated with mutations in pituitary transcriptional factors (POUIF1, PROP1, LHX3, and HESX1). The syndrome of resistance to thyroid hormone is rare, implies a hypothyroidism state for some tissues and is frequently associated with dominant autosomal mutations in the beta-receptor (TRss).

Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response to a cellular phone call after mental stress in healthy children and adolescents: A pilot study.

PubMed

Geronikolou, Styliani A; Chamakou, Aikaterini; Mantzou, Aimilia; Chrousos, George; KanakaGantenbein, Christina

2015-12-01

The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate-keeper" of the organism's response to every somatic or mental stress. This prospective study aims to investigate the HPA-axis response to a cellular phone call exposure after mental stress in healthy children and adolescents and to assess the possible predictive role of baseline endocrine markers to this response. Two groups of healthy school-age children aged 11-14 (12.5±1.5) years were included in the study, the one comprising those who are occasional users of a cellular phone (Group A) while the second those who do regularly use one (Group B). Blood samples were obtained from all participants at 8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin, and cortisol levels determination. The participants performed the Trier Social Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after the TSST-C and 10' and 20' after a 5 minute cellular phone call. Significant changes in the salivary cortisol levels were noted between 10' and 20' mins after the cellular phone call with different responses between the two groups. Baseline thyroid hormone levels seem to predict the cortisol response to mental stress mainly in group A, while HOMA had no impact on salivary cortisol response at any phase of the test, in either group. HPA axis response to cellular phone after mental stress in children and adolescents follow a different pattern in frequent users than in occasional users that seems to be influenced by the baseline thyroid hormone levels. Copyright © 2015 Elsevier B.V. All rights reserved.

THYROSIM App for Education and Research Predicts Potential Health Risks of Over-the-Counter Thyroid Supplements.

PubMed

Han, Simon X; Eisenberg, Marisa; Larsen, P Reed; DiStefano, Joseph

2016-04-01

Computer simulation tools for education and research are making increasingly effective use of the Internet and personal devices. To facilitate these activities in endocrinology and metabolism, a mechanistically based simulator of human thyroid hormone and thyrotropin (TSH) regulation dynamics was developed and further validated, and it was implemented as a facile and freely accessible web-based and personal device application: the THYROSIM app. This study elucidates and demonstrates its utility in a research context by exploring key physiological effects of over-the-counter thyroid supplements. THYROSIM has a simple and intuitive user interface for teaching and conducting simulated "what-if" experiments. User-selectable "experimental" test-input dosages (oral, intravenous pulses, intravenous infusions) are represented by animated graphical icons integrated with a cartoon of the hypothalamic-pituitary-thyroid axis. Simulations of familiar triiodothyronine (T3), thyroxine (T4), and TSH temporal dynamic responses to these exogenous stimuli are reported graphically, along with normal ranges on the same single interface page; and multiple sets of simulated experimental results are superimposable to facilitate comparative analyses. This study shows that THYROSIM accurately reproduces a wide range of published clinical study data reporting hormonal kinetic responses to large and small oral hormone challenges. Simulation examples of partial thyroidectomies and malabsorption illustrate typical usage by optionally changing thyroid gland secretion and/or gut absorption rates--expressed as percentages of normal--as well as additions of oral hormone dosing, all directly on the interface, and visualizing the kinetic responses to these challenges. Classroom and patient education usage--with public health implications--is illustrated by predictive simulated responses to nonprescription thyroid health supplements analyzed previously for T3 and T4 content. Notably, it was found that T3 in supplements has potentially more serious pathophysiological effects than does T4--concomitant with low-normal TSH levels. Some preparations contain enough T3 to generate thyrotoxic conditions, with supernormal serum T3-spiking and subnormal serum T4 and TSH levels and, in some cases, with normal or low-normal range TSH levels due to thyroidal axis negative feedback. These results suggest that appropriate regulation of these products is needed.

Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models.

PubMed

Yakar, Shoshana; Isaksson, Olle

2016-06-01

The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regulation of skeletal growth and mineral acquisition by the GH/IGF-1 axis: Lessons from mouse models

PubMed Central

Yakar, Shoshana; Isaksson, Olle

2015-01-01

The growth hormone (GH) and its downstream mediator, the insulin-like growth factor-1 (IGF-1), construct a pleotropic axis affecting growth, metabolism, and organ function. Serum levels of GH/IGF-1 rise during pubertal growth and associate with peak bone acquisition, while during aging their levels decline and associate with bone loss. The GH/IGF-1 axis was extensively studied in numerous biological systems including rodent models and cell cultures. Both hormones act in an endocrine and autocrine/paracrine fashion and understanding their distinct and overlapping contributions to skeletal acquisition is still a matter of debate. GH and IGF-1 exert their effects on osteogenic cells via binding to their cognate receptor, leading to activation of an array of genes that mediate cellular differentiation and function. Both hormones interact with other skeletal regulators, such as sex-steroids, thyroid hormone, and parathyroid hormone, to facilitate skeletal growth and metabolism. In this review we summarized several rodent models of the GH/IGF-1 axis and described key experiments that shed new light on the regulation of skeletal growth by the GH/IGF-1 axis. PMID:26432542

Associations between complex OHC mixtures and thyroid and cortisol hormone levels in East Greenland polar bears.

PubMed

Bechshøft, T Ø; Sonne, C; Dietz, R; Born, E W; Muir, D C G; Letcher, R J; Novak, M A; Henchey, E; Meyer, J S; Jenssen, B M; Villanger, G D

2012-07-01

The multivariate relationship between hair cortisol, whole blood thyroid hormones, and the complex mixtures of organohalogen contaminant (OHC) levels measured in subcutaneous adipose of 23 East Greenland polar bears (eight males and 15 females, all sampled between the years 1999 and 2001) was analyzed using projection to latent structure (PLS) regression modeling. In the resulting PLS model, most important variables with a negative influence on cortisol levels were particularly BDE-99, but also CB-180, -201, BDE-153, and CB-170/190. The most important variables with a positive influence on cortisol were CB-66/95, α-HCH, TT3, as well as heptachlor epoxide, dieldrin, BDE-47, p,p'-DDD. Although statistical modeling does not necessarily fully explain biological cause-effect relationships, relationships indicate that (1) the hypothalamic-pituitary-adrenal (HPA) axis in East Greenland polar bears is likely to be affected by OHC-contaminants and (2) the association between OHCs and cortisol may be linked with the hypothalamus-pituitary-thyroid (HPT) axis. Copyright © 2012 Elsevier Inc. All rights reserved.

Hypothalamic-pituitary-thyroid axis function in women with a menstrually related mood disorder: association with histories of sexual abuse

PubMed Central

Bunevicius, Adomas; Leserman, Jane; Girdler, Susan

2012-01-01

Introduction We previously reported a unique hypothalamic-pituitary-thyroid (HPT) axis profile in women with a menstrually related mood disorder (MRMD) who also had a history of sexual abuse (SA). In the present study, we sought to extend that work by examining the association of a SA history with HPT-axis disturbance in both MRMD and non-MRMD women. Methods Fifty-seven women met prospective criteria for MRMD (23 with a SA history) and 52 women were non-MRMD (18 with a SA history). Thyroid stimulating hormone (TSH), T4, (total and free) and T3 (total and free) were evaluated in serum together with thyroid hormone ratios reflecting T4 to T3 conversion. Results MRMD women, compared with non-MRMD women, had elevated T3/T4 ratios (ps≤0.01; reflecting increased conversion of T4 to T3) and lower free and total T4 concentrations (ps=0.01). Higher T3/T4 ratios and lower T4 concentrations predicted more severe premenstrual symptomatology in all women. A SA history, irrespective of MRMD status, was associated with elevated TSH concentrations (p=0.03). However, in MRMD women, a SA history was associated with elevated T3 concentrations (p=0.049), whereas in non-MRMD women, a SA history was associated with decreased T3 concentrations (p=0.02). Conclusions A MRMD and a SA history are associated with independent as well as interactive effects on the HPT-axis. The evidence that a MRMD moderates the influence of SA on T3 concentrations contributes to a growing body of work suggesting that a SA history may identify a distinct subgroup of women with MRMD. PMID:23001392

Effect of functionally significant deiodinase single nucleotide polymorphisms on drinking behavior in alcohol dependence: an exploratory investigation

PubMed Central

Lee, MR; Schwandt, ML; Bollinger, JW; Dias, AA; Oot, EN; Goldman, D; Hodgkinson, CA; Leggio, L

2016-01-01

Background Abnormalities of the hypothalamic-pituitary-thyroid (HPT) axis have been reported in alcoholism, however, there is no definitive agreement on the specific thyroid abnormalities and their underlying mechanisms in alcohol dependence (AD). The biological activity of thyroid hormones or the availability of T3 is regulated by the three deiodinase enzymes D1, D2 and D3. In the context of alcohol use, functionally significant single nucleotide polymorphisms (SNP’s) of these deiodinase genes may play a role in HPT dysfunction. Methods The present study explored the effect of three functionally significant SNP’s (D1: rs2235544, D2: rs225014 and rs12885300) of deiodinase genes on drinking behavior and thyroid stimulating hormone (TSH) levels in alcohol dependent (N=521) and control subjects (N=228). Results Rs225014 was associated with significant differences in the amount of naturalistic alcohol drinking assessed by the Timeline Follow-Back (TLFB). Alcohol-dependent subjects had significantly higher thyroid stimulating hormone levels compared to controls; however, there was no effect of genotype on TSH levels for either group. Conclusions These findings extend previous studies on thyroid dysfunction in alcoholism and provide novel, albeit preliminary, information by linking functionally significant genetic polymorphisms of the deiodinase enzymes with alcohol drinking behavior. PMID:26207529

Use of TSHβ:EGFP transgenic zebrafish as a rapid in vivo model for assessing thyroid-disrupting chemicals

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

Ji, Cheng; Graduate University of Chinese Academy of Sciences, Beijing; Jin, Xia

Accumulating evidence indicates that a wide range of chemicals have the ability to interfere with the hypothalamic–pituitary–thyroid (HPT) axis. Novel endpoints should be evaluated in addition to existing methods in order to effectively assess the effects of these chemicals on the HPT axis. Thyroid-stimulating hormone subunit β (TSHβ) plays central regulatory roles in the HPT system. We identified the regulatory region that determines the expression level of zebrafish TSHβ in the anterior pituitary. In the transgenic zebrafish with EGFP driven by the TSHβ promoter, the similar responsive patterns between the expression levels of TSHβ:EGFP and endogenous TSHβ mRNA in themore » pituitary are observed following treatments with goitrogen chemicals and exogenous thyroid hormones (THs). These results suggest that the TSHβ:EGFP transgenic reporter zebrafish may be a useful alternative in vivo model for the assessment of chemicals interfering with the HPT system. Highlights: ► The promoter of zebrafish TSHβ gene has been identified. ► The stable TSHβ:EGFP transgenic zebrafish reporter germline has been generated. ► The EGFP in the transgenic fish recapitulated the pattern of pituitary TSHβ mRNA. ► The transgenic zebrafish may be an in vivo model for EDC assessment.« less

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2013-09-30

establishment of homeostasis. While the HPA axis and physiological processes driven by the GCs are essential for an individual’s ability to respond and...relying upon methods which include capture-release health assessments. Stress and reproductive hormones (cortisol, aldosterone , thyroid...in the Ashepoo, Combahee and Edisto (ACE) Basin, also in South Carolina. Laboratory Analyses Hormone concentrations (cortisol, aldosterone

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormones Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2014-09-30

While the HPA axis and physiological processes driven by the GCs are essential for an individual’s ability to respond and adapt to stress, prolonged...relying upon methods which include capture-release health assessments. Stress and reproductive hormones (cortisol, aldosterone , thyroid, testosterone...the Ashepoo, Combahee and Edisto (ACE) Basin, also in South Carolina. Laboratory Analyses Hormone concentrations (cortisol, aldosterone

Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital.

PubMed

Schraplau, Anne; Schewe, Bettina; Neuschäfer-Rube, Frank; Ringel, Sebastian; Neuber, Corinna; Kleuser, Burkhard; Püschel, Gerhard P

2015-02-03

Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. Copyright © 2014. Published by Elsevier Ireland Ltd.

The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible interactions in the control of body temperature.

PubMed

Mazzoccoli, G; Giuliani, A; Carughi, S; De Cata, A; Puzzolante, F; La Viola, M; Urbano, N; Perfetto, F; Tarquini, R

2004-10-01

Melatonin plays a role in the regulation of biological rhythms, body temperature presents circadian variations with lower levels during nighttime, when melatonin levels are very high, and thyroid hormones influence shiver independent thermogenesis. We have investigated on possible interactions between the hypothalamic-pituitary-thyroid axis and melatonin in the control of body temperature in humans. Peripheral blood samples for thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free-thyroxine (FT4), melatonin levels determination and body temperature measurements were obtained every four hours for 24-hours starting at 0600 h in a controlled temperature and light-dark environment from ten healthy males, aged 38-65 (mean age +/-s.e. 57.4+/-3.03, mean body mass index +/-s.e. 25.5+/-0.75). We calculated fractional variation and correlation on single time point hormone serum levels and tested whether the time-qualified data series showed consistent pattern of circadian variation. A statistically significant difference was evidenced for the fractional variation of daytime TSH serum levels (0600 h-1000 h vs. 1000 h-1400 h, p=0.01, 1000 h-1400 h vs. 1400 h-1800 h, p=0.0001, 1400 h-1800 h vs. 1800 h-2200 h, p=0.001) and for the fractional variation of FT4 serum levels at 1800 h-2200 h vs. 2200 h-0200 h (p=0.02). FT4 serum levels correlated positively with TRH serum levels at 1000 h (r=0.67, P=0.03) and at 1400 h (r=0.63, p=0.04), negatively with TSH serum levels at 2200 h (r=-0.67, p=0.03), negatively with melatonin serum levels at 2200 h (r=-0.64, p=0.04) and at 0200 h (r=-0.73, p=0.01). TRH serum levels correlated positively with TSH serum levels at 0200 h (r=0.65, p=0.04) and at 0600 h (r=0.64, p=0.04). Body temperature correlated positively with FT4 serum levels at 1000 h (r=0.63, p=0.04) and negatively with melatonin serum levels at 0200 h (r=-0.64, p=0.04). A clear circadian rhythm was validated for body temperature (with acrophase in the morning) and melatonin, TRH and TSH secretion (with acrophase at night), while FT4 serum level changes presented ultradian periodicity (with acrophase in the morning). Changes of TSH serum levels are smaller and those of FT4 are greater at night, when melatonin levels are higher, so that the response of anterior pituitary to hypothalamic TRH and of thyroid to hypophyseal TSH may be influenced by the pineal hormone that may modulate the hypothalamic-pituitary-thyroid axis function and influence the circadian rhythm of body temperature.

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2011-09-30

support the existence of these same stress response pathways in marine mammals. While the HPA axis and physiological processes driven by the GCs are...cortisol, aldosterone , thyroid and reproductive hormones) have been routinely measured in blood as part of the health assessment which also includes a

The effect of dermal benzophenone-2 administration on immune system activity, hypothalamic-pituitary-thyroid axis activity and hematological parameters in male Wistar rats.

PubMed

Broniowska, Żaneta; Ślusarczyk, Joanna; Starek-Świechowicz, Beata; Trojan, Ewa; Pomierny, Bartosz; Krzyżanowska, Weronika; Basta-Kaim, Agnieszka; Budziszewska, Bogusława

2018-04-13

Benzophenones used as UV filters, in addition to the effects on the skin, can be absorbed into the blood and affect the function of certain organs. So far, their effects on the sex hormone receptors and gonadal function have been studied, but not much is known about their potential action on other systems. The aim of the present study was to determine the effect of benzophenone-2 (BP-2) on immune system activity, hypothalamic-pituitary-thyroid (HPT) axis activity and hematological parameters. BP-2 was administered dermally, twice daily at a dose of 100 mg/kg for 4-weeks to male Wistar rats. Immunological and hematological parameters and HPT axis activity were assayed 24 h after the last administration. It was found that BP-2 did not change relative weights of the thymus and spleen and did not exert toxic effect on tymocytes and splenocytes. However, this compound increased proliferative activity of splenocytes, enhanced metabolic activity of splenocytes and thymocytes and nitric oxide production of these cells. In animals exposed to BP-2, the HPT axis activity was increased, as evidenced by reduction in the thyroid stimulating hormone (TRH) level and increase in free fraction of triiodothyronine (fT3) and thyroxin (fT4) in blood. BP-2 had no effect on leukocyte, erythrocyte and platelet counts or on morphology and hemoglobin content in erythrocytes. The conducted research showed that dermal, sub-chronic BP-2 administration evoked hyperthyroidism, increased activity or function of the immune cells but did not affect hematological parameters. We suggest that topical administration of BP-2 leading to a prolonged elevated BP-2 level in blood causes hyperthyroidism, which in turn may be responsible for the increased immune cell activity or function. However, only future research can explain the mechanism and functional importance of the changes in thyroid hormones and immunological parameters observed after exposure to BP-2. Copyright © 2018 Elsevier B.V. All rights reserved.

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2012-09-30

and free- ranging individuals support the existence of these same stress response pathways in marine mammals. While the HPA axis and physiological ... aldosterone , thyroid and reproductive hormones) have been routinely measured in blood as part of the health assessment which also includes a complete...was developed during the workshop held in late-August. For all stress-related hormones (cortisol, aldosterone , T3, T4, and Free T4), correlational

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2012-09-30

support the existence of these same stress response pathways in marine mammals. While the HPA axis and physiological processes driven by the GCs are...characterization of stress and stressors, provides unique opportunities to address questions related to stress. Serum hormones (cortisol, aldosterone , thyroid...during the workshop held in late-August. For all stress-related hormones (cortisol, aldosterone , T3, T4, and Free T4), correlational tests and

The skeletal consequences of thyrotoxicosis.

PubMed

Nicholls, Jonathan J; Brassill, Mary Jane; Williams, Graham R; Bassett, J H Duncan

2012-06-01

Euthyroid status is essential for normal skeletal development and the maintenance of adult bone structure and strength. Established thyrotoxicosis has long been recognised as a cause of high bone turnover osteoporosis and fracture but more recent studies have suggested that subclinical hyperthyroidism and long-term suppressive doses of thyroxine (T4) may also result in decreased bone mineral density (BMD) and an increased risk of fragility fracture, particularly in postmenopausal women. Furthermore, large population studies of euthyroid individuals have demonstrated that a hypothalamic-pituitary-thyroid axis set point at the upper end of the normal reference range is associated with reduced BMD and increased fracture susceptibility. Despite these findings, the cellular and molecular mechanisms of thyroid hormone action in bone remain controversial and incompletely understood. In this review, we discuss the role of thyroid hormones in bone and the skeletal consequences of hyperthyroidism.

Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles

PubMed Central

Marshall, Pamela A; Jurutka, Peter W; Wagner, Carl E; van der Vaart, Arjan; Kaneko, Ichiro; Chavez, Pedro I; Ma, Ning; Bhogal, Jaskaran S; Shahani, Pritika; Swierski, Johnathon C; MacNeill, Mairi

2015-01-01

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1). PMID:26038698

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

PubMed

Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

2015-09-01

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.

Differential response of TRHergic neurons of the hypothalamic paraventricular nucleus (PVN) in female animals submitted to food-restriction or dehydration-induced anorexia and cold exposure.

PubMed

Jaimes-Hoy, Lorraine; Joseph-Bravo, Patricia; de Gortari, Patricia

2008-02-01

TRH neurons of the hypothalamic paraventricular nucleus (PVN), regulate pituitary-thyroid axis (HPT). Fasting activates expression of orexigenic peptides from the arcuate nucleus, increases corticosterone while reduces leptin, and pro-TRH mRNA levels despite low serum thyroid hormone concentration (tertiary hypothyroidism). TRH synthesis is positively regulated by anorexigenic peptides whose expression is reduced in fasting. The model of dehydration-induced anorexia (DIA) leads to decreased voluntary food intake but peptide expression in the arcuate is similar to forced-food restriction (FFR), where animals remain hungered. We compared the response of HPT axis of female Wistar rats submitted to DIA (2.5% saline solution, food ad libitum, 7 days) with FFR (provided with the amount of food ingested by DIA) and naïve (N) group fed ad libitum, as well as their response to acute cold exposure. Pro-TRH and pro-CRH mRNA levels in the PVN were measured by RT-PCR, TRH content, serum concentration of TSH and thyroid hormones by radioimmunoassay. DIA rats reduced 80% their food consumption compared to N, decreased PVN pro-CRH expression, serum estradiol and leptin levels, increased corticosterone similar to FFR. HPT axis of DIA animals failed to adapt: FFR presented tertiary hypothyroidism and DIA, primary. Response to cold stimulation leading to increased pro-TRH mRNA levels and TRH release was preserved under reduced energy availability in FFR rats but not in DIA, although the dynamics of hormonal release differed: TSH release augmented only in naïve; thyroxine in all but highest in DIA, and triiodothyronine in FFR and DIA suggesting a differential regulation of deiodinases.

Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

PubMed

Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

2016-12-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Anxiety- and Depression-like Behaviors and Hyperactivity in a Type 3 Deiodinase-Deficient Mouse Showing Brain Thyrotoxicosis and Peripheral Hypothyroidism

PubMed Central

Stohn, J. Patrizia; Martinez, M. Elena; Hernandez, Arturo

2016-01-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 −/− mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 −/− mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 −/− mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. PMID:27580013

Action of specific thyroid hormone receptor α(1) and β(1) antagonists in the central and peripheral regulation of thyroid hormone metabolism in the rat.

PubMed

van Beeren, Hermina C; Kwakkel, Joan; Ackermans, Mariëtte T; Wiersinga, Wilmar M; Fliers, Eric; Boelen, Anita

2012-12-01

The iodine-containing drug amiodarone (Amio) and its noniodine containing analogue dronedarone (Dron) are potent antiarrhythmic drugs. Previous in vivo and in vitro studies have shown that the major metabolite of Amio, desethylamiodarone, acts as a thyroid hormone receptor (TR) α(1) and β(1) antagonist, whereas the major metabolite of Dron debutyldronedarone acts as a selective TRα(1) antagonist. In the present study, Amio and Dron were used as tools to discriminate between TRα(1) or TRβ(1) regulated genes in central and peripheral thyroid hormone metabolism. Three groups of male rats received either Amio, Dron, or vehicle by daily intragastric administration for 2 weeks. We assessed the effects of treatment on triiodothyronine (T(3)) and thyroxine (T(4)) plasma and tissue concentrations, deiodinase type 1, 2, and 3 mRNA expressions and activities, and thyroid hormone transporters monocarboxylate transporter 8 (MCT8), monocarboxylate transporter 10 (MCT10), and organic anion transporter 1C1 (OATP1C1). Amio treatment decreased serum T(3), while serum T(4) and thyrotropin (TSH) increased compared to Dron-treated and control rats. At the central level of the hypothalamus-pituitary-thyroid axis, Amio treatment decreased hypothalamic thyrotropin releasing hormone (TRH) expression, while increasing pituitary TSHβ and MCT10 mRNA expression. Amio decreased the pituitary D2 activity. By contrast, Dron treatment resulted in decreased hypothalamic TRH mRNA expression only. Upon Amio treatment, liver T(3) concentration decreased substantially compared to Dron and control rats (50%, p<0.01), but liver T(4) concentration was unaffected. In addition, liver D1, mRNA, and activity decreased, while the D3 activity and mRNA increased. Liver MCT8, MCT10, and OATP1C1 mRNA expression were similar between groups. Our results suggest an important role for TRα1 in the regulation of hypothalamic TRH mRNA expression, whereas TRβ plays a dominant role in pituitary and liver thyroid hormone metabolism.

[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.

Inherited tertiary hypothyroidism in Sprague-Dawley rats.

PubMed

Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T

2007-05-07

Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.

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

PubMed

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

2018-05-17

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

Thyroid endocrine system disruption by pentachlorophenol: an in vitro and in vivo assay.

PubMed

Guo, Yongyong; Zhou, Bingsheng

2013-10-15

The present study aimed to evaluate the disruption caused to the thyroid endocrine system by pentachlorophenol (PCP) using in vitro and in vivo assays. In the in vitro assay, rat pituitary GH3 cells were exposed to 0, 0.1, 0.3, and 1.0 μM PCP. PCP exposure significantly downregulated basal and triiodothyronine (T3)-induced Dio 1 transcription, indicating the antagonistic activity of PCP in vitro. In the in vivo assay, zebrafish embryos were exposed to 0, 1, 3, and 10 μg/L of PCP until 14 days post-fertilization. PCP exposure resulted in decreased thyroxine (T4) levels, but elevated contents of whole-body T3. PCP exposure significantly upregulated the mRNA expression of genes along hypothalamic-pituitary-thyroid (HPT) axis, including those encoding thyroid-stimulating hormone, sodium/iodide symporter, thyroglobulin, Dio 1 and Dio 2, alpha and beta thyroid hormone receptor, and uridinediphosphate-glucuronosyl-transferase. PCP exposure did not influence the transcription of the transthyretin (TTR) gene. The results indicate that PCP potentially disrupts the thyroid endocrine system both in vitro and in vivo. Copyright © 2013 Elsevier B.V. All rights reserved.

[Hormonal axes in obesity: cause or effect?].

PubMed

Lordelo, Roberta A; Mancini, Marcio C; Cercato, Cíntia; Halpern, Alfredo

2007-02-01

Several endocrine changes have been described in the obesity state. The corticotropic axis is hyperresponsive and there is enhancement of hormonal clearance, but cortisol levels are within the normal range. It is important to characterize a pseudo-Cushing in obesity. Leptin seems to be a permissive hormone for the beginning of puberty. In adults, gonadotropines are normal, and hyperandrogenism and hyperestrogenism are found. In women, insulin resistance has a central role in polycystic ovarian syndrome (POS), which is associated to ovarian hyperandrogenemia. In obese subjects, growth hormone (GH) is generally low and IGF1 is normal. Thyroid function is commonly normal in obese subjects.

Fenugreek, A Potent Hypoglycaemic Herb Can Cause Central Hypothyroidism Via Leptin - A Threat To Diabetes Phytotherapy.

PubMed

Majumdar, Jayjeet; Chakraborty, Pratip; Mitra, Analava; Sarkar, Nirmal Kumar; Sarkar, Supriti

2017-07-01

Fenugreek ( Trigonella foenum graecum) , a medicinal herb with potent antihyperglycaemic and hypoglycaemic effects, is used to treat diabetes. This study is aimed to explore the interaction of fenugreek seed extract (FSE) and HPT (hypothalamic-pituitary-thyroid) axis in context of leptin secretion which have important role in normal and type-1 diabetic subjects. FSE (confirmed to contain trigonelline, diosgenin, 4 hydroxyisoleucine) was gavaged (0.25 gm/kg body weight/day) to normal and alloxan-induced type-1 diabetic rats for 4 weeks. Expression of hypothalamic prepro-TRH (Thyrotropin releasing hormone) mRNA, serum levels of TRH, TSH (Thyroid stimulating hormone), fT 3 , fT 4 , insulin, leptin, glucose; thyroperoxidase activity and growth of thyroid gland, food intake, adiposity index were also studied FSE significantly down regulated prepro-TRH mRNA expression; decreased serum TRH, TSH, fT 3 , fT 4 levels, and regressed thyroid gland in FSE-fed normal and diabetic rats than those observed in normal diet-fed control and diabetic rats. FSE decreased (p<0.005-0.001) adiposity index and leptin secretion, increased food intake and body weight in all FSE-fed rats. FSE improved insulin secretion, decreased glucose level but impaired HPT axis in diabetic rats, indicating insulin-independent central hypothyroidism. Results suggested that the dominant signal to hypothalamus suppressing HPT axis is the fall in leptin level which i resulted from decreased adiposity index following FSE feeding. Fenugreek simultaneously having hypoglycaemic and hypothyroidal actions raises questions whether it can be safely used to treat diabetes and/or hyperthyroidism as was suggested by many workers. © Georg Thieme Verlag KG Stuttgart · New York.

The different requirement of L-T4 therapy in congenital athyreosis compared with adult-acquired hypothyroidism suggests a persisting thyroid hormone resistance at the hypothalamic-pituitary level.

PubMed

Bagattini, Brunella; Cosmo, Caterina Di; Montanelli, Lucia; Piaggi, Paolo; Ciampi, Mariella; Agretti, Patrizia; Marco, Giuseppina De; Vitti, Paolo; Tonacchera, Massimo

2014-11-01

Levothyroxine (l-T4) is commonly employed to correct hormone deficiency in children with congenital hypothyroidism (CH) and in adult patients with iatrogenic hypothyroidism. To compare the daily weight-based dosage of the replacement therapy with l-T4 in athyreotic adult patients affected by CH and adult patients with thyroid nodular or cancer diseases treated by total thyroidectomy. A total of 36 adult patients (27 females and nine males) aged 18-29 years were studied; 13 patients (age: 21.5±2.1, group CH) had athyreotic CH treated with l-T4 since the first days of life. The remaining 23 patients (age: 24±2.7, group AH) had hypothyroidism after total thyroidectomy (14 patients previously affected by nodular disease and nine by thyroid carcinoma with clinical and biochemical remission). Patient weight, serum free thyroid hormones, TSH, thyroglobulin (Tg), anti-Tg, and anti-thyroperoxidase antibodies were measured. Required l-T4 dosage was evaluated. At the time of the observations, all patients presented free thyroid hormones within the normal range and TSH between 0.8 and 2 μIU/ml. Patients had undetectable Tg and anti-thyroid antibodies. The daily weight-based dosage of the replacement therapy with l-T4 to reach euthyroidism in patients of group CH was significantly higher than that in those of group AH (2.16±0.36 vs 1.73±0.24 μg/kg, P<0.005). Patients of group CH treated with l-T4 had significantly higher serum TSH levels than patients of group AH (P=0.05) as well as higher FT4 concentrations. To correct hypothyroidism, patients of group CH required a daily l-T4 dose/kg higher than group AH patients, despite higher levels of TSH. The different requirement of replacement therapy between adult patients with congenital and those with surgical athyroidism could be explained by a lack of thyroid hormones since fetal life in CH, which could determine a different set point of the hypothalamus-pituitary-thyroid axis. © 2014 European Society of Endocrinology.

Thyroid function and obesity.

PubMed

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

2012-10-01

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

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

Low submetamorphic doses of dexamethasone and thyroxine induce complete metamorphosis in the axolotl (Ambystoma mexicanum) when injected together.

PubMed

Kühn, Eduard R; De Groef, Bert; Grommen, Sylvia V H; Van der Geyten, Serge; Darras, Veerle M

2004-06-01

Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well described for all vertebrates and can be tracked down up to the level of gene expression. Both thyroid hormones and corticosteroids may induce morphological changes leading to metamorphosis climax in the neotenic Mexican axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis was induced with an injection of 25 microg T(4) on three alternate days as judged by a decrease in body weight and tail height together with complete gill resorption. This injection also resulted in elevated plasma concentrations of T(3) and corticosterone. Previous results have indicated that the same dose of dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127 (2002) 157). In a second series of experiments low doses of T(4) (0.5 microg) or DEX (5 microg) were ineffective to induce morphological changes. However, when these submetamorphic doses were injected together, morphological changes were observed within one week leading to complete metamorphosis. It is concluded that thyroid hormones combined with corticosteroids are essential for metamorphosis in the axolotl and that only high doses of either thyroid hormone or corticosteroid can induce morphological changes when injected separately.

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

PubMed

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

2004-02-01

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

Relationship between blood cadmium, lead, and serum thyroid measures in US adults - the National Health and Nutrition Examination Survey (NHANES) 2007-2010.

PubMed

Luo, Juhua; Hendryx, Michael

2014-04-01

Experimental studies have shown that both cadmium (Cd) and lead have potent endocrine disrupting activity. However, studies on whether these heavy metals disrupt thyroid system in humans, especially in general populations with low levels of exposure, are sparse. The study analyzed 6,231 participants aged 20 and older with measurements from 2007-2010 of the National Health and Nutrition Examination Survey (NHANES) to investigate whether whole blood Cd and lead level are associated with serum thyroid hormones measures. Our study suggests that thyroid function may be disrupted by both Cd and lead exposures in the general population and the specific roles of Cd and lead exposure on thyroid axis may differ by sex. However, the mechanisms by which these heavy metals may disrupt thyroid system function in general population needs to be further investigated.

Alteration of thyroid hormone concentrations in juvenile Chinook salmon (Oncorhynchus tshawytscha) exposed to polybrominated diphenyl ethers, BDE-47 and BDE-99.

PubMed

Arkoosh, Mary R; Van Gaest, Ahna L; Strickland, Stacy A; Hutchinson, Greg P; Krupkin, Alex B; Dietrich, Joseph P

2017-03-01

Polybrominated diphenyl ethers (PBDEs) have been used as flame-retardants in consumer products and are currently detected in salmon globally. The two most predominant PBDE congeners found in salmon are BDE-47 (2,2',4,4'-tetrabromodiphenyl ether) and BDE-99 (2,2',4,4',5-pentabromodiphenyl ether). In the present study, groups of juvenile Pacific Chinook salmon were fed five environmentally relevant concentrations of either BDE-47 (0.3-552 ng total PBDEs/g food), BDE-99 (0.3-580 ng total PBDEs/g food), or nearly equal mixtures of both congeners (0.7-690 ng total PBDEs/g food) for 39-40 days. The concentrations of circulating total thyroid hormones, thyroxine (T 4 ) and 3,5,3'-triiodothyronine (T 3 ), were measured using a hormone-specific time-resolved fluoroimmunoassay to determine if PBDE exposure disrupts the hypothalamic-pituitary-thyroid endocrine axis. The concentrations of both circulating T 4 and T 3 were altered in juvenile salmon by dietary uptake of BDE-99. Exposure to BDE-47 did not alter either T 3 or T 4 circulating hormone concentrations. However, exposure to a mixture of BDE-47 and BDE-99 reduced T 3 in fish with lower concentrations of total whole body PBDEs than with either congener alone at equivalent PBDE whole body concentrations. Accordingly, the disruption of PBDEs on circulating thyroid hormone concentrations has the potential to impact a number of critical functions in juvenile salmon including growth, parr-smolt transformation, and immunological processes. Published by Elsevier Ltd.

Testosterone and estradiol treatments differently affect pituitary-thyroid axis and liver deiodinase 1 activity in orchidectomized middle-aged rats.

PubMed

Šošić-Jurjević, B; Filipović, B; Renko, K; Miler, M; Trifunović, S; Ajdžanovič, V; Kӧhrle, J; Milošević, V

2015-12-01

We previously reported that orchidectomy (Orx) of middle-aged rats (15-16-month-old; MA) slightly affected pituitary-thyroid axis, but decreased liver deiodinase (Dio) type 1 and pituitary Dio2 enzyme activities. At present, we examined the effects of subsequent testosterone-propionate treatment (5mg/kg; Orx+T), and compared the effects of testosterone with the effects of estradiol-dipropionate (0.06mg/kg; Orx+E) treatment. Hormones were subcutaneously administered, daily, for three weeks, while Orx and sham-operated (SO) controls received only the vehicle. The applied dose of T did not alter serum TSH, T4 and T3 concentrations in Orx- MA, though it increased TSH when administrated to Orx young adults (2.5-month-old; Orx-YA). However, pituitaries of Orx-MA+T rats had higher relative intensity of immunofluorescence (RIF) for TSHβ; in their thyroids we found increased volume and height of follicular epithelium, decreased volume of the colloid and higher RIF for T4-bound to thyroglobulin (Tg-T4). Liver Dio1 activity was increased. E-treatment did not affect serum hormone levels, pituitary RIF for TSHβ, or liver Dio1 activity in Orx-MA rats. Thyroids had decreased relative volume and height of follicular epithelium, increased relative volume of the colloid, decreased volume of sodium-iodide symporter-immunopositive epithelium and lower RIF for Tg-T4. Detected changes were statistically significant. In conclusion, androgenization enhanced pituitary TSHβ RIF, thyroid activation and liver Dio1 enzyme activity in Orx-MA, without elevating serum TSH as in Orx-YA rats. Estrogenization induced pituitary enlargement with no effect on pituitary TSHβ RIF, serum TSH or liver Dio1 activity. E also induced alterations in thyroid histology that indicate mild suppression of its functioning, and contributed to thyroid blood vessel enlargement in Orx-MA rats. Copyright © 2015 Elsevier Inc. All rights reserved.

Conservation of the photoperiodic neuroendocrine axis among vertebrates: evidence from the teleost fish, Gasterosteus aculeatus

PubMed Central

O’Brien, Conor S.; Bourdo, Ryan; Bradshaw, William E.; Holzapfel, Christina M.; Cresko, William. A.

2012-01-01

Photoperiod, or length of day, has a predictable annual cycle, making it an important cue for the timing of seasonal behavior and development in many organisms. Photoperiod is widely used among temperate and polar animals to regulate the timing of sexual maturation. The proper sensing and interpretation of photoperiod can be tightly tied to an organism’s overall fitness. In photoperiodic mammals and birds the thyroid hormone pathway initiates sexual maturation, but the degree to which this pathway is conserved across other vertebrates is not well known. We use the threespine stickleback Gasterosteus aculeatus, as a representative teleost to quantify the photoperiodic response of key genes in the thyroid hormone pathway under controlled laboratory conditions. We find that the photoperiodic responses of the hormones are largely consistent amongst multiple populations, although differences suggest physiological adaptation to various climates. We conclude that the thyroid hormone pathway initiates sexual maturation in response to photoperiod in G. aculeatus, and our results show that more components of this pathway are conserved among mammals, birds, and teleost fish than was previously known. However, additional endocrinology, cell biology and molecular research will be required to define precisely which aspects of the pathway are conserved across vertebrates. PMID:22504272

Conservation of the photoperiodic neuroendocrine axis among vertebrates: evidence from the teleost fish, Gasterosteus aculeatus.

PubMed

O'Brien, Conor S; Bourdo, Ryan; Bradshaw, William E; Holzapfel, Christina M; Cresko, William A

2012-08-01

Photoperiod, or length of day, has a predictable annual cycle, making it an important cue for the timing of seasonal behavior and development in many organisms. Photoperiod is widely used among temperate and polar animals to regulate the timing of sexual maturation. The proper sensing and interpretation of photoperiod can be tightly tied to an organism's overall fitness. In photoperiodic mammals and birds the thyroid hormone pathway initiates sexual maturation, but the degree to which this pathway is conserved across other vertebrates is not well known. We use the threespine stickleback Gasterosteus aculeatus, as a representative teleost to quantify the photoperiodic response of key genes in the thyroid hormone pathway under controlled laboratory conditions. We find that the photoperiodic responses of the hormones are largely consistent amongst multiple populations, although differences suggest physiological adaptation to various climates. We conclude that the thyroid hormone pathway initiates sexual maturation in response to photoperiod in G. aculeatus, and our results show that more components of this pathway are conserved among mammals, birds, and teleost fish than was previously known. However, additional endocrinology, cell biology and molecular research will be required to define precisely which aspects of the pathway are conserved across vertebrates. Copyright © 2012 Elsevier Inc. All rights reserved.

Importance of Delphian Lymph Node Evaluation in Autoimmune Thyroiditis: Fact or Fiction?

PubMed Central

Ormeci, Tugrul; Çolakoğulları, Mukaddes; Orhan, İsrafil

2016-01-01

Summary Background Our main objective was to evaluate the association between autoimmune thyroiditis and the Delphian lymph node during different stages of thyroiditis. Material/Methods The relationships between the ultrasonography (US) results of thyroiditis and characteristics of the Delphian lymph node in different stages of AT were evaluated. Thyroid hormone and antibody levels were assessed. A total of 126 patients were divided into four groups according to the thyroid US findings: Group 1: control cases; Group 2: indeterminate cases; Group 3: established thyroiditis cases; Group 4: advanced-late stage thyroiditis cases. Indeterminate cases attended a 1-year follow-up, and the cases with a sonographic finding matching thyroiditis formed Group 2. Results The rate of Delphian lymph node presence in Group 4 was significantly higher than in Groups 1 and 2 (p<0.01). In addition, its presence was significantly higher in Group 3 than in Group 1 (p<0.05). Although there was a difference in Delphian lymph node presence between Groups 2 and 3, it was not significant (p=0.052), nor was there a significant difference between Groups 1 and 2 (p>0.05). Both the long and short axis measurements were significantly higher in Groups 2, 3, and 4 compared to those in the control group. However, the same increase was not observed in the long/short axis ratio. Conclusions Both the presence and dimensions of the Delphian lymph node were highly correlated with the progress of autoimmune thyroiditis. Evaluating the Delphian lymph nodes might prevent missing a diagnosis of autoimmune thyroiditis. PMID:26985243

The effect of lead intoxication on endocrine functions.

PubMed

Doumouchtsis, K K; Doumouchtsis, S K; Doumouchtsis, E K; Perrea, D N

2009-02-01

Studies on the effects of lead on the endocrine system are mainly based on occupationally lead-exposed workers and experimental animal models. Although evidence is conflicting, it has been reported that accumulation of lead affects the majority of the endocrine glands. In particular, it appears to have an effect on the hypothalamic-pituitary axis causing blunted TSH, GH, and FSH/LH responses to TRH, GHRH, and GnRH stimulation, respectively. Suppressed GH release has been reported, probably caused by reduced synthesis of GHRH, inhibition of GHRH release or reduced somatotrope responsiveness. Higher levels of PRL in lead intoxication have been reported. In short-term lead-exposed individuals, high LH and FSH levels are usually associated to normal testosterone concentrations, whereas in long-term exposed individuals' low testosterone levels do not induce high LH and FSH concentrations. These findings suggest that lead initially causes some subclinical testicular damage, followed by hypothalamic or pituitary disturbance when longer periods of exposure take place. Similarly, lead accumulates in granulosa cells of the ovary, causing delays in growth and pubertal development and reduced fertility in females. In the parenchyma of adrenals histological and cytological changes are demonstrated, causing changes in plasma basal and stress-mediated corticosterone concentrations and reduced cytosolic and nuclear glucocorticoid receptor binding. Thyroid hormone kinetics are also affected. Central defect of the thyroid axis or an alteration in T4 metabolism or binding to proteins may be involved in derangements in thyroid hormone action. Lead toxicity involves alterations on calcitropic hormones' homeostasis, which increase the risk of skeletal disorders.

Generalized Resistance to Thyroid Hormone Associated with a Mutation in the Ligand-Binding Domain of the Human Thyroid Hormone Receptor β

NASA Astrophysics Data System (ADS)

Sakurai, Akihiro; Takeda, Kyoko; Ain, Kenneth; Ceccarelli, Paola; Nakai, Akira; Seino, Susumu; Bell, Graeme I.; Refetoff, Samuel; Degroot, Leslie J.

1989-11-01

The syndrome of generalized resistance to thyroid hormone is characterized by elevated circulating levels of thyroid hormone in the presence of an overall eumetabolic state and failure to respond normally to triiodothyronine. We have evaluated a family with inherited generalized resistance to thyroid hormone for abnormalities in the thyroid hormone nuclear receptors. A single guanine --> cytosine replacement in the codon for amino acid 340 resulted in a glycine --> arginine substitution in the hormone-binding domain of one of two alleles of the patient's thyroid hormone nuclear receptor β gene. In vitro translation products of this mutant human thyroid hormone nuclear receptor β gene did not bind triiodothyronine. Thus, generalized resistance to thyroid hormone can result from expression of an abnormal thyroid hormone nuclear receptor molecule.

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

PubMed

Ohara, Noriyuki; Tsujino, Taro; Maruo, Takeshi

2004-11-01

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

Positive Correlation between Serum Osteocalcin and Testosterone in Male Hyperthyroidism Patients with High Bone Turnover.

PubMed

Zhong, N; Xu, B; Cui, R; Xu, M; Su, J; Zhang, Z; Liu, Y; Li, L; Sheng, C; Sheng, H; Qu, S

2016-07-01

Animal studies suggested that there is an independent bone-osteocalcin-gonadal axis, except of the hypothalamic-pituitary-gonadal axis. Based on this hypothesis, the higher osteocalcin during the high bone turnover should be followed by higher testosterone formation. Yet such clinical evidence is limited. The patients with uncontrolled hyperthyroidism are proper model with high bone turnover. If this hypothesis is true, there should be high testosterone level in patients with uncontrolled hyperthyroidism. Therefore, Graves' disease patients were recruited to study the correlation between osteocalcin and testosterone. 50 male hyperthyroidism patients with Graves' disease and 50 health persons matched by age and gender were enrolled in our cross-section study. Serum markers for thyroid hormone, sex hormone and bone metabolic markers including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin (OC), C-terminal telopeptide fragments of type I collagen (CTX) were examined. The demographic parameters such as duration of disease were also collected. All data was analyzed by SPSS 20.0. High testosterone and osteocalcin level was observed in the hyperthyroidism patients (T 36.35±10.72 nmol/l and OC 46.79±26.83 ng/ml). In simple Pearson correlation, testosterone was positively associated with OC (r=0.486, P<0.001), and this positive relation still existed after adjusted for age, BMI, smoking, drinking, duration of disease, FT3, FT4, LH, FSH, CTX in multi-linear regression analysis (See Model 1-4). In male hyperthyroidism patients, osteocalcin was positively correlated with serum testosterone, which indirectly supports the hypothesis that serum osteocalcin participates in the regulation of sex hormone. © Georg Thieme Verlag KG Stuttgart · New York.

Effects of forced swimming stress on thyroid function, pituitary thyroid-stimulating hormone and hypothalamus thyrotropin releasing hormone expression in adrenalectomy Wistar rats.

PubMed

Sun, Qiuyan; Liu, Aihua; Ma, Yanan; Wang, Anyi; Guo, Xinhong; Teng, Weiping; Jiang, Yaqiu

2016-11-01

In order to study the impact that is imposed on the hypothalamic-pituitary-thyroid (HPT) axis of adrenalectomy male Wistar rats by stress caused by swimming, the blood level of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), the expression of TSHβ mRNA at the pituitary and thyrotropin releasing hormone (TRH) expression at the paraventricular nucleus (PVN) were measured. A total of 50 male Wistar rats of 6-8 weeks of age and with an average weight of 190-210 grams were randomly divided into the following two groups: The surgical (without adrenal glands) and non-surgical (adrenalectomy) group. These two groups were then divided into the following five groups, according to the time delay of sacrifice following forced swim (10 min, 2 h, 12 h and 24 h) and control (not subjected to swimming) groups. A bilateral adrenalectomy animal model was established. Serum TSH in the blood was measurement by chemiluminescent immunoassay, and cerebrum tissue were excised for the measurement of TRH expression using an immunohistochemistry assay. In addition, pituitaries were excised for the extraction of total RNA. Finally, reverse transcription-quantitative polymerase chain reaction was performed for quantitation of TSHβ. Following swimming, the serum T3, T4 and TSH, the TSHβ mRNA expression levels in the pituitary and the TRH expression in the PVN of the surgical group were gradually increased. In the non-surgical group, no significant differences were observed in the serum T3, T4 and TSH levels compared with the control group. The TSHβ mRNA expression at the pituitary showed a similar result. Furthermore, the TRH expression at PVN was gradually increased and stress from swimming could increase the blood T4, T3 and TSH levels, TSHβ mRNA expression at the pituitary and TRH expression at the PVN in adrenalectomy Wistar rats. Moreover, the index in the surgical group changed significantly compared with the non-surgical group. In conclusion, the results suggest that there is a positive correlation between stress from forced swimming and the variation of the HPT axis.

Female nurses' burnout symptoms: No association with the Hypothalamic-pituitary-thyroid (HPT) axis.

PubMed

Guo, Yufang; Lam, Louisa; Luo, Yuanhui; Plummer, Virginia; Cross, Wendy; Li, Hui; Yin, Yizhen; Zhang, Jingping

2017-03-01

Across the world, hospital nurses experience a high level of burnout. Exploring biochemical markers of burnout could help to understand physiological changes and may provide useful evidence for preventing burnout symptoms. The current study included 94 female nurses from one Chinese third-level hospital. The Maslach Burnout Inventory-General Survey (MBI-GS) was used to investigate burnout symptoms: emotional exhaustion, cynicism, reduced professional efficacy, as well as the burnout average. The HPT axis was tested by checking blood levels of thyroid-stimulating hormone (TSH), thyroxin (T 4 ) and triiodothyronine (T 3 ). Nonparametric tests showed that no significant difference in biochemical markers was found between the burnout and non-burnout groups. Spearman correlation analysis found that biochemical markers had no significant association with burnout symptoms, except weakly negative associations between reduced professional efficacy and blood pressure and heart rate. These findings show a rather poor correlation of the HPT axis on burnout symptoms. Expanding the biochemical index of the HPT axis, comparing well-defined samples and using longitudinal studies are recommended for further studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thyroid Function and Obesity

PubMed Central

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

2012-01-01

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

A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.

PubMed

Porcu, Eleonora; Medici, Marco; Pistis, Giorgio; Volpato, Claudia B; Wilson, Scott G; Cappola, Anne R; Bos, Steffan D; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M; Nolte, Ilja M; O'Connell, Jeffrey R; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J; Buckley, Brendan M; Camaschella, Clara; de Craen, Anton J M; Davies, Gail; de Visser, Marieke C H; Ford, Ian; Forsen, Tom; Frayling, Timothy M; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T; Hermus, Ad R; Hofman, Albert; Houwing-Duistermaat, Jeanine J; Jensen, Richard A; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D; Nagaraja, Ramaiah; Netea-Maier, Romana T; Palotie, Aarno; Persani, Luca; Piras, Maria G; Psaty, Bruce M; Räikkönen, Katri; Richards, J Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M; Sattar, Naveed; Shields, Beverley M; Soranzo, Nicole; Starr, John M; Stott, David J; Sweep, Fred C G J; Usala, Gianluca; van der Klauw, Melanie M; van Heemst, Diana; van Mullem, Alies; Vermeulen, Sita H; Visser, W Edward; Walsh, John P; Westendorp, Rudi G J; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J; Eriksson, Johan G; Ferrucci, Luigi; Fox, Caroline S; Jukema, J Wouter; Kiemeney, Lambertus A; Pramstaller, Peter P; Schlessinger, David; Shuldiner, Alan R; Slagboom, Eline P; Uitterlinden, André G; Vaidya, Bijay; Visser, Theo J; Wolffenbuttel, Bruce H R; Meulenbelt, Ingrid; Rotter, Jerome I; Spector, Tim D; Hicks, Andrew A; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism.

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

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth

PubMed Central

Black, Laurel; Bennfors, Grace; Parsons, Trish E.; Elsalanty, Mohammed E.; Yu, Jack C.; Weinberg, Seth M.; Cray, James J.

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology. PMID:27959899

Effects of In Utero Thyroxine Exposure on Murine Cranial Suture Growth.

PubMed

Howie, R Nicole; Durham, Emily L; Black, Laurel; Bennfors, Grace; Parsons, Trish E; Elsalanty, Mohammed E; Yu, Jack C; Weinberg, Seth M; Cray, James J

2016-01-01

Large scale surveillance studies, case studies, as well as cohort studies have identified the influence of thyroid hormones on calvarial growth and development. Surveillance data suggests maternal thyroid disorders (hyperthyroidism, hypothyroidism with pharmacological replacement, and Maternal Graves Disease) are linked to as much as a 2.5 fold increased risk for craniosynostosis. Craniosynostosis is the premature fusion of one or more calvarial growth sites (sutures) prior to the completion of brain expansion. Thyroid hormones maintain proper bone mineral densities by interacting with growth hormone and aiding in the regulation of insulin like growth factors (IGFs). Disruption of this hormonal control of bone physiology may lead to altered bone dynamics thereby increasing the risk for craniosynostosis. In order to elucidate the effect of exogenous thyroxine exposure on cranial suture growth and morphology, wild type C57BL6 mouse litters were exposed to thyroxine in utero (control = no treatment; low ~167 ng per day; high ~667 ng per day). Thyroxine exposed mice demonstrated craniofacial dysmorphology (brachycranic). High dose exposed mice showed diminished area of the coronal and widening of the sagittal sutures indicative of premature fusion and compensatory growth. Presence of thyroid receptors was confirmed for the murine cranial suture and markers of proliferation and osteogenesis were increased in sutures from exposed mice. Increased Htra1 and Igf1 gene expression were found in sutures from high dose exposed individuals. Pathways related to the HTRA1/IGF axis, specifically Akt and Wnt, demonstrated evidence of increased activity. Overall our data suggest that maternal exogenous thyroxine exposure can drive calvarial growth alterations and altered suture morphology.

21 CFR 862.1690 - Thyroid stimulating hormone test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as...

21 CFR 862.1690 - Thyroid stimulating hormone test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known as...

Thyrotropin-releasing hormone controls mitochondrial biology in human epidermis.

PubMed

Knuever, Jana; Poeggeler, Burkhard; Gáspár, Erzsébet; Klinger, Matthias; Hellwig-Burgel, Thomas; Hardenbicker, Celine; Tóth, Balázs I; Bíró, Tamás; Paus, Ralf

2012-03-01

Mitochondrial capacity and metabolic potential are under the control of hormones, such as thyroid hormones. The most proximal regulator of the hypothalamic-pituitary-thyroid (HPT) axis, TRH, is the key hypothalamic integrator of energy metabolism via its impact on thyroid hormone secretion. Here, we asked whether TRH directly modulates mitochondrial functions in normal, TRH-receptor-positive human epidermis. Organ-cultured human skin was treated with TRH (5-100 ng/ml) for 12-48 h. TRH significantly increased epidermal immunoreactivity for the mitochondria-selective subunit I of respiratory chain complex IV (MTCO1). This resulted from an increased MTCO1 transcription and protein synthesis and a stimulation of mitochondrial biogenesis as demonstrated by transmission electron microscopy and TRH-enhanced mitochondrial DNA synthesis. TRH also significantly stimulated the transcription of several other mitochondrial key genes (TFAM, HSP60, and BMAL1), including the master regulator of mitochondrial biogenesis (PGC-1α). TRH significantly enhanced mitochondrial complex I and IV enzyme activity and enhanced the oxygen consumption of human skin samples, which shows that the stimulated mitochondria are fully vital because the main source for cellular oxygen consumption is mitochondrial endoxidation. These findings identify TRH as a potent, novel neuroendocrine stimulator of mitochondrial activity and biogenesis in human epidermal keratinocytes in situ. Thus, human epidermis offers an excellent model for dissecting neuroendocrine controls of human mitochondrial biology under physiologically relevant conditions and for exploring corresponding clinical applications.

A post-publication analysis of the idealized upper reference value of 2.5 mIU/L for TSH: Time to support the thyroid axis with magnesium and iron especially in the setting of reproduction medicine.

PubMed

Moncayo, Roy; Moncayo, Helga

2017-06-01

Laboratory medicine approaches the evaluation of thyroid function mostly through the single determination of the blood level of thyroid stimulating hormone (TSH). Some authors have suggested an upper reference value for TSH of 2.5 mIU/L. This suggestion has not been confirmed by recent clinical studies. These studies have delivered a clinically valid reference range going from 0.3 to 3.5 mIU/L. These values are valid for both for the general population as well as in the setting of fertility and pregnancy. Current biochemical evidence about the elements required to maintain thyroid function shows that these not only include dietary iodine but also magnesium, iron, selenium and coenzyme Q10. Iron is important for the synthesis of thyroid peroxidase; magnesium-ATP contributes to the active process of iodine uptake; iodine has to be sufficiently present in the diet; selenium acts through selenoproteins to protect the thyroid cell during hormone synthesis and in deiodination of thyroxine; coenzyme Q10 influences thyroid vascularity. As a consequence, good clinical practice requires additional biochemical information on the blood levels of magnesium, selenium, coenzyme Q10 as well as iron status. Since these elements are also important for the maintenance of reproductive function, we postulate that they constitute the connecting link between both endocrine systems.

2,4,6-Tribromophenol Interferes with the Thyroid Hormone System by Regulating Thyroid Hormones and the Responsible Genes in Mice

PubMed Central

Lee, Dongoh; Ahn, Changhwan; Hong, Eui-Ju; An, Beum-Soo; Hyun, Sang-Hwan; Choi, Kyung-Chul; Jeung, Eui-Bae

2016-01-01

2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems PMID:27420076

2,4,6-Tribromophenol Interferes with the Thyroid Hormone System by Regulating Thyroid Hormones and the Responsible Genes in Mice.

PubMed

Lee, Dongoh; Ahn, Changhwan; Hong, Eui-Ju; An, Beum-Soo; Hyun, Sang-Hwan; Choi, Kyung-Chul; Jeung, Eui-Bae

2016-07-12

2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems.

Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

PubMed

Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi

2017-02-06

Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating hormone receptor antibody, which is bioactive but less reactive on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, or the effect of reduced levels of circulating thyroid-stimulating hormone receptor antibody upon improvement of thyroid autoimmunity with thiamazole treatment. Physicians should keep in mind that patients with Graves' disease may show thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results that do not reflect the severity of Graves' disease or indicate the outcome of the disease, and that active Graves' disease may persist even after negative results on thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Timely performance of thyroid function tests in combination with sensitive imaging tests, including thyroid ultrasound and scintigraphy, are necessary to evaluate the severity of Graves' disease and treatment efficacy.

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

The adrenocortical response of tufted puffin chicks to nutritional deficits

USGS Publications Warehouse

Kitaysky, A.S.; Romano, Marc D.; Piatt, John F.; Wingfield, J.C.; Kikuchi, M.

2005-01-01

In several seabirds, nutritional state of a nest-bound chick is negatively correlated with the activity of its hypothalamus-pituitary-adrenal (HPA) axis. Increased corticosterone (cort) secretion has been shown to facilitate changes in behavior that allow hungry chicks to obtain more food from parents. However, if parents are not willing/able to buffer their young from temporary food shortages, increased cort secretion could be detrimental to undernourished chicks. In a system where parents are insensitive to chick demands, low benefits and high costs of activation of the HPA-axis in hungry chicks should lead to a disassociation of the nutritional state of the young and the activity of its HPA-axis. We tested this novel hypothesis for the tufted puffin (Fratercula cirrhata), a seabird with intermittent provisioning of a nest-bound semi-precocial chick. We examined the HPA-axis activity of captive chicks exposed to the following: (1) a short-term (24 h) food deprivation; and (2) an array of prolonged (3 weeks) restrictions in feeding regimens. We found that in response to a short-term food deprivation chicks decreased baseline levels of cort and thyroid hormones. In response to prolonged restrictions, food-limited chicks exhibited signs of nutritional deficit: they had lower body mass, endogenous lipid reserves, and thyroid hormone titers compared to chicks fed ad libitum. However, baseline and maximum acute stress-induced levels of cort were also lower in food-restricted chicks compared to those of chicks fed ad libitum. These results support a major prediction of the study hypothesis that puffin chicks suppress HPA-axis activity in response to short- and long-term nutritional deficits. This physiological adaptation may allow a chick to extend its development in the nest, while eluding detrimental effects of chronic cort elevation. 

[Painless thyroiditis].

PubMed

Okamura, Ken; Fujikawa, Megumi; Bandai, Sachiko

2006-12-01

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

Thyroid hormone effects on mitochondrial energetics.

PubMed

Harper, Mary-Ellen; Seifert, Erin L

2008-02-01

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

Effect of Metformin on Hypothalamic-Pituitary-Thyroid Axis Activity in Elderly Antipsychotic-Treated Women With Type 2 Diabetes and Subclinical Hypothyroidism: A Preliminary Study.

PubMed

Krysiak, Robert; Szkróbka, Witold; Okopień, Bogusław

2018-05-01

Metformin was found to reduce elevated serum thyrotropin levels, and this effect was partially determined by endogenous dopaminergic tone. The aim of this study was to compare the effect of metformin treatment on hypothalamic-pituitary-thyroid axis activity in elderly women with subclinical hypothyroidism treated with antipsychotic agents and not receiving this drug. The study population consisted of 34 elderly women with subclinical hypothyroidism, 16 of whom received antipsychotic drugs. Because of coexistent type 2 diabetes, these women were treated with metformin (2.55-3 g daily). Glucose homeostasis markers as well as serum levels of thyrotropin, free thyroid hormones and prolactin were measured at the beginning of the study and 6 months later. Thirty women completed the study. With the exception of prolactin, baseline serum levels of the assessed hormones were comparable in both study groups. Although metformin reduced serum thyrotropin levels in both groups, this effect was more pronounced in the antipsychotic-treated than in the antipsychotic-naive patients. The effect on serum prolactin was observed only in antipsychotic-treated patients. The impact on serum thyrotropin levels correlated with improvement in insulin sensitivity and with a reduction in prolactin levels. Free thyroxine and free triiodothyronine remained at a similar level throughout the study. The obtained results indicate that metformin reduces serum thyrotropin levels in elderly women, and this effect is particularly pronounced in women with diminished dopaminergic transmission. © 2017, The American College of Clinical Pharmacology.

Maturation of human hypothalamic-pituitary-thyroid function and control.

PubMed

Fisher, D A; Nelson, J C; Carlton, E I; Wilcox, R B

2000-03-01

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Elevated serum levels of free triiodothyronine in adolescent boys with gynaecomastia compared with controls.

PubMed

Mieritz, Mikkel G; Sorensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Hagen, Casper P; Hilsted, Linda; Andersson, Anna-Maria; Juul, Anders

2014-08-01

Pubertal gynaecomastia is a frequent phenomenon occurring in 20-40% of otherwise healthy adolescent boys. Little is known about the aetiology of pubertal gynaecomastia. Markedly elevated thyroid hormone levels in adults with hyperthyroidism are associated with gynaecomastia. A cross-sectional examination of 444 healthy boys with and without pubertal gynaecomastia. We evaluated TSH, triiodothyronine (T3), thyroxine (T4), free T4 and free T3 in a cohort of healthy boys with and without pubertal gynaecomastia. Boys with gynaecomastia had significantly higher serum free T3, even after correction for age, BMI and pubertal stage. After inclusion of IGF1 in the model the differences disappeared. TSH, T4, free T4 and T3 did not differ between the groups. We speculate that the GH/IGF1 axis and thyroid hormones interact and influence the development of pubertal gynaecomastia. © 2014 European Society of Endocrinology.

Thyroiditis: an integrated approach.

PubMed

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

2014-09-15

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

Effects of Levothyroxine Administration and Withdrawal on the Hypothalamic-Pituitary-Thyroid Axis in Euthyroid Dogs.

PubMed

Ziglioli, V; Panciera, D L; Troy, G C; Monroe, W E; Boes, K M; Refsal, K R

2017-05-01

Chronic supplementation can suppress the hypothalamic-pituitary-thyroid axis (HPTA) and make it difficult to assess thyroid function after withdrawal of levothyroxine. To determine whether the HPTA is suppressed after levothyroxine administration in euthyroid dogs and the time required for resolution of any suppression. Twenty-eight healthy euthyroid dogs. A prospective, randomized study administering levothyroxine to euthyroid dogs for 8 weeks (group 1) or 16 weeks (group 2). Serum concentrations of total thyroxine (T 4 ), free thyroxine (fT 4 ) by equilibrium dialysis, thyroid stimulating hormone; thyrotropin (TSH), and 3,5,3'-triiodothyronine (T 3 ) were measured every 4 weeks during supplementation and for 16 weeks after levothyroxine was discontinued. Mean serum concentrations of T 4 and fT 4 were significantly higher (P < .0001) and TSH was lower (P < .0001) in all dogs during levothyroxine administration compared to baseline. Mean serum concentrations of T 4 , fT 4, and TSH in both groups, beginning 1 week after levothyroxine was discontinued, were significantly different (P < .01) compared to values during levothyroxine administration but not compared to baseline values (P > .3). Assessing thyroid function tests 1 week after cessation of levothyroxine at 26 μg/kg once a day for up to 16 weeks will provide an accurate assessment of thyroid function in healthy euthyroid dogs. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Dietary Exposure to 2,2′,4,4′-Tetrabromodiphenyl Ether (PBDE-47) Alters Thyroid Status and Thyroid Hormone–Regulated Gene Transcription in the Pituitary and Brain

PubMed Central

Lema, Sean C.; Dickey, Jon T.; Schultz, Irvin R.; Swanson, Penny

2008-01-01

Background Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs may show reduced plasma thyroid hormone (TH), but it is not known whether PBDEs impact TH-regulated pathways in target tissues. Objective We examined the effects of dietary exposure to 2,2′,4,4′-tetrabromodiphenyl ether (PBDE-47)—commonly the highest concentrated PBDE in human tissues—on plasma TH levels and on gene transcripts for glycoprotein hormone α-subunit (GPHα) and thyrotropin β-subunit (TSHβ) in the pituitary gland, the autoinduced TH receptors α and β in the brain and liver, and the TH-responsive transcription factor basic transcription element-binding protein (BTEB) in the brain. Methods Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE-47 at two doses (2.4 μg/pair/day or 12.3 μg/pair/day) for 21 days. Results Minnows exposed to PBDE-47 had depressed plasma thyroxine (T4), but not 3,5,3′-triiodothyronine (T3). This decline in T4 was accompanied by elevated mRNA levels for TStHβ (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor αin the brain of females and decreased mRNA for TH receptor β in the brain of both sexes, without altering these transcripts in the liver. In males, PBDE-47 exposure also reduced brain transcripts for BTEB. Conclusions Our results indicate that dietary exposure to PBDE-47 alters TH signaling at multiple levels of the hypothalamic-pituitary-thyroid axis and provide evidence that TH-responsive pathways in the brain may be particularly sensitive to disruption by PBDE flame retardants. PMID:19079722

Thyroid-stimulating Hormone (TSH): Measurement of Intracellular, Secreted, and Circulating Hormone in Xenopus laevis and Xenopus tropicalis.

EPA Science Inventory

Thyroid Stimulating Hormone (TSH) is a hormone produced in the pituitary that stimulates the thyroid gland to grow and produce thyroid hormone (TH). The concentration of TH controls developmental changes that take place in a wide variety of organisms. Many use the metaphoric ch...

Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

PubMed

Ahmed, R G

2016-09-01

Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between vitamin A deficiency and the thyroid axis in clinically stable patients with liver cirrhosis related to hepatitis C virus.

PubMed

El-Eshmawy, Mervat M; Arafa, Mona M; Elzehery, Rasha R; Elhelaly, Rania M; Elrakhawy, Mohamed M; El-Baiomy, Azza A

2016-09-01

Vitamin A deficiency (VAD) and altered thyroid function are commonly encountered in patients with liver cirrhosis. The link between vitamin A metabolism and thyroid function has been previously identified. The aim of this study was to explore the association between VAD and the thyroid axis in clinically stable patients with cirrhosis related to hepatitis C virus (HCV). One hundred and twelve patients with clinically stable HCV-related cirrhosis and 56 healthy controls matched for age, sex, and socioeconomic status were recruited for this study. Vitamin A status, liver function, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), reverse triiodothyronine (rT3), anti-thyroid peroxidase antibodies (anti-TPO), and thyroid volume were evaluated. The prevalence of VAD among patients with HCV-related cirrhosis was 62.5% compared with 5.4% among controls (P < 0.001). Patients with HCV-related cirrhosis had significantly higher FT4, FT3, TSH, and thyroid volume than did healthy controls. Of the 112 patients initially recruited, 18 were excluded (patients with subclinical hypothyroidism and/or anti-TPO positive), so a total of 94 patients with HCV-related cirrhosis were divided into 2 groups according to vitamin A status: VAD and normal vitamin A. Patients with VAD had significantly lower vitamin A intake and serum albumin and higher serum bilirubin, FT4, FT3, and TSH than patients with normal vitamin A status. Multiple logistic regression analysis revealed that VAD was associated with Child-Pugh score (β = 0.11, P = 0.05) and TSH (β = -1.63, P = 0.02) independently of confounding variables. We conclude that VAD may be linked to central hyperthyroidism in patients with clinically stable HCV-related liver cirrhosis.

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.

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

PubMed

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

2000-01-01

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

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

PubMed

Köhrle, Josef

2007-06-01

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

Leptin as a Modulator of Neuroendocrine Function in Humans

PubMed Central

Khan, Sami M.; Hamnvik, Ole-Petter R.; Brinkoetter, Mary

2012-01-01

Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemia can be a congenital or acquired condition, and is associated with alterations of the aforementioned axes aimed at promoting survival. More specifically, gonadotropin levels decrease and become less pulsatile under conditions of energy deprivation, and these changes can be at least partially reversed through leptin administration in physiological replacement doses. Similarly, leptin deficiency is associated with thyroid axis abnormalities including abnormal levels of thyrotropin-releasing hormone, and leptin administration may at least partially attenuate this effect. Leptin deficiency results in decreased insulin-like growth factor 1 levels which can be partially ameliorated through leptin administration, and leptin appears to have a much more pronounced effect on the growth of rodents than that of humans. Similarly, adrenal axis function is regulated more tightly by low leptin in rodents than in humans. In addition to congenital leptin deficiency, conditions that may be associated with decreased leptin levels include hypothalamic amenorrhea, anorexia nervosa, and congenital or acquired lipodystrophy syndromes. Accumulating evidence from proof of concept studies suggests that leptin administration, in replacement doses, may ameliorate neuroendocrine abnormalities in individuals who suffer from these conditions. PMID:22665330

Pathogenesis of Hyperthyroidism.

PubMed

Singh, Ishita; Hershman, Jerome M

2016-12-06

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

Endocrine control of osmoregulation in teleost fish

USGS Publications Warehouse

McCormick, S.D.

2001-01-01

SYNOPSIS. As the primary link between environmental change and physiological response, the neuroendocrinesystem is a critical part of osmoregulatory adaptations. Cortisol has been viewpd as 'the' seawater-adapting hormone in fish and prolactin as 'the' fresh water adapting hormone. Recent evidence indicates that the growth hormone/insulin-like growth factor I axis is also important in seawater adaptation in several teleosts of widely differing evolutionary lineages. In salmonids, growth hormone acts in synergy with cortisol to increase seawater tolerance, at least partly through the upregulation of gill cortisol receptors. Cortisol under some conditions may promote ion uptake and interacts with prolactin during acclimation to fresh water. The osmoregulatory actions of growth hormone and prolactin are antagonistic. In some species, thyroid hormones support the action of growth hormone and cortisol in promoting seawater acclimation. Although a broad generalization that holds for all teleosts is unlikely, our current understanding indicates that growth hormone promotes acclimation to seawater, prolactin promotes acclimation to fresh water, and cortisol interacts with both of these hormones thus having a dual osmoregulatory function.

Hypothyroidism: etiology, diagnosis, and management.

PubMed

Almandoz, Jaime P; Gharib, Hossein

2012-03-01

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

Withdrawal From Chronic Nicotine Reduces Thyroid Hormone Levels and Levothyroxine Treatment Ameliorates Nicotine Withdrawal-Induced Deficits in Hippocampus-Dependent Learning in C57BL/6J Mice

PubMed Central

Leach, Prescott T.; Holliday, Erica; Kutlu, Munir G.

2015-01-01

Introduction: Cigarette smoking alters a variety of endocrine systems including thyroid hormones. Altered thyroid hormone signaling may lead to a subclinical or overt hypothyroid condition that could contribute to nicotine withdrawal-related symptoms, such as cognitive deficits. Thus, normalizing thyroid hormone levels may represent a novel therapeutic target for ameliorating nicotine withdrawal-associated cognitive deficits. Methods: The current studies conducted an analysis of serum thyroid hormone levels after chronic and withdrawal from chronic nicotine treatment in C57BL/6J mice using an enzyme-linked immunosorbent assay. The present studies also evaluated the effect of synthetic thyroid hormone (levothyroxine) on contextual and cued memory. Results: The current studies found that nicotine withdrawal reduces secreted thyroid hormone levels by 9% in C57BL/6J mice. Further, supplemental thyroid hormone not only enhanced memory in naïve animals, but also ameliorated deficits in hippocampus-dependent learning associated with nicotine withdrawal. Conclusions: These results suggest that smokers attempting to quit should be monitored closely for changes in thyroid function. If successfully treated, normalization of thyroid hormone levels may ameliorate some deficits associated with nicotine withdrawal and this may lead to higher rates of successful abstinence. PMID:25358661

Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

EPA Science Inventory

Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

Thyroid hormone and the central control of homeostasis.

PubMed

Warner, Amy; Mittag, Jens

2012-08-01

It has long been known that thyroid hormone has profound direct effects on metabolism and cardiovascular function. More recently, it was shown that the hormone also modulates these systems by actions on the central autonomic control. Recent studies that either manipulated thyroid hormone signalling in anatomical areas of the brain or analysed seasonal models with an endogenous fluctuation in hypothalamic thyroid hormone levels revealed that the hormone controls energy turnover. However, most of these studies did not progress beyond the level of anatomical nuclei; thus, the neuronal substrates as well as the molecular mechanisms remain largely enigmatic. This review summarises the evidence for a role of thyroid hormone in the central autonomic control of peripheral homeostasis and advocates novel strategies to address thyroid hormone action in the brain on a cellular level.

Aged PROP1 Deficient Dwarf Mice Maintain ACTH Production

PubMed Central

Bavers, David L.; Beuschlein, Felix; Mortensen, Amanda H.; Keegan, Catherine E.; Hammer, Gary D.; Camper, Sally A.

2011-01-01

Humans with PROP1 mutations have multiple pituitary hormone deficiencies (MPHD) that typically advance from growth insufficiency diagnosed in infancy to include more severe growth hormone (GH) deficiency and progressive reduction in other anterior pituitary hormones, eventually including adrenocorticotropic hormone (ACTH) deficiency and hypocortisolism. Congenital deficiencies of GH, prolactin, and thyroid stimulating hormone have been reported in the Prop1null (Prop1-/-) and the Ames dwarf (Prop1df/df) mouse models, but corticotroph and pituitary adrenal axis function have not been thoroughly investigated. Here we report that the C57BL6 background sensitizes mutants to a wasting phenotype that causes approximately one third to die precipitously between weaning and adulthood, while remaining homozygotes live with no signs of illness. The wasting phenotype is associated with severe hypoglycemia. Circulating ACTH and corticosterone levels are elevated in juvenile and aged Prop1 mutants, indicating activation of the pituitary-adrenal axis. Despite this, young adult Prop1 deficient mice are capable of responding to restraint stress with further elevation of ACTH and corticosterone. Low blood glucose, an expected side effect of GH deficiency, is likely responsible for the elevated corticosterone level. These studies suggest that the mouse model differs from the human patients who display progressive hormone loss and hypocortisolism. PMID:22145038

A Meta-Analysis of Thyroid-Related Traits Reveals Novel Loci and Gender-Specific Differences in the Regulation of Thyroid Function

PubMed Central

Volpato, Claudia B.; Wilson, Scott G.; Cappola, Anne R.; Bos, Steffan D.; Deelen, Joris; den Heijer, Martin; Freathy, Rachel M.; Lahti, Jari; Liu, Chunyu; Lopez, Lorna M.; Nolte, Ilja M.; O'Connell, Jeffrey R.; Tanaka, Toshiko; Trompet, Stella; Arnold, Alice; Bandinelli, Stefania; Beekman, Marian; Böhringer, Stefan; Brown, Suzanne J.; Buckley, Brendan M.; Camaschella, Clara; de Craen, Anton J. M.; Davies, Gail; de Visser, Marieke C. H.; Ford, Ian; Forsen, Tom; Frayling, Timothy M.; Fugazzola, Laura; Gögele, Martin; Hattersley, Andrew T.; Hermus, Ad R.; Hofman, Albert; Houwing-Duistermaat, Jeanine J.; Jensen, Richard A.; Kajantie, Eero; Kloppenburg, Margreet; Lim, Ee M.; Masciullo, Corrado; Mariotti, Stefano; Minelli, Cosetta; Mitchell, Braxton D.; Nagaraja, Ramaiah; Netea-Maier, Romana T.; Palotie, Aarno; Persani, Luca; Piras, Maria G.; Psaty, Bruce M.; Räikkönen, Katri; Richards, J. Brent; Rivadeneira, Fernando; Sala, Cinzia; Sabra, Mona M.; Sattar, Naveed; Shields, Beverley M.; Soranzo, Nicole; Starr, John M.; Stott, David J.; Sweep, Fred C. G. J.; Usala, Gianluca; van der Klauw, Melanie M.; van Heemst, Diana; van Mullem, Alies; H.Vermeulen, Sita; Visser, W. Edward; Walsh, John P.; Westendorp, Rudi G. J.; Widen, Elisabeth; Zhai, Guangju; Cucca, Francesco; Deary, Ian J.; Eriksson, Johan G.; Ferrucci, Luigi; Fox, Caroline S.; Jukema, J. Wouter; Kiemeney, Lambertus A.; Pramstaller, Peter P.; Schlessinger, David; Shuldiner, Alan R.; Slagboom, Eline P.; Uitterlinden, André G.; Vaidya, Bijay; Visser, Theo J.; Wolffenbuttel, Bruce H. R.; Meulenbelt, Ingrid; Rotter, Jerome I.; Spector, Tim D.; Hicks, Andrew A.; Toniolo, Daniela; Sanna, Serena; Peeters, Robin P.; Naitza, Silvia

2013-01-01

Thyroid hormone is essential for normal metabolism and development, and overt abnormalities in thyroid function lead to common endocrine disorders affecting approximately 10% of individuals over their life span. In addition, even mild alterations in thyroid function are associated with weight changes, atrial fibrillation, osteoporosis, and psychiatric disorders. To identify novel variants underlying thyroid function, we performed a large meta-analysis of genome-wide association studies for serum levels of the highly heritable thyroid function markers TSH and FT4, in up to 26,420 and 17,520 euthyroid subjects, respectively. Here we report 26 independent associations, including several novel loci for TSH (PDE10A, VEGFA, IGFBP5, NFIA, SOX9, PRDM11, FGF7, INSR, ABO, MIR1179, NRG1, MBIP, ITPK1, SASH1, GLIS3) and FT4 (LHX3, FOXE1, AADAT, NETO1/FBXO15, LPCAT2/CAPNS2). Notably, only limited overlap was detected between TSH and FT4 associated signals, in spite of the feedback regulation of their circulating levels by the hypothalamic-pituitary-thyroid axis. Five of the reported loci (PDE8B, PDE10A, MAF/LOC440389, NETO1/FBXO15, and LPCAT2/CAPNS2) show strong gender-specific differences, which offer clues for the known sexual dimorphism in thyroid function and related pathologies. Importantly, the TSH-associated loci contribute not only to variation within the normal range, but also to TSH values outside the reference range, suggesting that they may be involved in thyroid dysfunction. Overall, our findings explain, respectively, 5.64% and 2.30% of total TSH and FT4 trait variance, and they improve the current knowledge of the regulation of hypothalamic-pituitary-thyroid axis function and the consequences of genetic variation for hypo- or hyperthyroidism. PMID:23408906

Hyperthyroidism: Diagnosis and Treatment.

PubMed

Kravets, Igor

2016-03-01

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

Novel neural pathways for metabolic effects of thyroid hormone.

PubMed

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

2010-04-01

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

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

PubMed

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

2011-06-01

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

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

PubMed

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

2013-08-06

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

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

PubMed Central

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

2013-01-01

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

Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

NASA Astrophysics Data System (ADS)

Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

2017-03-01

Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

Role of co-regulators in metabolic and transcriptional actions of thyroid hormone.

PubMed

Astapova, Inna

2016-04-01

Thyroid hormone (TH) controls a wide range of physiological processes through TH receptor (TR) isoforms. Classically, TRs are proposed to function as tri-iodothyronine (T3)-dependent transcription factors: on positively regulated target genes, unliganded TRs mediate transcriptional repression through recruitment of co-repressor complexes, while T3 binding leads to dismissal of co-repressors and recruitment of co-activators to activate transcription. Co-repressors and co-activators were proposed to play opposite roles in the regulation of negative T3 target genes and hypothalamic-pituitary-thyroid axis, but exact mechanisms of the negative regulation by TH have remained elusive. Important insights into the roles of co-repressors and co-activators in different physiological processes have been obtained using animal models with disrupted co-regulator function. At the same time, recent studies interrogating genome-wide TR binding have generated compelling new data regarding effects of T3, local chromatin structure, and specific response element configuration on TR recruitment and function leading to the proposal of new models of transcriptional regulation by TRs. This review discusses data obtained in various mouse models with manipulated function of nuclear receptor co-repressor (NCoR or NCOR1) and silencing mediator of retinoic acid receptor and thyroid hormone receptor (SMRT or NCOR2), and family of steroid receptor co-activators (SRCs also known as NCOAs) in the context of TH action, as well as insights into the function of co-regulators that may emerge from the genome-wide TR recruitment analysis. © 2016 Society for Endocrinology.

Central irisin administration suppresses thyroid hormone production but increases energy consumption in rats.

PubMed

Tekin, Suat; Erden, Yavuz; Ozyalin, Fatma; Onalan, Ebru Etem; Cigremis, Yilmaz; Colak, Cemil; Tekedereli, Ibrahim; Sandal, Suleyman

2018-05-01

Irisin, which is secreted from the skeletal muscle in response to physical exercise and defined as a thermogenic peptide, may play an important role in energy metabolism. Thyroid hormones, which are one of the other influential factors on the metabolic status, increase heat production and are the main regulators of energy metabolism. This study was conducted to determine the possible effects of irisin administration on thyroid hormones. Forty adult male Wistar albino rats were used in the study. The rats were equally divided into 4 groups (n = 10). The brain infusion kit was implanted in the groups, and irisin (or solvent as control) was centrally administered to the rats via osmotic mini pumps for 7 days. During the experiment, food consumption, body weights, and body temperatures of the animals were recorded. Food intake was significantly increased in the groups treated with irisin (p < 0.05), but their body weights were not changed. Hypothalamic TRH gene expression, serum TSH, fT3, and fT4 levels were significantly lower in the groups treated with irisin as compared to the naive and control groups (p < 0.05). In addition, irisin increased UCP1 mRNA expression in white and brown adipose tissue and UCP3 mRNA expression in muscle tissue in rats and also raised their body temperature (p < 0.05). Consequently, although central irisin administration has inhibitory effects on the hypothalamic-pituitary-thyroid axis, it seems to be an important agent in the regulation of food intake and energy metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

Attachment Strategies and Neuroendocrine Biomarkers in Obese Children.

PubMed

Pinto, Inês; Wilkinson, Simon; Virella, Daniel; Alves, Marta; Calhau, Conceição; Coelho, Rui

2016-05-01

Quality of the parent-infant relationship influences the mechanisms of development of the child's physiological stress regulation. This study explored associations between attachment strategies and both cortisol and thyroid stimulating hormone, hypothesized to be respectively a potential mediator and a potential intervening variable of the mother-child relationship in obese children. A sample of 83 obese children (46 boys), aged 10.9 (1.8) years was recruited from a child obesity clinic. Obesity was defined by body mass index percentile adjusted for age and sex. Metabolic biomarkers were measured by routine methods. Attachment strategies were assessed with self and parent-report questionnaires. Family functioning was assessed with parent-reported questionnaires (FACES-III). Multivariate linear regression analyses were performed. Type A, avoidant attachment strategies, had significant positive association with thyroid stimulating hormone levels and negative association with cortisol levels (R2 = 0.352). Type B, secure attachment strategies, had significant positive associations with both hypothyroidism and body mass index percentile (R2 = 0.541). 'Insecure attachment' (types A and C combined) strategies showed some evidence of positive association with thyroid stimulating hormone (R2 = 0.250). These findings suggest that there may be commonalities in the regulation of hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes. Processes involved in development of the type A attachment strategy appear to be associated with effects on the regulatory mechanisms of the hypothalamic-pituitary-adrenal axis. In obese children, different attachment strategies are associated with diverse metabolic profiles. How this may contribute to developing differentiated treatment approaches remains to be explored.

[Thyroid hormone metabolism and action].

PubMed

Köhrle, Josef

2004-05-01

Reductive deiodination of thyroid hormones at the phenolic and tyrosyl ring leads to the activation or inactivation of the thyromimetic activity inherent to thyroid hormones. Alterations in the activities of the three selenocysteine-containing enzymes, the iodothyronine deiodinases, have been reported during development and in specific cells and tissues of the adult organism. Furthermore, pathophysiological changes in the deiodinase expression lead to therapeutically relevant disturbances of the homeostasis of thyroid hormones. Metabolisation of thyroid hormones by conjugation of their phenolic 4'-OH group, their alanine side chain or cleavage of their diphenylether bridge also contributes to both local and systemic supply of thyromimetic activity or hormone degradation. Further components mediating the pleiotropic action of thyroid hormones in part include redundant T3 receptors, binding and transport proteins, metabolising enzymes and T3-regulated gene products. This is achieved in a finely tuned manner with multiple feedback control, malfunction or complete failure of individual components and networks involved in the iodothyronine metabolism and thyroid hormone action can thus be compensated or prevented.

Assessment of criteria used by veterinary practitioners to diagnose hypothyroidism in sighthounds and investigation of serum thyroid hormone concentrations in healthy Salukis.

PubMed

Shiel, Robert E; Sist, MaryDee; Nachreiner, Raymond F; Ehrlich, Claire P; Mooney, Carmel T

2010-02-01

To assess use of serum thyroid hormone concentrations by veterinarians to diagnose hypothyroidism in sighthounds and to evaluate serum thyroid hormone concentrations in healthy Salukis. Retrospective case series and cross-sectional study. 398 sighthounds of various breeds with a diagnosis of hypothyroidism and 283 healthy Salukis. Pretreatment thyroid hormone assay results from sighthounds subsequently classified as hypothyroid by practitioners were retrieved from a laboratory database. In healthy Salukis, serum concentrations of total thyroxine (T(4)), free T(4), total triiodothyronine (T(3)), free T(3), and thyroid-stimulating hormone (TSH) and antibodies against thyroglobulin and thyroid hormones were assayed. Records indicated hypothyroidism had been diagnosed in 303 (76.1%) sight-hounds on the basis of low serum thyroid hormone concentrations alone and in 30 (7.5%) others despite all thyroid hormone indices being within reference limits. Only 65 (16.3%) dogs had a high TSH concentration or positive thyroglobulin autoantibody result to support the diagnosis. In healthy Salukis, median (reference limits) serum concentrations of total T(4), free T(4), total T(3), free T(3), and TSH were 13.0 nmol/L (2.8 to 40.0 nmol/L), 12.0 pmol/L (2.0 to 30.3 pmol/L), 1.0 nmol/L (0.4 to 2.1 nmol/L), 4.0 pmol/L (1.6 to 7.7 pmol/L), and 0.18 ng/mL (0 to 0.86 ng/mL), respectively. Diagnosis of hypothyroidism by practitioners was most often made without adequate supportive laboratory evidence. Thyroid hormone values in healthy Salukis differed markedly from standard reference limits for some, but not all, thyroid hormone indices. Breed-specific reference limits should be used when interpreting thyroid hormone profiles of sighthounds.

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 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.

HISTORICAL AND CURRENT PERSPECTIVE IN THE USE OF THYROID EXTRACTS FOR THE TREATMENT OF HYPOTHYROIDISM.

PubMed

Hennessey, James V

2015-10-01

To describe the history, refinements, implementation, physiology, and clinical outcomes achieved over the past several centuries of thyroid hormone replacement strategies. A Medline search was initiated using the following search terms: bioidentical thyroid hormone, thyroid hormone extract, combination thyroxine (T4) and tri-iodothyronine (T3) therapy, homeopathic thyroid hormone therapy, and thyroid hormone replacement. Pertinent articles of interest were identified by title (and where available abstract) for further review. Additional references were identified during a review of the identified literature. A rich history of physician intervention in thyroid dysfunction was identified dating back more than 2 millennia. Although not precisely documented, thyroid ingestion from animal sources had been used for centuries but was finally scientifically described and documented in Europe over 130 years ago. Since the reports by Bettencourt and Murray, there has been a continuous documentation of outcomes, refinement of hormone preparation production, and updating of recommendations for the most effective and safe use of these hormones for relieving the symptoms of hypothyroidism. As the thyroid extract preparations contain both levothyroxine (LT4) and liothyronine (LT3), current guidelines do not endorse their use as controlled studies do not clearly document enhanced objective outcomes compared with LT4 monotherapy. Among current issues cited, the optimum ratio of LT4 to LT3 has yet to be determined, and the U.S. Food and Drug Administration (FDA) does not appear to be monitoring the thyroid hormone ratios or content in extract preparations on the market. Taken together, these limitations are important detriments to the use of thyroid extract products. The evolution of thyroid hormone therapies has been significant over the extended period of time they have been in use to treat hypothyroidism. Although numerous websites continue to advocate the use of thyroid hormone extracts as a superior therapy for hypothyroidism, none of the most recent guidelines of major endocrine societies recommend thyroid extract use for hypothyroidism.

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.

Neurodevelopmental Consequences of Low-Level Thyroid Hormone Disruption Induced by Environmental Contaminants

EPA Science Inventory

Inadequate levels of thyroid hormone during critical developmental periods lead to stunted growth, mental retardation, and neurological 'cretinism'. Animal models of developmental thyroid hormone deficiency mirror well the impact of severe insults to the thyroid system. However, ...

The hypothalamus–pituitary–thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

USGS Publications Warehouse

Carr, J.A.; Patino, Reynaldo

2011-01-01

Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health.

The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

USGS Publications Warehouse

Carr, J.A.; Patino, R.

2011-01-01

Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health. ?? 2010 Elsevier Inc.

Evaluation of ammonium perchlorate in the endocrine disruptor screening and testing program's male pubertal protocol: ability to detect effects on thyroid endpoints.

PubMed

Stoker, T E; Ferrell, J M; Laws, S C; Cooper, R L; Buckalew, A

2006-11-10

The U.S. EPA Endocrine Disruptor Screening Program (EDSP) Tier 1 male pubertal protocol was designed as a screen to detect endocrine-disrupting chemicals which may alter reproductive development or thyroid function. One purpose of this in vivo screening protocol is to detect thyrotoxicants via a number of different mechanisms of action, such as thyroid hormone synthesis or clearance. Here we evaluate the ability of this EDSP male pubertal protocol to detect the known thyrotoxicant ammonium perchlorate as an endocrine disruptor. Ammonium perchlorate is a primary ingredient in rocket fuel, fertilizers, paints, and lubricants. Over the past 50 years, potassium perchlorate has been used to treat hyperthyroidism in humans. Perchlorate alters thyroid hormone secretion by competitively inhibiting iodide uptake by the thyroid gland. In this study, ammonium perchlorate was administered at 62.5, 125, 250, and 500 mg/kg to male Wistar rats based on a pilot study of oral dosing. Doses of 125-500 mg/kg perchlorate decreased T4 in a dose-dependent manner. TSH was significantly increased in a dose-responsive manner at the same doses, while T3 was unchanged at any dose. Thyroid histology was significantly altered at all doses, even at the 62.5 mg/kg, with a clear dose-dependent decrease in colloid area and increase in follicular cell height. No effects on preputial separation, a marker of pubertal progression, or reproductive tract development were observed at any dose. These results demonstrate that the male pubertal protocol is useful for detecting thyrotoxicants which target the thyroid axis by this mechanism (altered uptake of iodide). This study also found that perchlorate exposure during this period did not alter any of the reproductive developmental endpoints.

[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.

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.

Direct effects of thyroid hormones on hepatic lipid metabolism.

PubMed

Sinha, Rohit A; Singh, Brijesh K; Yen, Paul M

2018-05-01

It has been known for a long time that thyroid hormones have prominent effects on hepatic fatty acid and cholesterol synthesis and metabolism. Indeed, hypothyroidism has been associated with increased serum levels of triglycerides and cholesterol as well as non-alcoholic fatty liver disease (NAFLD). Advances in areas such as cell imaging, autophagy and metabolomics have generated a more detailed and comprehensive picture of thyroid-hormone-mediated regulation of hepatic lipid metabolism at the molecular level. In this Review, we describe and summarize the key features of direct thyroid hormone regulation of lipogenesis, fatty acid β-oxidation, cholesterol synthesis and the reverse cholesterol transport pathway in normal and altered thyroid hormone states. Thyroid hormone mediates these effects at the transcriptional and post-translational levels and via autophagy. Given these potentially beneficial effects on lipid metabolism, it is possible that thyroid hormone analogues and/or mimetics might be useful for the treatment of metabolic diseases involving the liver, such as hypercholesterolaemia and NAFLD.

Thyroid Hormone, Cancer, and Apoptosis.

PubMed

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

2016-06-13

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

Thyroid Hormone and Seasonal Rhythmicity

PubMed Central

Dardente, Hugues; Hazlerigg, David G.; Ebling, Francis J. P.

2014-01-01

Living organisms show seasonality in a wide array of functions such as reproduction, fattening, hibernation, and migration. At temperate latitudes, changes in photoperiod maintain the alignment of annual rhythms with predictable changes in the environment. The appropriate physiological response to changing photoperiod in mammals requires retinal detection of light and pineal secretion of melatonin, but extraretinal detection of light occurs in birds. A common mechanism across all vertebrates is that these photoperiod-regulated systems alter hypothalamic thyroid hormone (TH) conversion. Here, we review the evidence that a circadian clock within the pars tuberalis of the adenohypophysis links photoperiod decoding to local changes of TH signaling within the medio-basal hypothalamus (MBH) through a conserved thyrotropin/deiodinase axis. We also focus on recent findings which indicate that, beyond the photoperiodic control of its conversion, TH might also be involved in longer-term timing processes of seasonal programs. Finally, we examine the potential implication of kisspeptin and RFRP3, two RF-amide peptides expressed within the MBH, in seasonal rhythmicity. PMID:24616714

Forever young: Endocrinology of paedomorphosis in the Mexican axolotl (Ambystoma mexicanum).

PubMed

De Groef, Bert; Grommen, Sylvia V H; Darras, Veerle M

2018-05-16

The Mexican axolotl (Ambystoma mexicanum) is a salamander species that does not undergo metamorphosis, resulting in the retention of juvenile characteristics in the mature breeding stage (paedomorphosis). Here we review the endocrinological studies investigating the proximate cause of axolotl paedomorphosis with a focus on the hypothalamo-pituitary-thyroid (HPT) axis. It is well established that axolotl paedomorphosis is a consequence of low activity of the HPT axis. The pituitary hormone thyrotropin (TSH) is capable of inducing metamorphosis in the axolotl, which indicates that all processes and interactions in the HPT axis below the pituitary level are functional, but that TSH release is impaired. In metamorphosing species, TSH secretion is largely controlled by the hypothalamic neuropeptide corticotropin-releasing hormone (CRH), which seems to have lost its thyrotropic activity in the axolotl. However, preliminary experiments have not yet confirmed a role for faulty CRH signalling in axolotl paedomorphosis. Other hypothalamic factors and potential pituitary inhibitors need to be investigated to identify their roles in amphibian metamorphosis and axolotl paedomorphosis. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-07-01

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

Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyroidal Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice

PubMed Central

Fontes, Klaus N.; Cabanelas, Adriana; Bloise, Flavia F.; de Andrade, Cherley Borba Vieira; Souza, Luana L.; Wilieman, Marianna; Trevenzoli, Isis H.; Agra, Lais C.; Silva, Johnatas D.; Bandeira-Melo, Christianne; Silva, Pedro L.; Rocco, Patricia R. M.; Ortiga-Carvalho, Tania M.

2017-01-01

Fasting and sepsis induce profound changes in thyroid hormone (TH) central and peripheral metabolism. These changes affect TH action and are called the non-thyroidal illness syndrome (NTIS). To date, it is still debated whether NTIS represents an adaptive response or a real hypothyroid state at the tissue level. Moreover, even though it has been considered the same syndrome, we hypothesized that fasting and sepsis induce a distinct set of changes in thyroid hormone metabolism. Herein, we aimed to evaluate the central and peripheral expression of genes involved in the transport (MCT8/Slc16a2 and MCT10/Slc16a10), metabolism (Dio1, Dio2, and Dio3) and action (Thra and Thrb) of TH during NTIS induced by fasting or sepsis. Male mice were subjected to a 48 h period of fasting or cecal ligation and puncture (CLP)-induced sepsis. At the peripheral level, fasting led to: (1) reduced serum thyroxine (T4) and triiodothyronine (T3), expression of Dio1, Thra, Slc16a2, and MCT8 protein in liver; (2) increased hepatic Slc16a10 and Dio3 expression; and (3) decreased Slc16a2 and Slc16a10 expressions in the thyroid gland. Fasting resulted in reduction of Tshb expression in the pituitary and increased expression of Dio2 in total hypothalamus, arcuate (ARC) and paraventricular (PVN) nucleus. CLP induced sepsis resulted in reduced: (1) T4 serum levels; (2) Dio1, Slc16a2, Slc16a10, Thra, and Thrb expression in liver as well as Slc16a2 expression in the thyroid gland (3) Thrb and Tshb mRNA expression in the pituitary; (4) total leukocyte counts in the bone marrow while increased its number in peritoneal and pleural fluids. In summary, fasting- or sepsis-driven NTIS promotes changes in the set point of hypothalamus-pituitary-thyroid axis through different mechanisms. Reduced hepatic THRs expression in conjunction with reduced TH transporters expression in the thyroid gland may indicate, respectively, reduction in the peripheral action and in the secretion of TH, which may contribute to the low TH serum levels observed in both models. PMID:29118715

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...

Neurotoxicity of Thyroid Disrupting Contaminants

EPA Science Inventory

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

Thyroid hormone and obesity.

PubMed

Pearce, Elizabeth N

2012-10-01

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

3,5-Diiodo-L-Thyronine (3,5-T2) Exerts Thyromimetic Effects on Hypothalamus-Pituitary-Thyroid Axis, Body Composition, and Energy Metabolism in Male Diet-Induced Obese Mice

PubMed Central

Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S.; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

2015-01-01

Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity. PMID:25322465

3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice.

PubMed

Jonas, Wenke; Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

2015-01-01

Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity.

The emergence of levothyroxine as a treatment for hypothyroidism.

PubMed

Hennessey, James V

2017-01-01

To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies. A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified. Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines. The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.

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

PubMed

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

2013-07-01

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

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

Sex Differences in Brain Thyroid Hormone Levels during Early Post-Hatching Development in Zebra Finch (Taeniopygia guttata).

PubMed

Yamaguchi, Shinji; Hayase, Shin; Aoki, Naoya; Takehara, Akihiko; Ishigohoka, Jun; Matsushima, Toshiya; Wada, Kazuhiro; Homma, Koichi J

2017-01-01

Thyroid hormones are closely linked to the hatching process in precocial birds. Previously, we showed that thyroid hormones in brain had a strong impact on filial imprinting, an early learning behavior in newly hatched chicks; brain 3,5,3'-triiodothyronine (T3) peaks around hatching and imprinting training induces additional T3 release, thus, extending the sensitive period for imprinting and enabling subsequent other learning. On the other hand, blood thyroid hormone levels have been reported to increase gradually after hatching in altricial species, but it remains unknown how the brain thyroid hormone levels change during post-hatching development of altricial birds. Here, we determined the changes in serum and brain thyroid hormone levels of a passerine songbird species, the zebra finch using radioimmunoassay. In the serum, we found a gradual increase in thyroid hormone levels during post-hatching development, as well as differences between male and female finches. In the brain, there was clear surge in the hormone levels during development in males and females coinciding with the time of fledging, but the onset of the surge of thyroxine (T4) in males preceded that of females, whereas the onset of the surge of T3 in males succeeded that of females. These findings provide a basis for understanding the functions of thyroid hormones during early development and learning in altricial birds.

Liothyronine

MedlinePlus

... the thyroid gland does not produce enough thyroid hormone). Liothyronine is also used to treat a goiter ( ... where the thyroid gland produces too much thyroid hormone). Liothyronine is in a class of medications called ...

Induction of metamorphosis in the sand dollar Peronella japonica by thyroid hormones.

PubMed

Saito, M; Seki, M; Amemiya, S; Yamasu, K; Suyemitsu, T; Ishihara, K

1998-06-01

The larva of the sand dollar Peronella japonica lacks a mouth and gut, and undergoes metamorphosis into a juvenile sand dollar without feeding. In the present study, it was found that thyroid hormones accelerate the metamorphosis of P. japonica larvae. The contents of thyroid hormones in larvae increased gradually during development. Thiourea and potassium perchlorate, inhibitors of thyroid hormone synthesis, delayed larval metamorphosis and simultaneously repressed an increase in the content of thyroxine in the larval body. These results suggest that the P. japonica larva has a system for synthesis of thyroid hormones that act as factors for inducing metamorphosis.

Gestational 3,3',4,4',5-pentachlorobiphenyl (PCB 126) exposure disrupts fetoplacental unit: Fetal thyroid-cytokines dysfunction.

PubMed

Ahmed, R G; El-Gareib, A W; Shaker, H M

2018-01-01

Exposure to polychlorinated biphenyls (PCBs) is related to several endocrine disorders. This study examined the effect of maternal exposure of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on the fetoplacental unit and fetal thyroid-cytokine axis during the pregnancy. Pregnant albino rats received PCB 126 (20 or 40μg/kgb.wt.) by oral gavage from gestation day (GD) 1 to 20. Potential effects of PCB 126 were evaluated by following the histopathological changes in the placenta by Haematoxylin and Eosin (H&E) stain and measuring the maternofetal thyroid axis (ELIZA), maternofetal body weight, and fetal growth markers (ELIZA), and cytokines (ELIZA) at embryonic day (ED) 20. Placental tissues of both treated groups showed hyperemia, hemorrhage, degeneration and apoptosis in labyrinth layer and spiral artery at GD 20. Both administrations of PCB 126 elevated serum thyrotropin (TSH) concentration, and decreased free thyroxine (FT4) and free triiodothyronine (FT3) concentrations, resulting in a maternofetal hypothyroidism. The presence of hypothyroidism increased fetal serum concentration of transforming growth factor-β (TGF-β), leptin (LEP), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and decreased the fetal serum insulin growth factor-I (IGF-I), IGF-II, insulin, adiponectin (ADP), and growth hormone (GH) in both treated groups at ED 20. However, the increase in resistin (RETN) and interferon-γ (IFN-γ) was non-significant in low-dose group and highly significant in high-dose group. Simultaneously, the reduction in body weight of the dams and fetuses was observed in both PCB 126 groups of examined day with respect to the control group. The maternal PCB 126 distorted the fetoplacental unit might disrupt the fetal thyroid-cytokines axis and prenatal development. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between thyroid functions and urinary growth hormone secretion in patients with hyper- and hypothyroidism.

PubMed

Murao, K; Takahara, J; Sato, M; Tamaki, M; Niimi, M; Ishida, T

1994-10-01

Thyroid hormone plays an important role in growth hormone (GH) synthesis and secretion. To study the relationship between thyroid function and urinary GH secretion in the hyperthyroid and hypothyroid states, we measured thyroid hormones, simultaneously with serum and urinary GH levels, in 54 patients with thyroid diseases. GH-releasing hormone (GRH) test was performed in 18 patients in order to evaluate serum and urinary GH responses to GRH in hyper- and hypothyroid states. Serum thyroid hormone levels were strongly correlated with the urinary GH levels in the patients, and the correlation was greater than that between serum thyroid hormone and serum GH levels. Urinary GH levels were significantly higher in the hyperthyroid patients than in the euthyroid and hypothyroid patients, although serum GH levels were not significantly different among these three groups. Serum GH response to GRH was significantly decreased in hyperthyroid patients as compared to euthyroid patients. However, urinary GH levels after GRH administration were not decreased in the hyperthyroid patients. These results suggest that hyperthyroid states increase GH in urine and may accelerate the urinary clearance of GH.

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

PubMed Central

Falconer, I R; Jacks, F

1975-01-01

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

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...

Screening the Tox21 10K library for thyroid stimulating hormone receptor agonist and antagonist activity (SOT annual meeting)

EPA Science Inventory

Thyroid-stimulating hormone (TSH) regulates thyroid hormone (TH) production via binding to its receptor (TSHR). The roles of TSHR in human pathologies including hyper/hypothyroidism, Grave’s disease, and thyroid cancer are known, but it is currently unknown whether TSHR is an imp...

Stimulation of thyroid hormone secretion by thyrotropin in beluga whales, Delphinapterus leucas.

PubMed Central

St Aubin, D J

1987-01-01

Bovine thyroid stimulating hormone administered to three beluga whales, Delphinapterus leucas, was effective in producing an increase in circulating levels of triiodothyronine and thyroxine. A single dose of 10 I.U. of thyroid stimulating hormone resulted in a 145% increase in triiodothyronine and a 35% increase in thyroxine after nine hours in a whale tested within two hours after capture. The response was less pronounced in an animal tested with the same does on two occasions after four and eight weeks in captivity. In the third whale, 10 I.U. of thyroid stimulating hormone given on each of three consecutive days produced a marked increase in triiodothyronine and thyroxine. The elevation of thyroxine concentration persisted for at least two days after the last injection of thyroid stimulating hormone. A subsequent decrease in thyroxine to levels below baseline signalled the suppression of endogenous thyroid stimulating hormone. This preliminary study helps to establish a protocol for testing thyroid function in cetaceans. PMID:3651900

Evidence that thyroid hormone induces olfactory cellular proliferation in salmon during a sensitive period for imprinting.

PubMed

Lema, Sean C; Nevitt, Gabrielle A

2004-09-01

Salmon have long been known to imprint and home to natal stream odors, yet the mechanisms driving olfactory imprinting remain obscure. The timing of imprinting is associated with elevations in plasma thyroid hormone levels, with possible effects on growth and proliferation of the peripheral olfactory system. Here, we begin to test this idea by determining whether experimentally elevated plasma levels of 3,5,3'-triiodothyronine (T(3)) influence cell proliferation as detected by the 5-bromo-2'-deoxyuridine (BrdU) cell birth-dating technique in the olfactory epithelium of juvenile coho salmon (Oncorhynchus kisutch). We also explore how natural fluctuations in thyroxine (T(4)) relate to proliferation in the epithelium during the parr-smolt transformation. In both studies, we found that BrdU labeled both single and clusters of mitotic cells. The total number of BrdU-labeled cells in the olfactory epithelium was significantly greater in fish with artificially elevated T(3) compared with placebo controls. This difference in proliferation was restricted to the basal region of the olfactory epithelium, where multipotent progenitor cells differentiate into olfactory receptor neurons. The distributions of mitotic cluster sizes differed significantly from a Poisson distribution for both T(3) and placebo treatments, suggesting that proliferation tends to be non-random. Over the course of the parr-smolt transformation, changes in the density of BrdU cells showed a positive relationship with natural fluctuations in plasma T(4). This relationship suggests that even small changes in thyroid activity can stimulate the proliferation of neural progenitor cells in the salmon epithelium. Taken together, our results establish a link between the thyroid hormone axis and measurable anatomical changes in the peripheral olfactory system.

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

Deiodinases, Organic Anion Transporter Polypeptide Polymorphisms, and Thyroid Hormones in Patients with Myocardial Infarction.

PubMed

Brozaitiene, Julija; Skiriute, Daina; Burkauskas, Julius; Podlipskyte, Aurelija; Jankauskiene, Edita; Serretti, Alessandro; Mickuviene, Narseta

2018-04-01

To investigate the association among deiodinases (DIO), organic anion-transporting polypeptide 1C1 (OATP1C1) gene polymorphisms, and thyroid hormones (THs) in patients with acute myocardial infarction (AMI). In summary, 290 patients with AMI were evaluated for sociodemographic and clinical characteristics, coronary artery disease (CAD) risk factors, and comorbidities, as well as circulating thyroid-stimulating hormone and TH (triiodothyronine [T3], thyroxine [T4], free T3, free T4, and reverse T3) levels. Ten single nucleotide polymorphisms for thyroid axis related genes: DIO1 (rs11206244-C/T, rs12095080-A/G, rs2235544-A/C), DIO2 (rs225014-T/C, rs225015-G/A), DIO3 (rs945006-T/G), and OATP1C1 (rs10444412-T/C, rs10770704-C/T, rs1515777-A/G, rs974453-G/A) were genotyped. Marginal associations were observed between the DIO1, DIO2, and OATP1C1 gene polymorphisms and almost all analyzed THs (p's < 0.05). After controlling for potential confounders, the OATP1C1 rs1515777-A/G minor allele homozygous genotype (G/G) was associated with a decrease in circulating free T3 and free T3/free T4. In the AMI cohort, associations between: DIO1 rs12095080 and hypertension; DIO2 rs225015 and diabetes mellitus; and the OATP1C1 rs974453 genotype, and AMI type were established. DIO1 and DIO2 gene polymorphisms are mainly associated with T3, free T4, free T3/free T4, and [natural-log transformed (ln)] reverse T3 levels, while the OATP1C1 minor allele homozygous genotype is associated with free T3 and free T3/free T4 in CAD patients after AMI.

Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal

PubMed Central

Martinez, Bridget; Soñanez-Organis, José G.; Vázquez-Medina, José Pablo; Viscarra, Jose A.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

2013-01-01

SUMMARY Food deprivation in mammals is typically associated with reduced thyroid hormone (TH) concentrations and deiodinase content and activity to suppress metabolism. However, in prolonged-fasted, metabolically active elephant seal pups, TH levels are maintained, if not elevated. The functional relevance of this apparent paradox is unknown and demonstrates variability in the regulation of TH levels, metabolism and function in food-deprived mammals. To address our hypothesis that cellular TH-mediated activity is upregulated with fasting duration, we quantified the mRNA expression and protein content of adipose and muscle deiodinase type I (DI1) and type II (DI2), and TH receptor beta-1 (THrβ-1) after 1, 3 and 7 weeks of fasting in northern elephant seal pups (N=5–7 per week). Fasting did not decrease the concentrations of plasma thyroid stimulating hormone, total triiodothyronine (tT3), free T3, total thyroxine (tT4) or free T4, suggesting that the hypothalamic–pituitary–thyroid axis is not suppressed, but rather maintained during fasting. Mean mRNA expression of adipose DI1 and DI2 increased threefold and fourfold, respectively, and 20- and 30-fold, respectively, in muscle. With the exception of adipose DI1, protein expression of adipose DI2 and muscle DI1 and DI2 increased twofold to fourfold. Fasting also increased adipose (fivefold) and muscle (fourfold) THrβ-1 mRNA expression, suggesting that the mechanisms mediating cellular TH activity are upregulated with prolonged fasting. The data demonstrate a unique, atypical mechanism of TH activity and regulation in mammals adapted to prolonged food deprivation in which the potential responsiveness of peripheral tissues and cellular TH activity are increased, which may contribute to their lipid-based metabolism. PMID:24307712

The interrelationships of thyroid and growth hormones: effect of growth hormone releasing hormone in hypo- and hyperthyroid male rats.

PubMed

Root, A W; Shulman, D; Root, J; Diamond, F

1986-01-01

Growth hormone (GH) and the thyroid hormones interact in the hypothalamus, pituitary and peripheral tissues. Thyroid hormone exerts a permissive effect upon the anabolic and metabolic effects of GH, and increases pituitary synthesis of this protein hormone. GH depresses the secretion of thyrotropin and the thyroid hormones and increases the peripheral conversion of thyroxine to triiodothyronine. In the adult male rat experimental hypothyroidism produced by ingestion of propylthiouracil depresses the GH secretory response to GH-releasing hormone in vivo and in vitro, reflecting the lowered pituitary stores of GH in the hypothyroid state. Short term administration of large amounts of thyroxine with induction of the hyperthyroid state does not affect the in vivo GH secretory response to GH-releasing hormone in this animal.

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

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.

Intermittent changing axis deviation with intermittent left anterior hemiblock during atrial flutter with subclinical hyperthyroidism.

PubMed

Patanè, Salvatore; Marte, Filippo

2009-06-26

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with CHD or mortality from cardiovascular causes but it is usually associated with a higher heart rate and a higher risk of supraventricular arrhythmias including atrial fibrillation and atrial flutter. Intermittent changing axis deviation during atrial fibrillation has also rarely been reported. We present a case of intermittent changing axis deviation with intermittent left anterior hemiblock in a 59-year-old Italian man with atrial flutter and subclinical hyperthyroidism. To our knowledge, this is the first report of intermittent changing axis deviation with intermittent left anterior hemiblock in a patient with atrial flutter.

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

PubMed

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

2016-06-01

Findings from national surveys suggest that everyone in the United States is exposed to perchlorate. At high doses, perchlorate, thiocyanate, and nitrate inhibit iodide uptake into the thyroid and decrease thyroid hormone production. Small changes in thyroid hormones during pregnancy, including changes within normal reference ranges, have been linked to cognitive function declines in the offspring. We evaluated the potential effects of low environmental exposures to perchlorate on thyroid function. Serum thyroid hormones and anti-thyroid antibodies and urinary perchlorate, thiocyanate, nitrate, and iodide concentrations were measured in 1,880 pregnant women from San Diego County, California, during 2000-2003, a period when much of the area's water supply was contaminated from an industrial plant with perchlorate at levels near the 2007 California regulatory standard of 6 μg/L. Linear regression was used to evaluate associations between urinary perchlorate and serum thyroid hormone concentrations in models adjusted for urinary creatinine and thiocyanate, maternal age and education, ethnicity, and gestational age at serum collection. The median urinary perchlorate concentration was 6.5 μg/L, about two times higher than in the general U.S. Adjusted associations were identified between increasing log10 perchlorate and decreasing total thyroxine (T4) [regression coefficient (β) = -0.70; 95% CI: -1.06, -0.34], decreasing free thyroxine (fT4) (β = -0.053; 95% CI: -0.092, -0.013), and increasing log10 thyroid-stimulating hormone (β = 0.071; 95% CI: 0.008, 0.133). These results suggest that environmental perchlorate exposures may affect thyroid hormone production during pregnancy. This could have implications for public health given widespread perchlorate exposure and the importance of thyroid hormone in fetal neurodevelopment. Steinmaus C, Pearl M, Kharrazi M, Blount BC, Miller MD, Pearce EN, Valentin-Blasini L, DeLorenze G, Hoofnagle AN, Liaw J. 2016. Thyroid hormones and moderate exposure to perchlorate during pregnancy in women in Southern California. Environ Health Perspect 124:861-867; http://dx.doi.org/10.1289/ehp.1409614.

Exposure to butachlor causes thyroid endocrine disruption and promotion of metamorphosis in Xenopus laevis.

PubMed

Li, Shuying; Li, Meng; Wang, Qiangwei; Gui, Wenjun; Zhu, Guonian

2016-06-01

Butachlor is extensively applied in rice paddy ecosystem in china, and has been widespread contaminant in the aquatic environment. Here, Xenopus laevis was used for the evaluation of teratogenesis developmental toxicity, and disruption of thyroid system when exposure to different concentrations of butachlor by window phase exposure. Acute toxicity investigation shown that 96 h-LC50 value of butachlor was 1.424 mg L(-1) and 0.962 mg L(-1) for tadpoles (starting from stages 46/47) and embryos (starting from stages 8/9), respectively. Exposure to butachlor caused malformation, including abnormal eye, pericardial edema, enlarged proctodaeum and bent tail. Window phase exposure test indicated that butachlor significantly promote the contents of whole-body thyroid hormones (THs, T3 and T4) at higher levels, indicating thyroid endocrine disruption. At 7 days, exposure to butachlor up-regulated the mRNA expression of genes involved in THs synthesis and metabolism (tshα, tg, tpo and dio1) and THs receptors (trα and trβ). At 14 days, up-regulation of the mRNA expression of genes related to THs synthesis and metabolism (tshα, tshβ, tg, tpo, dio1, dio2 and ttr) and THs receptors (trβ) were also observed after the exposure to butachlor. At 21 days, butachlor up-regulated the mRNA expression of tshα, tg, tpo genes and down-regulated the mRNA expression of tshβ, tg, dio1, ttr and trα genes. These results showed that butachlor could change the mRNA expression of genes involved in the HPT axis and increase whole-body thyroid hormones levels of X. laevis tadpoles in a dose- and time-dependent manner, causing thyroid endocrine disruption and developmental toxicity. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Thyroid hormones and coronary artery calcification in euthyroid men and women.

PubMed

Zhang, Yiyi; Kim, Bo-Kyoung; Chang, Yoosoo; Ryu, Seungho; Cho, Juhee; Lee, Won-Young; Rhee, Eun-Jung; Kwon, Min-Jung; Rampal, Sanjay; Zhao, Di; Pastor-Barriuso, Roberto; Lima, Joao A; Shin, Hocheol; Guallar, Eliseo

2014-09-01

Overt and subclinical hypothyroidism are risk factors for atherosclerosis. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). We conducted a cross-sectional study of 41 403 apparently healthy young and middle-aged men and women with normal thyroid hormone levels. Free thyroxin, free triiodothyronine, and thyroid-stimulating hormone levels were measured by electrochemiluminescent immunoassay. CAC score was measured by multidetector computed tomography. The multivariable adjusted CAC ratios comparing the highest versus the lowest quartile of thyroid hormones were 0.74 (95% confidence interval, 0.60-0.91; P for trend <0.001) for free thyroxin, 0.81 (0.66-1.00; P for trend=0.05) for free triiodothyronine, and 0.78 (0.64-0.95; P for trend=0.01) for thyroid-stimulating hormone. Similarly, the odds ratios for detectable CAC (CAC >0) comparing the highest versus the lowest quartiles of thyroid hormones were 0.87 (0.79-0.96; P for linear trend <0.001) for free thyroxin, 0.90 (0.82-0.99; P for linear trend=0.02) for free triiodothyronine, and 0.91 (0.83-1.00; P for linear trend=0.03) for thyroid-stimulating hormone. In a large cohort of apparently healthy young and middle-aged euthyroid men and women, low-normal free thyroxin and thyroid-stimulating hormone were associated with a higher prevalence of subclinical coronary artery disease and with a greater degree of coronary calcification. © 2014 American Heart Association, Inc.

Organizational Changes to Thyroid Regulation in Alligator mississippiensis: Evidence for Predictive Adaptive Responses

PubMed Central

Boggs, Ashley S. P.; Lowers, Russell H.; Cloy-McCoy, Jessica A.; Guillette, Louis J.

2013-01-01

During embryonic development, organisms are sensitive to changes in thyroid hormone signaling which can reset the hypothalamic-pituitary-thyroid axis. It has been hypothesized that this developmental programming is a ‘predictive adaptive response’, a physiological adjustment in accordance with the embryonic environment that will best aid an individual's survival in a similar postnatal environment. When the embryonic environment is a poor predictor of the external environment, the developmental changes are no longer adaptive and can result in disease states. We predicted that endocrine disrupting chemicals (EDCs) and environmentally-based iodide imbalance could lead to developmental changes to the thyroid axis. To explore whether iodide or EDCs could alter developmental programming, we collected American alligator eggs from an estuarine environment with high iodide availability and elevated thyroid-specific EDCs, a freshwater environment contaminated with elevated agriculturally derived EDCs, and a reference freshwater environment. We then incubated them under identical conditions. We examined plasma thyroxine and triiodothyronine concentrations, thyroid gland histology, plasma inorganic iodide, and somatic growth at one week (before external nutrition) and ten months after hatching (on identical diets). Neonates from the estuarine environment were thyrotoxic, expressing follicular cell hyperplasia (p = 0.01) and elevated plasma triiodothyronine concentrations (p = 0.0006) closely tied to plasma iodide concentrations (p = 0.003). Neonates from the freshwater contaminated site were hypothyroid, expressing thyroid follicular cell hyperplasia (p = 0.01) and depressed plasma thyroxine concentrations (p = 0.008). Following a ten month growth period under identical conditions, thyroid histology (hyperplasia p = 0.04; colloid depletion p = 0.01) and somatic growth (body mass p<0.0001; length p = 0.02) remained altered among the contaminated sites. This work supports the hypothesis that embryonic EDC exposure or iodide imbalance could induce adult metabolic disease states, thereby stressing the need to consider the multiple environmental variables present during development. PMID:23383213

Effects of Sample Handling and Analytical Procedures on Thyroid Hormone Concentrations in Pregnant Women's Plasma.

PubMed

Villanger, Gro Dehli; Learner, Emily; Longnecker, Matthew P; Ask, Helga; Aase, Heidi; Zoeller, R Thomas; Knudsen, Gun P; Reichborn-Kjennerud, Ted; Zeiner, Pål; Engel, Stephanie M

2017-05-01

Maternal thyroid function is a critical mediator of fetal brain development. Pregnancy-related physiologic changes and handling conditions of blood samples may influence thyroid hormone biomarkers. We investigated the reliability of thyroid hormone biomarkers in plasma of pregnant women under various handling conditions. We enrolled 17 pregnant women; collected serum and plasma were immediately frozen. Additional plasma aliquots were subjected to different handling conditions before the analysis of thyroid biomarkers: storage at room temperature for 24 or 48 hours before freezing and an extra freeze-thaw cycle. We estimated free thyroid hormone indices in plasma based on T3 uptake. High correlations between plasma and serum (>0.94) and intraclass correlation coefficients for plasma handling conditions (0.96 to 1.00) indicated excellent reliability for all thyroid hormone biomarkers. Delayed freezing and freeze-thaw cycles did not affect reliability of biomarkers of thyroid function in plasma during pregnancy. See video abstract at, http://links.lww.com/EDE/B180.

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

USDA-ARS?s Scientific Manuscript database

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

TSH (Thyroid-stimulating hormone) test

MedlinePlus

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

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

PubMed

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

2016-03-01

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

Effects of phenobarbital on thyroid hormone contabolism in rat hepatocytes

EPA Science Inventory

Hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations in rodents. PB induction of hepatic xenobiotic metabolizing enzymes increases thyroid hormones catabolism and biliary elimination. This study examines the catabolism and cl...

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

PubMed

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

1996-05-15

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

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

2014-01-01

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

Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyoidal Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice.

PubMed

Fontes, Klaus N; Cabanelas, Adriana; Bloise, Flavia F; de Andrade, Cherley Borba Vieira; Souza, Luana L; Wilieman, Marianna; Trevenzoli, Isis H; Agra, Lais C; Silva, Johnatas D; Bandeira-Melo, Christianne; Silva, Pedro L; Rocco, Patricia R M; Ortiga-Carvalho, Tania M

2017-01-01

Fasting and sepsis induce profound changes in thyroid hormone (TH) central and peripheral metabolism. These changes affect TH action and are called the non-thyroidal illness syndrome (NTIS). To date, it is still debated whether NTIS represents an adaptive response or a real hypothyroid state at the tissue level. Moreover, even though it has been considered the same syndrome, we hypothesized that fasting and sepsis induce a distinct set of changes in thyroid hormone metabolism. Herein, we aimed to evaluate the central and peripheral expression of genes involved in the transport (MCT8/ Slc16a2 and MCT10/ Slc16a10 ), metabolism ( Dio1, Dio2 , and Dio3 ) and action ( Thra and Thrb ) of TH during NTIS induced by fasting or sepsis. Male mice were subjected to a 48 h period of fasting or cecal ligation and puncture (CLP)-induced sepsis. At the peripheral level, fasting led to: (1) reduced serum thyroxine (T 4 ) and triiodothyronine (T 3 ), expression of Dio1, Thra, Slc16a2 , and MCT8 protein in liver; (2) increased hepatic Slc16a10 and Dio3 expression; and (3) decreased Slc16a2 and Slc16a10 expressions in the thyroid gland. Fasting resulted in reduction of Tshb expression in the pituitary and increased expression of Dio2 in total hypothalamus, arcuate (ARC) and paraventricular (PVN) nucleus. CLP induced sepsis resulted in reduced: (1) T 4 serum levels; (2) Dio1, Slc16a2, Slc16a10, Thra , and Thrb expression in liver as well as Slc16a2 expression in the thyroid gland (3) Thrb and Tshb mRNA expression in the pituitary; (4) total leukocyte counts in the bone marrow while increased its number in peritoneal and pleural fluids. In summary, fasting- or sepsis-driven NTIS promotes changes in the set point of hypothalamus-pituitary-thyroid axis through different mechanisms. Reduced hepatic THRs expression in conjunction with reduced TH transporters expression in the thyroid gland may indicate, respectively, reduction in the peripheral action and in the secretion of TH, which may contribute to the low TH serum levels observed in both models.

Thyroid-stimulation hormone-receptor antibodies as a predictor of thyrosuppressive drug therapy outcome in Graves' disease patients.

PubMed

Aleksić, Aleksandar Z; Aleksić, Željka; Manić, Saška; Mitov, Vladimir; Jolić, Aleksandar

2014-01-01

Graves' disease is autoimmune hyperthyroidism caused by pathological stimulation of thyroid-stimulation hormone-receptor antibodies. The decision on changing the therapy can be made on time by determining the prognostic factors of thyrosuppressive drug therapy outcome. The aim of the study was to determine the significance of thyroid-stimulation hormone-receptor antibodies level on the prediction of therapy outcome. The study was prospective and involved 106 drug-treated patients with newly diagnosed Graves' disease. Thyroid-stimulation hormone-receptor antibodies level was measured at the beginning of therapy, during therapy and 12 months after it had been introduced. No statistically significant difference in the level of thyroid-stimulation hormone-receptor antibodies was found at the beginning of disease and 12 months after the introduction of thyrosuppressive drug therapy among the patients who had been in remission and those who had not. Regardless of the outcome, thyroid-stimulation hormone-receptor antibodies level significantly decreased in all patients 12 months after the therapy had been introduced. The level of thyroid-stimulation hormone-receptor antibodies at the beginning of disease and 12 months after the introduction of therapy cannot predict the outcome of thyrosuppressive drug therapy.

Selenium and the control of thyroid hormone metabolism.

PubMed

Köhrle, Josef

2005-08-01

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

Association between thyroid hormones and TRAIL.

PubMed

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

2017-11-01

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

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...

Establishing Adverse Outcome Pathways of Thyroid Hormone Disruption in an Amphibian Model

EPA Science Inventory

The Adverse Outcome Pathway (AOP) provides a framework for understanding the relevance of toxicology data in ecotoxicological hazard assessments. The AOP concept can be applied to many toxicological pathways including thyroid hormone disruption. Thyroid hormones play a critical r...

Thyrotropin-producing pituitary adenoma simultaneously existing with Graves' disease: a case report.

PubMed

Arai, Nobuhiko; Inaba, Makoto; Ichijyo, Takamasa; Kagami, Hiroshi; Mine, Yutaka

2017-01-06

Thyrotropin-producing pituitary tumor is relatively rare. In particular, concurrent cases associated with Graves' disease are extremely rare and only nine cases have been reported so far. We describe a case of a thyrotropin-producing pituitary adenoma concomitant with Graves' disease, which was successfully treated. A 40-year-old Japanese woman presented with mild signs of hyperthyroidism. She had positive anti-thyroid-stimulating hormone receptor antibody, anti-thyroglobulin antibody, and anti-thyroid peroxidase antibody. Her levels of serum thyroid-stimulating hormone, which ranged from low to normal in the presence of high levels of serum free thyroid hormones, were considered to be close to a state of syndrome of inappropriate secretion of thyroid-stimulating hormone. Magnetic resonance imaging showed a macropituitary tumor. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease was suspected. Initial therapy included anti-thyroid medication, which was immediately discontinued due to worsening symptoms. Subsequently, surgical therapy for the pituitary tumor was conducted, and her levels of free thyroid hormones, including the thyroid-stimulating hormone, became normal. On postoperative examination, her anti-thyroid-stimulating hormone receptor antibody levels decreased, and the anti-thyroglobulin antibody became negative. The coexistence of thyrotropin-producing pituitary adenoma and Graves' disease is rarely reported. The diagnosis of this condition is complicated, and the appropriate treatment strategy has not been clearly established. This case suggests that physicians should consider the coexistence of thyrotropin-producing pituitary adenoma with Graves' disease in cases in which thyroid-stimulating hormone values range from low to normal in the presence of thyrotoxicosis, and the surgical treatment of thyrotropin-producing pituitary adenoma could be the first-line therapy in patients with both thyrotropin-producing pituitary adenoma and Graves' disease.

Hyperthyroidism

PubMed Central

2016-01-01

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves’ disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves’ disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment. PMID:27038492

Hyperthyroidism.

PubMed

De Leo, Simone; Lee, Sun Y; Braverman, Lewis E

2016-08-27

Hyperthyroidism is characterised by increased thyroid hormone synthesis and secretion from the thyroid gland, whereas thyrotoxicosis refers to the clinical syndrome of excess circulating thyroid hormones, irrespective of the source. The most common cause of hyperthyroidism is Graves' disease, followed by toxic nodular goitre. Other important causes of thyrotoxicosis include thyroiditis, iodine-induced and drug-induced thyroid dysfunction, and factitious ingestion of excess thyroid hormones. Treatment options for Graves' disease include antithyroid drugs, radioactive iodine therapy, and surgery, whereas antithyroid drugs are not generally used long term in toxic nodular goitre, because of the high relapse rate of thyrotoxicosis after discontinuation. β blockers are used in symptomatic thyrotoxicosis, and might be the only treatment needed for thyrotoxicosis not caused by excessive production and release of the thyroid hormones. Thyroid storm and hyperthyroidism in pregnancy and during the post-partum period are special circumstances that need careful assessment and treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-04-01

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

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).

[Hypophysis-adrenal and thyroid secretion at law order staff depending on professional loading].

PubMed

Koubassov, R V; Barachevsky, Yu E; Ivanov, A M

2015-01-01

A current etiological and pathogenic opinion about human health disturbance thereupon extreme factor effects is shown that this cause is principal mechanism of regulatory system (neuroimmunoendocrine complex) distress. In endocrine link occurs hormonal disbalance in hypothalamus-hypophysis axis, physiological interrelation disturbances in central-peripheral gland system (hypophysis-adrenal, hypophysis-thyroid) and metabolism abnormalities subsequently. Our aim was to determine the particular content of adrenocorticotropic and thyrothrophin hormone, cortisol, thyroxin and triiodthyronine features at law order staff in dependence from professional loading. It's provided two investigation series among law order staff groups--combatants, ordinary policemen and military school students. The investigation period for all people corresponds to combat mission beginning and its finish. In blood serum an adrenocorticotropic (ACTH) and thyrothrophin (TSH) hormone, cortisol, thyroxin (T) and triiodthyronine (T) levels were determined. A higher ACTH and TSH levels detected at combatants in both investigation series. A cortisol, T4 and T3 at combatants before military mission were least in comparative with other groups, but after mission it indexes were largest. Prolonged changes of endocrine secretory function that lead to hormonal disbalance can result to adaptation derangement. In connection with it in medical providing system for person that undergo extreme negative professional factors it's necessary create a special endocrine link with the view of organism resistance and life viability to extreme emergency factors and for prevention of pathological conditions.

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.

Experimental study on neuroendocrinological and immunological characteristics of the military-trained artillerymen.

PubMed

Li, Xin; Huang, Wen-xu; Lu, Ju-ming; Yang, Guang; Ma, Fang-ling; Lan, Ya-ting; Meng, Jun-hua; Dou, Jing-tao

2012-04-01

Over one million soldiers were treated for battle- or training-fatigue during World War II. Of all ground combat troops, 37% were discharged for psychiatric reasons due to fatigue. The neuroendocrinological and immunological systems played important roles in the work-related fatigue of military personnel. The aim of this study was to investigate the characteristics of fatigue associated with military operations, and we observed changes in the regulatory functions of the neuroendocrinological and immunological systems that may provide theoretical support for improving the combat effectiveness of armies. A total of 240 soldiers from the Field Artillery regiment were selected as subjects. Researchers and subjects received training before participating in the study. Data of the subjects' medical histories, physical examinations, scores on a fatigue assessment scale, and assessments of pituitary-adrenal hormones (adrenal cortical hormone (ACTH), cortical hormone (F), and 24-hour urine-free cortisol (UFC)), pituitary-gonadal hormones (luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, estradiol (E2), and prolactin (PRL)), pituitary-thyroid hormones (thyroid-stimulating hormone (TSH), thyroxine (TT4), triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3)), and cellular immune parameters (CD3(+), CD4(+), CD8(+), CD4(+)/CD8(+), B, and NK cells) were investigated before and after large-scale and high-intensity field exercises. Data were statistically analyzed with Student's t test using SPSS software (version 13.0), and P values < 0.05 were deemed to be significant. After the high-intensity military training, the scores on the fatigue scale reflected significant increases of feeling of unpleasantness among soldiers. Additionally, the symptom checklist showed notable increases in somatization scores and significant decreases in psychoticism scores. After intensive military work, levels of plasma ACTH, F, and UFC of soldiers were decreased (P < 0.01). The level of testosterone decreased significantly after the maneuver ((23.51 ± 6.49) versus (18.89 ± 5.89) nmol/L; P < 0.001), whereas the thyroid function (TT3, FT4, and FT3) was markedly increased after the maneuver (P < 0.01). The number of CD3(+), CD4(+), CD4(+)/CD8(+) cells, and B lymphocytes were decreased (P < 0.05), and NK cells were increased (P < 0.001) after the maneuver. Following high-intensity military operations, the psychological tolerance of soldiers was depressed. And the hypoadrenocorticism (the functional decreases of hypothalamic-pituitary-gonadal and abnormal pituitary-thyroid axis) contributed to the increased levels of fatigue. Hypoimmunity may increase the susceptibility to diseases after high-intensity military operations.

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

Thyroid hormone concentrations in captive and free-ranging West Indian manatees (Trichechus manatus).

PubMed

Ortiz, R M; MacKenzie, D S; Worthy, G A

2000-12-01

Because thyroid hormones play a critical role in the regulation of metabolism, the low metabolic rates reported for manatees suggest that thyroid hormone concentrations in these animals may also be reduced. However, thyroid hormone concentrations have yet to be examined in manatees. The effects of captivity, diet and water salinity on plasma total triiodothyronine (tT(3)), total thyroxine (tT(4)) and free thyroxine (fT(4)) concentrations were assessed in adult West Indian manatees (Trichechus manatus). Free-ranging manatees exhibited significantly greater tT(4) and fT(4) concentrations than captive adults, regardless of diet, indicating that some aspect of a captive existence results in reduced T(4) concentrations. To determine whether this reduction might be related to feeding, captive adults fed on a mixed vegetable diet were switched to a strictly sea grass diet, resulting in decreased food consumption and a decrease in body mass. However, tT(4) and fT(4) concentrations were significantly elevated over initial values for 19 days. This may indicate that during periods of reduced food consumption manatees activate thyroid-hormone-promoted lipolysis to meet water and energetic requirements. Alterations in water salinity for captive animals did not induce significant changes in thyroid hormone concentrations. In spite of lower metabolic rates, thyroid hormone concentrations in captive manatees were comparable with those for other terrestrial and marine mammals, suggesting that the low metabolic rate in manatees is not attributable to reduced circulating thyroid hormone concentrations.

A Hormonally Active Malignant Struma Ovarii

PubMed Central

Lara, Carolina; Salame, Latife; Padilla-Longoria, Rafael

2016-01-01

Struma ovarii is a rare monodermal variant of ovarian teratoma that contains at least 50% thyroid tissue. Less than 8% of struma ovarii cases present with clinical and biochemical evidence of thyrotoxicosis due to ectopic production of thyroid hormone and only 5% undergo malignant transformation into a papillary thyroid carcinoma. Only isolated cases of hormonally active papillary thyroid carcinoma developing within a struma ovarii have been reported in the literature. We report the case of a 36-year-old woman who presented with clinical signs and symptoms of hyperthyroidism as well as a left adnexal mass, which proved to be a thyroid hormone-producing, malignant struma ovarii. PMID:27882257

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.

Thyroid and the Heart

PubMed Central

Grais, Ira Martin; Sowers, James R.

2015-01-01

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

Unstable Thyroid Function in Older Adults Is Caused by Alterations in Both Thyroid and Pituitary Physiology and Is Associated with Increased Mortality.

PubMed

Mammen, Jennifer S; McGready, John; Ladenson, Paul W; Simonsick, Eleanor M

2017-11-01

Average thyrotropin (TSH) levels are known to be higher in older adults when measured in cross-sectional populations. Possible etiologies include differential survival, neutral aging changes, or increased disease prevalence at older ages. This study aimed to elucidate the mechanisms underlying changing thyroid function during aging, and to determine the association of changes with survival, by analyzing the individual thyroid axis over time. Individual patterns of changing TSH and free thyroxine (fT4) were determined in 640 participants in the Baltimore Longitudinal Study of Aging who had at least three measures of serum TSH and fT4, not on medications, over an average of seven years of follow-up. Participants with changing phenotypes were identified based on quintiles for both slopes. Those with alterations in primary thyroid gland function demonstrated intact negative feedback (rising TSH with declining fT4 or declining TSH with rising fT4). Other participants had a parallel rise or fall of TSH and fT4 levels, consistent with pituitary dysfunction. Predictors of phenotype were analyzed by logistic regression. Differential survival between thyroid aging phenotypes was analyzed using multivariate Cox regression. While the majority of participants at all ages had stable thyroid function, changes were more common among older adults, with 32.3% of those aged >80 years but only 9.5% of those aged <60 years demonstrating thyroid function changes in the highest and lowest quintiles. Regression to the mean accounts for some of the changes, for example increased baseline TSH was associated with a falling TSH pattern (odds ratio = 1.4 [confidence interval 1.1-1.7] per 1 mIU/L). Importantly, changing thyroid function in either the upper or lower quintiles of slope for TSH and fT4 was associated with increased risk of death compared to stable thyroid status (hazard ratio = 5.4 [confidence interval 3.1-9.5]). Changing thyroid hormone function is increasingly common at older ages and is associated with decreased survival. Nonetheless, the tendency for abnormal thyroid function tests to resolve, along with altered pituitary responsiveness underlying some TSH elevations, suggests that an elevated TSH level should be not assumed to represent subclinical hypothyroidism in older adults. Thus, caution is appropriate when determining the need for thyroid hormone supplements in older adults.

Thyroid hormone metabolism and environmental chemical exposure

PubMed Central

2012-01-01

Background Polychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism. Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort. Methods Vena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels. Results The current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group. Conclusion Once again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones. PMID:22759492

Pituitary Tumors

MedlinePlus

... or milk production), sex hormones (control the menstrual cycle and other sexual functions), thyroid gland hormones (control the thyroid gland), adrenal gland hormones, and vasopressin (a hormone involved in water and electrolyte balance). Symptoms of pituitary adenoma and ...

THYROID HORMONE DISRUPTION: FROM KINETICS TO DYNAMICS.

EPA Science Inventory

A wide range of chemicals with diverse structures act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are chemicals that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormones (THs), or change circulating or t...

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

PubMed

Song, F; Yi, H L

2018-05-07

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

New approaches to thyroid hormones and purinergic signaling.

PubMed

Silveira, Gabriel Fernandes; Buffon, Andréia; Bruno, Alessandra Nejar

2013-01-01

It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling.

New Approaches to Thyroid Hormones and Purinergic Signaling

PubMed Central

Silveira, Gabriel Fernandes; Buffon, Andréia; Bruno, Alessandra Nejar

2013-01-01

It is known that thyroid hormones influence a wide variety of events at the molecular, cellular, and functional levels. Thyroid hormones (TH) play pivotal roles in growth, cell proliferation, differentiation, apoptosis, development, and metabolic homeostasis via thyroid hormone receptors (TRs) by controlling the expression of TR target genes. Most of these effects result in pathological and physiological events and are already well described in the literature. Even so, many recent studies have been devoted to bringing new information on problems in controlling the synthesis and release of these hormones and to elucidating mechanisms of the action of these hormones unconventionally. The purinergic system was recently linked to thyroid diseases, including enzymes, receptors, and enzyme products related to neurotransmitter release, nociception, behavior, and other vascular systems. Thus, throughout this text we intend to relate the relationship between the TH in physiological and pathological situations with the purinergic signaling. PMID:23956925

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...

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

EPA Science Inventory

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

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

EPA Science Inventory

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

Gene Expression as a Biomarker of Effect of Thyroid Hormone Action in Developing Brain: Relation to Serum Hormones.

EPA Science Inventory

Disruption of thyroid hormone (TH) homeostasis is a known effect of environmental contaminants. Although animal models of developmental TH deficiency can predict the impact of severe insults to the thyroid system, the effects of moderate TH insufficiencies have proved more diffic...

Thyroid Hormone in the Clinic and Breast Cancer.

PubMed

Hercbergs, Aleck; Mousa, Shaker A; Leinung, Matthew; Lin, Hung-Yun; Davis, Paul J

2018-06-01

There is preclinical and recent epidemiological evidence that thyroid hormone supports breast cancer. These observations raise the issue of whether management of breast cancer in certain settings should include consideration of reducing the possible contribution of thyroid hormone to the advancement of the disease. In a preliminary experience, elimination of the clinical action of endogenous L-thyroxine (T 4 ) in patients with advanced solid tumors, including breast cancer, has favorably affected the course of the cancer, particularly when coupled with administration of exogenous 3,5,3'-triiodo-L-thyronine (T 3 ) (euthyroid hypothyroxinemia). We discuss in the current brief review the possible clinical settings in which to consider whether endogenous thyroid hormone-or exogenous thyroid hormone in the patient with hypothyroidism and coincident breast cancer-is significantly contributing to breast cancer outcome.

Levothyroxine

MedlinePlus

Levothyroxine, a thyroid hormone, is used to treat hypothyroidism, a condition where the thyroid gland does not ... hormone.Levothyroxine is also used to treat congenital hypothyroidism (cretinism) and goiter (enlarged thyroid gland). Levothyroxine is ...

Hormonal and reproductive risk factors of papillary thyroid cancer: A population-based case-control study in France.

PubMed

Cordina-Duverger, Emilie; Leux, Christophe; Neri, Monica; Tcheandjieu, Catherine; Guizard, Anne-Valérie; Schvartz, Claire; Truong, Thérèse; Guénel, Pascal

2017-06-01

The three times higher incidence of thyroid cancer in women compared to men points to a role of female sex hormones in its etiology. However the effects of these factors are poorly understood. We analyzed the association between thyroid cancer and hormonal and reproductive factors among women enrolled in CATHY, a population-based case-control study conducted in France. The study included 430 cases of papillary thyroid cancer and 505 controls frequency-matched on age and area of residence. The odds ratios for thyroid cancer increased with age at menarche (p trend 0.05). Postmenopausal women were at increased risk, as compared to premenopausal women, particularly if menopause followed an ovariectomy, and for women with age at menopause <55years. In addition, use of oral contraceptives and menopausal hormone therapy reduced the association with thyroid cancer by about one third, and breastfeeding by 27%. Overall, these findings provide evidence that the risk of thyroid cancer increases with later age at menarche and after menopause, and decreases with use of oral contraceptives and menopausal hormone therapy. These findings confirm an implication of hormonal factors in papillary thyroid cancer risk, whose mechanisms need to be elucidated. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hyperthyroidism.

PubMed

Maji, D

2006-10-01

Hyperthyroidism is a clinical situation where there is excess thyroid hormones in the circulation due to increased synthesis of hormone from a hyperactive thyroid gland. Common causes are Graves' disease, toxic multinodular goitre and toxic solitary nodule. Excess thyroid hormones in the circulation are also found in thyroiditis (hormone leakage) and excess exogenous thyroxine intake. Thyrotoxicosis is the term applied when there is excess thyroid hormone in the circulation due to any cause. Thyrotoxicosis can be easily diagnosed by high serum level of thyroxine (T4) and triiodothyronine (T3) and low serum level of thyroid stimulating hormone (TSH). Hyperthyroidism is confirmed by high isotope (I 131 or Tc99) uptake by the thyroid gland, while in thyroiditis it will be low. Treatment of hyperthyroidism depends on the underlying cause. Antithyroid drugs, 1131 therapy and surgery are the options of treatment of hyperthyroidism. Surgery is the preferred treatment for toxic adenoma and toxic multinodular goitre, while 1131 therapy may be suitable in some cases. Antithyroid drugs and 1131 therapy are mostly preferred for Graves' disease. Beta-adrenergic blockers are used for symptomatic relief in most patients of thyrotoxicosis due to any cause. Other rare causes of hyperthyroidism like, amiodarone induced thyrotoxicosis, choriocarcinoma, thyrotropin secreting pituitary tumour are difficult to diagnose as well as to treat.

Subclinical Hyperthyroidism: When to Consider Treatment.

PubMed

Donangelo, Ines; Suh, Se Young

2017-06-01

Subclinical hyperthyroidism is defined by a low or undetectable serum thyroid-stimulating hormone level, with normal free thyroxine and total or free triiodothyronine levels. It can be caused by increased endogenous production of thyroid hormone (e.g., in Graves disease, toxic nodular goiter, or transient thyroiditis), by administration of thyroid hormone to treat malignant thyroid disease, or by unintentional excessive replacement therapy. The prevalence of subclinical hyperthyroidism in the general population is about 1% to 2%; however, it may be higher in iodinedeficient areas. The rate of progression to overt hyperthyroidism is higher in persons with thyroid-stimulating hormone levels less than 0.1 mIU per L than in persons with low but detectable thyroid-stimulating hormone levels. Subclinical hyperthyroidism is associated with an increased risk of atrial fibrillation and heart failure in older adults, increased cardiovascular and all-cause mortality, and decreased bone mineral density and increased bone fracture risk in postmenopausal women. However, the effectiveness of treatment in preventing these conditions is unclear. A possible association between subclinical hyperthyroidism and quality-of-life parameters and cognition is controversial. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for thyroid dysfunction in asymptomatic persons. The American Thyroid Association and the American Association of Clinical Endocrinologists recommend treating patients with thyroid-stimulating hormone levels less than 0.1 mIU per L if they are older than 65 years or have comorbidities such as heart disease or osteoporosis.

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.

The hippocampal formation: morphological changes induced by thyroid, gonadal and adrenal hormones.

PubMed

Gould, E; Woolley, C S; McEwen, B S

1991-01-01

The hippocampal formation is of considerable interest due to its proposed role in a number of important functions, including learning and memory processes. Manipulations of thyroid, gonadal and adrenal hormones have been shown to influence hippocampal physiology as well as learning and memory. The cellular events which underlie these hormone-induced functional changes are largely unexplored. However, studies suggest that hormonal manipulations during development and in adulthood result in dramatic morphological changes within the hippocampal formation. Because neuronal physiology has been suggested to depend upon neuronal morphology, we have been determining the morphologic sensitivity of hippocampal neurons to thyroid and steroid hormones in an effort to elucidate possible structural mechanisms to account for differences in hippocampal function. In this review, hormone-induced structural changes in the developing and adult hippocampal formation are discussed, with particular emphasis on their functional relevance. Sex differences, as well as the developmental effects of thyroid hormone and glucocorticoids, are described. Moreover, the effects of ovarian steroids, thyroid hormone and glucocorticoids on neuronal morphology in the hippocampal formation of the adult rat are reviewed. These hormone-induced structural changes may account, at least in part, for previously reported hormone-induced changes in hippocampal function.

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

Ahren, B.

The thyroid gland is known to harbor cholinergic and VIPergic nerves. In the present study, the influences of cholinergic stimulation by carbachol, cholinergic blockade by methylatropine and stimulation with various VIP sequences on basal, TSH-induced and VIP-induced thyroid hormone secretion were investigated in vivo in mice. The mice were pretreated with /sup 125/I and thyroxine; the subsequent release of /sup 125/I is an estimation of thyroid hormone secretion. It was found that basal radioiodine secretion was inhibited by both carbachol and methylatropine. Furthermore, TSH-induced radioiodine secretion was inhibited already by a low dose of carbachol. Moreover, a high dose ofmore » carbachol could inhibit VIP-induced radioiodine secretion. Methylatropine did not influence TSH- or VIP-stimulated radioiodine secretion, but counteracted the inhibitory action of carbachol on TSH- and VIP-induced radioiodine release. In addition, contrary to VIP, six various synthesized VIP fragments had no effect on basal or stimulated radioiodine release. It is concluded that basal thyroid hormone secretion is inhibited by both cholinergic activation and blockade. Furthermore, TSH-induced thyroid hormone secretion is more sensitive to inhibition with cholinergic stimulation than is VIP-induced thyroid hormone secretion. In addition, the VIP stimulation of thyroid hormone secretion seems to require the full VIP sequence.« less

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

PubMed

Martínez-Sánchez, Noelia; Seoane-Collazo, Patricia; Contreras, Cristina; Varela, Luis; Villarroya, Joan; Rial-Pensado, Eva; Buqué, Xabier; Aurrekoetxea, Igor; Delgado, Teresa C; Vázquez-Martínez, Rafael; González-García, Ismael; Roa, Juan; Whittle, Andrew J; Gomez-Santos, Beatriz; Velagapudi, Vidya; Tung, Y C Loraine; Morgan, Donald A; Voshol, Peter J; Martínez de Morentin, Pablo B; López-González, Tania; Liñares-Pose, Laura; Gonzalez, Francisco; Chatterjee, Krishna; Sobrino, Tomás; Medina-Gómez, Gema; Davis, Roger J; Casals, Núria; Orešič, Matej; Coll, Anthony P; Vidal-Puig, Antonio; Mittag, Jens; Tena-Sempere, Manuel; Malagón, María M; Diéguez, Carlos; Martínez-Chantar, María Luz; Aspichueta, Patricia; Rahmouni, Kamal; Nogueiras, Rubén; Sabio, Guadalupe; Villarroya, Francesc; López, Miguel

2017-07-05

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Pituitary apoplexy

MedlinePlus

... body's sex glands produce little or no hormones) Hypothyroidism (thyroid gland does not make enough thyroid hormone) ... other missing hormones are not replaced, symptoms of hypothyroidism and hypogonadism may develop.

A review on hyperthyroidism: thyrotoxicosis under surveillance.

PubMed

Mansourian, Azad Reza

2010-11-15

Thyrotoxicosis exhibit collective clinical manifestation, caused by excessive serum thyroid hormones particularity thyroxin. The clinical signs and symptoms included general alteration of metabolic process leading to weight loss fatigue and weakness and some specific disorders such as cardiovascular, neuromuscular reproductive gastrointestinal dermatological and bone disorders. The diagnosis of thyrotoxicosis relay on the thyroid function test carried out by the laboratory serum measurement of thyroxin, triiodothyronine and thyroid stimulating hormones accompanied by other para-medical examinations suggested by clinicians and endociologicst. In thyrotoxicosis serum level of thyroid hormones and thyroxin in particular elevated accompanied by pituitary thyroid stimulating hormone suppression reaching to undetectable level in sever thyrotoxicosis. Among the most common cause of thyrotoxicosis are, thyroid autoimmunity diseases thyroid toxic, adenoma toxic nodular and multinodular hyperthyroidism. The main aim behind this review is to explore the clinical manifestation, the causative factors, diagnosis, metabolic disorder occur due to thyrotoxicosis.

Disruption of thyroid hormone functions by low dose exposure of tributyltin: an in vitro and in vivo approach.

PubMed

Sharan, Shruti; Nikhil, Kumar; Roy, Partha

2014-09-15

Triorganotins, such as tributyltin chloride (TBTCl), are environmental contaminants that are commonly found in the antifouling paints used in ships and other vessels. The importance of TBTCl as an endocrine-disrupting chemical (EDC) in different animal models is well known; however, its adverse effects on the thyroid gland are less understood. Hence, in the present study, we aimed to evaluate the thyroid-disrupting effects of this chemical using both in vitro and in vivo approaches. We used HepG2 hepatocarcinoma cells for the in vitro studies, as they are a thyroid hormone receptor (TR)-positive and thyroid responsive cell line. For the in vivo studies, Swiss albino male mice were exposed to three doses of TBTCl (0.5, 5 and 50μg/kg/day) for 45days. TBTCl showed a hypo-thyroidal effect in vivo. Low-dose treatment of TBTCl exposure markedly decreased the serum thyroid hormone levels via the down-regulation of the thyroid peroxidase (TPO) and thyroglobulin (Tg) genes by 40% and 25%, respectively, while augmenting the thyroid stimulating hormone (TSH) levels. Thyroid-stimulating hormone receptor (TSHR) expression was up-regulated in the thyroid glands of treated mice by 6.6-fold relative to vehicle-treated mice (p<0.05). In the transient transactivation assays, TBTCl suppressed T3 mediated transcriptional activity in a dose-dependent manner. In addition, TBTCl was found to decrease the expression of TR. The present study thus indicates that low concentrations of TBTCl suppress TR transcription by disrupting the physiological concentrations of T3/T4, followed by the recruitment of NCoR to TR, providing a novel insight into the thyroid hormone-disrupting effects of this chemical. Copyright © 2014 Elsevier Inc. All rights reserved.

Associations between Repeated Measures of Maternal Urinary Phthalate Metabolites and Thyroid Hormone Parameters during Pregnancy

PubMed Central

Johns, Lauren E.; Ferguson, Kelly K.; McElrath, Thomas F.; Mukherjee, Bhramar; Meeker, John D.

2016-01-01

Background: Maintaining thyroid homeostasis during pregnancy is essential for normal fetal growth and development. Growing evidence suggests that phthalates interfere with normal thyroid function. Few human studies have investigated the degree to which phthalates may affect thyroid hormone levels in particularly susceptible populations such as pregnant women. Objectives: We examined the associations between repeated measures of urinary phthalate metabolites and plasma thyroid hormone levels in samples collected at up to four time points per subject in pregnancy. Additionally, we investigated the potential windows of susceptibility to thyroid hormone disturbances related to study visit of sample collection. Methods: Data were obtained from pregnant women (n = 439) participating in a nested case–control study of preterm birth with 116 cases and 323 controls. We measured 9 phthalate metabolite concentrations in urine samples collected at up to four study visits per subject during pregnancy (median = 10, 18, 26, and 35 weeks of gestation, respectively). We also measured a panel of thyroid function markers in plasma collected at the same four time points per subject during pregnancy. Results: Although our results were generally null, in repeated measures analyses we observed that phthalate metabolites were largely inversely associated with thyrotropin and positively associated with free and total thyroid hormones. Cross-sectional analyses by study visit revealed that the magnitude and/or direction of these relationships varied by timing of exposure during gestation. Conclusions: These results support previous reports showing the potential for environmental phthalate exposure to alter circulating levels of thyroid hormones in pregnant women. Citation: Johns LE, Ferguson KK, McElrath TF, Mukherjee B, Meeker JD. 2016. Associations between repeated measures of maternal urinary phthalate metabolites and thyroid hormone parameters during pregnancy. Environ Health Perspect 124:1808–1815; http://dx.doi.org/10.1289/EHP170 PMID:27152641

THYROID HORMONE RECEPTOR BETA GENE MUTATION (P453A) IN A TURKISH FAMILY PRODUCING RESISTANCE TO THYROID HORMONE

PubMed Central

Bayraktaroglu, Taner; Noel, Janet; Mukaddes, Nahit Motavalli; Refetoff, Samuel

2018-01-01

Two members of a Turkish family, a mother and son, had thyroid function tests suggestive of resistance to thyroid hormone (RTH). The clinical presentation was, however, different. The mother (proposita) had palpitation, weakness, tiredness, nervousness, dry mouth and was misdiagnosed as having multinodular toxic goiter which was treated with antithyroid drugs and partial thyroidectomy. Her younger son had attention deficit hyperactivity disorder and primary encopresis, but normal intellectual quotient. Both had elevated serum iodothyronine levels with nonsuppressed thyrotropin. A mutation in one allele of the thyroid hormone receptor beta gene (P453A) was identified, providing a genetic confirmation for the diagnosis of RTH. PMID:18561095

Effects of a multivitamin/multimineral supplement on young males with physical overtraining: a placebo-controlled, randomized, double-blinded cross-over trial.

PubMed

Li, Xin; Huang, Wen Xu; Lu, Ju Ming; Yang, Guang; Ma, Fang Ling; Lan, Ya Ting; Meng, Jun Hua; Dou, Jing Tao

2013-07-01

To investigate the effects of vitamin-mineral supplement on young males with physical overtraining. Two hundred and forty male Chinese field artillery personnel who undertook large scale and endurance military training and were on ordinary Chinese diet were randomized to receive a multivitamin/multimineral supplement or a placebo for 1 week. After a 1-week wash-out period, a cross-over with 1 week course of a placebo or multivitamin/multimineral supplement was conducted. Blood and urine samples were analyzed for adrenal, gonadal and thyroid hormones. In addition, cellular immune parameters (CD3+, CD3+CD4+, CD3+CD8+, CD4/CD8, CD3-CD56+, CD3-CD19+) were examined and psychological tests were performed before and after the training program and nutrition intervention. After a large scale and endurance military training, the participants showed significantly increased thyroid function, decreased adrenal cortex, testosterone and immunological function, and significantly increased somatization, anger and tension. Compared to placebo, multivitamin/ multimineral intervention showed significant effects on functional recovery of the pituitary - adrenal axis, pituitary-gonadal axis, pituitary- thyroid axis and immune system as well as psychological parameters. High-intensity military operations have significant impacts on the psychology, physical ability and neuroendocrine-immune system in young males. Appropriate supplementation of multivitamin/multimineral can facilitate the recovery of the psychology, physical ability and neuroendocrine-immune system in young males who take ordinary Chinese diet. Copyright © 2013 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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.

Homeostatic Control of the Thyroid–Pituitary Axis: Perspectives for Diagnosis and Treatment

PubMed Central

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

2015-01-01

The long-held concept of a proportional negative feedback control between the thyroid and pituitary glands requires reconsideration in the light of more recent studies. Homeostatic equilibria depend on dynamic inter-relationships between thyroid hormones and pituitary thyrotropin (TSH). They display a high degree of individuality, thyroid-state-related hierarchy, and adaptive conditionality. Molecular mechanisms involve multiple feedback loops on several levels of organization, different time scales, and varying conditions of their optimum operation, including a proposed feedforward motif. This supports the concept of a dampened response and multistep regulation, making the interactions between TSH, FT4, and FT3 situational and mathematically more complex. As a homeostatically integrated parameter, TSH becomes neither normatively fixed nor a precise marker of euthyroidism. This is exemplified by the therapeutic situation with l-thyroxine (l-T4) where TSH levels defined for optimum health may not apply equivalently during treatment. In particular, an FT3–FT4 dissociation, discernible FT3–TSH disjoint, and conversion inefficiency have been recognized in l-T4-treated athyreotic patients. In addition to regulating T4 production, TSH appears to play an essential role in maintaining T3 homeostasis by directly controlling deiodinase activity. While still allowing for tissue-specific variation, this questions the currently assumed independence of the local T3 supply. Rather it integrates peripheral and central elements into an overarching control system. On l-T4 treatment, altered equilibria have been shown to give rise to lower circulating FT3 concentrations in the presence of normal serum TSH. While data on T3 in tissues are largely lacking in humans, rodent models suggest that the disequilibria may reflect widespread T3 deficiencies at the tissue level in various organs. As a consequence, the use of TSH, valuable though it is in many situations, should be scaled back to a supporting role that is more representative of its conditional interplay with peripheral thyroid hormones. This reopens the debate on the measurement of free thyroid hormones and encourages the identification of suitable biomarkers. Homeostatic principles conjoin all thyroid parameters into an adaptive context, demanding a more flexible interpretation in the accurate diagnosis and treatment of thyroid dysfunction. PMID:26635726

Thyroid disease and the cardiovascular system.

PubMed

Danzi, Sara; Klein, Irwin

2014-06-01

Thyroid hormones, specifically triiodothyronine (T3), have significant effects on the heart and cardiovascular system. Hypothyroidism, hyperthyroidism, subclinical thyroid disease, and low T3 syndrome each cause cardiac and cardiovascular abnormalities through both genomic and nongenomic effects on cardiac myocytes and vascular smooth muscle cells. In compromised health, such as occurs in heart disease, alterations in thyroid hormone metabolism may further impair cardiac and cardiovascular function. Diagnosis and treatment of cardiac disease may benefit from including analysis of thyroid hormone status, including serum total T3 levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Thyrotrophin-releasing hormone decreases feeding and increases body temperature, activity and oxygen consumption in Siberian hamsters.

PubMed

Schuhler, S; Warner, A; Finney, N; Bennett, G W; Ebling, F J P; Brameld, J M

2007-04-01

Thyrotrophin-releasing hormone (TRH) is known to play an important role in the control of food intake and energy metabolism in addition to its actions on the pituitary-thyroid axis. We have previously shown that central administration of TRH decreases food intake in Siberian hamsters. This species is being increasingly used as a physiological rodent model in which to understand hypothalamic control of long-term changes in energy balance because it accumulates fat reserves in long summer photoperiods, and decreases food intake and body weight when exposed to short winter photoperiods. The objectives of our study in Siberian hamsters were: (i) to investigate whether peripheral administration of TRH would mimic the effects of central administration of TRH on food intake and whether these effects would differ dependent upon the ambient photoperiod; (ii) to determine whether TRH would have an effect on energy expenditure; and (iii) to investigate the potential sites of action of TRH. Both peripheral (5-50 mg/kg body weight; i.p.) and central (0.5 microg/ml; i.c.v.) administration of TRH decreased food intake, and increased locomotor activity, body temperature and oxygen consumption in the Siberian hamster, with a rapid onset and short duration of action. Systemic treatment with TRH was equally effective in suppressing feeding regardless of ambient photoperiod. The acute effects of TRH are likely to be centrally mediated and independent of its role in the control of the production of thyroid hormones. We conclude that TRH functions to promote a catabolic energetic state by co-ordinating acute central and chronic peripheral (thyroid-mediated) function.

Features of selenium metabolism in humans living under the conditions of North European Russia.

PubMed

Parshukova, Olga; Potolitsyna, Natalya; Shadrina, Vera; Chernykh, Aleksei; Bojko, Evgeny

2014-08-01

Selenium supplementation and its effects on Northerners have been little studied. The aim of our study was to assess the selenium levels of the inhabitants of North European Russia, the seasonal aspects of selenium supplementation, and the interrelationships between selenium levels and the levels of thyroid gland hormones. To study the particular features of selenium metabolism in Northerners over the course of 1 year, 19 healthy male Caucasian volunteers (18-21 years old) were recruited for the present study. The subjects were military guards in a Northern European region of Russia (Syktyvkar, Russia, 62°N latitude) who spent 6-10-h outdoors daily. The study was conducted over a 12-month period. Selenium levels, glutathione peroxidase (GP) activity, as well as total triiodothyronine (T3), total thyroxin (T4), free thyroxin, free triiodothyronine, and thyrotropin (TSH) levels, were determined in the blood serum. The study subjects showed low levels of plasma selenium throughout the year. We observed a noticeable decrease in plasma selenium levels during the period from May to August, with the lowest levels in July. Selenium levels in the military guards correlated with the levels of selenium-dependent GP enzyme activity throughout the year. Additionally, we demonstrated a significant correlation between selenium and pituitary-thyroid axis hormones (total T3, free T4, and TSH) in periods in which plasma selenium levels were lower than the established normal ranges. Over the course of 1 year, low levels of plasma selenium affect GP activity and thyroid hormone levels in humans living in North European Russia.

Selenium glutathione peroxidase activities and thyroid functions in human individuals

NASA Astrophysics Data System (ADS)

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

1996-04-01

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

Decreased alertness

MedlinePlus

... involves the brain Liver failure Thyroid conditions that cause low thyroid hormone levels or very high thyroid hormone levels Brain disorders or injury, such as: Dementia or Alzheimer disease Head trauma Seizure Stroke Infections that affect ...

Hyperthyroidism and the Heart.

PubMed

Osuna, Patricia Mejia; Udovcic, Maja; Sharma, Morali D

2017-01-01

Thyroid hormones have a significant impact on cardiac function and structure. Excess thyroid hormone affects cardiovascular hemodynamics, leading to high-output heart failure and, in late stages, dilated cardiomyopathy. In this review, we discuss how hyperthyroidism affects cardiovascular pathophysiology and molecular mechanisms and examine the complications caused by excess thyroid hormone, such as heart failure and atrial fibrillation.

Implication from thyroid function decreasing during chemotherapy in breast cancer patients: chemosensitization role of triiodothyronine

PubMed Central

2013-01-01

Background Thyroid hormones have been shown to regulate breast cancer cells growth, the absence or reduction of thyroid hormones in cells could provoke a proliferation arrest in G0-G1 or weak mitochondrial activity, which makes cells insensitive to therapies for cancers through transforming into low metabolism status. This biological phenomenon may help explain why treatment efficacy and prognosis vary among breast cancer patients having hypothyroid, hyperthyroid and normal function. Nevertheless, the abnormal thyroid function in breast cancer patients has been considered being mainly caused by thyroid diseases, few studied influence of chemotherapy on thyroid function and whether its alteration during chemotherapy can influence the respose to chemotherapy is still unclear. So, we aimed to find the alterations of thyroid function and non-thyroidal illness syndrome (NTIS) prevalence druing chemotherapy in breast cancer patients, and investigate the influence of thyroid hormones on chemotherapeutic efficacy. Methods Thyroid hormones and NTIS prevalence at initial diagnosis and during chemotherapy were analyzed in 685 breast diseases patients (369 breast cancer, 316 breast benign lesions). The influence of thyroid hormones on chemotherapeutic efficacy was evaluated by chemosensitization test, to compare chemotherapeutic efficacy between breast cancer cells with chemotherapeutics plus triiodothyronine (T3) and chemotherapeutics only. Results In breast cancer, NTIS prevalence at the initial diagnosis was higher and increased during chemotherapy, but declined before the next chemotherapeutic course. Thyroid hormones decreased signigicantly during chemotherapy. T3 can enhance the chemosensitivity of MCF-7 to 5-Fu and taxol, with progression from G0-G1 phase to S phase. The similar chemosensitization role of T3 were found in MDA-MB-231. We compared chemotherapeutic efficacy among groups with different usage modes of T3, finding pretreatment with lower dose of T3, using higher dose of T3 together with 5-Fu or during chemotherapy with 5-Fu were all available to achieve chemosensitization, but pretreatment with lower dose of T3 until the end of chemotherapy may be a safer and more efficient therapy. Conclusions Taken together, thyroid hormones decreasing during chemotherapy was found in lots of breast cancer patients. On the other hand, thyroid hormones can enhance the chemotherapeutic efficacy through gatherring tumor cells in actively proliferating stage, which may provide a new adjuvant therapy for breast cancer in furture, especially for those have hypothyroidism during chemotherapy. PMID:23829347

Asymptomatic hyperthyroidism in older adults: is it a distinct clinical and laboratory entity?

PubMed

Mooradian, Arshag D

2008-01-01

Hyperthyroidism is the result of increased serum free thyroid hormone levels and is associated with a well recognized set of clinical signs and symptoms. However, older patients who develop hyperthyroidism tend to have fewer hyperadrenergic signs and an increased incidence of weight loss, cardiac arrhythmias and, occasionally, apathetic mood. This article highlights the paucity of clinical signs and symptoms of hyperthyroidism in older people and reviews the potential biochemical changes in thyroid hormone physiology that may account for an altered clinical presentation in older people with hyperthyroidism. First, a brief vignette from our own clinical practice is described to highlight an unusual presentation of hyperthyroidism in an older woman. The subject is then reviewed on the basis of relevant articles identified through a MEDLINE search of the English literature, using the key words 'hyperthyroidism' and 'aging'. The available evidence indicates that the clinical syndrome of asymptomatic hyperthyroidism in older adults appears to be distinct from the more widely recognized syndromes of apathetic hyperthyroidism or thyroid hormone resistance. Age-related changes in thyroid hormone economy and reduced cellular uptake of thyroid hormone as well as changes in thyroid hormone regulation of gene expression may account for reduced manifestations of hyperthyroidism in older adults. Thus, in addition to the well known changes in thyroid gland anatomy and function with aging, there may be an age-related resistance to thyroid hormone action. Asymptomatic hyperthyroidism may well be a syndrome that is currently under-diagnosed.

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.

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

PubMed

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

2015-01-01

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

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

PubMed Central

2014-01-01

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

PCBs Alter Dopamine Mediated Function in Aging Workers

DTIC Science & Technology

2007-01-01

Thyroid Hormone Function Analysis of serum samples collected for thyroid hormone function (T3, T4, free T3, free T4, and TSH levels) has been conducted by...Thyroid Hormone Measure Mean sem Mean sem TSH 2.06 0.13 2.55 0.36 T4 7.94 0.18 8.72 0.22 Free T4 1.23 0.02 1.22 0.03 T3 133 3.05 122 2.74...FreeT3 5.31 0.08 4.56 0.08 TSH = Thyroid Stimulating Hormone T4 = Thyroxine T3 = 3,5,3-Triidothyronine Investigators Meetings and

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

PubMed

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

2016-12-01

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

Clinical associations of maternal thyroid function with foetal brain development: Epidemiological interpretation and overview of available evidence.

PubMed

Korevaar, Tim I M; Tiemeier, Henning; Peeters, Robin P

2018-04-24

Thyroid hormone is an important regulator of early brain development, particularly during early stages of gestation during which foetal thyroid hormone availability depends on the maternal transfer of thyroid hormones. There is a wide range of experimental studies showing that low maternal thyroid hormone availability is associated with suboptimal brain development parameters. While few clinical studies have shown that overt maternal hypothyroidism is associated with lower child IQ, the question whether more subclinical changes in maternal thyroid function could also lead to suboptimal foetal brain development. In this review, we put the latter studies in perspective and discuss their interpretation from an epidemiological and clinical perspective. Furthermore, we extend this discussion to also include future perspective and identify important knowledge gaps in the field. © 2018 John Wiley & Sons Ltd.

Follow-up of congenital heart disease patients with subclinical hypothyroidism.

PubMed

Martínez-Quintana, Efrén; Rodríguez-González, Fayna

2015-08-01

Subclinical hypothyroidism or mild thyroid failure is a common problem in patients without known thyroid disease. Demographic and analytical data were collected in 309, of which 181 were male and 128 were female, congenital heart disease (CHD) patients. CHD patients with thyroid-stimulating hormone above 5.5 mIU/L were also followed up from an analytical point of view to determine changes in serum glucose, cholesterol, N-terminal pro b-type natriuretic peptide, and C-reactive protein concentrations. Of the CHD patients, 35 (11.3%) showed thyroid-stimulating hormone concentration above 5.5 mIU/L. Of them, 27 were followed up during 2.4±1.2 years - 10 were under thyroid hormone replacement treatment, and 17 were not. Of the 27 patients (25.9%), 7 with subclinical hypothyroidism had positive anti-thyroid peroxidase, and 3 of them (42.8%) with positive anti-thyroid peroxidase had Down syndrome. Down syndrome and hypoxaemic CHD patients showed higher thyroid-stimulating hormone concentrations than the rest of the congenital patients (p<0.001). No significant differences were observed in serum thyroxine, creatinine, uric acid, lipids, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations before and after the follow-up in those CHD patients with thyroid-stimulating hormone above 5.5 mIU/L whether or not they received levothyroxine therapy. CHD patients with subclinical hypothyroidism showed no significant changes in serum thyroxine, cholesterol, C-reactive protein, or N-terminal pro b-type natriuretic peptide concentrations whether or not they were treated with thyroid hormone replacement therapy.

Hormonal changes in humans during spaceflight.

PubMed

Strollo, F

1999-01-01

Readers of this review may feel that there is much more that we do not know about space endocrinology than what we know. Several reasons for this state of affairs have been given: 1. the complexity of the field of endocrinology with its still increasing number of known hormones, releasing factors and precursors, and of the interactions between them through various feedback mechanisms 2. the difficulty in separating the microgravity effects from the effects of stress from launch, isolation and confinement during flight, reentry, and postflight re-adaptation 3. the experimental limitations during flight, such as limited number of subjects, limited number of samples, impossibility of collecting triple samples for pulsatile hormones like growth hormone 4. the disturbing effects of countermeasures used by astronauts 5. the inadequacy of postflight samples for conclusions about inflight values 6. limitations of conclusions from animal experiments and space simulation studies The endocrinology field is divided in to nine systems or axes, which are successively reviewed: 1. Rapid bone demineralization in the early phase of spaceflight that, when unopposed, leads to catastrophic effects after three months but that slows down later. The endocrine mechanism, apart from the effect of exercise as a countermeasure, is not yet understood. 2. The hypothalamic-pituitary-adrenal axis is involved in stress reactions, which complicate our understanding and makes postflight analysis dubious. 3. In the hypothalamic-pituitary-gonadal axis, pulsatility poses a problem for obtaining representative values (e.g., for luteinizing hormone). Reproduction of rats in space is possible, but much more needs to be known about this aspect, particularly in women, before the advent of space colonies, but also in males because some evidence for reversible testicular dysfunction in space has been found. 4. The hypothalamic-pituitary-somato-mammotrophic axis involves prolactin and growth hormone. The latter also acts as a stress hormone and its secretion is greatly decreased in spaceflown rats, but not in astronauts, which may be due to differences in the regulation of growth hormone secretion between rats and humans. 5. The hypothalamic-pituitary-thyroid axis involves the thyroid hormones thyroxine and triiodothyronine, which are lowered in space, suggesting mild hypothyroidism. 6. The renin-angiotensin-aldosterone axis, which regulates water and electrolytes, involves antidiuretic hormone and two natriuretic peptides and shows paradoxical behavior in space. 7. Erythrocyte mass regulation involves erythropoietin, and space anemia is still not explained. 8. The endocrine pancreas involves insulin and glucagon, with loss of insulin sensitivity in space due to lack of exercise, which phenomenon requires more study before the advent of space colonies. 9. The sympathetic system acts through epinephrine, norepinephrine and dopamine and seems to have an increased activity in space in contrast to what had been widely believed. From the foregoing conclusions, it is clear that much further study is needed in all fields of space endocrinology. On the other hand, future studies will allow us to understand what happens in a given endocrine subsystem in the absence of the "gravity factor", the perturbing factor to which the human race has become adapted through thousands of years of evolution. This should provide us with a fuller understanding of the internal homeostatic mechanisms. An important point is that some endocrine systems seem to undergo changes in space that resemble those observed during senescence, but after spaceflight, recovery always occurs within weeks or months after return. This is particularly true for the systems regulating bone and muscle metabolism and reproduction, exactly as happens with the immune, neurosensory, and cardiovascular systems. Further space research may help us find new insights in the pathophysiology of aging and hopefully define novel prev

Thyroid hormone action on intermediary metabolism. Part I: respiration, thermogenesis and carbohydrate metabolism.

PubMed

Müller, M J; Seitz, H J

1984-01-02

The effect of thyroid hormones on mitochondrial respiration are summarized: T3 directly stimulates mitochondrial respiration and the synthesis of adenosine 5'-triphosphate (ATP). Cytosolic ATP availability is increased by a thyroid hormone-induced increase in adenine nucleotide translocation across the mitochondrial membrane; the steady state ATP concentration and the cytosolic ATP/adenosine 5'-diphosphate (ADP) ratio is even decreased in hyperthyroid tissues because of the simultaneous stimulation of the synthesis and consumption of ATP. With regard to the thyroid hormone-induced energy wasting processes, heart work, intra- and interorgan futile cycling and Na+/K+-ATPase are involved to varying degrees. As a consequence of the thyroid hormone-induced hydrolysis of ATP, thermogenesis is increased in hyper- and decreased in hypothyroidism. Despite an increased rate of glucose utilization, clinical and experimental hyperthyroidism is often characterized by an abnormal oral glucose tolerance test. This finding is due to the thyroid hormone-induced increase in intestinal glucose absorption as well as the still enhanced endogenous glucose production in the liver. Hypothyroid patients show a reduced glucose tolerance test because of a decrease in intestinal glucose absorption and a sometimes reduced glucose turnover. The thyroid hormone-induced alterations in glucose metabolism are most probably not due to alterations in serum insulin levels and/or to a peripheral insulin resistance at the receptor level.

Efficacy of a food supplement in patients with hashimoto thyroiditis.

PubMed

Nordio, M; Basciani, S

2015-01-01

Thyroid inflammation has been commonly seen in recent decades, due to a series of factors and is considered as the most frequent thyroid illness. It is characterized by some distinctive traits, which include morphological and hormonal modifications, often in association with an elevated anti-thyroid autoantibody title. The aim of the therapy is to improve symptoms as fast as possible, treating inflammation and subsequent hypothyroidism, when present. Therefore, we evaluated the efficacy of a Food Supplement (FS) containing enzymes which is commonly used in various inflammatory processes and is able to modulate immune reactions during inflammation in a very rapid and efficacious way. An open, controlled study was then designed and 45 patients with Hashimoto thyroiditis were enrolled and divided into 3 groups (FS alone; thyroid hormones alone; FS plus thyroid hormones). Blood, morphological and subjective parameters were considered. The results obtained indicate that the FS used in our study is efficacious and safe when used alone and/or in combination with thyroid hormones in the treatment of autoimmune thyroiditis, as documented by the improvement of the majority of the parameters considered. The efficacy was considered faster than thyroid hormones alone as far as subjective symptomatology is considered. In conclusion, the use of the food supplement evaluated herein during inflammation may be considered an additional tool in clinicians’ hands, when facing patients with autoimmune thyroiditis, especially in presence of subjective symptomatology, in order to rapidly alleviate it.

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...

Changing axis deviation and paroxysmal atrial flutter associated with subclinical hyperthyroidism.

PubMed

Patanè, Salvatore; Marte, Filippo

2010-10-08

Subclinical hyperthyroidism is an increasingly recognized entity that is defined as a normal serum free thyroxine and free triiodothyronine levels with a thyroid-stimulating hormone level suppressed below the normal range and usually undetectable. It has been reported that subclinical hyperthyroidism is not associated with coronary heart disease or mortality from cardiovascular causes but it is sufficient to induce arrhythmias including atrial fibrillation and atrial flutter. It has also been reported that increased factor X activity in patients with subclinical hyperthyroidism represents a potential hypercoagulable state. Rarely, it has also been reported intermittent changing axis deviation during atrial fibrillation and during atrial flutter. We present a case of paroxysmal atrial flutter and changing axis deviation associated with subclinical hyperthyroidism, in a 76-year-old Italian man. Also this case focuses attention on the importance of a correct evaluation of subclinical hyperthyroidism. Copyright © 2008 Elsevier Ireland Ltd. All rights reserved.

Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

ERIC Educational Resources Information Center

Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

2015-01-01

Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

Hyperthyroidism and the Heart

PubMed Central

Osuna, Patricia Mejia; Udovcic, Maja; Sharma, Morali D.

2017-01-01

Thyroid hormones have a significant impact on cardiac function and structure. Excess thyroid hormone affects cardiovascular hemodynamics, leading to high-output heart failure and, in late stages, dilated cardiomyopathy. In this review, we discuss how hyperthyroidism affects cardiovascular pathophysiology and molecular mechanisms and examine the complications caused by excess thyroid hormone, such as heart failure and atrial fibrillation. PMID:28740583

Unexplained high thyroid stimulating hormone: a "BIG" problem.

PubMed

Mendoza, Heidi; Connacher, Alan; Srivastava, Rajeev

2009-01-01

Macro-hormones and macro-enzymes are high molecular weight conjugates of hormones or enzymes, respectively, often with immunoglobulins. These are referred to as macromolecular complexes, and may cause artefactually elevated biochemical tests results. Macro enzymes of the most commonly measured serum enzymes have been identified and are recognised as a source of elevated measurements that may cause diagnostic confusion; macro-creatine kinase and macro-amylase are the two better known macro-enzymes in clinical practice. Literature on macro-hormones is largely restricted to macro-prolactin. We present a case of a clinically euthyroid patient, who had persistently elevated thyroid stimulating hormone (TSH) but free thyroxine within the reference limits. She underwent repeated thyroid investigations and thyroid hormone interference studies, until macro-TSH was identified as the most likely cause of unexplained elevated TSH. Following the identification and characterisation of this biochemical abnormality, she is no longer subject to repeated blood tests for assessment of thyroid function; the patient currently remains clinically euthyroid.

Impaired hair growth and wound healing in mice lacking thyroid hormone receptors.

PubMed

Contreras-Jurado, Constanza; García-Serrano, Laura; Martínez-Fernández, Mónica; Ruiz-Llorente, Lidia; Paramio, Jesus M; Aranda, Ana

2014-01-01

Both clinical and experimental observations show that the skin is affected by the thyroidal status. In hypothyroid patients the epidermis is thin and alopecia is common, indicating that thyroidal status might influence not only skin proliferation but also hair growth. We demonstrate here that the thyroid hormone receptors (TRs) mediate these effects of the thyroid hormones on the skin. Mice lacking TRα1 and TRβ (the main thyroid hormone binding isoforms) display impaired hair cycling associated to a decrease in follicular hair cell proliferation. This was also observed in hypothyroid mice, indicating the important role of the hormone-bound receptors in hair growth. In contrast, the individual deletion of either TRα1 or TRβ did not impair hair cycling, revealing an overlapping or compensatory role of the receptors in follicular cell proliferation. In support of the role of the receptors in hair growth, TRα1/TRβ-deficient mice developed alopecia after serial depilation. These mice also presented a wound-healing defect, with retarded re-epithelialization and wound gaping, associated to impaired keratinocyte proliferation. These results reinforce the idea that the thyroid hormone nuclear receptors play an important role on skin homeostasis and suggest that they could be targets for the treatment of cutaneous pathologies.

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

PubMed

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

2015-06-01

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

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

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

PubMed

Alghazo, Jaafar M

2017-02-01

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

Developmental Exposure to Perchlorate Alters Synaptic Transmission in Hippocampus of the Adult Rat

PubMed Central

Gilbert, Mary E.; Sui, Li

2008-01-01

Background Perchlorate is an environmental contaminant that blocks iodine uptake into the thyroid gland and reduces thyroid hormones. This action of perchlorate raises significant concern over its effects on brain development. Objectives The purpose of this study was to evaluate neurologic function in rats after developmental exposure to perchlorate. Methods Pregnant rats were exposed to 0, 30, 300, or 1,000 ppm perchlorate in drinking water from gestational day 6 until weaning. Adult male offspring were evaluated on a series of behavioral tasks and neurophysiologic measures of synaptic function in the hippocampus. Results At the highest perchlorate dose, triiodothyronine (T3) and thyroxine (T4) were reduced in pups on postnatal day 21. T4 in dams was reduced relative to controls by 16%, 28%, and 60% in the 30-, 300-, and 1,000-ppm dose groups, respectively. Reductions in T4 were associated with increases in thyroid-stimulating hormone in the high-dose group. No changes were seen in serum T3. Perchlorate did not impair motor activity, spatial learning, or fear conditioning. However, significant reductions in baseline synaptic transmission were observed in hippocampal field potentials at all dose levels. Reductions in inhibitory function were evident at 300 and 1,000 ppm, and augmentations in long-term potentiation were observed in the population spike measure at the highest dose. Conclusions Dose-dependent deficits in hippocampal synaptic function were detectable with relatively minor perturbations of the thyroid axis, indicative of an irreversible impairment in synaptic transmission in response to developmental exposure to perchlorate. PMID:18560531

Thyroid hormones and female reproduction.

PubMed

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

2018-05-14

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

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

Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of corticosteroid induced diabetes mellitus: involvement of thyroid hormones.

PubMed

Gholap, S; Kar, A

2003-06-01

The efficacy of Inula racemosa (root) and Gymnema sylvestre (leaf) extracts either alone or in combination was evaluated in the amelioration of corticosteroid-induced hyperglycaemia in mice. Simultaneously thyroid hormone levels were estimated by radio-immunoassay (RIA) in order to ascertain whether the effects are mediated through thyroid hormones or not. While the corticosteroid (dexamethasone) administration increased the serum glucose concentration, it decreased serum concentrations of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Administration of the two plant extracts either alone or in combination decreased the serum glucose concentration in dexamethasone induced hyperglycaemic animals. However, the administration of Inula racemosa and Gymnema sylvestre extracts in combination proved to be more effective than the individual extracts. These effects were comparable to a standard corticosteroid-inhibiting drug, ketoconazole. As no marked changes in thyroid hormone concentrations were observed by the administration of any of the plant extracts in dexamethasone treated animals, it is further suggested that these plant extracts may not prove to be effective in thyroid hormone mediated type II diabetes, but for steroid induced diabetes.

Oral triiodothyronine normalizes triiodothyronine levels after surgery for pediatric congenital heart disease*.

PubMed

Marwali, Eva M; Boom, Cindy E; Sakidjan, Indriwanto; Santoso, Anwar; Fakhri, Dicky; Kartini, Ay; Kekalih, Aria; Schwartz, Steven M; Haas, Nikolaus A

2013-09-01

This study was conducted to determine if oral triiodothyronine supplementation could prevent the decrease of serum triiodothyronine levels that commonly occurs after cardiopulmonary bypass for pediatric congenital heart surgery. Secondary objectives included identifying any significant adverse effects of oral triiodothyronine supplementation, including any effects on the thyroid/pituitary axis. Randomized, placebo-controlled, doubleblind clinical trial Operating room and ICU. Infants and children younger than 2 years of age undergoing congenital heart surgery using cardiopulmonary bypass (n = 43). Subjects were assigned to placebo (n = 15, group A) or one of two treatment groups: a low-dose group (group B, n = 14, 0.5 mcg/kg triiodothyronine orally every 24 hr for 3 d) or a high-dose group (group C, n = 14, 0.5 mcg/kg triiodothyronine orally every 12 hr for 3 d). Thyroid hormone, including total and free triiodothyronine levels at predetermined time points, potential side effects indicating hyperthyroidism, indicators of the thyroid-pituitary axis, and clinical endpoints. Oral triiodothyronine supplementation twice-daily maintained serum triiodothyronine levels within normal limits in group C, whereas serum levels progressively declined in groups A and B. A statistically significant difference in triiodothyronine levels between the treatment groups occurred between 18 and 36 hours post cross-clamp release, with the largest difference in serum levels between group C and group A noted at 36 hours post cross-clamp release (total triiodothyronine, 0.71 ± 0.15 [0.34-1.08] ng/mL [p < 0.01]; free triiodothyronine, 2.56 ± 0.49 [1.33-3.79] pg/mL [p < 0.01]). There was no evidence of hyperthyroidism or suppression of the pituitary-thyroid axis in either treatment group Oral triiodothyronine supplementation at a dose of 0.5 mcg/kg every 12 hours for 3 days can maintain total and free triiodothyronine levels within normal limits after open-heart surgery using cardiopulmonary bypass for congenital heart disease.

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

PubMed

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

2013-03-01

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

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

PubMed

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

2016-09-01

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

The effect of adrenaline and noradrenaline on hormone secretion and blood flow from the thyroid vein in sheep with exteriorized thyroids.

PubMed

Falconer, I R

1967-02-01

1. Emotional stimulus to the sheep has previously been shown to cause increased thyroid hormone secretion; the influence of adrenaline and noradrenaline in this process has been investigated.2. Sheep bearing exteriorized thyroid glands on carotid artery-jugular vein loops were used. Thyroid vein blood was collected through a cannula in the jugular vein within the loop, and blood flow was measured by a plethysmographic technique.3. (131)I (50 muc) was injected intramuscularly (I.M.) into the sheep, and 4-7 days later the concentration of total and protein bound (131)I in thyroid vein blood was measured in samples taken every 10 min for 4 hr. Intracarotid injections of 1 mug, I.V. injections of 5 mug, or I.V. infusions at 10 mug/min for 10 min, of adrenaline or noradrenaline were administered 1.5 hr after commencement of sampling. Blood flow from the thyroid was measured in similar experiments.4. No significant changes in thyroid hormone secretion could be attributed to adrenaline or noradrenaline, and it was concluded that circulating catecholamines do not influence the release of thyroid hormone observed after brief emotional stimulus in the sheep.

The Thr92Ala 5′ Type 2 Deiodinase Gene Polymorphism Is Associated with a Delayed Triiodothyronine Secretion in Response to the Thyrotropin-Releasing Hormone–Stimulation Test: A Pharmacogenomic Study

PubMed Central

Butler, Peter W.; Smith, Sheila M.; Linderman, Joyce D.; Brychta, Robert J.; Alberobello, Anna Teresa; Dubaz, Ornella M.; Luzon, Javier A.; Skarulis, Monica C.; Cochran, Craig S.; Wesley, Robert A.; Pucino, Frank

2010-01-01

Background The common Thr92Ala D2 polymorphism has been associated with changes in pituitary–thyroid axis homeostasis, but published results are conflicting. To investigate the effects of the Thr92Ala polymorphism on intrathyroidal thyroxine (T4) to triiodothyronine (T3) conversion, we designed prospective pharmacogenomic intervention aimed to detect differences in T3 levels after thyrotropin (TSH)-releasing hormone (TRH)–mediated TSH stimulation of the thyroid gland. Methods Eighty-three healthy volunteers were screened and genotyped for the Thr92Ala polymorphism. Fifteen volunteers of each genotype (Thr/Thr, Thr/Ala, and Ala/Ala) underwent a 500 mcg intravenous TRH stimulation test with serial measurements of serum total T3 (TT3), free T4, and TSH over 180 minutes. Results No differences in baseline thyroid hormone levels were seen among the study groups. Compared to the Thr/Thr group, the Ala/Ala group showed a significantly lower TRH-stimulated increase in serum TT3 at 60 minutes (12.07 ± 2.67 vs. 21.07 ± 2.86 ng/dL, p = 0.029). Thr/Ala subjects showed an intermediate response. Compared to Thr/Thr subjects, the Ala/Ala group showed a blunted rate of rise in serum TT3 as measured by mean time to 50% maximum delta serum TT3 (88.42 ± 6.84 vs. 69.56 ± 6.06 minutes, p = 0.028). Subjects attained similar maximal (180 minutes) TRH-stimulated TT3 levels. TRH-stimulated TSH and free T4 levels were not significantly different among the three genotype groups. Conclusions The commonly occurring Thr92Ala D2 variant is associated with a decreased rate of acute TSH-stimulated T3 release from the thyroid consistent with a decrease in intrathyroidal deiodination. These data provide a proof of concept that the Thr92Ala polymorphism is associated with subtle changes in thyroid hormone homeostasis. PMID:21054208

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

[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.

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

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.

Impact of light exposure on thyroid-stimulating hormone results using the Siemens Advia Centaur TSH-3Ultra assay.

PubMed

Armer, Jane; Giles, Diane; Lancaster, Ian; Brownbill, Kathryn

2017-09-01

Background Thyroid-stimulating hormone (TSH) is used as the first-line test of thyroid function. Siemens Healthcare Diagnostics recommend that Siemens Centaur reagents must be protected from light in the assay information and on reagent packaging. We have compared the effect of light exposure on results using Siemens TSH-3Ultra and follicle-stimulating hormone reagents. The thyroid-stimulating hormone reagent includes fluoroscein thiocyanate whereas the follicle-stimulating hormone reagent does not. Methods Three levels of quality controls were analysed using SiemensTSH-3Ultra and follicle-stimulating hormone reagent packs that had been kept protected from light or exposed to light at 6-h intervals for 48 h and then at 96 h. Results Thyroid-stimulating hormone results were significantly lower after exposure of TSH-3Ultra reagent packs to light. Results were >15% lower at all three levels of quality control following 18 h of light exposure and continued to decrease until 96 h. There was no significant difference in follicle-stimulating hormone results whether reagents had been exposed to or protected from light. Conclusions Thyroid-stimulating hormone results but not follicle-stimulating hormone results are lowered after exposure of reagent packs to light. Laboratories must ensure that TSH-3Ultra reagents are not exposed to light and analyse quality control samples on every reagent pack to check that there has not been light exposure prior to delivery. The labelling on TSH-3Ultra reagent packs should reflect the significant effect of light exposure compared with the follicle-stimulating hormone reagent. We propose that the effect of light exposure on binding of fluoroscein thiocyanate to the solid phase antibody causes the falsely low results.

Insufficient documentation for clinical efficacy of selenium supplementation in chronic autoimmune thyroiditis, based on a systematic review and meta-analysis.

PubMed

Winther, Kristian Hillert; Wichman, Johanna Eva Märta; Bonnema, Steen Joop; Hegedüs, Laszlo

2017-02-01

By a systematic review and meta-analysis to investigate clinically relevant effects of selenium supplementation in patients with chronic autoimmune thyroiditis. Controlled trials in adults (≥18 years) with autoimmune thyroiditis, comparing selenium with or without levothyroxine substitution, versus placebo and/or levothyroxine substitution, were eligible for inclusion. Identified outcomes were serum thyrotropin (thyroid stimulating hormone) levels in LT4-untreated patients, thyroid ultrasound and health-related quality of life. Eleven publications, covering nine controlled trials, were included in the systematic review. Random effects model meta-analyses were performed in weighted mean difference for thyroid stimulating hormone, ultrasound and health-related quality of life. Quality of evidence was assessed per outcome, using GRADE. Meta-analyses showed no change in thyroid stimulating hormone, or improvements in health-related quality of life or thyroid echogenicity (ultrasound), between levothyroxine substitution-untreated patients assigned to selenium supplementation or placebo. Three trials found some improvement in wellbeing in patients receiving levothyroxine substitution, but could not be synthesized in a meta-analysis. The quality of evidence ranged from very low to low for thyroid stimulating hormone as well as ultrasound outcomes, and low to moderate for health-related quality of life, and was generally downgraded due to small sample sizes. We found no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound, in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients. Future well-powered RCTs, evaluating e.g. disease progression or health-related quality of life, are warranted before determining the relevance of selenium supplementation in autoimmune thyroiditis.

Selenium deficiency inhibits the conversion of thyroidal thyroxine (T4) to triiodothyronine (T3) in chicken thyroids.

PubMed

Lin, Shi-lei; Wang, Cong-wu; Tan, Si-ran; Liang, Yang; Yao, Hai-dong; Zhang, Zi-wei; Xu, Shi-wen

2014-12-01

Selenium (Se) influences the metabolism of thyroid hormones in mammals. However, the role of Se deficiency in the regulation of thyroid hormones in chickens is not well known. In the present study, we examined the levels of thyroidal triiodothyronine (T3), thyroidal thyroxine (T4), free triiodothyronine, free thyroxine (FT4), and thyroid-stimulating hormone in the serum and the mRNA expression levels of 25 selenoproteins in chicken thyroids. Then, principal component analysis (PCA) was performed to analyze the relationships between the selenoproteins. The results indicated that Se deficiency influenced the conversion of T4 to T3 and induced the accumulation of T4 and FT4. In addition, the mRNA expression levels of the selenoproteins were generally decreased by Se deficiency. The PCA showed that eight selenoproteins (deiodinase 1 (Dio1), Dio2, Dio3, thioredoxin reductase 2 (Txnrd2), selenoprotein i (Seli), selenoprotein u (Selu), glutathione peroxidase 1 (Gpx1), and Gpx2) have similar trends, which indicated that they may play similar roles in the metabolism of thyroid hormones. The results showed that Se deficiency inhibited the conversion of T4 to T3 and decreased the levels of the crucial metabolic enzymes of the thyroid hormones, Dio1, Dio2, and Dio3, in chickens. In addition, the decreased selenoproteins (Dio1, Dio2, Dio3, Txnrd2, Seli, Selu, Gpx1, and Gpx2) induced by Se deficiency may indirectly limit the conversion of T4 to T3 in chicken thyroids. The information presented in this study is helpful to understand the role of Se in the thyroid function of chickens.

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.

Paradigm Shift in Thyroid Hormone Mechanism of Action | Center for Cancer Research

Cancer.gov

Thyroid hormone (TH) is one of the primary endocrine regulators of human metabolism and homeostasis. Acting through three forms of the thyroid hormone receptor (THR; alpha-1, beta-1, and beta-2), TH regulates target gene expression in nearly every cell in the body, modulating fundamental processes, such as basal metabolic rate, long bone growth, and neural maturation. TH is

The relationship of deiodinase 1 genotype and thyroid function to lifetime history of major depression in three independent populations.

PubMed

Philibert, Robert A; Beach, Steven R H; Gunter, Tracy D; Todorov, Alexandre A; Brody, Gene H; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-07-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1,555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime MD and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone, free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3'UTR of DIO1 (rs11206244), were associated with altered FT4 levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. Copyright © 2011 Wiley-Liss, Inc.

The Relationship of Deiodinase 1 Genotype and Thyroid Function to Lifetime History of Major Depression in Three Independent Populations

PubMed Central

Philibert, Robert A.; Beach, Steven R. H.; Gunter, Tracy D.; Todorov, Alexandre A.; Brody, Gene H.; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-01-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime major depression and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone (TSH), free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3’ UTR of DIO1 (rs11206244), were associated with altered free thyroxine (FT4) levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. PMID:21563302

Inappropriate Suppression of Thyrotropin Concentrations in Young Patients with Thyroid Nodules Including Thyroid Cancer: The Fukushima Health Management Survey.

PubMed

Suzuki, Satoru; Nakamura, Izumi; Suzuki, Satoshi; Ohkouchi, Chiyo; Mizunuma, Hiroshi; Midorikawa, Sanae; Fukushima, Toshihiko; Ito, Yuko; Shimura, Hiroki; Ohira, Tetsuya; Matsuzuka, Takashi; Ohtsuru, Akira; Abe, Masafumi; Yamashita, Shunichi; Suzuki, Shinichi

2016-05-01

Serum thyroid hormone concentration is regulated through the hypothalamic-pituitary-thyroid axis. This study aimed to clarify the relationships between thyroid hormone regulation and ultrasonographic findings in subjects with thyroid nodules detected during thyroid ultrasound examination for the Fukushima Health Management Survey. As of October 31, 2014, a total of 296,253 subjects, who had been living in Fukushima Prefecture at the time of the Fukushima nuclear power plant accident and were aged ≤18 years on March 11, 2011, participated in two concurrent screening programs. In the primary screening, thyroid nodules were detected in 2241 subjects. A secondary confirmatory thyroid ultrasound examination and blood sampling for thyroid function tests were performed on 2004 subjects. The subjects were reassessed and classified into disease-free subjects (Group 1), subjects with cysts only (Group 2), subjects with nodules (Group 3), and subjects with malignancy or suspected malignancy (Group 4). Serum concentrations of free triiodothyronine (fT3), free thyroxine (fT4), thyrotropin (TSH), thyroglobulin, and the fT3/fT4 ratio were classified according to the diagnoses. Inverse relationships between age and log TSH values (Spearman's correlation r = -0.311, p = 0.015), serum fT3 concentration (r = -0.688, p < 0.001), and the fT3/fT4 ratio (r = -0.520, p < 0.001) were observed in Group 1. When analysis of covariance with Bonferroni post hoc comparisons was used in the four groups, the log TSH values were significantly lower in both Group 3 and Group 4 compared with Group 1 and Group 2 after correcting for age (p < 0.001; Group 1 vs. Group 3, p = 0.016; Group 1 vs. Group 4, p = 0.022; Group 2 vs. Group 3, p = 0.001; Group 2 vs. Group 4, p = 0.008). However, no significant differences were observed between the four groups regarding levels of fT3, fT4, fT3/fT4 ratio, and thyroglobulin (p = 0.304, 0.340, 0.208, and 0.583, respectively). TSH suppression can be present in response to illness, including thyroid nodules, in young subjects. Low TSH levels may be associated with the finding of papillary thyroid cancer as well as with thyroid nodules in children and adolescents.

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.

Effects of thyroid hormone status on metabolic pathways of arachidonic acid in mice and humans: A targeted metabolomic approach.

PubMed

Yao, Xuan; Sa, Rina; Ye, Cheng; Zhang, Duo; Zhang, Shengjie; Xia, Hongfeng; Wang, Yu-cheng; Jiang, Jingjing; Yin, Huiyong; Ying, Hao

2015-01-01

Symptoms of cardiovascular diseases are frequently found in patients with hypothyroidism and hyperthyroidism. However, it is unknown whether arachidonic acid metabolites, the potent mediators in cardiovascular system, are involved in cardiovascular disorders caused by hyperthyroidism and hypothyroidism. To answer this question, serum levels of arachidonic acid metabolites in human subjects with hypothyroidism, hyperthyroidism and mice with hypothyroidism or thyroid hormone treatment were determined by a mass spectrometry-based method. Over ten arachidonic acid metabolites belonging to three catalytic pathways: cyclooxygenases, lipoxygenases, and cytochrome P450, were quantified simultaneously and displayed characteristic profiles under different thyroid hormone status. The level of 20-hydroxyeicosatetraenoic acid, a cytochrome P450 metabolite, was positively correlated with thyroid hormone level and possibly contributed to the elevated blood pressured in hyperthyroidism. The increased prostanoid (PG) I2 and decreased PGE2 levels in hypothyroid patients might serve to alleviate atherosclerosis associated with dyslipidemia. The elevated level of thromboxane (TX) A2, as indicated by TXB2, in hyperthyroid patients and mice treated with thyroid hormone might bring about pulmonary hypertension frequently found in hyperthyroid patients. In conclusion, our prospective study revealed that arachidonic acid metabolites were differentially affected by thyroid hormone status. Certain metabolites may be involved in cardiovascular disorders associated with thyroid diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

The interruption of thyroid and interrenal and the inter-hormonal interference in fish: does it promote physiologic adaptation or maladaptation?

PubMed

Peter, Valsa S; Peter, M C Subhash

2011-12-01

Endocrines, the chief components of chemical centers which produce hormones in tune with intrinsic and extrinsic clues, create a chemical bridge between the organism and the environment. In fishes also hormones integrate and modulate many physiologic functions and its synthesis, release, biological actions and metabolic clearance are well regulated. Consequently, thyroid hormones (THs) and cortisol, the products of thyroid and interrenal axes, have been identified for their common integrative actions on metabolic and osmotic functions in fish. On the other hand, many anthropogenic chemical substances, popularly known as endocrine disrupting chemicals, have been shown to disrupt the hormone-receptor signaling pathways in a number fish species. These chemicals which are known for their ability to induce endocrine disruption particularly on thyroid and interrenals can cause malfunction or maladaptation of many vital processes which are involved in the development, growth and reproduction in fish. On the contrary, evidence is presented that the endocrine interrupting agents (EIAs) can cause interruption of thyroid and interrenals, resulting in physiologic compensatory mechanisms which can be adaptive, though such hormonal interactions are less recognized in fishes. The EIAs of physical, chemical and biological origins can specifically interrupt and modify the hormonal interactions between THs and cortisol, resulting in specific patterns of inter-hormonal interference. The physiologic analysis of these inter-hormonal interruptions during acclimation and post-acclimation to intrinsic or extrinsic EIAs reveals that combinations of anti-hormonal, pro-hormonal or stati-hormonal interference may help the fish to fine-tune their metabolic and osmotic performances as part of physiologic adaptation. This novel hypothesis on the phenomenon of inter-hormonal interference and its consequent physiologic interference during thyroid and interrenal interruption thus forms the basis of physiologic acclimation. This interfering action of TH and cortisol during hormonal interruption may subsequently promote ecological adaptation in fish as these physiologic processes ultimately favor them to survive in their hostile environment. Copyright © 2011 Elsevier Inc. All rights reserved.

Potential protective effect of Pistacia lentiscus oil against chlorpyrifos-induced hormonal changes and oxidative damage in ovaries and thyroid of female rats.

PubMed

Chebab, Samira; Mekircha, Fatiha; Leghouchi, Essaid

2017-12-01

The purpose of this study was to evaluate the protective effect of Pistacia lentiscus oil (PLO), known for its antioxidant properties, on chlorpyrifos (CPF)-induced alterations in the thyroid, reproductive hormone levels, and oxidative damage in the ovaries and thyroid of adult Wistar rats. The animals were treated with orally administered PLO (2 mL/kg), CPF (6.75 mg/kg), and a combination of CPF and PLO for 30 days. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (Pg), estradiol (E 2 ), triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) were assessed using chemiluminescence assay. Malondialdehyde (MDA), protein carbonyl (PC), and reduced glutathione (GSH) levels were examined in the ovaries and thyroid glands. The oil principal volatile compounds detected by gas chromatography analysis were: myrcene, α-pinene and limonene (26.21, 22.66 and 10.33%, respectively). No significant differences were observed between serum concentrations of TSH and FSH in the examined experimental groups. However, serum concentrations of LH, E 2 , Pg, T3, and T4 decreased significantly in CPF-treated rats in comparison with the controls. The body weight and relative weight of ovaries and thyroids in this group were also significantly reduced. The MDA and PC content increased significantly, while the GSH content was markedly depressed in the thyroid and ovaries of rats treated with CPF. Co-administration of PLO and CPF effectively ameliorated the adverse effects; the oxidative damage was reduced and the levels of thyroid and reproductive hormones restored to a normal range. In conclusion, it appears that PLO substantially alleviates the CPF-induced oxidative damage and hormonal alterations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2014-09-01

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

Maternal thyroid hormone trajectories during pregnancy and child behavioral problems.

PubMed

Endendijk, Joyce J; Wijnen, Hennie A A; Pop, Victor J M; van Baar, Anneloes L

2017-08-01

There is ample evidence demonstrating the importance of maternal thyroid hormones, assessed at single trimesters in pregnancy, for child cognition. Less is known, however, about the course of maternal thyroid hormone concentrations during pregnancy in relation to child behavioral development. Child sex might be an important moderator, because there are sex differences in externalizing and internalizing behavioral problems. The current study examined the associations between maternal thyroid hormone trajectories versus thyroid assessments at separate trimesters of pregnancy and child behavioral problems, as well as sex differences in these associations. In 442 pregnant mothers, serum levels of TSH and free T4 (fT4) were measured at 12, 24, and 36weeks gestation. Both mothers and fathers reported on their children's behavioral problems, between 23 and 60months of age. Latent growth mixture modeling was used to determine the number of different thyroid hormone trajectories. Three trajectory groups were discerned: 1) highest and non-increasing TSH with lowest fT4 that decreased least of the three trajectories; 2) increasing TSH and decreasing fT4 at intermediate levels; 3) lowest and increasing TSH with highest and decreasing fT4. Children of mothers with the most flattened thyroid hormone trajectories (trajectory 1) showed the most anxiety/depression symptoms. The following trimester-specific associations were found: 1) lower first-trimester fT4 was associated with more child anxiety/depression, 2) higher first-trimester TSH levels were related to more attention problems in boys only. A flattened course of maternal thyroid hormone concentrations during pregnancy was a better predictor of child anxiety/depression than first-trimester fT4 levels. Copyright © 2017 Elsevier Inc. All rights reserved.

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study

PubMed Central

Meissner, H. O.; Mscisz, A.; Reich-Bilinska, H.; Mrozikiewicz, P.; Bobkiewicz-Kozlowska, T.; Kedzia, B.; Lowicka, A.; Barchia, I.

2006-01-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene’s Score (GMS) and Kupperman’s Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT). PMID:23675006

Hormone-Balancing Effect of Pre-Gelatinized Organic Maca (Lepidium peruvianum Chacon): (III) Clinical responses of early-postmenopausal women to Maca in double blind, randomized, Placebo-controlled, crossover configuration, outpatient study.

PubMed

Meissner, H O; Mscisz, A; Reich-Bilinska, H; Mrozikiewicz, P; Bobkiewicz-Kozlowska, T; Kedzia, B; Lowicka, A; Barchia, I

2006-12-01

This is the second, conclusive part of the clinical study on clinical responses of early-postmenopausal women to standardized doses of pre-Gelatinized Organic Maca (Maca-GO). Total of 34 Caucasian women volunteers participated in a double-blind, randomized, four months outpatient crossover configuration Trial. After fulfilling the criteria of being early-postmenopausal: blood Estrogen (E2<40 pg/ml) and Follicle Stimulating Hormone (FSH>30 IU/ml) at admission, they were randomly allocated to Placebo (P) and Maca-GO (M) treatments (2 groups of 11 participants each). Two 500 mg vegetable hard gel capsules with Maca-GO or Placebo powder were self-administered twice daily with meals (total 2 g/day). At admission and follow-up monthly intervals, body mass index (BMI), blood pressure, levels of gonadal, pituitary, thyroid and adrenal hormones, lipids and key minerals were measured. Bone markers were determined after four months M and P use in 12 participants. Menopausal symptoms were assessed according to Greene's Score (GMS) and Kupperman's Index (KMI). Data were analyzed using multivariate technique on blocs of monthly. Results and canonical variate technique was applied to GMS and KMI matrices. Two months application of Maca-GO stimulated (P<0.05) production of E2, suppressed (P<0.05) blood FSH, Thyroid (T3) and Adrenocorticotropic hormones, Cortisol, and BMI, increased (P<0.05) low density lipoproteins, blood Iron and alleviated (P<0.001) menopausal symptoms. Maca-GO noticeably increased bone density markers. In conclusion, Maca-GO applied to early-postmenopausal women (i) acted as a toner of hormonal processes along the Hypothalamus-Pituitary-Ovarian axis, (ii) balanced hormone levels and (iii) relieved symptoms of menopausal discomfort, (hot flushes and night sweating in particular), thus, (iv) exhibited a distinctive function peculiar to adaptogens, providing an alternative non-hormonal plant option to reduce dependence on hormone therapy programs (HRT).

Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

PubMed

Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

2015-08-01

The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p < 0.001). There was no gender difference in terms of H scores for aromatase expression and double immunohistochemical staining results (p > 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p < 0.001; r = -0.593, p < 0.001; r = -0.650, p < 0.001, respectively). Also, H scores for aromatase co-expression of each hormone were negatively correlated with the H scores for the corresponding hormone (r = -0.503, p < 0.001 for PRL-aromatase and PRL; r = -0.470, p < 0.001 for GH-aromatase, and GH; r = -0.641, p < 0.001 for TSH-aromatase and TSH). H scores for mean aromatase, GH-aromatase, TSH-aromatase were invariant of age (p > 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

Seasoning ingredients in a medium-fat diet regulate lipid metabolism in peripheral tissues via the hypothalamic-pituitary axis in growing rats.

PubMed

Tanaka, Mitsuru; Yasuoka, Akihito; Yoshinuma, Haruka; Saito, Yoshikazu; Asakura, Tomiko; Tanabe, Soichi

2018-03-01

We fed rats noodle (N) -diet containing 30 wt.% instant noodle with a 26% fat-to-energy ratio for 30 days (N-group). Compared with rats that were fed the same amount of nutrients (C-group), the N-group showed lower liver triacylglycerol levels and higher fecal cholesterol levels. We then analyzed transcriptome of the hypothalamic-pituitary (HP), the liver and the white adipose tissue (WAT). Thyroid stimulating hormone (Tshb), and its partner, glycoprotein hormone genes were up-regulated in the HP of N-group. Sterol regulatory element binding transcription factors were activated in the liver of N-group, while an up-regulation of the angiogenic signal occurred in the WAT of N-group. N-group showed higher urine noradrenaline (NA) level suggesting that these tissue signals are regulated by NA and Tshb. The N-diet contains 0.326 wt.% glutamate, 0.00236 wt.% 6-shogaol and Maillard reaction products. Our results suggest that these ingredients may affect lipid homeostasis via the HP axis.

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

PubMed

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

2012-05-01

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

Follicular thyroglobulin induces cathepsin H expression and activity in thyrocytes

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

Oda, Kenzaburo; Laboratory of Molecular Diagnostics, Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, 4-2-1 Aoba-cho, Higashimurayama, Tokyo 189-0002; Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Toho University, 5-21-16 Omorinishi, Ota, Tokyo 143-8540

Thyroglobulin (Tg) stored in thyroid follicles exerts a potent negative-feedback effect on each step of pre-hormone biosynthesis, including Tg gene transcription and iodine uptake and organification, by suppressing the expression of specific transcription factors that regulate these steps. Pre-hormones are stored in the follicular colloid before being reabsorbed. Following lysosomal proteolysis of its precursor, thyroid hormone (TH) is released from thyroid follicles. Although the suppressive effects of follicular Tg on each step of pre-hormone biosynthesis have been extensively characterized, whether follicular Tg accumulation also affects hormone reabsorption, proteolysis, and secretion is unclear. In this study we explored whether follicular Tgmore » can regulate the expression and function of the lysosomal endopeptidases cathepsins. We found that in the rat thyroid cell line FRTL-5 follicular Tg induced cathepsin H mRNA and protein expression, as well as cathepsin H enzyme activity. Double immunofluorescence staining showed that Tg endocytosis promoted cathepsin H translocalization into lysosomes where it co-localized with internalized Tg. These results suggest that cathepsin H is an active participant in lysosome-mediated pre-hormone degradation, and that follicular Tg stimulates mobilization of pre-hormones by activating cathepsin H-associated proteolysis pathways. - Highlights: • Follicular Tg increases cathepsin H mRNA and protein levels in rat thyroid cells. • Follicular Tg increases cathepsin H enzyme activity in rat thyroid cells. • After Tg stimulation cathepsin H co-localizes to lysosomes with follicular Tg. • Cathepsin H promotes hormone secretion by lysosome-mediated mechanisms.« less

Alien/CSN2 gene expression is regulated by thyroid hormone in rat brain.

PubMed

Tenbaum, Stephan P; Juenemann, Stefan; Schlitt, Thomas; Bernal, Juan; Renkawitz, Rainer; Muñoz, Alberto; Baniahmad, Aria

2003-02-01

Alien has been described as a corepressor for the thyroid hormone receptor (TR). Corepressors are coregulators that mediate gene silencing of DNA-bound transcriptional repressors. We describe here that Alien gene expression in vivo is regulated by thyroid hormone both in the rat brain and in cultured cells. In situ hybridization revealed that Alien is widely expressed in the mouse embryo and also throughout the rat brain. Hypothyroid animals exhibit lower expression of both Alien mRNAs and protein levels as compared with normal animals. Accordingly, we show that Alien gene is inducible after thyroid hormone treatment both in vivo and in cell culture. In cultured cells, the hormonal induction is mediated by either TRalpha or TRbeta, while cells lacking detectable amounts of functional TR lack hormonal induction of Alien. We have detected two Alien-specific mRNAs by Northern experiments and two Alien-specific proteins in vivo and in cell lines by Western analysis, one of the two forms representing the CSN2 subunit of the COP9 signalosome. Interestingly, both Alien mRNAs and both detected proteins are regulated by thyroid hormone in vivo and in cell lines. Furthermore, we provide evidence for the existence of at least two Alien genes in rodents. Taken together, we conclude that Alien gene expression is under control of TR and thyroid hormone. This suggests a negative feedback mechanism between TR and its own corepressor. Thus, the reduction of corepressor levels may represent a control mechanism of TR-mediated gene silencing.

[Primary hypothyroidism associated with empty sella turcica and hypopituitarism].

PubMed

Milosević, Maja; Stojanović, Milos; Nesović, Milica

2005-01-01

Empty sella syndrome is a rather frequent neuroradiological finding in the general population and can be associated with hypopituitarism. Examinations reveal low pituitary hormone levels and lack of response to stimuli. Most patients suffer from central hypothyroidism as part of pituitary insufficiency. Primary hypothyroidism is a rare finding in these patients. We present 3 patients: one female and two male, suffering from complete hypopituitarism, as part of the empty sella syndrome diagnosed due to low concentrations of all pituitary hormones, elevated TSH and low thyroid hormones. TRH, LHRH, ACTH and ITT tests, as well as IGF1 have confirmed hypopituitarism and primary hypothyroidism. CT and NMR in all three patients showed empty sella without a tumor in it. The diagnosis of primary hypothyrodism in the first patient was made before hypopituitarism has taken place, or at the same time in the second patient, whereas in the third patient it was diagnosed twenty years later. In two patients anti-TPO and anti-Tg antibody levels were high, and in the third patient they were not elevated. It can be assumed that the etiology of primary hypothyrodism in all three patients was of autoimmune origin, which caused thyroid hypofunction. High level of TSH in all three patients and especially in the patient whose hypopituitarism was diagnosed twenty years later, showed presence of thyrotrophic cells in the pituitary. Evaluation of the hypothalamic-pituitary-thyroid axis was carried out during the complete substitution therapy of hypopituitarism. Diagnosing primary hypothyroidism associated with hypopituitarism helps improving the knowledge on empty sella syndrome and points to different clinical syndromes characterized by lack of mixoedema, although approach to therapy is the same for both primary and central hypothyroidism.

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8.

PubMed

Johannes, Jörg; Jayarama-Naidu, Roopa; Meyer, Franziska; Wirth, Eva Katrin; Schweizer, Ulrich; Schomburg, Lutz; Köhrle, Josef; Renko, Kostja

2016-04-01

Thyroid hormones (THs) are charged and iodinated amino acid derivatives that need to pass the cell membrane facilitated by thyroid hormone transmembrane transporters (THTT) to exert their biological function. The importance of functional THTT is affirmed by the devastating effects of mutations in the human monocarboxylate transporter (MCT) 8, leading to a severe form of psychomotor retardation. Modulation of THTT function by pharmacological or environmental compounds might disturb TH action on a tissue-specific level. Therefore, it is important to identify compounds with relevant environmental exposure and THTT-modulating activity. Based on a nonradioactive TH uptake assay, we performed a screening of 13 chemicals, suspicious for TH receptor interaction, to test their potential effects on THTT in MCT8-overexpressing MDCK1-cells. We identified silymarin, an extract of the milk thistle, to be a potent inhibitor of T3 uptake by MCT8. Because silymarin is a complex mixture of flavonolignan substances, we further tested its individual components and identified silychristin as the most effective one with an IC50 of approximately 100 nM. The measured IC50 value is at least 1 order of magnitude below those of other known THTT inhibitors. This finding was confirmed by T3 uptake in primary murine astrocytes expressing endogenous Mct8 but not in MCT10-overexpressing MDCK1-cells, indicating a remarkable specificity of the inhibitor toward MCT8. Because silymarin is a frequently used adjuvant therapeutic for hepatitis C infection and chronic liver disease, our observations raise questions regarding its safety with respect to unwanted effects on the TH axis.

The prevalence of impaired glucose regulation in anxiety disorder patients and the relationship with hypothalamic-pituitary-adrenal axis and hypothalamic-pituitary-thyroid axis activity.

PubMed

Zhou, Yaling; Dong, Zaiquan; A, Ruhan; Liao, Zongbing; Guo, Jing; Liu, Cancan; Sun, Xueli

2016-08-29

To investigate the prevalence of impaired glucose regulation (IGR) in patients with anxiety disorders and the relationship with hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes function. From September 2013 to May 2015, a total of 646 patients with anxiety disorders who matched the criteria of the 10 th revision of the International Statistical Classification of Diseases and Related Health Problems participated in our study, which was conducted in the Psychiatric Inpatient Department of the West China Hospital of Sichuan University. The results from 75-g glucose tolerance tests, and morning (8:00 am) serum cortisol (PTC), adrenocorticotropic hormone༈ACTH), thyroid-stimulating hormone (TSH), TT3, TT4, FT3, and FT4 levels were collected. The Hamilton Anxiety Scale was administered to assess the severity of anxiety. SPSS 17.0 software was used for statistical analysis. The crude prevalence of impaired glucose regulation was 24.61% in patients with anxiety disorders patients. In the 18-40 year age group with impaired glucose regulation (IGR), both ACTH and PTC levels were higher than the control group (P<0.05). In the 61-75 year age group with IGR, the TSH level was lower and the FT4 level was higher than the control group (P<0.05). The results herein partially confirm that the prevalence of IGR in patients with anxiety disorders is high. Impaired glucose in the younger age group is closely associated with HPA axis function, while impaired glucose in the older age group is closely associated with HPT axis alteration. Therefore, routine blood glucose and endocrine function testing in patients with anxiety disorder is of clinical importance to prevent the development of diabetes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Deregulation of the growth hormone/insulin-like growth factor-1 axis in adults with cystic fibrosis.

PubMed

Pascucci, C; De Biase, R V; Savi, D; Quattrucci, S; Isidori, A M; Lubrano, C; Gnessi, L; Lenzi, A

2018-05-01

Patients with cystic fibrosis (CF) present with signs and symptoms that overlap with those of adult growth hormone deficiency (GHD) syndrome: loss of muscle mass, bone fragility and lower stress tolerance. In literature, the prevalence of GHD in pediatric CF patients is higher than general population, but these studies have been performed on children with growth delay. To our knowledge, there are no studies on adult patients. The aim of this paper is to evaluate GH-IGF1 axis in an adult CF population. Fifty clinically stable adult patients, 30 males; age 36 ± 2 years; BMI 21.39 ± 0.22 kg/m 2 and FEV 1 67 ± 4% were studied. Data regarding glycometabolic status and results of pituitary, thyroid, parathyroid, gonadal and adrenal function tests were recorded. All patients underwent a GH releasing hormone (GHRH) + Arginine stimulation test to confirm a GHD. GHRH + Arginine test revealed the presence of GHD in 16 patients (32%); specifically 7 patients had a severe deficiency and 9 a partial deficiency. Adult patients with CF may show GHD. These patients should be followed over time to assess if the GHD could impact the clinical progression of CF.

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.

Iodine excess exposure during pregnancy and lactation impairs maternal thyroid function in rats

PubMed Central

Salgueiro, Rafael Barrera; Vitzel, Kaio Fernando; Pantaleão, Thiago; Corrêa da Costa, Vânia Maria

2017-01-01

Adequate maternal iodine consumption during pregnancy and lactation guarantees normal thyroid hormones (TH) production, which is crucial to the development of the fetus. Indeed, iodine deficiency is clearly related to maternal hypothyroidism and deleterious effects in the fetal development. Conversely, the effects of iodine excess (IE) consumption on maternal thyroid function are still controversial. Therefore, this study aimed to investigate the impact of IE exposure during pregnancy and lactation periods on maternal hypothalamus–pituitary–thyroid axis. IE-exposed dams presented reduced serum TH concentration and increased serum thyrotropin (TSH) levels. Moreover, maternal IE exposure increased the hypothalamic expression of Trh and the pituitary expression of Trhr, Dio2, Tsha and Tshb mRNA, while reduced the Gh mRNA content. Additionally, IE-exposed dams presented thyroid morphological alterations, increased thyroid oxidative stress and decreased expression of thyroid genes/proteins involved in TH synthesis, secretion and metabolism. Furthermore, Dio1 mRNA expression and D1 activity were reduced in the liver and the kidney of IE-treated animals. Finally, the mRNA expression of Slc5a5 and Slc26a4 were reduced in the mammary gland of IE-exposed rats. The latter results are in accordance with the reduction of prolactin expression and serum levels in IE-treated dams. In summary, our study indicates that the exposure to IE during pregnancy and lactation induces primary hypothyroidism in rat dams and impairs iodide transfer to the milk. PMID:28814477

A Rapid Cytoplasmic Mechanism for PI3 Kinase Regulation by the Nuclear Thyroid Hormone Receptor, TRβ, and Genetic Evidence for Its Role in the Maturation of Mouse Hippocampal Synapses In Vivo

PubMed Central

Martin, Negin P.; Fernandez de Velasco, Ezequiel Marron; Mizuno, Fengxia; Scappini, Erica L.; Gloss, Bernd; Erxleben, Christian; Williams, Jason G.; Stapleton, Heather M.; Gentile, Saverio

2014-01-01

Several rapid physiological effects of thyroid hormone on mammalian cells in vitro have been shown to be mediated by the phosphatidylinositol 3-kinase (PI3K), but the molecular mechanism of PI3K regulation by nuclear zinc finger receptor proteins for thyroid hormone and its relevance to brain development in vivo have not been elucidated. Here we show that, in the absence of hormone, the thyroid hormone receptor TRβ forms a cytoplasmic complex with the p85 subunit of PI3K and the Src family tyrosine kinase, Lyn, which depends on two canonical phosphotyrosine motifs in the second zinc finger of TRβ that are not conserved in TRα. When hormone is added, TRβ dissociates and moves to the nucleus, and phosphatidylinositol (3, 4, 5)-trisphosphate production goes up rapidly. Mutating either tyrosine to a phenylalanine prevents rapid signaling through PI3K but does not prevent the hormone-dependent transcription of genes with a thyroid hormone response element. When the rapid signaling mechanism was blocked chronically throughout development in mice by a targeted point mutation in both alleles of Thrb, circulating hormone levels, TRβ expression, and direct gene regulation by TRβ in the pituitary and liver were all unaffected. However, the mutation significantly impaired maturation and plasticity of the Schaffer collateral synapses on CA1 pyramidal neurons in the postnatal hippocampus. Thus, phosphotyrosine-dependent association of TRβ with PI3K provides a potential mechanism for integrating regulation of development and metabolism by thyroid hormone and receptor tyrosine kinases. PMID:24932806

Intrinsic Regulation of Thyroid Function by Thyroglobulin

PubMed Central

Sellitti, Donald F.

2014-01-01

Background: The established paradigm for thyroglobulin (Tg) function is that of a high molecular weight precursor of the much smaller thyroid hormones, triiodothyronine (T3) and thyroxine (T4). However, speculation regarding the cause of the functional and morphologic heterogeneity of the follicles that make up the thyroid gland has given rise to the proposition that Tg is not only a precursor of thyroid hormones, but that it also functions as an important signal molecule in regulating thyroid hormone biosynthesis. Summary: Evidence supporting this alternative paradigm of Tg function, including the up- or downregulation by colloidal Tg of the transcription of Tg, iodide transporters, and enzymes employed in Tg iodination, and also the effects of Tg on the proliferation of thyroid and nonthyroid cells, is examined in the present review. Also discussed in detail are potential mechanisms of Tg signaling in follicular cells. Conclusions: Finally, we propose a mechanism, based on experimental observations of Tg effects on thyroid cell behavior, that could account for the phenomenon of follicular heterogeneity as a highly regulated cycle of increasing and decreasing colloidal Tg concentration that functions to optimize thyroid hormone production through the transcriptional activation or suppression of specific genes. PMID:24251883

Thyroid hormone use: trends in the United States from 1960 through 1988.

PubMed

Kaufman, S C; Gross, T P; Kennedy, D L

1991-01-01

Thyroid hormone preparations comprised over 1% of all prescriptions filled by retail pharmacies during 1988 in the conterminous United States, i.e., the 48 contiguous states. Their large market share gives the patterns of their use substantial public health importance. This article describes prescription thyroid hormone use in the United States from 1960 through 1988, using pharmaceutical marketing research data collected from panels of retail pharmacies and office-based physicians. Although the use of natural products has declined by over 50% since 1960, about one fourth of all thyroid hormone prescriptions were for natural preparations as recently as 1988. Per capita thyroid mentions (i.e., patient-physician contacts during which a thyroid agent of any kind was recommended, prescribed, dispensed, administered, ordered to be given by a hospital, or given as a sample) doubled during this period among those over 59 years old. Per capita mentions for synthetic thyroid products increased fourfold and tenfold among men and women in this age group, respectively. Use for weight loss, despite the label's boxed warning indicating it to be ineffective and potentially dangerous, has diminished but persists. Obesity was second only to hypothyroidism among the diagnoses underlying thyroid product mentions.

Preoperative Serum Thyrotropin to Thyroglobulin Ratio Is Effective for Thyroid Nodule Evaluation in Euthyroid Patients.

PubMed

Wang, Lina; Li, Hao; Yang, Zhongyuan; Guo, Zhuming; Zhang, Quan

2015-07-01

This study was designed to assess the efficiency of the serum thyrotropin to thyroglobulin ratio for thyroid nodule evaluation in euthyroid patients. Cross-sectional study. Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China. Retrospective analysis was performed for 400 previously untreated cases presenting with thyroid nodules. Thyroid function was tested with commercially available radioimmunoassays. The receiver operating characteristic curves were constructed to determine cutoff values. The efficacy of the thyrotropin:thyroglobulin ratio and thyroid-stimulating hormone for thyroid nodule evaluation was evaluated in terms of sensitivity, specificity, positive predictive value, positive likelihood ratio, negative likelihood ratio, and odds ratio. In receiver operating characteristic curve analysis, the area under the curve was 0.746 for the thyrotropin:thyroglobulin ratio and 0.659 for thyroid-stimulating hormone. With a cutoff point value of 24.97 IU/g for the thyrotropin:thyroglobulin ratio, the sensitivity, specificity, positive predictive value, positive likelihood ratio, and negative likelihood ratio were 78.9%, 60.8%, 75.5%, 2.01, and 0.35, respectively. The odds ratio for the thyrotropin:thyroglobulin ratio indicating malignancy was 5.80. With a cutoff point value of 1.525 µIU/mL for thyroid-stimulating hormone, the sensitivity, specificity, positive predictive value, positive likelihood ratio, and negative likelihood ratio were 74.0%, 53.2%, 70.8%, 1.58, and 0.49, respectively. The odds ratio indicating malignancy for thyroid-stimulating hormone was 3.23. Increasing preoperative serum thyrotropin:thyroglobulin ratio is a risk factor for thyroid carcinoma, and the correlation of the thyrotropin:thyroglobulin ratio to malignancy is higher than that for serum thyroid-stimulating hormone. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Weight-of-evidence analysis of human exposures to dioxins and dioxin-like compounds and associations with thyroid hormone levels during early development.

PubMed

Goodman, Julie E; Kerper, Laura E; Boyce, Catherine Petito; Prueitt, Robyn L; Rhomberg, Lorenz R

2010-10-01

Thyroid hormones play a critical role in the proper development of brain function and cell growth. Several epidemiological studies have been conducted to assess potential associations between pre- and post-natal exposure to dioxins or dioxin-like compounds (DLCs) and the levels of circulating thyroid hormones during early development. Dioxins and DLCs include chlorinated dibenzo-p-dioxins, chlorinated dibenzofurans, and mono- and non-ortho polychlorinated biphenyls (PCBs). We identified a total of 23 relevant epidemiological studies (21 cohort studies and 1 case-control study) that measured exposures to various types of dioxins and DLCs as well as markers of thyroid function, such as thyroid stimulating hormone (TSH), total thyroxine (T4), free T4, total triiodothyroxine (T3), free T3, and thyroid-binding globulin concentrations in cord blood or circulation. While some of the studies reported associations between concentrations of dioxins and/or DLCs and some biomarkers of thyroid function, the majority of the observed associations were not statistically significant. Moreover, there were no clear and consistent effects across studies for any of the hormone levels examined, and while a number of studies showed a statistically significant association with exposure for a given marker of thyroid function, other studies showed either no change or changes in the opposite direction for the same thyroid function marker. Similarly, when the results were analyzed considering developmental stage, there generally were no clear and consistent effects at any age from birth through 12 years of age. The absence of a clear correlation between background exposures to dioxins and DLCs and thyroid function biomarkers during development is not consistent with the hypothesis that background exposures to these chemicals cause effects on thyroid function during development. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Thyroid Diseases

MedlinePlus

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

Considering common sources of exposure in association studies - Urinary benzophenone-3 and DEHP metabolites are associated with altered thyroid hormone balance in the NHANES 2007-2008.

PubMed

Kim, Sujin; Kim, Sunmi; Won, Sungho; Choi, Kyungho

2017-10-01

Epidemiological studies have shown that thyroid hormone balances can be disrupted by chemical exposure. However, many association studies have often failed to consider multiple chemicals with possible common sources of exposure, rendering their conclusions less reliable. In the 2007-2008 National Health and Nutrition Examination Survey (NHANES) from the U.S.A., urinary levels of environmental phenols, parabens, and phthalate metabolites as well as serum thyroid hormones were measured in a general U.S. population (≥12years old, n=1829). Employing these data, first, the chemicals or their metabolites associated with thyroid hormone measures were identified. Then, the chemicals/metabolites with possible common exposure sources were included in the analytical model to test the sensitivities of their association with thyroid hormone levels. Benzophenone-3 (BP-3), bisphenol A (BPA), and a metabolite of di(2-ethylhexyl) phthalate (DEHP) were identified as significant determinants of decreased serum thyroid hormones. However, significant positive correlations were detected (p-value<0.05, r=0.23 to 0.45) between these chemicals/metabolites, which suggests that they might share similar exposure sources. In the subsequent sensitivity analysis, which included the chemicals/metabolite with potentially similar exposure sources in the model, we found that urinary BP-3 and DEHP exposure were associated with decreased thyroid hormones among the general population but BPA exposure was not. In association studies, the presence of possible common exposure sources should be considered to circumvent possible false-positive conclusions. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Thyroid hormone status and pituitary function in adult rats given oral doses of perfluorooctanesulfonate (PFOS)

EPA Science Inventory

Perfluorooctanesulfonate (PFOS) is widely distributed and persistent in humans and wildlife. Prior toxicological studies have reported decreased total and free thyroid hormones in serum without a major compensatory rise in thyrotropin (TSH) or altered thyroid gland histology. Alt...

[Thyroid hormones and the development of the nervous system].

PubMed

Mussa, G C; Zaffaroni, M; Mussa, F

1990-09-01

The growth and differentiation of the central nervous system are closely related to the presence of iodine and thyroid hormones. During the first trimester of human pregnancy the development of the nervous system depends entirely on the availability of iodine; after 12 week of pregnancy it depends on the initial secretion of iodothyronine by the fetal thyroid gland. During the early stages of the development of the nervous system a thyroid hormone deficit may provoke alterations in the maturation of both noble nervous cells (cortical pyramidal cells, Purkinje cells) and glial cells. Hypothyroidism may lead to cellular hypoplasia and reduced dendritic ramification, gemmules and interneuronal connections. Experimental studies in hypothyroid rats have also shown alterations in the content and organization of neuronal intracytoplasmatic microtubules, the biochemical maturation of synaptosomes and the maturation of nuclear and cytoplasmatic T3 receptors. Excess thyroid hormones during the early stages of development may also cause permanent damage to the central nervous system. Hyperthyroidism may initially induce an acceleration of the maturation processes, including the migration and differentiation of cells, the extension of the dendritic processes and synaptogenesis. An excess of thyroid hormones therefore causes neuronal proliferation to end precociously leading to a reduction of the total number of gemmules. Experimental research and clinical studies have partially clarified the correlation between the maturation of the nervous system and thyroid function during the early stages of development; both a deficit and excess of thyroid hormones may lead to permanent anatomo-functional damage to the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed

Johnson, Kaitlin M; Lema, Sean C

2011-07-01

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

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

PubMed

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

2016-08-01

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

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.

Thyroid and adrenal relationships

PubMed Central

Parsons, Victor; Ramsay, Ian

1968-01-01

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

IN VITRO METABOLISM OF THYROID HORMONES BY RECOMBINANT HUMAN UDP-GLUCORONOSYLTRANSFERASES AND SULFOTRANSFERASES

EPA Science Inventory

Endocrine disruptors can decrease thyroid hormone levels via the induction of hepatic uridinediphosphate-glucoronosyltransferases (UGTs) and sulfotransferases (SULTs). Due to their ability to catalyze glucuronidation and sulfation of hormones and xenobiotics, UGTs and SULTs play ...

Cytophysiological Changes in the Follicular Epithelium of the Thyroid Gland after Long-Term Exposure to Low Doses of Dichlorodiphenyltrichloroethane (DDT).

PubMed

Yaglova, N V; Yaglov, V V

2017-03-01

Exposure to endocrine disruptors is considered as a risk factor thyroid gland diseases. We analyzed cytophysiological changes in rat thyroid follicular epithelium after long-term exposure to low doses of the most widespread disruptor DDT. Analysis of thyroid hormone production and light and electron microscopy of thyroid gland samples revealed cytophysiological changes in thyroid epithelium related to impaired transport through the apical membrane, suppressed Golgi complex activity, and impaired thyrotrophic hormone regulation of the secretory functions of thyroid cells, which led to compensatory transition from merocrine to microapocrine secret release.

[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.

Tissue-engineered thyroid cell sheet rescued hypothyroidism in rat models after receiving total thyroidectomy comparing with nontransplantation models.

PubMed

Arauchi, Ayumi; Shimizu, Tatsuya; Yamato, Masayuki; Obara, Takao; Okano, Teruo

2009-12-01

For hormonal deficiency caused by endocrine organ diseases, continuous oral hormone administration is indispensable to supplement the shortage of hormones. In this study, as a more effective therapy, we have tried to reconstruct the three-dimensional thyroid tissue by the cell sheet technology, a novel tissue engineering approach. The cell suspension obtained from rat thyroid gland was cultured on temperature-responsive culture dishes, from which confluent cells detach as a cell sheet simply by reducing temperature without any enzymatic treatment. The 8-week-old Lewis rats were exposed to total thyroidectomy as hypothyroidism models and received thyroid cell sheet transplantation 1 week after total thyroidectomy. Serum levels of free triiodothyronine (fT(3)) and free thyroxine (fT(4)) significantly decreased 1 week after total thyroidectomy. On the other hand, transplantation of the thyroid cell sheets was able to restore the thyroid function 1 week after the cell sheet transplantation, and improvement was maintained for 4 weeks. Moreover, morphological analyses showed typical thyroid follicle organization, and anti-thyroid-transcription-factor-1 antibody staining demonstrated the presence of follicle epithelial cells. The presence of functional microvessels was also detected within the engineered thyroid tissues. In conclusion, our results indicate that thyroid cell sheets transplanted in a model of total thyroidectomy can reorganize histologically to resemble a typical thyroid gland and restore thyroid function in vivo. In this study, we are the first to confirm that engineered thyroid tissue can repair hypothyroidism models in rats and, therefore, cell sheet transplantation of endocrine organs may be suitable for the therapy of hormonal deficiency.

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...

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...

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...

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.

Combined 3D-QSAR, molecular docking and molecular dynamics study on thyroid hormone activity of hydroxylated polybrominated diphenyl ethers to thyroid receptors β

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

Li, Xiaolin; Ye, Li; Wang, Xiaoxiang

2012-12-15

Several recent reports suggested that hydroxylated polybrominated diphenyl ethers (HO-PBDEs) may disturb thyroid hormone homeostasis. To illuminate the structural features for thyroid hormone activity of HO-PBDEs and the binding mode between HO-PBDEs and thyroid hormone receptor (TR), the hormone activity of a series of HO-PBDEs to thyroid receptors β was studied based on the combination of 3D-QSAR, molecular docking, and molecular dynamics (MD) methods. The ligand- and receptor-based 3D-QSAR models were obtained using Comparative Molecular Similarity Index Analysis (CoMSIA) method. The optimum CoMSIA model with region focusing yielded satisfactory statistical results: leave-one-out cross-validation correlation coefficient (q{sup 2}) was 0.571 andmore » non-cross-validation correlation coefficient (r{sup 2}) was 0.951. Furthermore, the results of internal validation such as bootstrapping, leave-many-out cross-validation, and progressive scrambling as well as external validation indicated the rationality and good predictive ability of the best model. In addition, molecular docking elucidated the conformations of compounds and key amino acid residues at the docking pocket, MD simulation further determined the binding process and validated the rationality of docking results. -- Highlights: ► The thyroid hormone activities of HO-PBDEs were studied by 3D-QSAR. ► The binding modes between HO-PBDEs and TRβ were explored. ► 3D-QSAR, molecular docking, and molecular dynamics (MD) methods were performed.« less

Vascular and renal function in experimental thyroid disorders.

PubMed

Vargas, Félix; Moreno, Juan Manuel; Rodríguez-Gómez, Isabel; Wangensteen, Rosemary; Osuna, Antonio; Alvarez-Guerra, Miriam; García-Estañ, Joaquín

2006-02-01

This review focuses on the effects of thyroid hormones in vascular and renal systems. Special emphasis is given to the mechanisms by which thyroid hormones affect the regulation of body fluids, vascular resistance and, ultimately, blood pressure. Vascular function is markedly affected by thyroid hormones that produce changes in vascular reactivity and endothelial function in hyper- and hypothyroidism. The hypothyroid state is accompanied by a marked decrease in sensitivity to vasoconstrictors, especially to sympathetic agonists, alteration that may play a role in the reduced blood pressure of hypothyroid rats, as well as in the preventive effects of hypothyroidism on experimental hypertension. Moreover, in hypothyroid rats, the endothelium-dependent and nitric oxide donors vasodilation is reduced. Conversely, the vessels from hyperthyroid rats showed an increased endothelium-dependent responsiveness that may be secondary to the shear-stress induced by the hyperdynamic circulation, and that may contribute to the reduced vascular resistance characteristic of this disease. Thyroid hormones also have important effects in the kidney, affecting renal growth, renal haemodynamics, and salt and water metabolism. In hyperthyroidism, there is a resetting of the pressure-natriuresis relationship related to hyperactivity of the renin-angiotensin system, which contributes to the arterial hypertension associated with this endocrine disease. Moreover, thyroid hormones affect the development and/or maintenance of various forms of arterial hypertension. This review also describes recent advances in our understanding of thyroid hormone action on nitric oxide and oxidative stress in the regulation of cardiovascular and renal function and in the long-term control of blood pressure.

Prolonged weightlessness effect on postflight plasma thyroid hormones

NASA Technical Reports Server (NTRS)

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

1977-01-01

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

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

Gene Expression in Developing Brain is Altered by Modest Reductions in Circulating Levels of Thyroid Hormone.

EPA Science Inventory

Disruption of thyroid hormone (TH) homeostasis is a known effect of environmental contaminants. Although animal models of developmental TH deficiency can predict the impact of severe insults to the thyroid system, the effects of moderate TH insufficiencies have not been adequatel...

Predictive Modeling of a Mixture of Thyroid Hormone Disrupting Chemicals that Affect Production and Clearance of Thyroxine

EPA Science Inventory

Thyroid hormone (TH) disrupting compounds interfere with both thyroidal and extrathyroidal mechanisms to decrease circulating thyroxine (T4). This research tested the hypothesis that serum T4 concentrations of rodents exposed to a mixture of both TH synthesis inhibitors (pesticid...

Interpreting in vivo Effects of Thyroid Synthesis Inhibitors through the Lens of in vitro and ex vivo Assays

EPA Science Inventory

The US EPA has been charged to evaluate chemicals for their ability to disrupt endocrine pathways including estrogen, androgen, and thyroid hormone. Amphibian metamorphosis, which is regulated by thyroid hormone, is an ideal model system for investigating disruption of the thyroi...

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

PubMed

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

2011-12-01

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

Direct Regulation of Mitochondrial RNA Synthesis by Thyroid Hormone

PubMed Central

Enríquez, José A.; Fernández-Silva, Patricio; Garrido-Pérez, Nuria; López-Pérez, Manuel J.; Pérez-Martos, Acisclo; Montoya, Julio

1999-01-01

We have analyzed the influence of in vivo treatment and in vitro addition of thyroid hormone on in organello mitochondrial DNA (mtDNA) transcription and, in parallel, on the in organello footprinting patterns at the mtDNA regions involved in the regulation of transcription. We found that thyroid hormone modulates mitochondrial RNA levels and the mRNA/rRNA ratio by influencing the transcriptional rate. In addition, we found conspicuous differences between the mtDNA dimethyl sulfate footprinting patterns of mitochondria derived from euthyroid and hypothyroid rats at the transcription initiation sites but not at the mitochondrial transcription termination factor (mTERF) binding region. Furthermore, direct addition of thyroid hormone to the incubation medium of mitochondria isolated from hypothyroid rats restored the mRNA/rRNA ratio found in euthyroid rats as well as the mtDNA footprinting patterns at the transcription initiation area. Therefore, we conclude that the regulatory effect of thyroid hormone on mitochondrial transcription is partially exerted by a direct influence of the hormone on the mitochondrial transcription machinery. Particularly, the influence on the mRNA/rRNA ratio is achieved by selective modulation of the alternative H-strand transcription initiation sites and does not require the previous activation of nuclear genes. These results provide the first functional demonstration that regulatory signals, such as thyroid hormone, that modify the expression of nuclear genes can also act as primary signals for the transcriptional apparatus of mitochondria. PMID:9858589

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

Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc.

PubMed

Baltaci, Abdulkerim Kasım; Mogulkoc, Rasim

2017-06-01

Since zinc mediates the effects of many hormones or is found in the structure of numerous hormone receptors, zinc deficiency leads to various functional impairments in the hormone balance. And also thyroid hormones have important activity on metabolism and feeding. NPY and leptin are affective on food intake and regulation of appetite. The present study is conducted to determine how zinc supplementation and deficiency affect thyroid hormones (free and total T3 and T4), melatonin, leptin, and NPY levels in thyroid dysfunction in rats. The experiment groups in the study were formed as follows: Control (C); Hypothyroidism (PTU); Hypothyroidism+Zinc (PTU+Zn); Hypothyroidism+Zinc deficient; Hyperthyroidism (H); Hyperthyroidism+Zinc (H+Zn); and Hyperthyroidism+Zinc deficient. Thyroid hormone parameters (FT 3 , FT 4 , TT 3 , and TT 4 ) were found to be reduced in hypothyroidism groups and elevated in the hyperthyroidism groups. Melatonin values increased in hyperthyroidism and decreased in hypothyroidism. Leptin and NPY levels both increased in hypo- and hyperthyroidism. Zinc levels, on the other hand, decreased in hypothyroidism and increased in hyperthyroidism. Zinc supplementation, particularly when thyroid function is impaired, has been demonstrated to markedly prevent these changes.

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

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin

PubMed Central

2012-01-01

Background Dendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo. Methods Blood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry. Results Administration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations – CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 – one of the major costimulatory molecules – neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes. Conclusions In the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo. PMID:23199104

Distribution of subpopulations of dendritic cells in peripheral blood of patients treated with exogenous thyrotropin.

PubMed

Stasiołek, Mariusz; Adamczewski, Zbigniew; Puła, Bartosz; Krawczyk-Rusiecka, Kinga; Zygmunt, Arkadiusz; Borowiecka, Magdalena; Dzięgiel, Piotr; Lewiński, Andrzej

2012-11-30

Dendritic cells (DCs) play a major role as regulators of inflammatory events associated with thyroid pathology. The immunoregulatory function of DCs depends strongly on their subtype, as well as maturation and activation status. Numerous hormonal factors modulate the immune properties of DCs, however, little is known about effects exerted by the hypothalamus-pituitary-thyroid-axis. Recently, we have shown a direct regulatory influence of thyroid hormones (TH) on human DCs function. The aim of the present study was to analyze the effect of systemically administered thyrotropin (TSH) on human blood DCs ex vivo. Blood samples for the cytometric analysis of peripheral blood plasmacytoid and myeloid DCs subtypes were collected from patients subjected to total thyroidectomy because of differentiated thyroid carcinoma at 2 time points: (i) directly before the commencement of TSH administration and (ii) 5 days after first TSH injection. The whole blood quantitative and phenotypic analysis of plasmacytoid and myeloid DCs subtypes was performed by flow cytometry. Administration of TSH did not influence the percentage of plasmacytoid DCs in peripheral blood of study participants. Also the percentage of the two main myeloid DCs subpopulations - CD1c/BDCA1+ DCs and CD141/BDCA3+ DCs did not change significantly. TSH administration had no effect on the surface expression of CD86 - one of the major costimulatory molecules - neither in the whole peripheral blood mononuclear cell (PBMC) fraction nor in particular DCs subtypes. In the present study, we demonstrated no influence of systemic TSH administration on human peripheral blood DCs subtypes. These results are in accordance with our previous work suggesting the direct effect of TH on human DCs ex vivo.

Effects of neonatal hyperthyroidism on the development of the hypothalamic-pituitary-thyroid axis in the rat.

PubMed

Dussault, J H; Coulombe, P; Walker, P

1982-03-01

The acute and latent effects of neonatal hyperthyroidism (NH) on the hypothalamic-pituitary-thyroid axis were studied in the rat after treatment of newborn animals with L-T4 (0.4 microgram/g BW, daily) for a period of 12 days. NH was associated with a permanent reduction in body weight in both male and female rats, in addition to a delay in the attainment of peak concentrations of hypothalamic TRH and pituitary and serum TSH. Serum TSH, T4, and T3 concentrations also were significantly and permanently reduced in NH animals (P less than 0.01) after cessation of L-T4 treatment. The serum TSH secretory response to 1 microgram synthetic TRH also was evaluated in 120-day-old control and NH rats, before and after the administration of L-T4 (0.6 microgram/100 g BW for 7 days) or propylthiouracil (0.05% in the drinking water for 14 days). In the baseline state, adult NH rats had a net secretory response similar to that of controls (189.0 +/- 31.3 vs. 227.0 +/- 29.3 microgram/ml . min). Administration of T4 significantly decreased while propylthiouracil treatment significantly increased the net TSH secretory response of NH rats compared to similarly treated control rats. These data are compatible with the hypothesis that NH leads to a permanent resetting of the regulatory set-point for pituitary TSH secretion and to increased sensitivity to the feedback inhibitory effects of thyroid hormones.

Maternal phthalate exposure during the first trimester and serum thyroid hormones in pregnant women and their newborns.

PubMed

Yao, Hui-Yuan; Han, Yan; Gao, Hui; Huang, Kun; Ge, Xing; Xu, Yuan-Yuan; Xu, Ye-Qing; Jin, Zhong-Xiu; Sheng, Jie; Yan, Shuang-Qin; Zhu, Peng; Hao, Jia-Hu; Tao, Fang-Biao

2016-08-01

Animal and human studies have suggested that phthalate alters thyroid hormone concentrations. This study investigated the associations between phthalate exposure during the first trimester and thyroid hormones in pregnant women and their newborns. Pregnant women were enrolled from the prospective Ma'anshan Birth Cohort study in China. A standard questionnaire was completed by the women at the first antenatal visit. Seven phthalate metabolites were measured in one-spot urine at enrolment (10.0 ± 2.1 gestational weeks), as were thyroid hormone levels in maternal and cord sera. Multivariable linear regression showed that 1-standard deviation (SD) increase in natural log (ln)-transformed mono(2-ethylhexyl) phthalate (MEHP) and mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with 0.163 μg/dL (p = 0.001) and 0.173 μg/dL (p = 0.001) decreases in maternal total thyroxine (TT4). Both MEHP and MEHHP were negatively associated with maternal free thyroxine (FT4; β: -0.013, p < 0.001 and β: -0.011, p = 0.001, respectively) and positively associated with maternal thyroid-stimulating hormone (β: 0.101, p < 0.001; β: 0.132, p < 0.001, respectively). An inverse association was observed between monobenzyl phthalate and maternal TT4 and FT4. A 1-SD increase in ln-transformed monoethyl phthalate was inversely associated with maternal TT4 (β: -0.151, p = 0.002). By contrast, the concentrations of phthalate metabolites in urine were not associated with those of thyroid hormone in cord serum. Our analysis suggested that phthalate exposure during the first trimester disrupts maternal thyroid hormone levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Thyroid hormone actions on male reproductive system of teleost fish.

PubMed

Tovo-Neto, Aldo; da Silva Rodrigues, Maira; Habibi, Hamid R; Nóbrega, Rafael Henrique

2018-04-17

Thyroid hormones (THs) play important roles in the regulation of many biological processes of vertebrates, such as growth, metabolism, morphogenesis and reproduction. An increasing number of studies have been focused on the involvement of THs in the male reproductive system of vertebrates, in particular of fish. Therefore, this mini-review aims to summarize the main findings on THs role in male reproductive system of fish, focusing on sex differentiation, testicular development and spermatogenesis. The existing data in the literature have demonstrated that THs exert their roles at the different levels of the hypothalamic-pituitary-gonadal (HPG) axis. In general a positive correlation has been shown between THs and fish reproductive status; where THs are associated with testicular development, growth and maturation. Recently, the molecular mechanisms underlying the role of THs in spermatogenesis have been unraveled in zebrafish testis. THs promote germ cell proliferation and differentiation by increasing a stimulatory growth factor of spermatogenesis produced by Sertoli cells. In addition, THs enhanced the gonadotropin-induced androgen release in zebrafish testis. Next to their functions in the adult testis, THs are involved in the gonadal sex differentiation through modulating sex-related gene expression, and testicular development via regulation of Sertoli cell proliferation. In conclusion, this mini-review showed that THs modulate the male reproductive system during the different life stages of fish. The physiological and molecular mechanisms showed a link between the thyroid and reproduction, suggesting a possibly co-evolution and interdependence of these two systems. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Lipid profile and thyroid hormone status in the last trimester of pregnancy in single-humped camels (Camelus dromedarius).

PubMed

Omidi, Arash; Sajedi, Zhila; Montazer Torbati, Mohammad Bagher; Ansari Nik, Hossein

2014-04-01

Changes in lipid metabolism have been shown to occur during pregnancy. The thyroid hormones affect lipid metabolism. The present study was carried out to find out whether the last trimester of pregnancy affects thyroid hormones, thyroid-stimulating hormone (TSH), lipid, and lipoprotein profile in healthy dromedary camels. Twenty clinical healthy dromedary camels aged between 4-5 years were divided into two equal groups: (1) pregnant camels in their last trimester of pregnancy and (2) non-pregnant age-matched controls. Thyroid function tests were carried out by measuring serum levels of TSH, free thyroxin (fT4), total thyroxin (T4), free triiodothyronine (fT3), and total triiodothyronine (T3) by commercially available radio immunoassay kits. Total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL) cholesterol were analyzed using enzymatic/spectrophotometric methods while low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL), and total lipid (TL) were calculated using Friedewald's and Raylander's formula, respectively. Serum levels of TSH and thyroid hormones except fT4 did not show any significant difference between pregnant and non-pregnant camels. fT4 level was lower in the pregnant camels (P < 0.05). Serum levels of total cholesterol, triglyceride, total lipid, LDL cholesterol, HDL cholesterol, and VLDL did not show significant difference between pregnant and non-pregnant camels. All of these variables in pregnant camels were higher than non-pregnant. Based on the results of this study, the fetus load may not alter the thyroid status of the camel and the concentrations of thyroid hormones were not correlated with TSH and lipid profile levels in the healthy pregnant camels.

Paradigm Shift in Thyroid Hormone Mechanism of Action | Center for Cancer Research

Cancer.gov

Thyroid hormone (TH) is one of the primary endocrine regulators of human metabolism and homeostasis. Acting through three forms of the thyroid hormone receptor (THR; alpha-1, beta-1, and beta-2), TH regulates target gene expression in nearly every cell in the body, modulating fundamental processes, such as basal metabolic rate, long bone growth, and neural maturation. TH is also essential for proper development and differentiation of all cells of the human body.

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...

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

PubMed Central

Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

2015-01-01

Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

PubMed

Anastasiou, Olympia; Sydor, Svenja; Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K; Bechmann, Lars P; Gerken, Guido; Moeller, Lars C; Canbay, Ali

2015-01-01

Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

Hypothyroidism in Women.

PubMed

Dunn, Donna; Turner, Carla

2016-01-01

Hypothyroidism, a disease in which the thyroid gland does not make enough thyroid hormone, is the second most common endocrine disorder among women. Symptoms of hypothyroidism include fatigue, weight gain, alteration in cognition, infertility, and menstrual abnormalities. The most common cause of hypothyroidism in the United States is Hashimoto's thyroiditis. The American Thyroid Association recommends an initial screening for thyroid disease at age 35years and every 5years thereafter. Thyroid-stimulating hormone is highly sensitive to thyroid dysfunction and is used to evaluate thyroid disorders. Monotherapy with levothyroxine is the standard for treating hypothyroidism. Diagnosing hypothyroidism requires appropriate diagnostic tests to facilitate prompt diagnosis and treatment. © 2016 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses.

Combined effects of androgen anabolic steroids and physical activity on the hypothalamic-pituitary-gonadal axis.

PubMed

Hengevoss, Jonas; Piechotta, Marion; Müller, Dennis; Hanft, Fabian; Parr, Maria Kristina; Schänzer, Wilhelm; Diel, Patrick

2015-06-01

Analysing effects of pharmaceutical substances and training on feedback mechanisms of the hypothalamic-pituitary-gonadal axis may be helpful to quantify the benefit of strategies preventing loss of muscle mass, and in the fight against doping. In this study we analysed combined effects of anabolic steroids and training on the hypothalamic-pituitary-gonadal axis. Therefore intact male Wistar rats were dose-dependently treated with metandienone, estradienedione and the selective androgen receptor modulator (SARM) S-1. In serum cortisol, testosterone, 17β-estradiol (E2), prolactin, inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), Insulin-like growth factor 1 (IGF-1), and thyroxine (T4) concentrations were determined. Six human volunteers were single treated with 1-androstenedione. In addition abusing and clean body builders were analysed. Serum concentrations of inhibin B, IGF-1, cortisol, prolactin, T4, thyroid-stimulating hormone (TSH), testosterone and LH were determined. In rats, administration of metandienone, estradienedione and S-1 resulted in an increase of muscle fiber diameter. Metandienone and estradienedione but not S-1 administration significantly decreases LH and inhibin B serum concentration. Administration of estradienedione resulted in an increase of E2 and S-1 in an increase of cortisol. Single administration of 1-androstenedione in humans decreased cortisol and inhibin B serum concentrations. LH was not affected. In abusing body builders a significantly decrease of LH, TSH and inhibin B and an increase of prolactin, IGF-1 and T4 was detected. In clean body builders only T4 and TSH were affected. Copyright © 2015 Elsevier Ltd. All rights reserved.

Xenopus laevis deiodinase 3 expression for in vitro screening of potential chemical inhibitors

EPA Science Inventory

Thyroid hormones are essential for normal sequential development and metamorphosis of amphibian tissues and organs. Critical to this process are the deiodinase (DIO) enzymes which catalyze the removal of an iodine from thyroid hormones to either activate or inactivate the hormone...

Thyroid Allostasis–Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming

PubMed Central

Chatzitomaris, Apostolos; Hoermann, Rudolf; Midgley, John E.; Hering, Steffen; Urban, Aline; Dietrich, Barbara; Abood, Assjana; Klein, Harald H.; Dietrich, Johannes W.

2017-01-01

The hypothalamus–pituitary–thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions. PMID:28775711

No obvious sympathetic excitation after massive levothyroxine overdose: A case report.

PubMed

Xue, Jianxin; Zhang, Lei; Qin, Zhiqiang; Li, Ran; Wang, Yi; Zhu, Kai; Li, Xiao; Gao, Xian; Zhang, Jianzhong

2018-06-01

Thyrotoxicosis from an overdose of medicinal thyroid hormone is a condition that may be associated with a significant delay in onset of toxicity. However, limited literature is available regarding thyrotoxicosis attributed to excessive ingestion of exogenous thyroid hormone and most cases described were pediatric clinical researches. Herein, we presented the course of a patient who ingested a massive amount of levothyroxine with no obvious sympathetic excited symptoms exhibited and reviewed feasible treatment options for such overdoses. A 41-year-old woman patient with ureteral calculus ingested a massive amount of levothyroxine (120 tablets, equal to 6 mg in total) during her hospitalization. Her transient vital signs were unremarkable after ingestion except for significantly accelerated breathing rate of 45 times per minute. Initial laboratory findings revealed evidently elevated serum levels of thyroxine (T4) >320 nmol/L, free triiodothyronine (fT3) 10.44 pmol/L, and free thyroxine (fT4) >100 pmol/L. The patient had a history of hypothyroidism, which was managed with thyroid hormone replacement (levothyroxine 100 μg per day). Besides, she also suffered from systemic lupus erythematosus and chronic pancreatitis. This is a case of excessive ingestion of exogenous thyroid hormone in an adult. The interventions included use propranolol to prevent heart failure; utilize hemodialysis to remove redundant thyroid hormone from blood; closely monitor the vital signs, basal metabolic rate, blood biochemical indicators, and serum levels of thyroid hormone. The woman had no obvious symptoms of thyrotoxicosis. After 4 weeks, the results of thyroid function indicated that serum thyroid hormone levels were completely recovered to pre-ingestion levels. Accordingly, the levothyroxine was used again as before. Adults often exhibit more severe symptoms after intaking overdose levothyroxine due to their complex medical history and comorbidities than children. As for them, hemodialysis should be considered as soon as possible. Besides, diverse treatments according to specific symptoms and continuously monitoring were indispensable.

[Iodine and thyroid gland with or without nuclear catastrophe].

PubMed

Dilas, Ljiljana Todorović; Bajkin, Ivana; Icin, Tijana; Paro, Jovanka Novaković; Zavisić, Branka Kovacev

2012-01-01

Iodine, as a trace element, is a necessary and limiting substrate for thyroid gland hormone synthesis. It is an essential element that enables the thyroid gland to produce thyroid hormones thyroxine (T4) and triiodothyronine (T3). Synthesis of Thyroid Hormones and Iodine Metabolism. Three iodine molecules are added to make triiodothyronine, and four for thyroxine - the two key hormones produced by the thyroid gland. Iodine deficiency The proper daily amount of iodine is required for optimal thyroid function. Iodine deficiency can cause hypothyroidism, developmental brain disorders and goiter. Iodine deficiency is the single most common cause of preventable mental retardation and brain damage in the world. It also decreases child survival, causes goiters, and impairs growth and development. Iodine deficiency disorders in pregnant women cause miscarriages, stillbirths, and other complications. Children with iodine deficiency disorders can grow up stunted, apathetic, mentally retarded, and incapable of normal movements, speech or hearing. Excessive Iodine Intake. Excessive iodine intake, which can trigger a utoimmune thyroid disease and dysfunction. is on the other side. Iodine use in Case of Nuclear Catastrophe. In addition to other severe consuquences of radioactivity, high amount of radioactive iodine causes significant increase in incidence of thyroid gland carcinoma after some of the nuclear catastrophes (Hiroshima, Nagasaki, Chernobyl, Fukushima). The incidence of thyroid carcinoma was increased mostly in children. This paper was aimed at clarifying some of the possibilities of prevention according to the recommendations given by the World Health Organization.

Comparison of the in vitro effects of TCDD, PCB 126 and PCB 153 on thyroid-restricted gene expression and thyroid hormone secretion by the chicken thyroid gland.

PubMed

Katarzyńska, Dorota; Hrabia, Anna; Kowalik, Kinga; Sechman, Andrzej

2015-03-01

The aim of this study was to compare the in vitro effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3',4,4',5-pentachlorobiphenyl (PCB 126; a coplanar PCB congener) and 2,2'4,4',5,5'-hexachlorobiphenyl (PCB153; non-coplanar PCB) on mRNA expression of thyroid-restricted genes, i.e. sodium iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and thyroid hormone secretion from the thyroid gland of the laying chicken. Relative expression levels of NIS, TG and TPO genes and thyroxine (T4) and triiodothyronine (T3) secretion from the thyroidal explants were quantified by the real-time qPCR and RIA methods, respectively. In comparison with the control group, TCDD and PCB 126 significantly increased mRNA expression of TPO and TG genes. TCDD did not affect NIS mRNA levels, but PCB 126 decreased its expression. No effect of PCB 153 on the expression of these genes was observed. TCDD and PCB 126 significantly decreased T4 and T3 secretion. There was no significant effect of PCB 153 on these hormone secretions. In conclusion, the results obtained show that in comparison with non-coplanar PCB 153, TCDD and coplanar PCB 126 can directly affect thyroid hormone synthesis and secretion, and in consequence, they may disrupt the endocrine function of the thyroid gland of the laying chicken. Copyright © 2015 Elsevier B.V. All rights reserved.

APPLICATION OF ORGANIC IODINE SPECIES ANALYTICS: DETERMINING THYROID HORMONE STATUS IN ADULT DANIO RERIO AND DEVELOPING XENOPUS LAEVIS USING LC/ICP-MS

EPA Science Inventory

Disruption of normal thyroid function by xenobiotic chemicals is an important ecological issue. Theoretically, normal thyroid hormone (TH) homeostasis and action can be disrupted at several sites in the synthetic and elimination pathways. Indeed, xenobiotic chemicals, which are k...

Methyltestosterone-induced transient hyperthyroidism in a hypothyroid patient.

PubMed

Krysiak, R; Okopien, B

2013-01-01

In this paper we report different effects of methyltestosterone administration on thyroid function in two twin brothers, one of whom suffered from hypothyroidism, while the other was apparently healthy. Methyltestosterone, which is a non-aromatisable androgen, resulted in a marked reduction of thyroxine-binding globulin (TBG), irrespectively of the patient's hormonal status, while the impact on free thyroid hormones depended on baseline thyroid function. Our research shows that a possibility of the use of non-aromatisable androgens or other drugs affecting TBG levels should be taken into consideration in all hypothyroid patients receiving levothyroxine, in whom thyroid hormone status suddenly changes without any apparent reason.

Thyroid Surgery

MedlinePlus

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

Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Male Rats

EPA Pesticide Factsheets

behavioral measures of learning and memory in adult offspring of rats treated with thyroid hormone synthesis inhibitor, propylthiouracil.Electrophysiological measures of 'memory' in form of plasticity model known as long term potentiation (LTP)Molecular changes induced by LTPThis dataset is associated with the following publication:Gilbert , M., K. Sanchez-Huerta, and C. Wood. Mild Thyroid Hormone Insufficiency During Development Compromises Activity-Dependent Neuroplasticity in the Hippocampus of Adult Make Rats. ENDOCRINOLOGY. Endocrine Society, 157(2): 774-87, (2016).

SEX-STEROID AND THYROID HORMONE CONCENTRATIONS IN JUVENILE ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS) FROM CONTAMINATED AND REFERENCE LAKES IN FLORIDA, USA

EPA Science Inventory

Sex-steroid and thyroid hormones are critical regulators of growth and reproduction in all vertebrates, and several recent studies suggest that environmental chemicals can alter circulating concentrations of these hormones. This study examines plasma concentrations of estradiol-...

THYROID HORMONE INSUFFICIENCY AND BRAIN DEVELOPMENT -- DETERMINATION OF NEUROTOXICITY AT LOW LEVELS OF HORMONE DISRUPTION.

EPA Science Inventory

Thyroid hormone (TH) deficiencies during development produce deleterious effects on brain structure and function. The degree to which TH must be perturbed to induce neurotoxicity remains unclear. The present study was conducted as part of a Cooperative Agreement between US EPA, U...

Exercise training versus T3 and T4 hormones treatment: The differential benefits of thyroid hormones on the parasympathetic drive of infarcted rats.

PubMed

Teixeira, Rayane Brinck; Zimmer, Alexsandra; de Castro, Alexandre Luz; Carraro, Cristina Campos; Casali, Karina Rabello; Dias, Ingrid Gonçalves Machuca; Godoy, Alessandra Eifler Guerra; Litvin, Isnard Elman; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

2018-03-01

This study aimed to investigate whether beneficial effects of thyroid hormones are comparable to those provided by the aerobic exercise training, to verify its applicability as a therapeutic alternative to reverse the pathological cardiac remodeling post-infarction. Male rats were divided into SHAM-operated (SHAM), myocardial infarction (MI), MI subjected to exercise training (MIE), and MI who received T3 and T4 treatment (MIH) (n = 8/group). MI, MIE and MIH groups underwent an infarction surgery while SHAM was SHAM-operated. One-week post-surgery, MIE and MIH groups started the exercise training protocol (moderate intensity on treadmill), or the T3 (1.2 μg/100 g/day) and T4 (4.8 μg/100 g/day) hormones treatment by gavage, respectively, meanwhile SHAM and MI had no intervention for 9 weeks. The groups were accompanied until 74 days after surgery, when all animals were anesthetized, left ventricle echocardiography and femoral catheterization were performed, followed by euthanasia and left ventricle collection for morphological, oxidative stress, and intracellular kinases expression analysis. Thyroid hormones treatment was more effective in cardiac dilation and infarction area reduction, while exercise training provided more protection against fibrosis. Thyroid hormones treatment increased the lipoperoxidation and decreased GSHPx activity as compared to MI group, increased the t-Akt2 expression as compared to SHAM group, and increased the vascular parasympathetic drive. Thyroid hormones treatment provided differential benefits on the LV function and autonomic modulation as compared to the exercise training. Nevertheless, the redox unbalance induced by thyroid hormones highlights the importance of more studies targeting the ideal duration of this treatment. Copyright © 2018 Elsevier Inc. All rights reserved.

The Bottlenose Dolphin (Tursiops truncatus) as a Model to Understand Variation in Stress and Reproductive Hormone Measures in Relation to Sampling Matrix, Demographics, and Environmental Factors

DTIC Science & Technology

2013-09-30

physiological processes driven by the GCs are essential for an individual’s ability to respond and adapt to stress, prolonged elevation of GC hormones...capture-release health assessments. Stress and reproductive hormones (cortisol, aldosterone , thyroid, testosterone, progesterone) have been routinely...ACE) Basin, also in South Carolina. Laboratory Analyses Hormone concentrations (cortisol, aldosterone , reproductive and thyroid hormones) in

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.

Regulation of mammary gland sensitivity to thyroid hormones during the transition from pregnancy to lactation.

PubMed

Capuco, A V; Connor, E E; Wood, D L

2008-10-01

Thyroid hormones are galactopoietic and help to establish the mammary gland's metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I (DIO1), type II (DIO2) and type III (DIO3), thyroid hormone receptors alpha1 (TRalpha1), alpha2 (TRalpha2) and beta1 (TRbeta1), and retinoic acid receptors alpha (RXRalpha) and gamma (RXRgamma), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation (P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRbeta1 mRNA in mammary gland increased with onset of lactation, whereas TRalpha1 and TRalpha2 transcripts did not vary with physiological state. Conversely, quantity of RXRalpha mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRbeta1 and DIO2, and decreased RXRalpha, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

Low thyroid function is not associated with an accelerated deterioration in renal function.

PubMed

Meuwese, Christiaan L; van Diepen, Merel; Cappola, Anne R; Sarnak, Mark J; Shlipak, Michael G; Bauer, Douglas C; Fried, Linda P; Iacoviello, Massimo; Vaes, Bert; Degryse, Jean; Khaw, Kay-Tee; Luben, Robert N; Åsvold, Bjørn O; Bjøro, Trine; Vatten, Lars J; de Craen, Anton J M; Trompet, Stella; Iervasi, Giorgio; Molinaro, Sabrina; Ceresini, Graziano; Ferrucci, Luigi; Dullaart, Robin P F; Bakker, Stephan J L; Jukema, J Wouter; Kearney, Patricia M; Stott, David J; Peeters, Robin P; Franco, Oscar H; Völzke, Henry; Walsh, John P; Bremner, Alexandra; Sgarbi, José A; Maciel, Rui M B; Imaizumi, Misa; Ohishi, Waka; Dekker, Friedo W; Rodondi, Nicolas; Gussekloo, Jacobijn; den Elzen, Wendy P J

2018-04-18

Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

The thyroid hormone triiodothyronine controls macrophage maturation and functions: protective role during inflammation.

PubMed

Perrotta, Cristiana; Buldorini, Marcella; Assi, Emma; Cazzato, Denise; De Palma, Clara; Clementi, Emilio; Cervia, Davide

2014-01-01

The endocrine system participates in regulating macrophage maturation, although little is known about the modulating role of the thyroid hormones. In vitro results demonstrate a negative role of one such hormone, triiodothyronine (T3), in triggering the differentiation of bone marrow-derived monocytes into unpolarized macrophages. T3-induced macrophages displayed a classically activated (M1) signature. A T3-induced M1-priming effect was also observed on polarized macrophages because T3 reverses alternatively activated (M2) activation, whereas it enhances that of M1 cells. In vivo, circulating T3 increased the content of the resident macrophages in the peritoneal cavity, whereas it reduced the content of the recruited monocyte-derived cells. Of interest, T3 significantly protected mice against endotoxemia induced by lipopolysaccharide i.p. injection; in these damaged animals, decreased T3 levels increased the recruited (potentially damaging) cells, whereas restoring T3 levels decreased recruited and increased resident (potentially beneficial) cells. These data suggest that the anti-inflammatory effect of T3 is coupled to the modulation of peritoneal macrophage content, in a context not fully explained by the M1/M2 framework. Thyroid hormone receptor expression analysis and the use of different thyroid hormone receptor antagonists suggest thyroid hormone receptor β1 as the major player mediating T3 effects on macrophages. The novel homeostatic link between thyroid hormones and the pathophysiological role of macrophages opens new perspectives on the interactions between the endocrine and immune systems. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

Sharlin, David S.; Visser, Theo J.

2011-01-01

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

Thyroid hormones regulate anxiety in the male mouse.

PubMed

Buras, Alexander; Battle, Loxley; Landers, Evan; Nguyen, Tien; Vasudevan, Nandini

2014-02-01

Thyroid hormone levels are implicated in mood disorders in the adult human but the mechanisms remain unclear partly because, in rodent models, more attention has been paid to the consequences of perinatal hypo and hyperthyroidism. Thyroid hormones act via the thyroid hormone receptor (TR) α and β isoforms, both of which are expressed in the limbic system. TR's modulate gene expression via both unliganded and liganded actions. Though the thyroid hormone receptor (TR) knockouts and a transgenic TRα1 knock-in mouse have provided us valuable insight into behavioral phenotypes such as anxiety and depression, it is not clear if this is because of the loss of unliganded actions or liganded actions of the receptor or due to locomotor deficits. We used a hypothyroid mouse model and supplementation with tri-iodothyronine (T3) or thyroxine (T4) to investigate the consequences of dysthyroid hormone levels on behaviors that denote anxiety. Our data from the open field and the light-dark transition tests suggest that adult onset hypothyroidism in male mice produces a mild anxiogenic effect that is possibly due to unliganded receptor actions. T3 or T4 supplementation reverses this phenotype and euthyroid animals show anxiety that is intermediate between the hypothyroid and thyroid hormone supplemented groups. In addition, T3 but not T4 supplemented animals have lower spine density in the CA1 region of the hippocampus and in the central amygdala suggesting that T3-mediated rescue of the hypothyroid state might be due to lower neuronal excitability in the limbic circuit. Copyright © 2013 Elsevier Inc. All rights reserved.

Association between genetic polymorphism and levothyroxine bioavailability in hypothyroid patients.

PubMed

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

2018-03-28

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

[Thyroid function in patients with anorexia nervosa and depression].

PubMed

Natori, Y; Yamaguchi, N; Koike, S; Aoyama, A; Tsuchibuchi, S; Kojyo, K; Demura, R

1994-12-01

Thyroid hormone levels were measured in 21 patients with anorexia nervosa, 15 patients with depression and 16 patients with severe depression and were compared with those in 53 normal subjects. In anorexia nervosa and severe depressed patients, serum T3, T4, fT3, fT4 and T3/T4 ratio showed significantly lower values than those in normal subjects. However there was no difference between depressed patients and normal subjects. The serum TSH levels were within normal range in all of the studied subjects. Thus, thyroid hormone levels in severe depressed patients were similar to those in anorexia nervosa and the changes were inversely related to disease conditions. The supplementation of thyroid hormones to antidepressant relieved clinical symptoms in some of the severe depressed patients. These results suggested that the changes in thyroid hormone levels in anorexia nervosa and severe depression were mainly due to impaired conversion of T4 to T3 by increased cortisol secretion through emotional stress.

Endocrine System (For Parents)

MedlinePlus

... the thyroid gland through surgery or radiation treatments. Hypothyroidism. Hypothyroidism is when the levels of thyroid hormones in ... hormone production, is the most common cause of hypothyroidism in kids. Infants can also be born with ...

Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study.

PubMed

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

2016-01-01

Thyroid hormone is involved in the regulation of early brain development. Since the fetal thyroid gland is not fully functional until week 18-20 of pregnancy, neuronal migration and other crucial early stages of intrauterine brain development largely depend on the supply of maternal thyroid hormone. Current clinical practice mostly focuses on preventing the negative consequences of low thyroid hormone concentrations, but data from animal studies have shown that both low and high concentrations of thyroid hormone have negative effects on offspring brain development. We aimed to investigate the association of maternal thyroid function with child intelligence quotient (IQ) and brain morphology. In this population-based prospective cohort study, embedded within the Generation R Study (Rotterdam, Netherlands), we investigated the association of maternal thyroid function with child IQ (assessed by non-verbal intelligence tests) and brain morphology (assessed on brain MRI scans). Eligible women were those living in the study area at their delivery date, which had to be between April 1, 2002, and Jan 1, 2006. For this study, women with available serum samples who presented in early pregnancy (<18 weeks) were included. Data for maternal thyroid-stimulating hormone, free thyroxine, thyroid peroxidase antibodies (at weeks 9-18 of pregnancy), and child IQ (assessed at a median of 6·0 years of age [95% range 5·6-7·9 years]) or brain MRI scans (done at a median of 8·0 years of age [6·2-10·0]) were obtained. Analyses were adjusted for potential confounders including concentrations of human chorionic gonadotropin and child thyroid-stimulating hormone and free thyroxine. Data for child IQ were available for 3839 mother-child pairs, and MRI scans were available from 646 children. Maternal free thyroxine concentrations showed an inverted U-shaped association with child IQ (p=0·0044), child grey matter volume (p=0·0062), and cortex volume (p=0·0011). For both low and high maternal free thyroxine concentrations, this association corresponded to a 1·4-3·8 points reduction in mean child IQ. Maternal thyroid-stimulating hormone was not associated with child IQ or brain morphology. All associations remained similar after the exclusion of women with overt hypothyroidism and overt hyperthyroidism, and after adjustment for concentrations of human chorionic gonadotropin, child thyroid-stimulating hormone and free thyroxine or thyroid peroxidase antibodies (continuous or positivity). Both low and high maternal free thyroxine concentrations during pregnancy were associated with lower child IQ and lower grey matter and cortex volume. The association between high maternal free thyroxine and low child IQ suggests that levothyroxine therapy during pregnancy, which is often initiated in women with subclinical hypothyroidism during pregnancy, might carry the potential risk of adverse child neurodevelopment outcomes when the aim of treatment is to achieve high-normal thyroid function test results. The Netherlands Organisation for Health Research and Development (ZonMw) and the European Community's Seventh Framework Programme. Copyright © 2016 Elsevier Ltd. All rights reserved.

Molecular Aspects of Thyroid Hormone Actions

PubMed Central

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

2010-01-01

Cellular actions of thyroid hormone may be initiated within the cell nucleus, at the plasma membrane, in cytoplasm, and at the mitochondrion. Thyroid hormone nuclear receptors (TRs) mediate the biological activities of T3 via transcriptional regulation. Two TR genes, α and β, encode four T3-binding receptor isoforms (α1, β1, β2, and β3). The transcriptional activity of TRs is regulated at multiple levels. Besides being regulated by T3, transcriptional activity is regulated by the type of thyroid hormone response elements located on the promoters of T3 target genes, by the developmental- and tissue-dependent expression of TR isoforms, and by a host of nuclear coregulatory proteins. These nuclear coregulatory proteins modulate the transcription activity of TRs in a T3-dependent manner. In the absence of T3, corepressors act to repress the basal transcriptional activity, whereas in the presence of T3, coactivators function to activate transcription. The critical role of TRs is evident in that mutations of the TRβ gene cause resistance to thyroid hormones to exhibit an array of symptoms due to decreasing the sensitivity of target tissues to T3. Genetically engineered knockin mouse models also reveal that mutations of the TRs could lead to other abnormalities beyond resistance to thyroid hormones, including thyroid cancer, pituitary tumors, dwarfism, and metabolic abnormalities. Thus, the deleterious effects of mutations of TRs are more severe than previously envisioned. These genetic-engineered mouse models provide valuable tools to ascertain further the molecular actions of unliganded TRs in vivo that could underlie the pathogenesis of hypothyroidism. Actions of thyroid hormone that are not initiated by liganding of the hormone to intranuclear TR are termed nongenomic. They may begin at the plasma membrane or in cytoplasm. Plasma membrane-initiated actions begin at a receptor on integrin αvβ3 that activates ERK1/2 and culminate in local membrane actions on ion transport systems, such as the Na+/H+ exchanger, or complex cellular events such as cell proliferation. Concentration of the integrin on cells of the vasculature and on tumor cells explains recently described proangiogenic effects of iodothyronines and proliferative actions of thyroid hormone on certain cancer cells, including gliomas. Thus, hormonal events that begin nongenomically result in effects in DNA-dependent effects. l-T4 is an agonist at the plasma membrane without conversion to T3. Tetraiodothyroacetic acid is a T4 analog that inhibits the actions of T4 and T3 at the integrin, including angiogenesis and tumor cell proliferation. T3 can activate phosphatidylinositol 3-kinase by a mechanism that may be cytoplasmic in origin or may begin at integrin αvβ3. Downstream consequences of phosphatidylinositol 3-kinase activation by T3 include specific gene transcription and insertion of Na, K-ATPase in the plasma membrane and modulation of the activity of the ATPase. Thyroid hormone, chiefly T3 and diiodothyronine, has important effects on mitochondrial energetics and on the cytoskeleton. Modulation by the hormone of the basal proton leak in mitochondria accounts for heat production caused by iodothyronines and a substantial component of cellular oxygen consumption. Thyroid hormone also acts on the mitochondrial genome via imported isoforms of nuclear TRs to affect several mitochondrial transcription factors. Regulation of actin polymerization by T4 and rT3, but not T3, is critical to cell migration. This effect has been prominently demonstrated in neurons and glial cells and is important to brain development. The actin-related effects in neurons include fostering neurite outgrowth. A truncated TRα1 isoform that resides in the extranuclear compartment mediates the action of thyroid hormone on the cytoskeleton. PMID:20051527

Effects of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly on hormonal activity and structure of the thyroid gland in hypophysectomized young chickens and old hens.

PubMed

Kuznik, B I; Pateyuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2011-02-01

Hypophysectomy in 5-days chickens and old hens was followed by hormonal disturbances and structural changes in the thyroid gland. Administration of peptides Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthesized on the basis the amino acid composition of extracts from the anterior and posterior lobes of the pituitary gland, respectively, to hypophysectomized birds for 40 days significantly reduced the degree of these changes. The normalizing effect of synthetic peptides on the concentration of thyrotrophic hormone and thyroid hormones in old hens was less pronounced than in chickens.

Chronic food restriction and the circadian rhythms of pituitary-adrenal hormones, growth hormone and thyroid-stimulating hormone.

PubMed

Armario, A; Montero, J L; Jolin, T

1987-01-01

Adult male Sprague-Dawley rats were subjected to food restriction so that they ate 65% of food ingested by control rats. While control rats had free access to food over the 24-hour period, food-restricted rats were provided with food daily at 10 a.m. The experimental period lasted for 34 days. On day 35, rats from both experimental groups were killed at 08.00, 11.00, 14.00, 24.00 and 02.00 h. Food restriction modified the circadian rhythms of ACTH and corticosterone. In addition, total circulating corticosterone throughout the day was higher in food-restricted than in control rats. In contrast, food restriction resulted in depressed secretion of thyroid-stimulating hormone and growth hormone. The results indicate that time of food availability entrained circadian corticosterone rhythm but not thyroid-stimulating hormone and growth hormone rhythms.

Thyrotropin-induced hyperthyroidism caused by selective pituitary resistance to thyroid hormone. A new syndrome of "inappropriate secretion of TSH".

PubMed Central

Gershengorn, M C; Weintraub, B D

1975-01-01

An 18-yr-old woman with clinical and laboratory features of hyperthyroidism had persistently elevated serum levels of immunoreative thyrotropin (TSH). During 11 yr of follow-up there had been no evidence of a pituitary tumor. After thyrotropin-releasing hormone (TRH), there was a marked increase in TSH and secondarily in triiodothyronine (T3), the latter observation confirming the biologic activity of the TSH. Exogenous T3 raised serum T3 and several measurements of peripheral thyroid hormone effect, while decreasing serum TSH, thyroxine (T4), and thyroidal radioiodine uptake. After T3, the TRH-stimulated TSH response was decreased but was still inappropriate for the elevated serum T3 levels. Dexamethasone reduced serum TSH but did not inhibit TRH stimulation of TSH. Propylthiouracil reduced serum T4 and T3 and raised TSH. This patient represents a new syndrome of TSH-induced hyperthyroidism, differing from previous reports in the absence of an obvious pituitary tumor and in the responsiveness of the TSH to TRH stimulation and thyroid hormone suppression. This syndrome appears to be caused by a selective, partial resistance of the pituitary to the action of thyroid hormone. This case is also compared with previous reports in the literature of patients with elevated serum levels of immunoreactive TSH in the presence of elevated total and free thyroid hormones. A classification of these cases, termed "inappropriate secretion of TSH," is proposed. PMID:1159077

Utilizing mass spectrometry imaging to map the thyroid hormones triiodothyronine and thyroxine in Xenopus tropicalis tadpoles.

PubMed

Goto-Inoue, Naoko; Sato, Tomohiko; Morisasa, Mizuki; Kashiwagi, Akihiko; Kashiwagi, Keiko; Sugiura, Yuki; Sugiyama, Eiji; Suematsu, Makoto; Mori, Tsukasa

2018-02-01

Thyroid hormones are not only responsible for thermogenesis and energy metabolism in animals, but also have an important role in cell differentiation and development. Amphibian metamorphosis provides an excellent model for studying the remodeling of the body. This metamorphic organ remodeling is induced by thyroid hormones, and a larval body is thus converted into an adult one. The matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) imaging technology is expected to be a suitable tool for investigating small bioreactive molecules. The present study describes the distribution of the thyroid hormones, i.e., triiodothyronine (T3) and thyroxine (T4) and their inactive form reverse T3 (rT3) in Xenopus tropicalis tadpoles using two different types of imaging techniques, MS/MS and Fourier transform (FT)-MS imaging. As a result of MS/MS imaging, we demonstrated that T3 was mainly distributed in the gills. T4 was faintly localized in the eyes, inner gills, and intestine during metamorphosis. The intensity of T3 in the gills and the intensity of T4 in the body fluids were increased during metamorphosis. Moreover, the localization of the inactive form rT3 was demonstrated to be separate from T3, namely in the intestine and muscles. In addition, FT-MS imaging could utilize simultaneous imaging including thyroid hormone. This is the first report to demonstrate the molecular distribution of thyroid hormones themselves and to discriminate T3, T4, and rT3 in animal tissues.

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

PubMed

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

2015-11-10

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

Thyroid

MedlinePlus

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

Trends in thyroid hormone prescribing and consumption in the UK

PubMed Central

Mitchell, Anna L; Hickey, Bryan; Hickey, Janis L; Pearce, Simon HS

2009-01-01

Background Thyroid hormone replacement is one of the most commonly prescribed and cost effective treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications. This study aimed to provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine. Methods Data on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of a patient support organisation (the British Thyroid Foundation) who were taking levothyroxine was carried out. Results The amount of prescribed thyroid hormones used in England has more than doubled, from 7 to almost 19 million prescriptions, over the last 10 years. The duration of prescriptions has reduced from 60 to 45 days, on average over the same time. Two thousand five hundred and fifty one responses to the patient survey were received. Thirty eight percent of levothyroxine users reported receiving prescriptions of 28 days' duration. 59% of respondents reported being dissatisfied with 28-day prescribing. Conclusion Amongst users of levothyroxine, there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications, suggests that this is unlikely to be an economically effective public health policy. PMID:19432950

Silent pituitary macroadenoma co-secreting growth hormone and thyroid stimulating hormone.

PubMed

Sen, Orhan; Ertorer, M Eda; Aydin, M Volkan; Erdogan, Bulent; Altinors, Nur; Zorludemir, Suzan; Guvener, Nilgun

2005-04-01

Silent pituitary adenomas are a group of tumors showing heterogenous morphological features with no hormonal function observed clinically. To date no explanation has been provided as to why these tumors remain "silent". We report a case of a silent macroadenoma with both growth hormone (GH) and thyroid stimulating hormone (TSH) staining and secretion but with no clinical manifestations, in particular, the absence of features of acromegaly or hyperthyroidism. The relevant literature is reviewed.

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

Screening the ToxCast Phase I, II, and e1K Chemical Libraries for Inhibition of Deiodinase Type 1,2 and 3 Enzyme Activity

EPA Science Inventory

Thyroid hormone (TH) signaling and homeostasis is dependent upon coordination of multiple key events including thyroidal iodide uptake and hormone synthesis, and peripheral metabolism and elimination. Deiodinase enzymes play an essential role in converting the pro-hormone thyroxi...

Effects of enteral different-dose levothyroxine-sodium pretreatment on serum thyroid hormone levels and myocardial ischemia-reperfusion injury.

PubMed

Yang, Gui-Zhen; Xue, Fu-Shan; Liu, Ya-Yang; Li, Hui-Xian; Liu, Qing; Liao, Xu

2018-04-01

The available evidence shows that perioperative oral thyroid hormone can significantly attenuate the postoperative decline in the serum hormone level and improve postoperative hemodynamic and prognostic parameters. However, there has been no study assessing the effects of preoperative oral different-dose thyroid hormone on serum hormone levels and myocardial ischemia-reperfusion injury (IRI) after cardiac surgery. Forty-eight healthy Wistar rats, aged 35 days, were randomly allocated into six groups: Group BC, Group C and four pretreatment groups in which the rats were given levothyroxine-sodium of 10 μg, 20 μg, 40 μg and 80 μg/100 g. On the eighth day, the serum thyroid hormone levels were determined and then an isolated heart ischemia-reperfusion model was established with a Langendorff apparatus. Compared with Groups BC and C, serum thyroid hormone levels on the eighth day did not significantly change in Group 10 μg, but were significantly increased in Groups 20 μg, 40 μg and 80 μg. The cardiac enzyme myocardial-bound creatine kinase levels in the coronary effluent during reperfusion were significantly lower in Groups 10 μg and 20 μg and 40 μg than in Group C. The recovery rates of + dp/dt max and - dp/dt max at 30 min during reperfusion were significantly lower in Groups 40 μg and 80 μg than in Groups 10 μg and 20 μg. Compared with Group C, myocardial expressions of heat shock protein 70 and myosin heavy chain α were increased in the four experiment groups and myocardial expression of thyroid hormone receptor α1 was significantly increased in Groups 20 μg, 40 μg and 80 μg. The pretreatment with enterally smaller doses levothyroxine-sodium does not significantly affect serum thyroid hormone levels and produces protection against myocardial IRI, whereas pretreatment with enterally larger doses of levothyroxine-sodium can only provide an attenuated or insignificant cardioprotection because of hyperthyroxinemia. Cardioprotection by levothyroxine-sodium pretreatment is probably attributable to increased myocardial expression of heat shock protein 70 and myosin heavy chain α.

Thyroid hormones and changes in body weight and metabolic parameters in response to weight loss diets: the POUNDS LOST trial.

PubMed

Liu, G; Liang, L; Bray, G A; Qi, L; Hu, F B; Rood, J; Sacks, F M; Sun, Q

2017-06-01

The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight loss setting. Data analysis was conducted among 569 overweight and obese participants aged 30-70 years with normal thyroid function participating in the 2-year Prevention of Obesity Using Novel Dietary Strategies (POUNDS) LOST randomized clinical trial. Changes in body weight and RMR were assessed during the 2-year intervention. Thyroid hormones (free triiodothyronine (T3), free thyroxine (T4), total T3, total T4 and thyroid-stimulating hormone (TSH)), anthropometric measurements and biochemical parameters were assessed at baseline, 6 months and 24 months. Participants lost an average of 6.6 kg of body weight during the first 6 months and subsequently regained an average of 2.7 kg of body weight over the remaining period from 6 to 24 months. Baseline free T3 and total T3 were positively associated, whereas free T4 was inversely associated, with baseline body weight, body mass index and RMR. Total T4 and TSH were not associated with these parameters. Higher baseline free T3 and free T4 levels were significantly associated with a greater weight loss during the first 6 months (P<0.05) after multivariate adjustments including dietary intervention groups and baseline body weight. Comparing extreme tertiles, the multivariate-adjusted weight loss±s.e. was -3.87±0.9 vs -5.39±0.9 kg for free T3 (P trend =0.02) and -4.09±0.9 vs -5.88±0.9 kg for free T4 (P trend =0.004). The thyroid hormones did not predict weight regain in 6-24 months. A similar pattern of associations was also observed between baseline thyroid hormones and changes in RMR. In addition, changes in free T3 and total T3 levels were positively associated with changes in body weight, RMR, body fat mass, blood pressure, glucose, insulin, triglycerides and leptin at 6 months and 24 months (all P<0.05). In this diet-induced weight loss setting, higher baseline free T3 and free T4 predicted more weight loss, but not weight regain among overweight and obese adults with normal thyroid function. These findings reveal a novel role of thyroid hormones in body weight regulation and may help identify individuals more responsive to weight loss diets.

The assessment of thyroid autoantibody levels in euthyroid polycystic ovary syndrome patients.

PubMed

Hepşen, Sema; Karaköse, Melia; Çakal, Erman; Öztekin, Sanem; Ünsal, İlknur; Akhanlı, Pınar; Uçan, Bekir; Özbek, Mustafa

2018-04-27

Thyroid hormone abnormalities are commonly seen in polycystic ovary syndrome (PCOS) and have considerable effects on comorbidities. The association with PCOS and thyroid autoimmunity which lead to thyroid pathologies are not revealed clearly. We targeted to commentate anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-TG) antibody levels and thyroid autoimmunity in PCOS. 184 patients who got the diagnosis of PCOS regard to the revised 2003 Rotterdam criteria were embodied in this study. 106 age-matched female volunteers were included in the control group. Characteristics, biochemical parameters, thyroid hormone and autoantibody levels of groups were investigated. Although; we did not find out a statistically significant difference in TSH and sT4 levels between two groups (p>0.05), anti-TPO and anti-TG antibody levels were determined higher in PCOS group significantly (p<0.001). Anti-TPO Ab and anti-TG Ab positivity prevalence of PCOS patients were significantly higher as against to controls (p<0.001; p=0.01). Not only thyroid hormone levels but also thyroid autoantibody levels should be screened during the investigation of PCOS and the patients with positive results need to be followed up carefully in the long run.

Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.

PubMed

Alcántara-Alonso, Viridiana; Alvarez-Salas, Elena; Matamoros-Trejo, Gilberto; de Gortari, Patricia

2017-10-18

Individuals who consume a diet deficient in zinc (Zn-deficient) develop alterations in hypothalamic-pituitary-thyroid axis function, i.e., a low metabolic rate and cold insensitivity. Although those disturbances are related to primary hypothyroidism, intrauterine or postnatal Zn-deficient adults have an increased thyrotropin (TSH) concentration, but unchanged thyroid hormone (TH) levels and decreased body weight. This does not support the view that the hypothyroidism develops due to a low Zn intake. In addition, intrauterine or postnatal Zn-deficiency in weaned and adult rats reduces the activity of pyroglutamyl aminopeptidase II (PPII) in the medial-basal hypothalamus (MBH). PPII is an enzyme that degrades thyrotropin-releasing hormone (TRH). This hypothalamic peptide stimulates its receptor in adenohypophysis, thereby increasing TSH release. We analyzed whether earlier low TH is responsible for the high TSH levels reported in adults, or if TRH release is enhanced by Zn deficiency at weaning. Dams were fed a 2 ppm Zn-deficient diet in the period from one week prior to gestation and up to three weeks after delivery. We found a high release of hypothalamic TRH, which along with reduced MBH PPII activity, increased TSH levels in Zn-deficient pups independently of changes in TH concentration. We found that primary hypothyroidism did not develop in intrauterine Zn-deficient weaned rats and we confirmed that metal deficiency enhances TSH levels since early-life, favoring subclinical hypothyroidism development which remains into adulthood.

Developmental toxicity and thyroid hormone-disrupting effects of 2,4-dichloro-6-nitrophenol in Chinese rare minnow (Gobiocypris rarus).

PubMed

Chen, Rui; Yuan, Lilai; Zha, Jinmiao; Wang, Zijian

2017-04-01

In the present study, to evaluate embryonic toxicity and the thyroid-disrupting effects of 2,4-dichloro-6-nitrophenol (DCNP), embryos and adults of Chinese rare minnow (Gobiocypris rarus) were exposed to 2, 20, and 200μg/L DCNP. In the embryo-larval assay, increased percentages of mortality and occurrence of malformations, decreased percentage of hatching, and decreased body length and body weight were observed after DCNP treatment. Moreover, the whole-body T3 levels were significantly increased at 20 and 200μg/L treatments, whereas the T4 levels were markedly decreased significantly (p<0.05) for all DCNP concentrations. In the adult fish assay, plasma T3 levels were significantly increased whereas plasma T4 levels were significantly reduced in the fish treated with 20 and 200μg/L (p<0.05). In addition, DCNP exposure significantly changed the transcription levels of thyroid system related genes, including dio1, dio2, me, nis, tr, and ttr. The increased responsiveness of thyroid hormone and mRNA expression levels of thyroid system related genes suggested that DCNP could disrupt the thyroid hormone synthesis and transport pathways. Therefore, our findings provide new insights of DCNP as a thyroid hormone-disrupting chemical. Copyright © 2017 Elsevier B.V. All rights reserved.

Thyroid functional disease: an under-recognized cardiovascular risk factor in kidney disease patients

PubMed Central

Rhee, Connie M.; Brent, Gregory A.; Kovesdy, Csaba P.; Soldin, Offie P.; Nguyen, Danh; Budoff, Matthew J.; Brunelli, Steven M.; Kalantar-Zadeh, Kamyar

2015-01-01

Thyroid functional disease, and in particular hypothyroidism, is highly prevalent among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In the general population, hypothyroidism is associated with impaired cardiac contractility, endothelial dysfunction, atherosclerosis and possibly higher cardiovascular mortality. It has been hypothesized that hypothyroidism is an under-recognized, modifiable risk factor for the enormous burden of cardiovascular disease and death in CKD and ESRD, but this has been difficult to test due to the challenge of accurate thyroid functional assessment in uremia. Low thyroid hormone levels (i.e. triiodothyronine) have been associated with adverse cardiovascular sequelae in CKD and ESRD patients, but these metrics are confounded by malnutrition, inflammation and comorbid states, and hence may signify nonthyroidal illness (i.e. thyroid functional test derangements associated with underlying ill health in the absence of thyroid pathology). Thyrotropin is considered a sensitive and specific thyroid function measure that may more accurately classify hypothyroidism, but few studies have examined the clinical significance of thyrotropin-defined hypothyroidism in CKD and ESRD. Of even greater uncertainty are the risks and benefits of thyroid hormone replacement, which bear a narrow therapeutic-to-toxic window and are frequently prescribed to CKD and ESRD patients. In this review, we discuss mechanisms by which hypothyroidism adversely affects cardiovascular health; examine the prognostic implications of hypothyroidism, thyroid hormone alterations and exogenous thyroid hormone replacement in CKD and ESRD; and identify areas of uncertainty related to the interplay between hypothyroidism, cardiovascular disease and kidney disease requiring further investigation. PMID:24574542

Periods of sensitivity to thyroid hormone during the development of the organ of Corti.

PubMed

Uziel, A

1986-01-01

Cochlear structures are sensitive to the morphogenetic effect of thyroid hormone during the whole duration of maturation. For each structure, there exists a period of maximal sensitivity to thyroid hormone which corresponds to the period of development during which the structure of interest undergoes its main morphological changes (6 to 13 days for the inner sulcus epithelium, 6 to 10 days for the pillars, the 2nd and a part of the 3rd postnatal week for OHCs and their efferent innervation in rats). These periods of sensitivity can be considered as critical periods because cochlear structures are maximally vulnerable to thyroid deficiency during these periods.

Role of the Pineal Body Hormone in Thyroid Function; L'HORMONE EPIPHSAIRE INTERVIENT DANS LA DYNAMIQUE DU METABOLISME DE L'IODE

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

Milcou, S.M.; Costiner, E. et al.

To evaluate the action of the pineal body hormone on thyroid function, hyperactivity of the epiphysis was experimentally induced by administering pineal body hormone four hours before the experiment and then every four hours during the experiment. Iodine tagging was achieved by the intraperltoneal injection of carrierless'' I/sup 131/. The animals, which had been divided into batches of 10, were sacrificed every 2 hours until 48 hours had elapsed following the radioactive tagging. Measurements on the radioactivity of the thyroid and of the blood were carried out in vitro. The values obtained were used in order to draw up simultaneousmore » radioactivity curves applicable to the total radioactivity and to that attributable to inorganic and organic iodine, respectively. The curves showing the variation in the radioactivity reveal a delayed action of the pineal gland hormone which is different according to whether the functional thyroid units have a large or small time constant. (auth)« less

Contribution to the Study of Phosphate Uptake (P$sup 32$) at the Level of the Thyroid, The Suprarenals, and Testicles after Administration of Epiphysis Hormone; CONTRIBUTION A L'ETUDE DE LA PHOSPHOCAPTATION (P$sup 52$) AU NIVEAU DE LA THYROIDE DES SURRENALES ET DES TESTICULES APRES ADMINISTRATION DE L'EPIPHYSE-HORMONE

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

Negosscou, I.; Bojinescuu, Al.; Cocou, Fl.

1959-10-31

The phosphorus uptake by several endocrine glands after the administration of epiphysis hormone was studied by a tracer technique. After ten days of daily injections of the hormone into male albino rats, the rats received an injection of P/sup 32/. The hormone was again given 6, 12, and 18 hours after the P/sup 32/ injection. Some animals were killed 8 hours after the administration of phosphorus and the rest after 24 hours. The radioactivity of the epiphysis, hypophysis, thyroid, suprarenals, testicles, and seminal vesicles was determined. The results showed a functional inhibition of the phosphorus uptake in the thyroid, suprarenals,more » testicles, and seminal vesicles. A decrease in the phosphorus uptake by the hypophysis was also observed. (J.S.R.)« less

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

Influence of obesity and surgical weight loss on thyroid hormone levels.

PubMed

Chikunguwo, Silas; Brethauer, Stacy; Nirujogi, Vijaya; Pitt, Tracy; Udomsawaengsup, Suthep; Chand, Bipan; Schauer, Philip

2007-01-01

The pathophysiologic relationship between morbid obesity and thyroid hormones is not well understood. The goal of this study was to evaluate the influence of obesity and weight reduction after bariatric surgery on thyroid hormone levels. Patients who underwent gastric bypass or adjustable gastric banding at our institution, had no previous diagnosis of thyroid disorder, were not taking medication that could affect the thyroid function evaluation, and who were nonsmokers were included in this retrospective evaluation. The association between the thyroid-stimulating hormone (TSH) and free thyroxine (T(4)) levels and body mass index (BMI), and the influence of weight loss after bariatric surgery on these hormones were investigated at different points (preoperatively and 6 and 12 months after bariatric surgery). A total of 86 patients met the study criteria. The TSH levels correlated positively with BMI (P <.001, r = .91) within the BMI range of 30-67 kg/m(2). The mean BMI change from 49 to 32 kg/m(2) after bariatric surgery was associated with a mean reduction in the TSH level from 4.5 to 1.9 microU/mL. Free T(4) showed no association with BMI and was not significantly influenced by weight loss. Before bariatric surgery, 10.5% of the subjects had laboratory values consistent with subclinical hypothyroidism. After bariatric surgery, 100% of these patients experienced significant weight reduction with simultaneous resolution of their subclinical hypothyroidism. The results of our study have demonstrated a statistically significant positive association between serum TSH within the normal range and BMI. No association was found between BMI and free T(4) serum levels. The prevalence of subclinical hypothyroidism in study group was 10.5%. Weight loss after bariatric surgery improved or normalized thyroid hormone levels.

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase

PubMed Central

Wirth, Eva K.; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-01-01

Background The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). Objective: To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). Methods We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Results Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Conclusions Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated. PMID:26601078

High T3, Low T4 Serum Levels in Mct8 Deficiency Are Not Caused by Increased Hepatic Conversion through Type I Deiodinase.

PubMed

Wirth, Eva K; Rijntjes, Eddy; Meyer, Franziska; Köhrle, Josef; Schweizer, Ulrich

2015-09-01

The Allan-Herndon-Dudley syndrome is a severe psychomotor retardation accompanied by specific changes in circulating thyroid hormone levels (high T3, low T4). These are caused by mutations in the thyroid hormone transmembrane transport protein monocarboxylate transporter 8 (MCT8). To test the hypothesis that circulating low T4 and high T3 levels are caused by enhanced conversion of T4 via increased activity of hepatic type I deiodinase (Dio1). We crossed mice deficient in Mct8 with mice lacking Dio1 activity in hepatocytes. Translation of the selenoenzyme Dio1 was abrogated by hepatocyte-specific inactivation of selenoprotein biosynthesis. Inactivation of Dio1 activity in the livers of global Mct8-deficient mice does not restore normal circulating thyroid hormone levels. Our data suggest that although hepatic Dio1 activity is increased in Mct8-deficient mice, it does not cause the observed abnormal circulating thyroid hormone levels. Since global inactivation of Dio1 in Mct8-deficient mice does normalize circulating thyroid hormone levels, the underlying mechanism and relevant tissues involved remain to be elucidated.

Thyroid Hormone Indices in Computer Workers with Emphasis on the Role of Zinc Supplementation.

PubMed

Amin, Ahmed Ibrahim; Hegazy, Noha Mohamed; Ibrahim, Khadiga Salah; Mahdy-Abdallah, Heba; Hammouda, Hamdy A A; Shaban, Eman Essam

2016-06-15

This study aimed to investigate the effects of computer monitor-emitted radiation on thyroid hormones and the possible protective role of zinc supplementation. The study included three groups. The first group (group B) consisted of 42 computer workers. This group was given Zinc supplementation in the form of one tablet daily for eight weeks. The second group (group A) comprised the same 42 computer workers after zinc supplementation. A group of 63 subjects whose job does not entail computer use was recruited as a control Group (Group C). All participants filled a questionnaire including detailed medical and occupational histories. They were subjected to full clinical examination. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and zinc levels were measured in all participants. TSH, FT3, FT4 and zinc concentrations were decreased significantly in group B relative to group C. In group A, all tested parameters were improved when compared with group B. The obtained results revealed that radiation emitted from computers led to changes in TSH and thyroid hormones (FT3 and FT4) in the workers. Improvement after supplementation suggests that zinc can ameliorate hazards of such radiation on thyroid hormone indices.

Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study

NASA Astrophysics Data System (ADS)

Yang, Lin; Li, Jingguang; Lai, Jianqiang; Luan, Hemi; Cai, Zongwei; Wang, Yibaina; Zhao, Yunfeng; Wu, Yongning

2016-02-01

Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P < 0.001). The median ratios of major PFASs concentrations in fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = -0.261 to -0.170, all P < 0.05). Maternal triiodothyronin (T3) and free T3 (FT3) showed negative correlations with most fetal PFASs (r = -0.229 to -0.165 for T3; r = -0.293 to -0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans.

Thyroid Hormone Differentially Modulates Warburg Phenotype in Breast Cancer Cells

PubMed Central

Suhane, Sonal; Ramanujan, V Krishnan

2011-01-01

Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. PMID:21945435

Transducin β-like 1, X-linked and nuclear receptor co-‍repressor cooperatively augment the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors.

PubMed

Takamizawa, Tetsuya; Satoh, Tetsurou; Miyamoto, Tomoko; Nakajima, Yasuyo; Ishizuka, Takahiro; Tomaru, Takuya; Yoshino, Satoshi; Katano-Toki, Akiko; Nishikido, Ayaka; Sapkota, Santosh; Watanabe, Takuya; Okamura, Takashi; Ishida, Emi; Horiguchi, Kazuhiko; Matsumoto, Syunichi; Ishii, Sumiyasu; Ozawa, Atsushi; Shibusawa, Nobuyuki; Okada, Shuichi; Yamada, Masanobu

2018-05-23

Mutations in TBL1X, a component of the nuclear receptor co-repressor (N-CoR) and silencing mediator of retinoic acid and thyroid hormone receptor co-repressor complexes, have recently been implicated in isolated central hypothyroidism (CeH). However, the mechanisms by which TBL1X mutations affect negative feedback regulation in the hypothalamus-pituitary-thyroid axis remain unclear. N-CoR was previously reported to paradoxically enhance the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors (TR) in cell culture systems. We herein investigated whether TBL1X affects the unliganded TR-mediated stimulation of the promoter activities of genes negatively regulated by T3 in cooperation with N-CoR. In a hypothalamic neuronal cell line, the unliganded TR-mediated stimulation of the TRH gene promoter was significantly enhanced by co-transfected TBL1X, and the co-transfection of TBL1X with N-CoR further enhanced promoter activity. In contrast, the knockdown of endogenous Tbl1x using short interfering RNA significantly attenuated the N-CoR-mediated enhancement of promoter activity in the presence of unliganded TR. The co-transfection of N365Y or Y458C, TBL1X mutants identified in CeH patients, showed impaired co-activation with N-CoR for the ligand-independent stimulation of the TRH promoter by TR. In the absence of T3, similar or impaired enhancement of the TSHβ gene promoter by the wild type or TBL1X mutants, respectively, was observed in the presence of co-transfected TR and N-CoR in CV-1 cells. These results suggest that TBL1X is needed for the full activation of TRH and TSHβ gene promoters by unliganded TR. Mutations in TBL1X may cause CeH due to the impaired up-regulation of TRH and/or TSHβ gene transcription despite low T3 levels.

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.

78 FR 37803 - Agency Information Collection Activities; Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-24

... identify substances that have the potential to interact with the estrogen, androgen, or thyroid hormone... or thyroid hormone systems may proceed to Tier 2, which is designed to identify any adverse endocrine...

[Effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides on hormonal activity and thyroid morphology in hypophysectomized mature and old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2011-01-01

The aim of the paper was to investigate effects of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly peptides which were designed and synthesized on the basis of amino acid study of the hypophyseal anterior and posterior lobe peptides on the thyroid morphology and hormonal activity in mature chicken and old birds. Hypophysectomy was established to produce atrophic changes in the thyroid gland and development of secondary hypothyrosis. Administration of Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly tetrapeptides significantly prevented these impairments by increasing the levels of the thyroid-stimulating hormone (TSH) as well as T3 and T4. Restoration of the thyroid functions and morphology was registered to be greater in one-year-old chicken as compared to five-year-old ones.

(−) Arctigenin and (+) Pinoresinol Are Antagonists of the Human Thyroid Hormone Receptor β

PubMed Central

2015-01-01

Lignans are important biologically active dietary polyphenolic compounds. Consumption of foods that are rich in lignans is associated with positive health effects. Using modeling tools to probe the ligand-binding pockets of molecular receptors, we found that lignans have high docking affinity for the human thyroid hormone receptor β. Follow-up experimental results show that lignans (−) arctigenin and (+) pinoresinol are antagonists of the human thyroid hormone receptor β. The modeled complexes show key plausible interactions between the two ligands and important amino acid residues of the receptor. PMID:25383984

Effect of zinc supplementation on the status of thyroid hormones and Na, K, And Ca levels in blood following ethanol feeding.

PubMed

Pathak, R; Dhawan, D; Pathak, A

2011-05-01

The influence of zinc (Zn) on the serum levels of triiodothyronine (T(3)), thyroxine (T(4)), thyroid-stimulating hormone (TSH) and sodium (Na), potassium (K), and calcium (Ca) was evaluated following ethanol toxicity to the rats. To achieve this, male Wistar rats (150-195 g) were given 3 ml of 30% ethanol orally, and zinc was given in the form of zinc sulfate (227 mg/l) in their drinking water daily for 8 weeks. Ethanol feeding resulted in a slight decrease in T(3) and T(4) levels and a significant increase in thyroid-stimulating hormone concentration, which may be due to the direct stimulatory effect of ethanol on thyroid. Interestingly, when zinc was given to these rats, all the above levels were brought quite close to their normal levels, thus indicating the positive role of zinc in thyroid hormone metabolism. Serum Zn and Ca levels were found to be reduced, but Na levels were raised upon ethanol feeding. Restoration of normal levels of these metals upon zinc supplementation to ethanol fed rats confirms that zinc has potential in alleviating some of the altered thyroid functions following ethanol administration.

Efficacy of a Home-Based Exercise Program After Thyroidectomy for Thyroid Cancer Patients.

PubMed

Kim, Kyunghee; Gu, Mee Ock; Jung, Jung Hwa; Hahm, Jong Ryeal; Kim, Soo Kyoung; Kim, Jin Hyun; Woo, Seung Hoon

2018-02-01

The objective of this study was to determine the effect of a home-based exercise program on fatigue, anxiety, quality of life (QoL), and immune function of thyroid cancer patients taking thyroid hormone replacement after thyroidectomy. This quasi-experimental study with a non-equivalent control group included 43 outpatients taking thyroid hormone replacement after thyroidectomy (22 in the experimental group and 21 in the control group). After education about the home-based exercise program, subjects in the experimental group underwent 12 weeks of aerobic, resistance, and flexibility exercise. A comparative analysis was conducted between the two groups. Patients in the experimental group were significantly less fatigued or anxious (p < 0.01). They reported significantly improved QoL (p < 0.05) compared to those in the control group. Natural killer cell activity was significantly higher in the exercise group compared to that in the control group (p < 0.05). A home-based exercise program is effective in reducing fatigue and anxiety, improving QoL, and increasing immune function in patients taking thyroid hormone replacement after thyroidectomy. Therefore, such a home-based exercise program can be used as an intervention for patients who are taking thyroid hormone replacement after thyroidectomy.

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.

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.

Regulation of vernal migration in Gambel's white-crowned sparrows: Role of thyroxine and triiodothyronine.

PubMed

Pérez, Jonathan H; Furlow, J David; Wingfield, John C; Ramenofsky, Marilyn

2016-08-01

Appropriate timing of migratory behavior is critical for migrant species. For many temperate zone birds in the spring, lengthening photoperiod is the initial cue leading to morphological, physiological and behavior changes that are necessary for vernal migration and breeding. Strong evidence has emerged in recent years linking thyroid hormone signaling to the photoinduction of breeding in birds while more limited information suggest a potential role in the regulation of vernal migration in photoperiodic songbirds. Here we investigate the development and expression of the vernal migratory life history stage in captive Gambel's white-crowned sparrows (Zonotrichia leucophrys gambelii) in a hypothyroidic state, induced by chemical inhibition of thyroid hormone production. To explore possible variations in the effects of the two thyroid hormones, triiodothyronine and thyroxine, we subsequently performed a thyroid inhibition coupled with replacement therapy. We found that chemical inhibition of thyroid hormones resulted in complete abolishment of mass gain, fattening, and muscle hypertrophy associated with migratory preparation as well as resulting in failure to display nocturnal restlessness behavior. Replacement of thyroxine rescued all of these elements to near control levels while triiodothyronine replacement displayed partial or delayed rescue. Our findings support thyroid hormones as being necessary for the expression of changes in morphology and physiology associated with migration as well as migratory behavior itself. Copyright © 2016 Elsevier Inc. All rights reserved.

Food restriction in young Japanese quails: effects on growth, metabolism, plasma thyroid hormones and mRNA species in the thyroid hormone signalling pathway.

PubMed

Rønning, Bernt; Mortensen, Anne S; Moe, Børge; Chastel, Olivier; Arukwe, Augustine; Bech, Claus

2009-10-01

Young birds, in their post-natal growth period, may reduce their growth and metabolism when facing a food shortage. To examine how such responses can be mediated by endocrine-related factors, we exposed Japanese quail chicks to food restriction for either 2 days (age 6-8 days) or 5 days (age 6-11 days). We then measured growth and resting metabolic rate (RMR), and circulating 3,3',5-triiodo-l-thyronine (T3) and 3,5,3',5'-tetraiodothyronine (T4) levels as well as expression patterns of genes involved in growth (insulin-like growth factor-I: IGF-I) and thyroid hormone signalling (thyroid-stimulating hormone-beta: TSHbeta, type II iodothyronine deiodinase: D2, thyroid hormone receptors isoforms: TRalpha and TRbeta). The food-restricted chicks receiving a weight-maintenance diet showed reductions in structural growth and RMR. Plasma levels of both T3 and T4 were reduced in the food-restricted birds, and within the 5 days food-restricted group there was a positive correlation between RMR and T3. IGF-I mRNA showed significantly higher abundance in the liver of ad libitum fed birds at day 8 compared with food-restricted birds. In the brain, TSHbeta mRNA level tended to be lower in food-restricted quails on day 8 compared with controls. Furthermore, TRalpha expression was lower in the brain of food-restricted birds at day 8 compared with birds fed ad libitum. Interestingly, brain D2 mRNA was negatively correlated with plasma T3 levels, tending to increase with the length of food restriction. Overall, our results show that food restriction produced significant effects on circulating thyroid hormones and differentially affected mRNA species in the thyroid hormone signalling pathway. Thus, we conclude that the effects of food restriction observed on growth and metabolism were partly mediated by changes in the endocrine-related factors investigated.

Thyroid hormone modulates insulin-like growth factor-I(IGF-I) and IGF-binding protein-3, without mediation by growth hormone, in patients with autoimmune thyroid diseases.

PubMed

Inukai, T; Takanashi, K; Takebayashi, K; Fujiwara, Y; Tayama, K; Takemura, Y

1999-10-01

The expression and synthesis of insulin-like growth factor-1 (IGF-I) and IGF-binding protein-3 (IGFBP-3) are regulated by various hormones and nutritional conditions. We evaluated the effects of thyroid hormones on serum levels of IGF-I and IGFBP-3 levels in patients with autoimmune thyroid diseases including 54 patients with Graves' disease and 17 patients with Hashimoto's thyroiditis, and in 32 healthy age-matched control subjects. Patients were subdivided into hyperthyroid, euthyroid and hypothyroid groups that were untreated, or were treated with methylmercaptoimidazole (MMI) or L-thyroxine (L-T4). Serum levels of growth hormone (GH), IGF-I and IGFBP-3 were determined by radioimmunoassay. Serum GH levels did not differ significantly between the hyperthyroid and the age-matched euthyroid patients with Graves' disease. The serum levels of IGF-I and IGFBP-3 showed a significant positive correlation in the patients (R=0.616, P<0.001). The levels of both IGF-I and IFGBP-3 were significantly higher in the hyperthyroid patients with Graves' disease or in those with Hashimoto's thyroiditis induced by excess L-T4 administration than in control subjects. Patients with hypothyroid Graves' disease induced by the excess administration of MMI showed significantly lower IGFBP-3 levels as compared to those in healthy controls (P<0.05). Levels of IGFBP-3, but not IGF-I levels, showed a significant positive correlation with the levels of free T4 and free T3. In Graves' disease, levels of TPOAb, but not of TRAb, showed a significant positive correlation with IGFBP-3. We conclude that in patients with autoimmune thyroid diseases, thyroid hormone modulates the synthesis and/or the secretion of IGF-I and IGFBP-3, and this function is not mediated by GH.

Predictors of Malignancy in Patients with Cytologically Suspicious Thyroid Nodules

PubMed Central

Espiritu, Rachel P.; Bahn, Rebecca S.; Henry, Michael R.; Gharib, Hossein; Caraballo, Pedro J.; Morris, John C.

2011-01-01

Background Fine needle aspiration (FNA), although very reliable for cytologically benign and malignant thyroid nodules, has much lower predictive value in the case of suspicious or indeterminate nodules. We aimed to identify clinical predictors of malignancy in the subset of patients with suspicious FNA cytology. Methods We reviewed the electronic medical records of 462 patients who had FNA of thyroid nodules at our institution with a suspicious cytological diagnosis, and underwent surgery at Mayo Clinic between January 2004 and September 2008. Demographic data including age, gender, history of exposure to radiation and use of thyroid hormone was collected. The presence of single versus multiple nodules by ultrasonography, nodule size, and serum thyroid-stimulating harmone (TSH) level before thyroid surgery were recorded. Analysis of the latter was limited to patients not taking thyroid hormone or antithyroid drugs at the time of FNA. Results Of the 462 patients, 327 had lesions suspicious for follicular neoplasm (S-FN) or Hürthle cell neoplasm (S-HCN), 125 had cytology suspicious for papillary carcinoma (S-PC) and 10 had a variety of other suspicious lesions (medullary cancer, lymphoma and atypical). Malignancy rate for suspicious neoplastic lesions (FN+HCN) was ∼15%, whereas malignancy rate for lesions S-PC was 77%. Neither age, serum TSH level, or history of radiation exposure were associated with increased malignancy risk. The presence of multiple nodules (41.1% vs. 26.4%, p=0.0014) or smaller nodule size (2.6±1.8 cm vs. 2.9±1.6 cm, p=0.008) was associated with higher malignancy risk. In patients with cytology suspicious for neoplasm (FN, HCN) malignancy risk was higher in those receiving thyroid hormone therapy than in nonthyroid hormone users (37.7% vs. 16.5%, p=0.0004; odds ratio: 3.1), although serum TSH values did not differ significantly between thyroid hormone users and nonusers. Conclusion In patients with cytologically suspicious thyroid nodules, the presence of multiple nodules or smaller nodule size was associated with increased risk of malignancy. In addition, our study demonstrates for the first time, an increased risk of malignancy in patients with nodules suspicious for neoplasm who are taking thyroid hormone therapy. The reason for this association is unknown. PMID:22007937

Recent Advances in Thyroid Hormone Regulation: Toward a New Paradigm for Optimal Diagnosis and Treatment

PubMed Central

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

2017-01-01

In thyroid health, the pituitary hormone thyroid-stimulating hormone (TSH) raises glandular thyroid hormone production to a physiological level and enhances formation and conversion of T4 to the biologically more active T3. Overstimulation is limited by negative feedback control. In equilibrium defining the euthyroid state, the relationship between TSH and FT4 expresses clusters of genetically determined, interlocked TSH–FT4 pairs, which invalidates their statistical correlation within the euthyroid range. Appropriate reactions to internal or external challenges are defined by unique solutions and homeostatic equilibria. Permissible variations in an individual are much more closely constrained than over a population. Current diagnostic definitions of subclinical thyroid dysfunction are laboratory based, and do not concur with treatment recommendations. An appropriate TSH level is a homeostatic concept that cannot be reduced to a fixed range consideration. The control mode may shift from feedback to tracking where TSH becomes positively, rather than inversely related with FT4. This is obvious in pituitary disease and severe non-thyroid illness, but extends to other prevalent conditions including aging, obesity, and levothyroxine (LT4) treatment. Treatment targets must both be individualized and respect altered equilibria on LT4. To avoid amalgamation bias, clinically meaningful stratification is required in epidemiological studies. In conclusion, pituitary TSH cannot be readily interpreted as a sensitive mirror image of thyroid function because the negative TSH–FT4 correlation is frequently broken, even inverted, by common conditions. The interrelationships between TSH and thyroid hormones and the interlocking elements of the control system are individual, dynamic, and adaptive. This demands a paradigm shift of its diagnostic use. PMID:29375474

Effect of propranolol on thyroid homeostasis of healthy volunteers.

PubMed Central

Wilkins, M. R.; Franklyn, J. A.; Woods, K. L.; Kendall, M. J.

1985-01-01

The effect of propranolol on thyroid status was investigated by administering the drug in 2 therapeutic doses (80 mg b.d. and 120 mg b.d.) to 8 healthy volunteers and serially measuring total and free thyroid hormones and their major binding protein. Mean free T3 fell by 1.2 pmol/l (P less than 0.05) whilst mean free T4 and mean rT3 rose by 3.3 pmol/l (P less than 0.01) and 0.16 nmol/l (P less than 0.01) respectively. Mean thyroxine binding globulin (TBG) fell by 1.2 mg/l (P less than 0.001). Despite the change in free hormone levels there was no significant change in TSH. For the first time the effect of propranolol on circulating thyroid hormones and binding proteins in healthy subjects is apparent within one study. The biological significance of the change in free hormone levels is discussed. PMID:3927277

Management of hyper and hypo thyroid conditions

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

Locke, W.

1982-03-01

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

Role of Oxidative Stress in Thyroid Hormone-Induced Cardiomyocyte Hypertrophy and Associated Cardiac Dysfunction: An Undisclosed Story

PubMed Central

Elnakish, Mohammad T.; Ahmed, Amany A. E.; Mohler, Peter J.; Janssen, Paul M. L.

2015-01-01

Cardiac hypertrophy is the most documented cardiomyopathy following hyperthyroidism in experimental animals. Thyroid hormone-induced cardiac hypertrophy is described as a relative ventricular hypertrophy that encompasses the whole heart and is linked with contractile abnormalities in both right and left ventricles. The increase in oxidative stress that takes place in experimental hyperthyroidism proposes that reactive oxygen species are key players in the cardiomyopathy frequently reported in this endocrine disorder. The goal of this review is to shed light on the effects of thyroid hormones on the development of oxidative stress in the heart along with the subsequent cellular and molecular changes. In particular, we will review the role of thyroid hormone-induced oxidative stress in the development of cardiomyocyte hypertrophy and associated cardiac dysfunction, as well as the potential effectiveness of antioxidant treatments in attenuating these hyperthyroidism-induced abnormalities in experimental animal models. PMID:26146529

Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep.

PubMed

Johnsen, L; Lyckegaard, N B; Khanal, P; Quistorff, B; Raun, K; Nielsen, M O

2018-05-01

We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming. Twin-pregnant sheep ( n  = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood). Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T 3 , T 3 :T 4 and T 3 :TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH. Conclusions : The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk. © 2018 The authors.

Fetal over- and undernutrition differentially program thyroid axis adaptability in adult sheep

PubMed Central

Johnsen, L; Lyckegaard, N B; Khanal, P; Quistorff, B; Raun, K; Nielsen, M O

2018-01-01

Objective We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming. Design Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood). Methods Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE). Results In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH. Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk. PMID:29794141

Effects of methimazole treatment on growth hormone (GH) response to GH-releasing hormone in patients with hyperthyroidism.

PubMed

Giustina, A; Ferrari, C; Bodini, C; Buffoli, M G; Legati, F; Schettino, M; Zuccato, F; Wehrenberg, W B

1990-12-01

In vitro studies have demonstrated that thyroid hormones can enhance basal and stimulated growth hormone secretion by cultured pituitary cells. However, both in man and in the rat the effects of high thyroid hormone levels on GH secretion are unclear. The aim of our study was to test the GH response to human GHRH in hyperthyroid patients and to evaluate the effects on GH secretion of short- and long-term pharmacological decrease of circulating thyroid hormones. We examined 10 hyperthyroid patients with recent diagnosis of Graves' disease. Twelve healthy volunteers served as controls. All subjects received a bolus iv injection of GHRH(1-29)NH2, 100 micrograms. Hyperthyroid patients underwent a GHRH test one and three months after starting antithyroid therapy with methimazole, 10 mg/day po. GH levels at 15, 30, 45, 60 min and GH peak after stimulus were significantly lower in hyperthyroid patients than in normal subjects. The GH peak was also delayed in hyperthyroid patients. After one month of methimazole therapy, most of the hyperthyroid patients had thyroid hormone levels in the normal range, but they did not show significant changes in GH levels after GHRH, and the GH peak was again delayed. After three months of therapy with methimazole, the hyperthyroid patients did not show a further significant decrease in serum thyroid hormone levels. However, mean GH levels from 15 to 60 min were significantly increased compared with the control study. The GH peak after GHRH was also earlier than in the pre-treatment study.(ABSTRACT TRUNCATED AT 250 WORDS)

Functional central hypothyroidism in the elderly.

PubMed

Sell, Maren A; Schott, Matthias; Tharandt, Lutz; Cissewski, Klaus; Scherbaum, Werner A; Willenberg, Holger S

2008-06-01

Previous studies have shown that blood concentrations of free thyroxin and basal thyroid-stimulating hormone (TSH) decrease during adult life. Suggested mechanisms include reduced thyroid activity resulting from decreased serum TSH concentrations, impairment of peripheral 5'-deiodinase, and an increase in reverse 3,5,3'-triiodothyronine due to non-thyroidal illness. However, testing of pituitary reserves leads to contradictory results and has infrequently been evaluated in studies. We investigated whether the response of TSH to thyrotropin-releasing hormone (TRH) is preserved during aging. This was tested in a cohort of 387 subjects aged 13 to 100 years in whom thyroid disease was excluded by normal thyroid ultrasound, normal values for free thyroxin, free triiodothyronin, TSH, and negative thyroid peroxidase antibodies. Serum concentrations of free thyroxin remained almost unchanged, whereas free triiodothyronin and TSH levels were lower in older subjects. In addition, the TSH response to TRH was blunted in older subjects, especially in male individuals. There is evidence that the decreased thyroid hormone levels observed in aging are due to lower TSH concentrations, and that lower TSH concentrations may be linked to an impaired pituitary activity.

A novel hypothyroid dwarfism due to the missense mutation Arg479Cys of the thyroid peroxidase gene in the mouse.

PubMed

Takabayashi, Shuji; Umeki, Kazumi; Yamamoto, Etsuko; Suzuki, Tohru; Okayama, Akihiko; Katoh, Hideki

2006-10-01

Recently, we found a novel dwarf mutation in an ICR closed colony. This mutation was governed by a single autosomal recessive gene. In novel dwarf mice, plasma levels of the thyroid hormones, T3 and T4, were reduced; however, TSH was elevated. Their thyroid glands showed a diffuse goiter exhibiting colloid deficiency and abnormal follicle epithelium. The dwarfism was improved by adding thyroid hormone in the diet. Gene mapping revealed that the dwarf mutation was closely linked to the thyroid peroxidase (Tpo) gene on chromosome 12. Sequencing of the Tpo gene of the dwarf mice demonstrated a C to T substitution at position 1508 causing an amino acid change from arginine (Arg) to cysteine (Cys) at codon 479 (Arg479Cys). Western blotting revealed that TPO protein of the dwarf mice was detected in a microsomal fraction of thyroid tissue, but peroxidase activity was not detected. These findings suggested that the dwarf mutation caused a primary congenital hypothyroidism by TPO deficiency, resulting in a defect of thyroid hormone synthesis.

[Low levels of TSH measured by a sensitive assay: do they reflect hyperthyroidism? A critical analysis of 580 cases].

PubMed

Rohmer, V; Ligeard-Ducoroy, A; Perdrisot, R; Beldent, V; Jallet, P; Bigorgne, J C

1990-05-12

Highly sensitive TSH assays make it easier to diagnose thyroid diseases. During one year, we performed 5,300 sensitive TSH assays (normal range: 0.15-4 mU/l) in various patients. The purpose of this work was to test the value of the low TSH plasma concentrations found in 580 patients. In 99.7 percent of the cases, low TSH levels were the consequence of a thyroid disorder or a treatment by thyroid hormones; non thyroidal illnesses were detected in only 0.3 percent. However, not all TSH values below 0.15 mU/l were associated with overt or occult thyrotoxicosis. When TSH was undetectable (less than 0.04 mU/l), and excluding thyroid hormone-treated patients, thyrotoxicosis was present in 97 percent of the cases. On the other hand, when TSH values were between 0.04 and 0.15 mU/l, 41 percent of the patients failed to show any sign or symptom of hyperthyroidism, although they had functioning thyroid nodules, multinodular goitre or iodine overload, or they received thyroid hormones.

Interaction of thyroid state and denervation on skeletal myosin heavy chain expression

NASA Technical Reports Server (NTRS)

Haddad, F.; Arnold, C.; Zeng, M.; Baldwin, K.

1997-01-01

The goal of this study was to examine the effects of altered thyroid state and denervation (Den) on skeletal myosin heavy chain (MHC) expression in the plantaris and soleus muscles. Rats were subjected to unilateral denervation (Den) and randomly assigned to one of three groups: (1) euthyroid; (2) hyperthyroid; (3) and hypothyroid. Denervation caused severe muscle atrophy and muscle-type specific MHC transformation. Denervation transformed the soleus to a faster muscle, and its effects required the presence of circulating thyroid hormone. In contrast, denervation transformed the plantaris to a slower muscle independently of thyroid state. Furthermore, thyroid hormone effects did not depend upon innervation status in the soleus, while they required the presence of the nerve in the plantaris. Collectively, these findings suggest that both thyroid hormone and intact nerve (a) differentially affect MHC transformations in fast and slow muscle; and (b) are important factors in regulating the optimal expression of both type I and IIB MHC genes. This research suggests that for patients with nerve damage and/or paralysis, both muscle mass and biochemical properties can also be affected by the thyroid state.

Thyroid hormone analogs for the treatment of dyslipidemia: past, present, and future.

PubMed

Delitala, Alessandro P; Delitala, Giuseppe; Sioni, Paolo; Fanciulli, Giuseppe

2017-11-01

Treatment of dyslipidemia is a major burden for public health. Thyroid hormone regulates lipid metabolism by binding the thyroid hormone receptor (TR), but the use of thyroid hormone to treat dyslipidemia is not indicated due to its deleterious effects on heart, bone, and muscle. Thyroid hormone analogs have been conceived to selectively activate TR in the liver, thus reducing potential side-effects. The authors searched the PubMed database to review TR and the action of thyromimetics in vitro and in animal models. Then, all double-blind, placebo controlled trials that analyzed the use of thyroid hormone analog for the treatment of dyslipidemia in humans were included. Finally, the ongoing research on the use of TR agonists was searched, searching the US National Institutes of Health Registry and the WHO International Clinical Trial Registry Platform (ICTRP). Thyromimetics were tested in humans for the treatment of dyslipidemia, as a single therapeutic agent or as an add-on therapy to the traditional lipid-lowering drugs. In most trials, thyromimetics lowered total cholesterol, low-density lipoprotein cholesterol, and triglycerides, but their use has been associated with adverse side-effects, both in pre-clinical studies and in humans. The use of thyromimetics for the treatment of dyslipidemia is not presently recommended. Future possible clinical applications might include their use to promote weight reduction. Thyromimetics might also represent an interesting alternative, both for the treatment of non-alcoholic steatohepatitis, and type 2 diabetes due to their positive effects on insulin sensitivity. Finally, additional experimental and clinical studies are needed for a better comprehension of the effect(s) of a long-term therapy.

TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves' disease and Graves' ophthalmopathy.

PubMed

Bufalo, N E; Dos Santos, R B; Marcello, M A; Piai, R P; Secolin, R; Romaldini, J H; Ward, L S

2015-05-01

Intronic thyroid-stimulating hormone receptor polymorphisms have been associated with the risk for both Graves' disease and Graves' ophthalmopathy, but results have been inconsistent among different populations. We aimed to investigate the influence of thyroid-stimulating hormone receptor intronic polymorphisms in a large well-characterized population of GD patients. We studied 279 Graves' disease patients (231 females and 48 males, 39.80 ± 11.69 years old), including 144 with Graves' ophthalmopathy, matched to 296 healthy control individuals. Thyroid-stimulating hormone receptor genotypes of rs179247 and rs12885526 were determined by Real Time PCR TaqMan(®) SNP Genotyping. A multivariate analysis showed that the inheritance of the thyroid-stimulating hormone receptor AA genotype for rs179247 increased the risk for Graves' disease (OR = 2.821; 95 % CI 1.595-4.990; p = 0.0004), whereas the thyroid-stimulating hormone receptor GG genotype for rs12885526 increased the risk for Graves' ophthalmopathy (OR = 2.940; 95 % CI 1.320-6.548; p = 0.0083). Individuals with Graves' ophthalmopathy also presented lower mean thyrotropin receptor antibodies levels (96.3 ± 143.9 U/L) than individuals without Graves' ophthalmopathy (98.3 ± 201.9 U/L). We did not find any association between the investigated polymorphisms and patients clinical features or outcome. We demonstrate that thyroid-stimulating hormone receptor intronic polymorphisms are associated with the susceptibility to Graves' disease and Graves' ophthalmopathy in the Brazilian population, but do not appear to influence the disease course.

Increased Oxidative Metabolism and Neurotransmitter Cycling in the Brain of Mice Lacking the Thyroid Hormone Transporter Slc16a2 (Mct8)

PubMed Central

Rodrigues, Tiago B.; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-13C) glucose and brain extracts prepared and analyzed by 13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood. PMID:24098341

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

PubMed

Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

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

PubMed

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

2011-03-01

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

Hormone levels

MedlinePlus

Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

Diagnosis and management of congenital hypothyroidism.

PubMed

Harrell, G B; Murray, P D

1998-03-01

Thyroid hormones are integral to the development and maturation of the central nervous system as well as normal growth and development. Comprehensive knowledge of the maturation and function of the thyroid gland is essential to understanding the pathophysiology of thyroid dysfunction. Early diagnosis and appropriate treatment in thyroid disease are imperative for normalization of thyroid hormone ratios. Optimal management includes early introduction and strict adherence to a regimen of L-thyroxine and routine monitoring of thyroid levels throughout life. Parents need to understand the importance of consistent medication administration and daily assessment of well-being because these actions are crucial to the attainment of an optimal level of development for infants with congenital hypothyroidism.

Is it possible to diagnose canine hypothyroidism?

PubMed

Panciera, D L

1999-04-01

A definitive diagnosis of hypothyroidism can be difficult because of the many clinical abnormalities associated with thyroid hormone deficiency, and the lack of readily available diagnostic tests with high sensitivity and specificity. Thyroid function tests should be performed only in dogs with clinical findings consistent with hypothyroidism. Measurement of serum total thyroxine (T4) concentration is a useful initial screening test since most hypothyroid dogs have values below the reference range. Serum free T4 concentration measured by equilibrium dialysis is a more sensitive and specific test of thyroid function than total T4 and is particularly useful in dogs with non-thyroidal illness or atypical clinical signs. Measurement of serum endogenous thyroid-stimulating hormone concentration is also helpful, but many hypothyroid dogs have normal results. The gold standard for diagnosis of hypothyroidism remains the thyroid-stimulating hormone response test. It should be used to confirm hypothyroidism when other tests do not agree with the clinical impression or if atypical signs or non-thyroidal illness exist or there has been administration of drugs known to alter thyroid function tests. Ultimately, a positive response to treatment is expected in hypothyroid dogs treated appropriately with levothyroxine.

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

PubMed

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

2013-07-01

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

Post-translational modifications of transthyretin affect the triiodonine-binding potential

PubMed Central

Henze, Andrea; Homann, Thomas; Serteser, Mustafa; Can, Ozge; Sezgin, Ozlem; Coskun, Abdurrahman; Unsal, Ibrahim; Schweigert, Florian J; Ozpinar, Aysel

2015-01-01

Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10), which is frequently affected by oxidative post-translational modifications. As Cys10 is part of the thyroid hormone-binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype- and site-specific manner with S-glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function-specific patterns of TTR with a substantial decrease in S-sulphonated, S-cysteinylglycinated and S-glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability. PMID:25311081

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

PubMed

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

2017-10-01

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

Computational Modeling of Thyroid Hormone Regulated Neurodevelopment for Chemical Prioritization (SOT)

EPA Science Inventory

Thyroid hormones (TH) are critical for normal brain development. Environmental chemicals may disrupt TH homeostasis through a variety of physiological systems including membrane transporters, serum transporters, synthesis and catabolic enzymes, and nuclear receptors. Current comp...

RISK ASSESSMENT OF THYROID HORMONE DISRUPTION AND MIXTURES IN MARINE BIOTA

EPA Science Inventory

Varieties of chemicals alter thyroid hormones (THs) in vertabrates. The importance of THs during neurodevelopment, suggest that these chemicals would likely be developmental neurotoxicants. A number of epidemiological studies have demonstrated associations between exposure to p...

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

PubMed

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

2010-09-01

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

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

PubMed Central

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

2010-01-01

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

Trimester specific reference intervals for thyroid function tests in normal Indian pregnant women.

PubMed

Sekhri, Tarun; Juhi, Juhi Agarwal; Wilfred, Reena; Kanwar, Ratnesh S; Sethi, Jyoti; Bhadra, Kuntal; Nair, Sirimavo; Singh, Satveer

2016-01-01

Accurate assessment of thyroid function during pregnancy is critical, for initiation of thyroid hormone therapy, as well as for adjustment of thyroid hormone dose in hypothyroid cases. We evaluated pregnant women who had no past history of thyroid disorders and studied their thyroid function in each trimester. 86 normal pregnant women in the first trimester of pregnancy were selected for setting reference intervals. All were healthy, euthyroid and negative for thyroid peroxidase antibody (TPOAb). These women were serially followed throughout pregnancy. 124 normal nonpregnant subjects were selected for comparison. Thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3) and anti-TPO were measured using Roche Elecsys 1010 analyzer. Urinary iodine content was determined by simple microplate method. The 2.5th and 97.5th percentiles were calculated as the reference intervals for thyroid hormone levels during each trimester. SPSS (version 14.0, SPSS Inc., Chicago, IL, USA) was used for data processing and analysis. The reference intervals for the first, second and third trimesters for the following parameters: TSH 0.09-6.65, 0.51-6.66, 0.91-4.86 µIU/mL, FT4 9.81-18.53, 8.52-19.43, 7.39-18.28 pM/L and FT3 3.1-6.35, 2.39-5.12, 2.57-5.68 pM/L respectively. Thyroid hormone concentrations significantly differed during pregnancy at different stages of gestation. The pregnant women in the study had median urinary iodine concentration of 150-200 µg/l during each trimester. The trimester-specific reference intervals for thyroid tests during pregnancy have been established for pregnant Indian women serially followed during pregnancy using 2.5th and 97.5th percentiles.

[Study of serum thrombomodulin(TM) levels in patients with hyper- or hypo- thyroidism].

PubMed

Soma, M; Maeda, Y; Matsuura, R; Sasaki, I; Kasakura, S; Saeki, Y; Ikekubo, K; Ishihara, T; Kurahachi, H; Sasaki, S; Tagami, T; Nakao, K

1997-01-01

We studies a relationship between the serum levels of thrombomodulin(TM) and the thyroid functions. Serum TM levels were measured in 48 patients with Graves' disease, 17 patients with primary hypothyroidism, 7 patients with subacute thyroiditis, 5 patients with painless thyroiditis and 2 patients with systematic Refetoff syndrome. These patients did not have malignant tumor, kidney failure, or blood vessel injury. Control sera were obtained from 42 healthy subjects. Serum levels of TM in patients with untreated Graves' disease were significantly higher(p < 0.001) compared with those in controls. Serum levels of TM in patients with hypothyroidism were not significantly changed as compared with those of controls. There were a positive correlation between the serum levels of TM and FT3 as well as FT4. Serial determinations of the serum levels of TM and thyroid function(FT3, FT4 and TH) in patients with Graves' disease during treatment showed that both the serum levels of TM and thyroid hormones (FT3 and FT4) lowered progressively during treatment. After normalization of serum FT3 and FT4, the serum TM levels returned to normal. However, the serum levels of TM in patients with destructive thyroiditis and Refetoff syndrome were normal in spite of high serum levels of thyroid hormones. These data suggest that an increase in serum levels of TM is not the direct result of thyroid hormones themselves but is the result of the prolonged hypermetabolic state induced by their peripheral activities. Thyroid hormones may stimulate the synthesis or metabolism of TM on the surface of vascular endothelial cells in the patients with Graves' disease.

Analysis of current thyroid function test ordering practices.

PubMed

Kluesner, Joseph K; Beckman, Darrick J; Tate, Joshua M; Beauvais, Alexis A; Kravchenko, Maria I; Wardian, Jana L; Graybill, Sky D; Colburn, Jeffrey A; Folaron, Irene; True, Mark W

2018-04-01

Current guidelines recommend thyroid stimulating hormone (TSH) alone as the best test to detect and monitor thyroid dysfunction, yet free thyroxine (FT4) and free triiodothyronine (FT3) are commonly ordered when not clinically indicated. Excessive testing can lead to added economic burden in an era of rising healthcare costs, while rarely contributing to the evaluation or management of thyroid disease. To evaluate our institution's practice in ordering thyroid function tests (TFTs) and to identify strategies to reduce inappropriate FT4 and FT3 testing. A record of all TFTs obtained in the San Antonio Military Health System during a 3-month period was extracted from the electronic medical record. The TFTs of interest were TSH, FT4, thyroid panel (TSH + FT4), FT3, total thyroxine (T4), and total triiodothyronine (T3). These were categorized based on the presence or absence of hypothyroidism. Between August 1 and October 31, 2016, there were 38 214 individual TFTs ordered via 28 597 total laboratory requests; 11 486 of these requests were in patients with a history of hypothyroidism. The number (percent) of laboratory requests fell into these patterns: TSH alone 14 919 (52.14%), TSH + FT4 7641 (26.72%), FT3 alone 3039 (10.63%), FT4 alone 1219 (4.26%), TSH + FT4 + FT3 783 (2.74%), and others 996 (3.48%); 36.0% of TFTs ordered were free thyroid hormones. Projected out to a year, using Department of Defense laboratory costs, $317 429 worth of TFTs would be ordered, with free thyroid hormone testing accounting for $107 720. Inappropriate ordering of free thyroid hormone tests is common. In an era of rising healthcare costs, inappropriate thyroid function testing is an ideal target for efforts to reduce laboratory overutilization, which in our system, could save up to $120 000 per year. Further evaluation is needed to determine strategies that can reduce excessive thyroid hormone testing. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.