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

PubMed Central

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

2002-01-01

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

Influence of thyroid function on glomerular filtration rate and other estimates of kidney function in two pediatric patients.

PubMed

Uemura, Osamu; Iwata, Naoyuki; Nagai, Takuhito; Yamakawa, Satoshi; Hibino, Satoshi; Yamamoto, Masaki; Nakano, Masaru; Tanaka, Kazuki

2018-05-01

To determine the optimal method of evaluating kidney function in patients with thyroid dysfunction, this study compared the estimated glomerular filtration rate derived from serum creatinine, cystatin C, or β2-microglobulin with inulin or creatinine clearance in two pediatric patients, one with hypothyroidism and the other with hyperthyroidism. It was observed that the kidney function decreased in a hypothyroid child and enhanced in a hyperthyroid child, with their kidney function becoming normalized by treatment with drugs, which normalized their thyroid function. Kidney function cannot be accurately evaluated using cystatin C-based or β2-microglobulin-based estimated glomerular filtration rate in patients with thyroid dysfunction, as these tests overestimated glomerular filtration rate in a patient with hypothyroidism and underestimated glomerular filtration rate in a patient with hyperthyroidism, perhaps through a metabolic rate-mediated mechanism. In both our patients, 24-h urinary creatinine secretion was identical before and after treatment, suggesting that creatinine production is not altered in patients with thyroid dysfunction. Therefore, kidney function in patients with thyroid dysfunction should be evaluated using creatinine-based estimated glomerular filtration rate.

Cardiopulmonary and Metabolic Effects of Yoga in Healthy Volunteers

PubMed Central

Divya, T Satheesh; Vijayalakshmi, MT; Mini, K; Asish, K; Pushpalatha, M; Suresh, Varun

2017-01-01

Background: Yoga the spiritual union of mind with the divine intelligence of the universe aims to liberate a human being from conflicts of body–mind duality. Beneficial cardiovascular and pulmonary effects of yoga are in par with aerobic exercise, even amounting to replace the exercise model. We conducted an interventional study in healthy volunteers, to analyze the impact of short-term yoga training on cardiovascular, pulmonary, autonomic function tests, lipid profile, and thyroid function tests. Materials and Methods: A sample of fifty new recruits attending the district yoga center was subject to 75 min yoga practice a day for 41 days. Basal values of cardiovascular, pulmonary, autonomic function tests, lipid profile, and thyroid function tests were recorded before yoga training and were reassessed for postyoga changes after 41 days. Results: After yoga practice there was a significant reduction in the resting heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure of the participants. Effects on autonomic function tests were variable and inconclusive. There was a significant increase in forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate after yoga. A significant reduction in body mass index was observed. Effects on metabolic parameters were promising with a significant reduction in fasting blood sugar level, serum total cholesterol, serum triglycerides serum low-density lipoprotein levels, and significant increase in high-density lipoprotein. There was no significant change in thyroid function tests after yoga. Conclusion: Short-term yoga practice has no effect on thyroid functions. Yoga practice was found beneficial in maintaining physiological milieu pertaining to cardiovascular and other metabolic parameters. PMID:29422741

Cardiopulmonary and Metabolic Effects of Yoga in Healthy Volunteers.

PubMed

Divya, T Satheesh; Vijayalakshmi, M T; Mini, K; Asish, K; Pushpalatha, M; Suresh, Varun

2017-01-01

Yoga the spiritual union of mind with the divine intelligence of the universe aims to liberate a human being from conflicts of body-mind duality. Beneficial cardiovascular and pulmonary effects of yoga are in par with aerobic exercise, even amounting to replace the exercise model. We conducted an interventional study in healthy volunteers, to analyze the impact of short-term yoga training on cardiovascular, pulmonary, autonomic function tests, lipid profile, and thyroid function tests. A sample of fifty new recruits attending the district yoga center was subject to 75 min yoga practice a day for 41 days. Basal values of cardiovascular, pulmonary, autonomic function tests, lipid profile, and thyroid function tests were recorded before yoga training and were reassessed for postyoga changes after 41 days. After yoga practice there was a significant reduction in the resting heart rate, systolic blood pressure, diastolic blood pressure, and mean blood pressure of the participants. Effects on autonomic function tests were variable and inconclusive. There was a significant increase in forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow rate after yoga. A significant reduction in body mass index was observed. Effects on metabolic parameters were promising with a significant reduction in fasting blood sugar level, serum total cholesterol, serum triglycerides serum low-density lipoprotein levels, and significant increase in high-density lipoprotein. There was no significant change in thyroid function tests after yoga. Short-term yoga practice has no effect on thyroid functions. Yoga practice was found beneficial in maintaining physiological milieu pertaining to cardiovascular and other metabolic parameters.

Differences in Brain Glucose Metabolism During Preparation for 131I Ablation in Thyroid Cancer Patients: Thyroid Hormone Withdrawal Versus Recombinant Human Thyrotropin.

PubMed

Jeong, Hyeonseok S; Choi, Eun Kyoung; Song, In-Uk; Chung, Yong-An; Park, Jong-Sik; Oh, Jin Kyoung

2017-01-01

In preparation for 131 I ablation, temporary withdrawal of thyroid hormone is commonly used in patients with thyroid cancer after total thyroidectomy. The current study aimed to investigate brain glucose metabolism and its relationships with mood or cognitive function in these patients using 18 F-fluoro-2-deoxyglucose positron emission tomography ( 18 F-FDG-PET). A total of 40 consecutive adult patients with thyroid carcinoma who had undergone total thyroidectomy were recruited for this cross-sectional study. At the time of assessment, 20 patients were hypothyroid after two weeks of thyroid hormone withdrawal, while 20 received thyroid hormone replacement therapy and were euthyroid. All participants underwent brain 18 F-FDG-PET scans and completed mood questionnaires and cognitive tests. Multivariate spatial covariance analysis and univariate voxel-wise analysis were applied for the image data. The hypothyroid patients were more anxious and depressed than the euthyroid participants. The multivariate covariance analysis showed increases in glucose metabolism primarily in the bilateral insula and surrounding areas and concomitant decreases in the parieto-occipital regions in the hypothyroid group. The level of thyrotropin was positively associated with the individual expression of the covariance pattern. The decreased 18 F-FDG uptake in the right cuneus cluster from the univariate analysis was correlated with the increased thyrotropin level and greater depressive symptoms in the hypothyroid group. These results suggest that temporary hypothyroidism, even for a short period, may induce impairment in glucose metabolism and related affective symptoms.

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.

IODINE AND THE THYROID

PubMed Central

Swingle, W. W.

1919-01-01

1. Amphibian metamorphosis depends upon the amount of iodine secured by the larvæ; the greater the quantity the more rapid the differentiation. 2. Bromine is physiologically inert when fed even in large quantities to frog larvæ, hence it cannot be substituted for iodine. Bromine feeding has no effect on the thyroid. 3. Iodine is the active constituent of the thyroid gland, in the Anura at any rate, and functions within the body by stimulating intracellular oxidations; it is apparently specific in its action. 4. The basal metabolism of patients suffering from athyreosis, whose metabolism is 40 per cent below normal, is very likely held at this figure and prevented from sinking lower to the death point by the introduction of iodine into the body through food and water. 5. The thyroid gland is an organ the function of which is the extraction from the circulation, storage, and supplying to the organism, under the pressure of its needs, the small quantities of iodine taken into the body. The chief function of this gland then is the utilization of iodine in small quantities. PMID:19871773

Comparative effects of in ovo exposure to sodium perchlorate on development, growth, metabolism, and thyroid function in the common snapping turtle (Chelydra serpentina) and red-eared slider (Trachemys scripta elegans).

PubMed

Eisenreich, Karen M; Dean, Karen M; Ottinger, Mary Ann; Rowe, Christopher L

2012-11-01

Perchlorate is a surface and groundwater contaminant found in areas associated with munitions and rocket manufacturing and use. It is a thyroid-inhibiting compound, preventing uptake of iodide by the thyroid gland, ultimately reducing thyroid hormone production. As thyroid hormones influence metabolism, growth, and development, perchlorate exposure during the embryonic period may impact embryonic traits that ultimately influence hatchling performance. We topically exposed eggs of red-eared sliders (Trachemys scripta) and snapping turtles (Chelydra serpentina) to 200 and 177 μg/g of perchlorate (as NaClO(4)), respectively, to determine impacts on glandular thyroxine concentrations, embryonic growth and development, and metabolic rates of hatchlings for a period of 2 months post-hatching. In red-eared sliders, in ovo perchlorate exposure delayed hatching, increased external yolk size at hatching, increased hatchling mortality, and reduced total glandular thyroxine concentrations in hatchlings. In snapping turtles, hatching success and standard metabolic rates were reduced, liver and thyroid sizes were increased, and total glandular thyroxine concentrations in hatchlings were reduced after exposure to perchlorate. While both species were negatively affected by exposure, impacts on red-eared sliders were most severe, suggesting that the slider may be a more sensitive sentinel species for studying effects of perchlorate exposure to turtles. Copyright © 2012 Elsevier Inc. 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...

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.

The Effect of a Three-Week Adaptation to a Low Carbohydrate/High Fat Diet on Metabolism and Cognitive Performance

DTIC Science & Technology

1990-04-11

triglycerides , insulin, glucagon, cholesterol (total, high density lipoprotein ( HDL ), low density lipoprotein (LDL)I, cortisol, thyroid hormone...thyroid function, triglycerides , total cholesterol , high density lipoprotein cholesterol ( HDL ), low density lipoprotein cholesterol (LDL), ketone... density lipoprotein ( HDL ) fraction of cholesterol was

The thyroid and environmental stress in mammals

NASA Technical Reports Server (NTRS)

Galton, V. A.

1977-01-01

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

Metabolic Reprogramming in Thyroid Carcinoma

PubMed Central

Coelho, Raquel Guimaraes; Fortunato, Rodrigo S.; Carvalho, Denise P.

2018-01-01

Among all the adaptations of cancer cells, their ability to change metabolism from the oxidative to the glycolytic phenotype is a hallmark called the Warburg effect. Studies on tumor metabolism show that improved glycolysis and glutaminolysis are necessary to maintain rapid cell proliferation, tumor progression, and resistance to cell death. Thyroid neoplasms are common endocrine tumors that are more prevalent in women and elderly individuals. The incidence of thyroid cancer has increased in the Past decades, and recent findings describing the metabolic profiles of thyroid tumors have emerged. Currently, several drugs are in development or clinical trials that target the altered metabolic pathways of tumors are undergoing. We present a review of the metabolic reprogramming in cancerous thyroid tissues with a focus on the factors that promote enhanced glycolysis and the possible identification of promising metabolic targets in thyroid cancer. PMID:29629339

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

PubMed

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

2018-04-01

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

Muscle cramps

MedlinePlus

... you been exercising heavily? Have you been drinking alcohol heavily? Blood tests may be done to check for the following: Calcium, potassium, or magnesium metabolism Kidney function Thyroid function Pain medicines may be ...

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

PubMed

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

2013-09-01

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

Oral manifestations of thyroid disorders and its management

PubMed Central

Chandna, Shalu; Bathla, Manish

2011-01-01

The thyroid is the major regulator of metabolism and affects all of the bodily functions. Thyroid dysfunction is the second most common glandular disorder of the endocrine system which may rear its head in any system in the body including the mouth. The oral cavity is adversely affected by either an excess or deficiency of these hormones. Before treating a patient who has thyroid disorder, the endocrinologist needs to be familiar with the oral manifestations of thyroid dysfunctions. The patient with a thyroid dysfunction, as well as the patient taking medications for it, requires proper risk management before considering dental treatment by the dentist. Thus, communication of dentist with endocrinologist must be bidirectional, to maintain patient's oral and thyroid health. PMID:21966646

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.

Endogenous subclinical hyperthyroidism and cardiovascular system: time to reconsider?

PubMed

Patanè, Salvatore; Marte, Filippo; Sturiale, Mauro

2011-05-19

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. Exogenous sublinical hyperthyroidism is a thyroid metabolic state caused by L-thyroxine administration. Endogenous subclinical hyperthyroidism is a thyroid metabolic state in patients with autonomously functioning thyroid nodule or multinodular goiter, various forms of thyroiditis, in areas with endemic goiter and particularly in elderly subjects. Endogenous subclinical hyperthyroidism is currently the subject of numerous studies and it yet remains controversial particularly as it relates to its treatment and to cardiovascular impact nevertheless established effects have been demonstrated. Recently, acute myocardial infarction without significant coronary stenoses and recurrent acute pulmonary embolism have been reported associated with subclinical hyperthyroidism without L-thyroxine administration. So, it is very important to recognize and to treat promptly also endogenous subclinical hyperthyroidism. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Pleiotropic Effects of Thyroid Hormones: Learning from Hypothyroidism

PubMed Central

Franco, Martha; Chávez, Edmundo; Pérez-Méndez, Oscar

2011-01-01

Hypothyroidism induces several metabolic changes that allow understanding some physiopathological mechanisms. Under experimental hypothyroid conditions in rats, heart and kidney are protected against oxidative damage induced by ischemia reperfusion. An increased resistance to opening of the permeability transition pore seems to be at the basis of such protection. Moreover, glomerular filtration rate of hypothyroid kidney is low as a result of adenosine receptors-induced renal vasoconstriction. The vascular tone of aorta is also regulated by adenosine in hypothyroid conditions. In other context, thyroid hormones regulate lipoprotein metabolism. High plasma level of LDL cholesterol is a common feature in hypothyroidism, due to a low expression of the hepatic LDL receptor. In contrast, HDL-cholesterol plasma levels are variable in hypothyroidism; several proteins involved in HDL metabolism and structure are expressed at lower levels in experimental hypothyroidism. Based on the positive influence of thyroid hormones on lipoprotein metabolism, thyromimetic drugs are promising for the treatment of dyslipidemias. In summary, hypothyroid status has been useful to understand molecular mechanisms involved in ischemia reperfusion, regulation of vascular function and intravascular metabolism of lipoproteins. PMID:21760977

Iodide transport: implications for health and disease

PubMed Central

2014-01-01

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

Italian Association of Clinical Endocrinologists (AME) & Italian Association of Clinical Diabetologists (AMD) Position Statement : Diabetes mellitus and thyroid disorders: recommendations for clinical practice.

PubMed

Guastamacchia, Edoardo; Triggiani, Vincenzo; Aglialoro, Alberto; Aiello, Antimo; Ianni, Lucia; Maccario, Mauro; Zini, Michele; Giorda, Carlo; Guglielmi, Rinaldo; Betterle, Corrado; Attanasio, Roberto; Borretta, Giorgio; Garofalo, Piernicola; Papini, Enrico; Castello, Roberto; Ceriello, Antonio

2015-06-01

Thyroid disease and diabetes mellitus, the most common disorders in endocrine practice, are not infrequently associated in the same subject. An altered thyroid function may affect glucose tolerance and worsen metabolic control in patients with diabetes. Thyrotoxicosis increases the risk of hyperglycemic emergencies, while a clinically relevant hypothyroidism may have a detrimental effect on glycemic control in diabetic patients. The association of alterations in thyroid function with diabetes mellitus may adversely affect the risk of cardiovascular and microvascular complications resulting from diabetes. Moreover, the treatments used for both diabetes and thyroid disease, respectively, can impact one other. Finally, multinodular goiter, but not thyroid carcinoma, was shown to be more prevalent in type 2 diabetes mellitus. Aim of the present Position Statement is to focus on the evidence concerning the association of thyroid disease and diabetes mellitus and to provide some practical suggestions for an updated clinical management.

Irisin levels increase after treatment in patients with newly diagnosed Hashimoto thyroiditis.

PubMed

Uc, Z A; Gorar, S; Mizrak, S; Gullu, S

2018-05-18

Irisin is a newly identified myokine secreted by skeletal muscle and has significant effects on body metabolism. Thyroidal functional state has a profound influence on the metabolism of human body. Therefore, the aim of this study was to investigate the possible changes in serum irisin concentrations before and after treatment in hypothyroid subjects. The study included 26 patients with overt hypothyroidism due to Hashimoto thyroiditis and 19 healthy subjects. Baseline serum thyroid function tests and presence of thyroid autoantibodies and levels of creatine kinase (CK) and irisin were measured in both groups. All measurements in the hypothyroid group were repeated after euthyroidism was achieved. Serum irisin levels were significantly lower in the hypothyroid groups than the control group (p < 0.001). Negative correlation between irisin and thyroid stimulating hormone and CK levels (r = - 0.623, p < 0.001 and r = - 0.389, p = 0.008, respectively) and a positive correlation between irisin and free thyroxine (fT4) levels (r = 0.570, p < 0.001) was found. Serum CK levels decreased significantly after treatment (p < 0.001). Serum irisin levels significantly increased (from 57.4 to 99.8 U/L, p < 0.001) when the hypothyroid patients were treated to achieve euthyroidism. To the best of our knowledge, this is the first study providing insight that low serum irisin levels significantly increased following treatment to euthyroid state in overt hypothyroid patients with Hashimoto thyroiditis. Larger scale studies are needed to confirm these results and to ensure irisin as a possible biomarker of Hashimoto's thyroiditis.

Triiodothyronine Facilitates Weaning From Extracorporeal Membrane Oxygenation by Improved Mitochondrial Substrate Utilization

PubMed Central

Files, Matthew D.; Kajimoto, Masaki; O'Kelly Priddy, Colleen M.; Ledee, Dolena R.; Xu, Chun; Des Rosiers, Christine; Isern, Nancy; Portman, Michael A.

2014-01-01

Background Extracorporeal membrane oxygenation (ECMO) provides a bridge to recovery after myocardial injury in infants and children, yet morbidity and mortality remain high. Weaning from the circuit requires adequate cardiac contractile function, which can be impaired by metabolic disturbances induced either by ischemia‐reperfusion and/or by ECMO. We tested the hypothesis that although ECMO partially ameliorates metabolic abnormalities induced by ischemia‐reperfusion, these abnormalities persist or recur with weaning. We also determined if thyroid hormone supplementation (triiodothyronine) during ECMO improves oxidative metabolism and cardiac function. Methods and Results Neonatal piglets underwent transient coronary ischemia to induce cardiac injury then were separated into 4 groups based on loading status. Piglets without coronary ischemia served as controls. We infused into the left coronary artery [2‐13C]pyruvate and [13C6, 15N]l‐leucine to evaluate oxidative metabolism by gas chromatography‐mass spectroscopy and nuclear magnetic resonance methods. ECMO improved survival, increased oxidative substrate contribution through pyruvate dehydrogenase, reduced succinate and fumarate accumulation, and ameliorated ATP depletion induced by ischemia. The functional and metabolic benefit of ECMO was lost with weaning, yet triiodothyronine supplementation during ECMO restored function, increased relative pyruvate dehydrogenase flux, reduced succinate and fumarate, and preserved ATP stores. Conclusions Although ECMO provides metabolic rest by decreasing energy demand, metabolic impairments persist, and are exacerbated with weaning. Treating ECMO‐induced thyroid depression with triiodothyronine improves substrate flux, myocardial oxidative capacity and cardiac contractile function. This translational model suggests that metabolic targeting can improve weaning. PMID:24650924

Triiodothyronine facilitates weaning from extracorporeal membrane oxygenation by improved mitochondrial substrate utilization.

PubMed

Files, Matthew D; Kajimoto, Masaki; O'Kelly Priddy, Colleen M; Ledee, Dolena R; Xu, Chun; Des Rosiers, Christine; Isern, Nancy; Portman, Michael A

2014-03-20

Extracorporeal membrane oxygenation (ECMO) provides a bridge to recovery after myocardial injury in infants and children, yet morbidity and mortality remain high. Weaning from the circuit requires adequate cardiac contractile function, which can be impaired by metabolic disturbances induced either by ischemia-reperfusion and/or by ECMO. We tested the hypothesis that although ECMO partially ameliorates metabolic abnormalities induced by ischemia-reperfusion, these abnormalities persist or recur with weaning. We also determined if thyroid hormone supplementation (triiodothyronine) during ECMO improves oxidative metabolism and cardiac function. Neonatal piglets underwent transient coronary ischemia to induce cardiac injury then were separated into 4 groups based on loading status. Piglets without coronary ischemia served as controls. We infused into the left coronary artery [2-(13)C]pyruvate and [(13)C6, (15)N]l-leucine to evaluate oxidative metabolism by gas chromatography-mass spectroscopy and nuclear magnetic resonance methods. ECMO improved survival, increased oxidative substrate contribution through pyruvate dehydrogenase, reduced succinate and fumarate accumulation, and ameliorated ATP depletion induced by ischemia. The functional and metabolic benefit of ECMO was lost with weaning, yet triiodothyronine supplementation during ECMO restored function, increased relative pyruvate dehydrogenase flux, reduced succinate and fumarate, and preserved ATP stores. Although ECMO provides metabolic rest by decreasing energy demand, metabolic impairments persist, and are exacerbated with weaning. Treating ECMO-induced thyroid depression with triiodothyronine improves substrate flux, myocardial oxidative capacity and cardiac contractile function. This translational model suggests that metabolic targeting can improve weaning.

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

PubMed

Löf, C; Patyra, K; Kero, A; Kero, J

2018-06-01

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

Thyroid function in lung cancer

PubMed Central

Ratcliffe, J G; Stack, B H R; Burt, R W; Ratcliffe, W A; Spilg, W G S; Cuthbert, J; Kennedy, R S

1978-01-01

Thyroid function was assessed at the time of initial diagnosis in 204 patients with lung cancer and compared with that of age and sex-matched patients with non-malignant lung disease. Abnormalities in thyroid function were found in 67 patients (33%). The most prevalent abnormality was a low T3 concentration; this was not associated with other clinical or biochemical evidence of hypothyroidism, but the short-term prognosis of these patients was worse than that of matched patients with lung cancer having normal T3 concentrations. Primary hypothyroidism occurred in three patients, low T4 concentrations and free thyroxine index (FTI) with normal thyrotrophin (TSH) concentrations in four patients, and moderately raised TSH with normal thyroid hormone concentrations in six patients; nine patients had a raised FTI with or without raised T4 concentration as the sole abnormality. Overall, the pattern of thyroid hormone metabolism in lung cancer was a tendency towards reduced T3 concentrations with significantly increased T4/T3 ratios and modestly increased 3,3′,5′-triiodothyronine (rT3) concentrations. The altered T4/T3 ratio was particularly noticeable in patients with anaplastic tumours of small (“oat cell”) and large cell types, but was not apparently related to detectable extrathoracic metastases. These data suggest that thyroid hormone metabolism is altered in patients with lung cancer by decreased 5′-monodeiodination of T4. The resulting low T3 concentrations and altered T4/T3 ratio may be partly responsible for the reduced ratio of androsterone to aetiocholanolone observed in lung cancer, which is known to be a poor prognostic sign. PMID:620266

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

PubMed

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

2004-06-01

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

Skeletal muscle expression of p43, a truncated thyroid hormone receptor α, affects lipid composition and metabolism.

PubMed

Casas, François; Fouret, Gilles; Lecomte, Jérome; Cortade, Fabienne; Pessemesse, Laurence; Blanchet, Emilie; Wrutniak-Cabello, Chantal; Coudray, Charles; Feillet-Coudray, Christine

2018-02-01

Thyroid hormone is a major regulator of metabolism and mitochondrial function. Thyroid hormone also affects reactions in almost all pathways of lipids metabolism and as such is considered as the main hormonal regulator of lipid biogenesis. The aim of this study was to explore the possible involvement of p43, a 43 Kda truncated form of the nuclear thyroid hormone receptor TRα1 which stimulates mitochondrial activity. Therefore, using mouse models overexpressing p43 in skeletal muscle (p43-Tg) or lacking p43 (p43-/-), we have investigated the lipid composition in quadriceps muscle and in mitochondria. Here, we reported in the quadriceps muscle of p43-/- mice, a fall in triglycerides, an inhibition of monounsaturated fatty acids (MUFA) synthesis, an increase in elongase index and an decrease in desaturase index. However, in mitochondria from p43-/- mice, fatty acid profile was barely modified. In the quadriceps muscle of p43-Tg mice, MUFA content was decreased whereas the unsaturation index was increased. In addition, in quadriceps mitochondria of p43-Tg mice, we found an increase of linoleic acid level and unsaturation index. Last, we showed that cardiolipin content, a key phospholipid for mitochondrial function, remained unchanged both in quadriceps muscle and in its mitochondria whatever the mice genotype. In conclusion, this study shows that muscle lipid content and fatty acid profile are strongly affected in skeletal muscle by p43 levels. We also demonstrate that regulation of cardiolipin biosynthesis by the thyroid hormone does not imply p43.

The Interaction Between Thyroid and Kidney Disease: An Overview of the Evidence

PubMed Central

Rhee, Connie M.

2016-01-01

Purpose of Review Hypothyroidism is highly prevalent in chronic kidney disease (CKD) patients, including those receiving dialysis. This review examines potential mechanistic links between thyroid and kidney disease; current evidence for hypothyroidism as a risk factor for de novo CKD and CKD progression; and studies of thyroid functional disorders, cardiovascular disease, and death in the CKD population. Recent Findings Epidemiologic data have demonstrated an incrementally higher prevalence of hypothyroidism with increasing severity of kidney dysfunction. Various thyroid functional test abnormalities are also commonly observed in CKD, due to alterations in thyroid hormone synthesis, metabolism, and regulation. While the mechanistic link between thyroid and kidney disease remains unclear, observational studies suggest hypothyroidism is associated with abnormal kidney structure and function. Previously thought to be a physiologic adaptation, recent studies show that hypothyroidism is associated with higher risk of cardiovascular disease and death in CKD. Summary A growing body of evidence suggests that hypothyroidism is a risk factor for incident CKD, CKD progression, and higher death risk in kidney disease patients. Rigorous studies are needed to determine impact of thyroid hormone replacement upon kidney disease progression, cardiovascular disease, and mortality, which may shed light into the causal implications of hypothyroidism in CKD. PMID:27428519

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

PubMed

Feisa, Snizhana V; Chopei, Ivan V

2018-01-01

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

Potential Influence of Selenium, Copper, Zinc and Cadmium on L-Thyroxine Substitution in Patients with Hashimoto Thyroiditis and Hypothyroidism.

PubMed

Rasic-Milutinovic, Z; Jovanovic, D; Bogdanovic, G; Trifunovic, J; Mutic, J

2017-02-01

Background: Besides genetic factors, it is known that some trace elements, as Selenium, Copper, and Zinc are essential for thyroid gland fuction and thyroid hormone metabolism. Moreover, there were some metals effect that suggested patterns associated with overt thyroid disease. Aim of study: Hashimoto thyroiditis (HT), chronic autoimune inflamation of thyroid gland with cosequtive hipothyroidism, is common disease in Serbia, and we thought it is worthwile to explore potential effects of essential and toxic metals and metalloides on thyroid function and ability to restore euthyroid status of them. Results: This cross-sectional, case-control, study investigated the status of essential elements (Selenium,Copper,and Zinc) and toxic metals and metalloides (Al, Cr, Mn, Co, As, Cd, Sb, Ba, Be, Pb and Ni) from the blood of 22 female, patients with Hashimoto thyroiditis and overt hypothyroidism, and compared it with those of 55 female healthy persons. We tried to establish the presence of any correlation between previous mentioned elements and thyroid function in hypothyroid patients and healthy participants. Conclusions: The results of our study suggested that the blood concentration of essential trace elements, especially the ratio of Copper, and Selenium may influence directly thyroid function in patients with HT and overt hypothyroidism.Thus, our findings may have implication to life-long substitution therapy in terms of l-thyroxine dose reduction. Furthermore, for the first time, our study shown potential toxic effect of Cadmium on thyroid function in HT patients, which may implicate the dose of l-thyroxine substitution. © Georg Thieme Verlag KG Stuttgart · New York.

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.

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

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.

Effects of drinking water monochloramine on lipid and thyroid metabolism in healthy men.

PubMed Central

Wones, R G; Deck, C C; Stadler, B; Roark, S; Hogg, E; Frohman, L A

1993-01-01

The purpose of this study was to determine whether a 4-week consumption of 1.5L per day of drinking water containing monochloramine at a concentration of 2 ppm (ppm = mg/L) or 15 ppm under controlled conditions would alter parameters of lipid or thyroid metabolism in healthy men. Forty-eight men completed an 8-week protocol during which diet (600 mg cholesterol per day, 40% calories as fat) and other factors known to affect lipid metabolism were controlled. During the first 4 weeks of the protocol, all subjects consumed distilled water. During the second 4 weeks, one-third of the subjects were assigned randomly to drink 1.5 L per day of water containing 2 ppm of monochloramine, to drink 1.5 L per day of water containing 15 ppm monochloramine, or to continue drinking distilled water. Four blood samples were collected from each subject at the end of each 4-week study period. Subjects drinking monochloramine at a concentration of 2 ppm showed no significant changes in total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoproteins A1, A2, or B when compared to the distilled water group. Parameters of thyroid function also were unchanged by exposure to monochloramine at this concentration. However, subjects drinking monochloramine at a concentration of 15 ppm experienced an increase in the level of apolipoprotein B. Other parameters of lipid and thyroid metabolism did not change. We conclude that consumption of drinking water containing 2 ppm of monochloramine does not alter parameters of lipid and thyroid metabolism in healthy men. Consumption of water containing 15 ppm monochloramine may be associated with increased levels of plasma apolipoprotein B. PMID:8319653

Thyroid function and cold acclimation in the hamster, Mesocricetus auratus

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

Tomasi, T.E.; Horwitz, B.A.

1987-02-01

Basal metabolic rate (BMR), thyroxine utilization rate (T4U), and triiodothyronine utilization rate (T3U) were measured in cold-acclimated (CA) and room temperature-acclimated (RA) male golden hamsters, Mesocricetus auratus. Hormone utilization rates were calculated via the plasma disappearance technique using SVI-labeled hormones and measuring serum hormone levels via radioimmunoassay. BMR showed a significant 28% increase with cold acclimation. The same cold exposure also produced a 32% increase in T4U, and a 204% increase in T3U. The much greater increase in T3U implies that previous assessments of the relationship between cold acclimation and thyroid function may have been underestimated and that cold exposuremore » induces both quantitative and qualitative changes in thyroid function. It is concluded that in the cold-acclimated state, T3U more accurately reflects thyroid function than does T4U. A mechanism for the cold-induced change in BMR is proposed.« less

Evidence of chemical stimulation of hepatic metabolism by an experimental acetanilide (FOE 5043) indirectly mediating reductions in circulating thyroid hormone levels in the male rat.

PubMed

Christenson, W R; Becker, B D; Wahle, B S; Moore, K D; Dass, P D; Lake, S G; Van Goethem, D L; Stuart, B P; Sangha, G K; Thyssen, J H

1996-02-01

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels were due to chemical induction of hepatic thyroid hormone metabolism was investigated. Treatment with FOE 5043 at a rate of 1000 ppm as a dietary admixture was found to significantly increase the clearance of [125I]T4 from the serum, suggesting an enhanced excretion of the hormone. In the liver, the activity of hepatic uridine glucuronosyl transferase, a major pathway of thyroid hormone biotransformation in the rat, increased in a statistically significant and dose-dependent manner; conversely, hepatic 5'-monodeiodinase activity trended downward with dose. Bile flow as well as the hepatic uptake and biliary excretion of [125I]T4 were increased following exposure to FOE 5043. Thyroidal function, as measured by the discharge of iodide ion in response to perchlorate, and pituitary function, as measured by the capacity of the pituitary to secrete thyrotropin in response to an exogenous challenge by hypothalamic thyrotropin releasing hormone, were both unchanged from the controlled response. These data suggest that the functional status of the thyroid and pituitary glands has not been altered by treatment with FOE 5043 and that reductions in circulating levels of T4 are being mediated indirectly through an increase in the biotransformation and excretion of thyroid hormone in the liver.

Functional hypothalamic amenorrhea: hypoleptinemia and disordered eating.

PubMed

Warren, M P; Voussoughian, F; Geer, E B; Hyle, E P; Adberg, C L; Ramos, R H

1999-03-01

Because the exact etiology of functional, or idiopathic, hypothalamic amenorrhea (FHA) is still unknown, FHA remains a diagnosis of exclusion. The disorder may be stress induced. However, mounting evidence points to a metabolic/nutritional insult that may be the primary causal factor. We explored the thyroid, hormonal, dietary, behavior, and leptin changes that occur in FHA, as they provide a clue to the etiology of this disorder. Fourteen cycling control and amenorrheic nonathletic subjects were matched for age, weight, and height. The amenorrheic subjects denied eating disorders; only after further, detailed questioning did we uncover a higher incidence of anorexia and bulimia in this group. The amenorrheic subjects demonstrated scores of abnormal eating twice those found in normal subjects (P < 0.05), particularly bulimic type behavior (P < 0.01). They also expended more calories in aerobic activity per day and had higher fiber intakes (P < 0.05); lower body fat percentage (P < 0.05); and reduced levels of free T4 (P < 0.05), free T3 (P < 0.05), and total T4 (P < 0.05), without a significant change in rT3 or TSH. Cortisol averaged higher in the amenorrheics, but not significantly, whereas leptin values were significantly lower (P < 0.05). Bone mineral density was significantly lower in the wrist (P < 0.05), with a trend to lower BMD in the spine (P < 0.08). Scores of emotional distress and depression did not differ between groups. The alterations in eating patterns, leptin levels, and thyroid function present in subjects with FHA suggest altered nutritional status and the suppression of the hypothalamic-pituitary-thyroid axis or the alteration of feedback set-points in women with FHA. Both lower leptin and thyroid levels parallel changes seen with caloric restriction. Nutritional issues, particularly dysfunctional eating patterns and changes in thyroid metabolism, and/or leptin effects may also have a role in the metabolic signals suppressing GnRH secretion and the pathogenesis of osteopenia despite normal body weight. These findings suggest that the mechanism of amenorrhea and low leptin in these women results mainly from a metabolic/nutritional insult.

Thyroid function in neonatal hypothyroidism.

PubMed

Dussault, J H; Letarte, J; Guyda, H; Laberge, C

1976-10-01

Various aspects of the thyroid function have been measured in 28 cases of neonatal hypothyroidism detected by means of the Quebec Screening Program for Metabolic Diseases. In all instances the T4 value in the blood of filter paper spot was below 2 SD of the mean of the day, averaging 0.39 +/- 0.04 ng/40 mul (mean +/- SEM) of eluted blood. The T4 value of a second similar sample averaged 0.22 +/- 0.04 ng/mul of eluted blood; this value was significantly lower than the first one. The serum T4 concentration was decreased in all the infants, whereas three of them had a normal serum TSH concentration. At least three groups of patients could be identified: (1) patients with primary thyroid failure, (2) those with secondary or tertiary hypothyrodism, and (3) those with abnormal synthesis of thyroid hormone.

Marked suppression of thyroid function in rats with gram-negative septicemia

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

Kan, M.K.; Garcia, J.F.; McRae, J.

1976-02-01

Gram-negative septicemia was induced in rats by two daily injections of fecal mixture into the thigh, after which the thyroid function was markedly suppressed for 2 days. Iodine metabolism was studied by organ radioassay and by imaging with a multiwire proportional chamber (MWPC) at various time intervals after intravenous injection of $sup 125$I. Plasma T$sub 3$, T$sub 4$, and TSH, measured by radioimmunoassays, were suppressed, as were the T$sub 3$-resin uptakes. Fractional blood supply to the thyroid glands of the infected rats, studied by the $sup 81$Rb uptake method, was also found to be markedly reduced. Sections of the thyroidmore » glands showed little structural change during the period of marked thyroid suppression. There was no biochemical evidence of renal failure in the septicemic rats. (auth)« less

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer

PubMed Central

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

2015-01-01

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

[Thyroid and pregnancy].

PubMed

Iwen, K A; Lehnert, H

2018-05-17

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

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.

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 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.

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

PubMed

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

2018-06-01

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

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

PubMed

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

2007-03-01

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

Mitochondrial Metabolism as a Treatment Target in Anaplastic Thyroid Cancer.

PubMed

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

2015-12-01

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

Does the Risk of Metabolic Syndrome Increase in Thyroid Cancer Survivors?

PubMed

Kim, Min-Hee; Huh, Jin-Young; Lim, Dong-Jun; Kang, Moo-Il

2017-07-01

The steep rise in thyroid cancer observed in recent decades has caused an increase in the population of long-term thyroid cancer survivors. Other than recurrences of cancer, the long-term health consequences of surviving thyroid cancer, particularly metabolic syndrome, have not yet been determined. The aim of this study was to estimate the risk of metabolic syndrome in thyroid cancer survivors. Population-based data from the Korean National Health and Nutrition Examination Survey (KNHANES) were used for the analysis. The data of KNHANES IV-VI from 2007-2014 were obtained. After excluding subjects who were under 19 years old, whose fasting interval was less than 8 hours, and whose data for predefined variables including metabolic syndrome components were incomplete, 34,347 subjects were analyzed. The incidence of metabolic syndrome and its components were evaluated in three groups: subjects with no history of thyroid cancer, subjects diagnosed with thyroid cancer within 3 years of the survey date, and subjects diagnosed more than 3 years before the survey date. Thyroid cancer diagnoses were made within 3 years of the survey date for 95 subjects (group 1, short-term survivors) and more than 3 years earlier than the survey date for 60 subjects (group 2, long-term survivors). Metabolic syndrome was frequently observed with clinical significance (odds ratio [OR] 1.986 [95% confidence interval [CI] 1.0-3.70], p = 0.030) in short-term survivors compared with subjects with no thyroid cancer history. Risks for having high blood pressure and high fasting glucose were estimated to be higher in the short-term survivor group (OR 2.115 [CI 1.23-3.64], p = 0.006 and OR 1.792 [CI 1.03-3.11], p = 0.038, respectively). No significant associations were noticed in the long-term survivor group when compared with the group with no thyroid cancer history. Risks for metabolic syndrome, especially high blood pressure and high fasting glucose, were increased in short-term survivors of thyroid cancer but not in long-term survivors when compared with subjects with no history of thyroid cancer.

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 ...

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.

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.

[Selenium treatment in thyreopathies].

PubMed

Sotak, Štefan

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

The effect of a ketogenic diet versus a high-carbohydrate, low-fat diet on sleep, cognition, thyroid function, and cardiovascular health independent of weight loss: study protocol for a randomized controlled trial.

PubMed

Iacovides, Stella; Meiring, Rebecca M

2018-01-23

Many physiological health benefits observed after following a ketogenic diet (KD) can be attributed to the associated weight loss. The KD has become more prominent as a popular health choice, not only in obese/overweight individuals, but also in healthy adults. The study aims to determine the effects of a KD, independent of weight loss, on various aspects of physiological health including: sleep, thyroid function, cognition, and cardio-metabolic health. The study will also aim to determine whether a change in basal metabolic rate may be associated with any changes observed. Twenty healthy men and women between 18 and 50 years of age will take part in this study. In a randomized controlled, cross-over design, participants will follow two isocaloric diets: a high-carbohydrate, low-fat diet (55% CHO, 20% fat, 25% protein) and a KD (15% CHO, 60% fat, 25% protein). Each dietary intervention will last for a minimum of 3 weeks, with a 1-week washout period in between. Before and after each diet, participants will be assessed for sleep quality, cognitive function, thyroid function, and basal metabolic rate. A blood sample will also be taken for the measurement of cardio-metabolic and immune markers. The present study will help in understanding the potential effects of a KD on aspects of physiological health in healthy adults, without the confounding factor of weight loss. The study aims to fill a significant void in the academic literature with regards to the benefits and/or risks of a KD in a healthy population, but will also explore whether diet-related metabolic changes may be responsible for the changes observed in physiological health. Pan African Clinical Trial Registry ( www.pactr.org ), trial number: PACTR201707002406306 . Registered on 20 July 2017.

[Metabolism of thyroid gland cells as affected by prolactin and emotional-physical stress].

PubMed

Strizhkov, V V

1991-01-01

A study was made of the role of prolactin (PRL) in the regulation of thyroid function in intact animals and in those exposed to stress (swimming was used as physical exercise). A single daily dose of 125 micrograms of PRL per 100 g of body mass was injected subcutaneously in 0.5 ml of saline solution during a week to male rats (control: intact rats; injection of 0.5 ml of saline solution subcutaneously). Redox enzymes; succinate dehydrogenase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, NAD.H2 and NADP.H2, ATPase and monoamine oxidase, total protein, RNA and glycogen in glandular cells were investigated histochemically 24 h after the last injection of PRL or saline, 30 min., 1, 2, 3, 5 and 7 hours after swimming or right after complete fatigue (in the presence of experimental hyperprolactinemia). A conclusion has been made that one of the most important mechanisms of the adaptive effect of PRL is its ability to suppress thyroid function, thus decreasing the metabolism level, which results in reduction of oxygen consumption and improves body tolerance to stress.

Hyperthyroidism increases brown fat metabolism in humans.

PubMed

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

2014-01-01

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

Effects of perfluorooctane sulfonate on rat thyroid hormone biosynthesis and metabolism.

PubMed

Yu, Wen-Guang; Liu, Wei; Jin, Yi-He

2009-05-01

The potential toxicity of perfluorooctane sulfonate (PFOS), an environmentally persistent organic pollutant, is of great concern. The present study examines the ability of PFOS to disturb thyroid function and the possible mechanisms involved in PFOS-induced thyroid hormone alteration. Male Sprague-Dawley rats were exposed to 1.7, 5.0, and 15.0 mg/L of PFOS in drinking water for 91 consecutive days. Serum was collected for analysis of total and free thyroxine (T4), total triiodothyronine (T3), and thyrotrophin (TSH). Thyroid and liver were removed for the measurement of endpoints closely related to thyroid hormone biosynthesis and metabolism following PFOS exposure. Determined endpoints were the messenger RNA (mRNA) levels for two isoforms of uridine diphosphoglucuronosyl transferases (UGT1A6 and UGT1A1) and type 1 deiodinase (DIO1) in liver, sodium iodide symporter (NIS), TSH receptor (TSHR), and DIO1 in thyroid as well as the activity of thyroid peroxidase (TPO). Serum total T4 level decreased significantly at all applied dosages, whereas total T3 level increased markedly only at 1.7 mg/L of PFOS. No statistically significant toxic effects of PFOS on serum TSH were observed. Hepatic UGTIA1, but not UGT1A6, mRNA was up-regulated at 5.0 and 15.0 mg/L of PFOS. Treatment with PFOS lowered hepatic DIO1 mRNA at 15.0 mg/L but increased thyroidal DIO1 mRNA dose dependently. The activity of TPO, NIS, and TSHR mRNA in thyroid were unaffected by PFOS treatment. These results indicate that increased hepatic T4 glucuronidation via UGT1A1 and increased thyroidal conversion of T4 to T3 via DIO1 were responsible in part for PFOS-induced hypothyroxinemia in rats.

Global epidemiology of hyperthyroidism and hypothyroidism.

PubMed

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

2018-05-01

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

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

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.

Thyroid hormone independent associations between serum TSH levels and indicators of bone turnover in cured patients with differentiated thyroid carcinoma.

PubMed

Heemstra, Karen A; van der Deure, Wendy M; Peeters, Robin P; Hamdy, Neveen A; Stokkel, Marcel P; Corssmit, Eleonora P; Romijn, Johannes A; Visser, Theo J; Smit, Johannes W

2008-07-01

It has been proposed that TSH has thyroid hormone-independent effects on bone mineral density (BMD) and bone metabolism. This concept is still controversial and has not been studied in human subjects in detail. We addressed this question by studying relationships between serum TSH concentration and indicators of bone turnover, after controlling for triiodothyronine (T(3)), free thyroxine (FT(4)), and non-thyroid factors relevant to BMD and bone metabolism. We also studied the contribution of the TSH receptor (TSHR)-Asp727Glu polymorphism to these relationships. We performed a cross-sectional study with 148 patients, who had been thyroidectomized for differentiated thyroid carcinoma. We measured BMD of the femoral neck and lumbar spine. FT(4), T(3), TSH, bone-specific alkaline phosphatase, procollagen type 1 aminoterminal propeptide levels, C-cross-linking terminal telopeptide of type I collagen, and urinary N-telopeptide of collagen cross-links were measured. Genotypes of the TSHR-Asp727Glu polymorphism were determined by Taqman assay. We found a significant, inverse correlation between serum TSH levels and indicators of bone turnover, which was independent of serum FT(4) and T(3) levels as well as other parameters influencing bone metabolism. We found that carriers of the TSHR-Asp727Glu polymorphism had an 8.1% higher femoral neck BMD, which was, however, no longer significant after adjusting for body mass index. We conclude that in this group of patients, serum TSH was related to indicators of bone remodeling independently of thyroid hormone levels. This may point to a functional role of the TSHR in bone in humans. Further research into this mechanism needs to be performed.

Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function.

PubMed

Bloise, Flavia F; van der Spek, Anne H; Surovtseva, Olga V; Ortiga-Carvalho, Tania Maria; Fliers, Eric; Boelen, Anita

2016-04-01

The diaphragm is the main respiratory muscle, and its function is compromised during severe illness. Altered local thyroid hormone (TH) metabolism may be a determinant of impaired muscle function during illness. This study investigates the effects of bacterial sepsis and chronic inflammation on muscle fiber type, local TH metabolism, and mitochondrial function in the diaphragm. Two mouse models were used: sepsis induced by S. pneumoniae infection or chronic inflammation induced by subcutaneous turpentine injection. In vitro, the effect of bacterial endotoxin (LPS) on mitochondrial function in C2C12 myotubes was studied. Sepsis induced a transient increase in the fiber type I profile and increased Dio3 expression while decreasing Dio2, Thra1, and Slc16a2 expression. Triiodothyronine positively regulated genes Tnni2 and Myog were decreased, indicating reduced TH signaling in the diaphragm. In contrast, chronic inflammation increased the fiber type II profile in the diaphragm as well as Thra1, Thrb1, and Myog expression while decreasing Dio3 expression, suggesting increased TH responsiveness during chronic inflammation. LPS-stimulated C2C12 myotubes showed decreased Dio2 expression and reduced basal oxygen consumption as well as non-mitochondrial respiration. The same respiratory profile was induced by Dio2 knockdown in myotubes. The in vivo results show differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, TH metabolism, and mitochondrial function, while the in vitro results point to a causal role for altered TH metabolism in functional muscle impairment. These findings may be relevant for the pathogenesis of impaired respiratory function in critical illness.

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.

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.

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

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.

Pesticides in mixture disrupt metabolic regulation: in silico and in vivo analysis of cumulative toxicity of mancozeb and imidacloprid on body weight of mice.

PubMed

Bhaskar, Rakesh; Mohanty, Banalata

2014-09-01

Pesticides acting as endocrine disrupting chemicals disrupt the homeostasis of body metabolism. The present study elucidated that the low dose coexposure of thyroid disrupting dithiocarbamate fungicide mancozeb (MCZ) and neonicotinoid insecticide imidacloprid (IMI) during lactation increased the risk of body weight gain in mice later in life. Body weight gain has been linked to pesticide-induced hypothyroidism and hyperprolactinemia and alteration of lipid profiles. In vivo results were substantiated with in silico molecular docking (MD) analysis that predicted the binding affinity of pesticides with thyroid hormone receptors (TRα and TRβ) and peroxisome proliferator activated receptor gamma (PPARγ), the major nuclear receptors of peripheral fat metabolism. Binding potency of MCZ and IMI was compared with that of T3, and its antagonist ethylene thiourea (ETU) as well as PPARγ agonist (rosiglitazone) and antagonist (HL005). MD simulation predicted that both MCZ and IMI may compete with T3 for binding with TRs. Imidazole group of IMI formed hydrogen bonds with TRs like that of ETU. MCZ may compete with rosiglitazone and HL005 for PPARγ, but IMI showed no affinity. Thus while both MCZ and IMI could disrupt the TRs functioning, MCZ alone may affect PPARγ. Coexposure of pesticides decreased the plasma thyroid hormones and increased the cholesterol and triglyceride. Individual pesticide exposure in low dose might not exert the threshold response to affect the receptors signaling further to cause hormonal/metabolic impairment. Thus, cumulative response of the mixture of thyroid disrupting pesticides can disrupt metabolic regulation through several pathways and contribute to gain in body weight. Copyright © 2014 Elsevier Inc. All rights reserved.

Physiological responses to environmental factors related to space flight

NASA Technical Reports Server (NTRS)

Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Mains, R. C.; Rahlmann, D. F.

1975-01-01

Physiological procedures and instrumentation developed for the measurement of hemodynamic and metabolic parameters during prolonged periods of weightlessness are described along with the physiological response of monkeys to weightlessness. Specific areas examined include: cardiovascular studies; thyroid function; blood oxygen transport; growth and reproduction; excreta analysis for metabolic balance studies; and electrophoretic separation of creatine phosphokinase isoenzymes in human blood.

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

[Serum cortisol level variations in thyroid diseases].

PubMed

Seck-Gassama; Ndoye, O; Mbodj, M; Akala, A; Cisse, F; Niang, M; Ndoye, R

2000-01-01

This work studies the thyroid disorders impact on adrenals glands by measuring total cortisol. Radioimmunoassays of thyroid hormones and cortisol were performed in 108 subjects, aged 20-52 years, with thyroid diseases. Our results show low cortisol values (80.35 nmol/L) in 4.77% of hyperthyroids, high values in 3.57% of hyperthyroids (1348.18 nmol/L) and 12.5% of hypothyroids (969.05 nmol/L). In hyperthyroidism, thyroid hormone stimulates the secretion of 11 ceto metabolites biologically inactive, unable to slow pituitary activity, inducing an increased production of endogene cortisol. Excessive catabolism can lead to the exhausting of overstimulated adrenal glands, and therefore to a decreased cortisol. In hypothyroidism, high cortisol results of increase cortisol half life and decrease of metabolic clearance. Control mechanisms often allow normal cortisol values. These alterations in functional activity of adrenal glands, seen in nearly 10% of these subjects, sometimes command a specific attitude in diagnosis and therapy.

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.

Vitamin D status in children with Hashimoto thyroiditis.

PubMed

Camurdan, Orhun M; Döğer, Esra; Bideci, Aysun; Celik, Nurullah; Cinaz, Peyami

2012-01-01

To investigate vitamin D status in children with Hashimoto thyroiditis. The study group consisted of 78 children recently diagnosed as Hashimoto thyroiditis and 74 subjects as the control group. Parameters of calcium metabolism, thyroid function tests, and 25-hydroxyvitamin D [25(OH)D] levels were measured. Vitamin D deficiency rate was significantly higher in the Hashimoto group compared with the control subjects (73.1% vs. 17.6%, p < 0.0001). In the Hashimoto group, mean 25(OH)D levels were significantly lower compared with the control group (31.2 +/- 11.5 versus 57.9 +/- 19.7 nmol/L, p < 0.001) and was inversely correlated with the anti-thyroid peroxidase (anti-TPO) levels (r = -0.30, p = 0.007). The higher vitamin D deficiency rates besides lower vitamin D levels in the Hashimoto group together with the inverse correlation between vitamin D and anti-TPO suggest that vitamin D deficiency may have a role in the autoimmune process in Hashimoto thyroiditis in children.

Using fractal analysis of thermal signatures for thyroid disease evaluation

NASA Astrophysics Data System (ADS)

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

2010-11-01

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

Estrogen-Related Receptor Alpha Modulates Lactate Dehydrogenase Activity in Thyroid Tumors

PubMed Central

Mirebeau-Prunier, Delphine; Le Pennec, Soazig; Jacques, Caroline; Fontaine, Jean-Fred; Gueguen, Naig; Boutet-Bouzamondo, Nathalie; Donnart, Audrey; Malthièry, Yves; Savagner, Frédérique

2013-01-01

Metabolic modifications of tumor cells are hallmarks of cancer. They exhibit an altered metabolism that allows them to sustain higher proliferation rates in hostile environment outside the cell. In thyroid tumors, the expression of the estrogen-related receptor α (ERRα), a major factor of metabolic adaptation, is closely related to the oxidative metabolism and the proliferative status of the cells. To elucidate the role played by ERRα in the glycolytic adaptation of tumor cells, we focused on the regulation of lactate dehydrogenases A and B (LDHA, LDHB) and the LDHA/LDHB ratio. Our study included tissue samples from 10 classical and 10 oncocytic variants of follicular thyroid tumors and 10 normal thyroid tissues, as well as samples from three human thyroid tumor cell lines: FTC-133, XTC.UC1 and RO82W-1. We identified multiple cis-acting promoter elements for ERRα, in both the LDHA and LDHB genes. The interaction between ERRα and LDH promoters was confirmed by chromatin immunoprecipitation assays and in vitro analysis for LDHB. Using knock-in and knock-out cellular models, we found an inverse correlation between ERRα expression and LDH activity. This suggests that thyroid tumor cells may reprogram their metabolic pathways through the up-regulation of ERRα by a process distinct from that proposed by the recently revisited Warburg hypothesis. PMID:23516535

Dental fluorosis, nutritional status, kidney damage, and thyroid function along with bone metabolic indicators in school-going children living in fluoride-affected hilly areas of Doda district, Jammu and Kashmir, India.

PubMed

Khandare, Arjun L; Gourineni, Shankar Rao; Validandi, Vakdevi

2017-10-23

A case-control study was undertaken among the school children aged 8-15 years to know the presence and severity of dental fluorosis, nutrition and kidney status, and thyroid function along with bone metabolic indicators in Doda district situated at high altitude where drinking water was contaminated and heat stress. This study included 824 participants with an age of 8-15 years. The results of the study reviled that dental fluorosis was significantly higher in affected than control area children. Urinary fluoride was significantly higher (p < 0.05) in affected children as compared to the control area school children. Nutritional status of affected children was lower than control area children. The chronic kidney damage (CKD) was higher in affected than control school children. Thyroid function was affected more in affected than control area schools. Serum creatinine, total alkaline phosphatase, parathyroid hormone, 1, 25(OH) 2 vitamin D, and osteocalcin were significantly higher in affected school children (p < 0.05) as compared to control school children, whereas there was no significant difference in triiodothyronine (T3), thyroxine (T4), and 25-OH vitamin D among the two groups. There was a significant decrease in thyroid-stimulating hormone (TSH) in the affected area school children compared to control. In conclusion, fluorotic area school children were more affected with dental fluorosis, kidney damage, along and some bone indicators as compared to control school children.

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.

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

PubMed

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

2016-03-01

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

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.

Cardiac Expression of Human Type 2 Iodothyronine Deiodinase Increases Glucose Metabolism and Protects Against Doxorubicin-induced Cardiac Dysfunction in Male Mice

PubMed Central

Hong, Eun-Gyoung; Kim, Brian W.; Young Jung, Dae; Hun Kim, Jong; Yu, Tim; Seixas Da Silva, Wagner; Friedline, Randall H.; Bianco, Suzy D.; Seslar, Stephen P.; Wakimoto, Hiroko; Berul, Charles I.; Russell, Kerry S.; Won Lee, Ki; Larsen, P. Reed; Bianco, Antonio C.

2013-01-01

Altered glucose metabolism in the heart is an important characteristic of cardiovascular and metabolic disease. Because thyroid hormones have major effects on peripheral metabolism, we examined the metabolic effects of heart-selective increase in T3 using transgenic mice expressing human type 2 iodothyronine deiodinase (D2) under the control of the α-myosin heavy chain promoter (MHC-D2). Hyperinsulinemic-euglycemic clamps showed normal whole-body glucose disposal but increased hepatic insulin action in MHC-D2 mice as compared to wild-type (WT) littermates. Insulin-stimulated glucose uptake in heart was not altered, but basal myocardial glucose metabolism was increased by more than two-fold in MHC-D2 mice. Myocardial lipid levels were also elevated in MHC-D2 mice, suggesting an overall up-regulation of cardiac metabolism in these mice. The effects of doxorubicin (DOX) treatment on cardiac function and structure were examined using M-mode echocardiography. DOX treatment caused a significant reduction in ventricular fractional shortening and resulted in more than 50% death in WT mice. In contrast, MHC-D2 mice showed increased survival rate after DOX treatment, and this was associated with a six-fold increase in myocardial glucose metabolism and improved cardiac function. Myocardial activity and expression of AMPK, GLUT1, and Akt were also elevated in MHC-D2 and WT mice following DOX treatment. Thus, our findings indicate an important role of thyroid hormone in cardiac metabolism and further suggest a protective role of glucose utilization in DOX-mediated cardiac dysfunction. PMID:23861374

Life-threatening metabolic alkalosis in Pendred syndrome

PubMed Central

Kandasamy, Narayanan; Fugazzola, Laura; Evans, Mark; Chatterjee, Krishna; Karet, Fiona

2011-01-01

Introduction Pendred syndrome, a combination of sensorineural deafness, impaired organification of iodide in the thyroid and goitre, results from biallelic defects in pendrin (encoded by SLC26A4), which transports chloride and iodide in the inner ear and thyroid respectively. Recently, pendrin has also been identified in the kidneys, where it is found in the apical plasma membrane of non-α-type intercalated cells of the cortical collecting duct. Here, it functions as a chloride–bicarbonate exchanger, capable of secreting bicarbonate into the urine. Despite this function, patients with Pendred syndrome have not been reported to develop any significant acid–base disturbances, except a single previous reported case of metabolic alkalosis in the context of Pendred syndrome in a child started on a diuretic. Case report We describe a 46-year-old female with sensorineural deafness and hypothyroidism, who presented with severe hypokalaemic metabolic alkalosis during inter-current illnesses on two occasions, and who was found to be homozygous for a loss-of-function mutation (V138F) in SLC26A4. Her acid–base status and electrolytes were unremarkable when she was well. Conclusion This case illustrates that, although pendrin is not usually required to maintain acid–base homeostasis under ambient condition, loss of renal bicarbonate excretion by pendrin during a metabolic alkalotic challenge may contribute to life-threatening acid–base disturbances in patients with Pendred syndrome. PMID:21551164

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.

Mode of carcinogenic action of pesticides inducing thyroid follicular cell tumors in rodents.

PubMed

Hurley, P M

1998-08-01

Of 240 pesticides screened for carcinogenicity by the U.S. Environmental Protection Agency Office of Pesticide Programs, at least 24 (10%) produce thyroid follicular cell tumors in rodents. Thirteen of the thyroid carcinogens also induce liver tumors, mainly in mice, and 9 chemicals produce tumors at other sites. Some mutagenic data are available on all 24 pesticides producing thyroid tumors. Mutagenicity does not seem to be a major determinant in thyroid carcinogenicity, except for possibly acetochlor; evidence is less convincing for ethylene thiourea and etridiazole. Studies on thyroid-pituitary functioning, including indications of thyroid cell growth and/or changes in thyroxine, triiodothyronine, or thyroid-stimulating hormone levels, are available on 19 pesticides. No such antithyroid information is available for etridiazole, N-octyl bicycloheptene dicarboximide, terbutryn, triadimefon, and trifluralin. Of the studied chemicals, only bromacil lacks antithyroid activity under study conditions. Intrathyroidal and extrathyroidal sites of action are found: amitrole, ethylene thiourea, and mancozeb are thyroid peroxidase inhibitors; and acetochlor, clofentezine, fenbuconazole, fipronil, pendimethalin, pentachloronitrobenzene, prodiamine, pyrimethanil, and thiazopyr seem to enhance the hepatic metabolism and excretion of thyroid hormone. Thus, with 12 pesticides that mode of action judgments can be made, 11 disrupt thyroid-pituitary homeostasis only; no chemical is mutagenic only; and acetochlor may have both antithyroid and some mutagenic activity. More information is needed to identify other potential antithyroid modes of thyroid carcinogenic action.

Thyroid function in the etiology of fatigue in breast cancer.

PubMed

Kumar, Nagi B; Fink, Angelina; Levis, Silvina; Xu, Ping; Tamura, Roy; Krischer, Jeffrey

2018-05-22

Cancer related fatigue (CRF), reported in about 90% of breast cancer patients receiving chemotherapy, and has a profound impact on physical function, psychological distress and quality of life. Although several etiological factors such as anemia, depression, chronic inflammation, neurological pathology and alterations in metabolism have been proposed, the mechanisms of CRF are largely unknown. We conducted a pilot, prospective, case-control study to estimate the magnitude of change in thyroid function in breast cancer patients from baseline to 24 months, compared to cancer-free, age-matched controls. Secondary objectives were to correlate changes in thyroid function and obesity over time with fatigue symptoms scores in this patient population. The proportion of women with breast cancer who developed subclinical or overt hypothyroidism (TSH >4.0 mIU/L) from baseline to year 1 was significantly greater compared to controls (9.6% vs. 5%; p=0.02). Subjects with breast cancer reported significantly worse fatigue symptoms than age-matched controls, as indicated by higher disruption indices (p<0.001 at baseline, p=0.02 at year 1, p=0.09 at year 2). Additionally, a significant interaction effect on disruption index score (p=0.019), general level of activity over time (p=0.006) and normal work activity (p= 0.002) was observed in the subgroup of women with BMI>30. Screening breast cancer patients for thyroid function status at baseline and serially post-treatment to evaluate the need for thyroid hormone replacement may provide for a novel strategy for treating chemotherapy-induced fatigue.

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.

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.

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.

Resistance to thyroid hormone due to defective thyroid receptor alpha.

PubMed

Moran, Carla; Chatterjee, Krishna

2015-08-01

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

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.

Lower-normal TSH is associated with better metabolic risk factors: a cross-sectional study on spanish men

USDA-ARS?s Scientific Manuscript database

Background and aims: Subclinical thyroid conditions, defined by normal thyroxin (T4) but abnormal thyroid-stimulating hormone (TSH) levels, may be associated with cardiovascular and metabolic risk. More recently, TSH levels within the normal range have been suggested to be associated with metabolic ...

New avenues for regulation of lipid metabolism by thyroid hormones and analogs

PubMed Central

Senese, Rosalba; Lasala, Pasquale; Leanza, Cristina; de Lange, Pieter

2014-01-01

Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3′-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through “non-genomic” pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism. PMID:25538628

New avenues for regulation of lipid metabolism by thyroid hormones and analogs.

PubMed

Senese, Rosalba; Lasala, Pasquale; Leanza, Cristina; de Lange, Pieter

2014-01-01

Weight loss due to negative energy balance is a goal in counteracting obesity and type 2 diabetes mellitus. The thyroid is known to be an important regulator of energy metabolism through the action of thyroid hormones (THs). The classic, active TH, 3,5,3'-triiodo-L-thyronine (T3) acts predominantly by binding to nuclear receptors termed TH receptors (TRs), that recognize TH response elements (TREs) on the DNA, and so regulate transcription. T3 also acts through "non-genomic" pathways that do not necessarily involve TRs. Lipid-lowering therapies have been suggested to have potential benefits, however, the establishment of comprehensive therapeutic strategies is still awaited. One drawback of using T3 in counteracting obesity has been the occurrence of heart rhythm disturbances. These are mediated through one TR, termed TRα. The end of the previous century saw the exploration of TH mimetics that specifically bind to TR beta in order to prevent cardiac disturbances, and TH derivatives such as 3,5-diiodo-L-thyronine (T2), that possess interesting biological activities. Several TH derivatives and functional analogs have low affinity for the TRs, and are suggested to act predominantly through non-genomic pathways. All this has opened new perspectives in thyroid physiology and TH derivative usage as anti-obesity therapies. This review addresses the pros and cons of these compounds, in light of their effects on energy balance regulation and on lipid/cholesterol metabolism.

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

Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism.

PubMed

Jansen, S W; Akintola, A A; Roelfsema, F; van der Spoel, E; Cobbaert, C M; Ballieux, B E; Egri, P; Kvarta-Papp, Z; Gereben, B; Fekete, C; Slagboom, P E; van der Grond, J; Demeneix, B A; Pijl, H; Westendorp, R G J; van Heemst, D

2015-06-19

Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism.

Subclinical hypothyroidism, lipid metabolism and cardiovascular disease.

PubMed

Delitala, Alessandro P; Fanciulli, Giuseppe; Maioli, Margherita; Delitala, Giuseppe

2017-03-01

Subclinical hypothyroidism is defined by elevated serum thyrotropin in presence of normal free thyroid hormones. Lipid metabolism is influenced by thyroid hormone and many reports showed that lipids status worsen along with TSH level. Subclinical hypothyroidism has been also linked to other cardiovascular risk factors such as alteration in blood pressure and increased atherosclerosis. Further evidences suggested that mild dysfunction of thyroid gland is associated with metabolic syndrome and heart failure. Thyrotropin level seems the best predictor of cardiovascular disease, in particular when its levels are above 10mU/L. However, despite these observations, there is no clear evidence that levothyroxine therapy in subjects with milder form of subclinical hypothyroidism could improve lipid status and the other cardiovascular risk factors. In this review, we address the effect of thyroid hormone and cardiovascular risk, with a focus on lipid metabolism. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Correlation of BAT activity with thyroid metabolic activity in patients with fibromyalgia

NASA Astrophysics Data System (ADS)

Costa, A. P. C.; Maia, J. M.; Brioschi, M. L.; Machado, J. E. M. M.

2017-03-01

The objective of this research is to correlate the brown fat activity (BAT) with the metabolic activity of thyroid in patients with fibromyalgia syndrome (FS). For the development of the research, it was select a database containing 132 patients of a thermography clinic, male and female, with age over 18 years old; where the images selected were anteroposterior orthostasis top and anteroposterior in cervical extension. In the program Flir Report, it was possible to demarcate the region of the left and right interscapular and thyroid of each patient by getting the respective temperatures, in addition to view the hyper-radiation ("signal of mantle") in the interscapular. Temperature was organized in table format, and statistical analysis was performed in the program Microcal Origin 6.0. As conclusion, it was found that the greater the metabolic activity of thyroid in patients with fibromyalgia, the greater will be the metabolic rate of brown fat (BAT).

Influence of thyroid status on hepatic alpha 1-adrenoreceptor responsiveness.

PubMed

Daza, F J; Parrilla, R; Martín-Requero, A

1997-12-01

The present work aimed to elucidate the influence of thyroid functional status on the alpha 1-adrenoreceptor-induced activation of hepatic metabolic functions. The experiments were performed in either a nonrecirculating liver perfusion system featuring continuous monitoring of portal pressure, PO2, pCa, and pH, or isolated hepatocytes from euthyroid, hyperthyroid, and hypothyroid rats. Hypothyroidism decreased the alpha 1-adrenergic stimulation of respiration, glycogen breakdown, and gluconeogenesis. These effects were accompanied by a decreased intracellular Ca2+ mobilization corroborating that those processes are regulated by the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway. Moreover, in hyperthyroid rats the alpha 1-adrenergic-induced increase in cytosolic Ca2+ was enhanced, and glucose synthesis or mobilization was not altered. The thyroid status influenced neither the alpha 1-adrenergic stimulation of vascular smooth muscle contraction nor the alpha 1-agonist-induced intracellular alkalinization and protein kinase C (PKC) activation. Thus the distinct impairment of the Ca(2+)-dependent branch of the alpha 1-adrenoreceptor signaling pathway by thyroid status provides a useful tool to investigate the role played by each signaling pathway, Ca2+ or PKC, in controlling hepatic functions.

Bioinorganic Activity of Technetium Radiopharmaceuticals.

ERIC Educational Resources Information Center

Pinkerton, Thomas C.; And Others

1985-01-01

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

SIGNIFICANCE OF EXPERIMENTAL STUDIES FOR ASSESSING ADVERSE EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS

EPA Science Inventory

The U.S. Environmental Protection Agency (US EPA) is developing an endocrine disruptor screening and testing program to detect chemicals that alter hypothalamic-pituitary-gonadal (HPG) function, estrogen, androgen, and thyroid (EAT) hormone synthesis or metabolism and induce andr...

Thyroid Disorders in Children and Adolescents with Type 1 Diabetes Mellitus in Isfahan, Iran

PubMed Central

Ardestani, Samaneh Khanpour; Keshteli, Ammar Hassanzadeh; Khalili, Noushin; Hashemipour, Mahin; Barekatain, Reihaneh

2011-01-01

Objective Studies in different populations have shown great variation in the prevalence of thyroid diseases in patients with type 1 diabetes mellitus (T1DM). Our aim was to study the prevalence of thyroid disorders such as autoimmunity of thyroid (AIT), thyroid dysfunction, and goiter in children and adolescents with T1DM, compared with age- and sex-matched healthy controls in Isfahan. Methods One hundred patients with T1DM who were referred to Isfahan Endocrine and Metabolism Research Center and 184 healthy schoolchildren matched for age and sex were included. They were examined for goiter by two endocrinologists. Thyroid function test and serum thyroid antibodies (anti-TPO Ab and anti-Tg Ab) were measured. Findings The prevalence of subclinical hypothyroidism was high in both groups (18%). T1DM patients had lower frequency of goiter (21% vs. 38%, P=0.001), and higher prevalence of positive AIT (22% vs. 8%, P=0.001), anti-TPO Ab positivity (19.3% vs. 5.3%, P=0.000), and anti-Tg Ab (11.1% vs. 6.4%, P=0.1) in comparison with the control group. Being positive for AIT in diabetic patients meant an odds ratio of 5 (CI 95%: 1.5-15.6) for thyroid dysfunction. There was no association between age, sex, duration of diabetes and HbA1C with serum anti-TPO Ab and anti-Tg Ab concentrations in this group. Conclusion Our results demonstrated the high prevalence of AIT and thyroid dysfunction in patients with T1DM. We suggest regular thyroid function and antibody testing in these patients. PMID:23056839

[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.

Influence of chronic exposure to cold environment on thyroid gland function in rabbits.

PubMed

Mustafa, S; Elgazzar, A

2014-07-01

Chronic exposure to cold can affect the thyroid gland. However, the effect on thyroid gland perfusion images and the ratio between thyroid hormones secretion were not addressed in any previous study. The present study investigates the effects of chronic cold exposure on thyroid gland function using radionuclide tracer and thyroid hormones secretion concentration. New Zealand white rabbits weighing approximately 1.8-2 kg were kept in a cold room (4°C) for 7 weeks. Thyroid scintigraphy was performed for cold exposed rabbits and a control rabbit group. Each rabbit was injected with 115 MBq (3.1 mCi) technetium-99m pertechnetate (99mTc pertechnetate). Studies were performed using Gamma camera equipped with a low energy, high resolution, pinhole collimator interfaced with a computer. Static images were acquired 20 min after administration of the radiotracer. Rabbits chronically exposed to cold had less body weights than control. Thyroid gland uptake is higher in rabbits chronically exposed to cold than controls using radionuclide perfusion study. The increase was proportional to the time period, so the increase after 7 weeks was greater than 5 weeks. There is also an increase in free triiodothyronine (FT3) and a decrease in free thyroxine (FT4) values. Our results indicate that thyroid gland uptake is higher in rabbits chronically exposed to cold than control and the increase was proportional to the duration. The decrease in rabbit body weights may be related to the increase in metabolism due to the increase of thyroid hormones. Chronic cold exposure also increased the conversion of T4 to T3, which is more potent in thermogenic effect. © Georg Thieme Verlag KG Stuttgart · New York.

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.

Correlations Between Nutrition Habits, Anxiety and Metabolic Parameters in Greek Healthy Adults.

PubMed

Lambrinakou, Stavroula; Katsa, Maria Efthymia; Zyga, Sofia; Ioannidis, Anastasios; Sachlas, Athanasios; Panoutsopoulos, Georgios; Pistikou, Anna Maria; Magana, Maria; Kougioumtzi Dimoligianni, Dafni Eleni; Kolovos, Petros; Rojas Gil, Andrea Paola

2017-01-01

Anxiety combined with nervousness and apprehension consist a focal response to different life conditions. Lifestyle habits, anxiety and biochemical markers are in a constant interaction. To investigate the prevalence of anxiety in healthy adults and its possible association with biochemical factors-lipid profile, liver markers, thyroid hormones-and lifestyle habits. Quantitative descriptive correlation study. A total of 100 healthy adults participated in the research. A specially designed questionnaire and Hamilton's scale were used. Anthropometric and biochemical analyses were performed. Overall, 61% of the participants presented moderate to very serious anxiety. The average score on the Hamilton scale was 13.82 (±9.000), with men exhibiting less stress than women. For p ≤ 0.05: Stress was positively correlated with impaired thyroid and hepatic function. Hepatic function was affected by both sugar products and water melon, which were positively correlated with total bilirubin and AST/SGOT respectively. Tomato, peppers and legumes were negatively correlated with AST/SGOT. Deep fried food was positively correlated with GGT and triglycerides. Legumes and fish were negatively correlated with CPK. Regarding the lipid metabolism, it was found that food cooked with oil was positively associated with uric acid, but non-cooked olive oil was negatively correlated with the risk for CAD. Thyroid function was negatively correlated with non-homemade food and pasta consumption and positively correlated with consumption of whole grains and green tea. Participants with subclinical hypothyroidism seemed to consume less vitamin B12, folic acid and vegetables. No direct correlation between lifestyle habits and anxiety was found. Nevertheless, eating habits influenced biochemical markers-especially the thyroid hormones-which may be indirectly responsible for anxiety and related moods.

The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.

PubMed

Faunes, Fernando; Gundermann, Daniel G; Muñoz, Rosana; Bruno, Renzo; Larraín, Juan

2017-05-15

Metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. It has been very well established that amphibian metamorphosis is mainly controlled by Thyroid Hormone (TH). Here, we show that the heterochronic gene Lin28 is downregulated during Xenopus laevis metamorphosis. Lin28 overexpression before activation of TH signaling delays metamorphosis and inhibits the expression of TH target genes. The delay in metamorphosis is rescued by incubation with exogenous TH, indicating that Lin28 works upstream or parallel to TH. High-throughput analyses performed before any delay on metamorphosis or change in TH signaling showed that overexpression of Lin28 reduces transcript levels of several hormones secreted by the pituitary, including the Thyroid-Stimulating Hormone (TSH), and regulates the expression of proteins involved in TH transport, metabolism and signaling, showing that Lin28 disrupts TH function at different levels. Our data demonstrates that the role of Lin28 in controlling developmental transitions is evolutionary conserved and establishes a functional interaction between Lin28 and thyroid hormone function introducing a new regulatory step in perinatal development with implications for our understanding of endocrine disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Different effects of fenofibrate on metabolic and cardiovascular risk factors in mixed dyslipidemic women with normal thyroid function and subclinical hypothyroidism.

PubMed

Krysiak, Robert; Gilowski, Wojciech; Szkrobka, Witold; Okopien, Bogusław

2014-12-01

Subclinical hypothyroidism is suggested to increase cardiovascular risk. No previous study compared the effect of any fibrate on plasma levels of lipids and other cardiovascular risk factors in patients with different thyroid function status. The study included three age-, weight- and lipid-matched groups of women with mixed dyslipidemia in different thyroid function status: patients with untreated subclinical hypothyroidism (group 1, n = 18), women with treated hypothyroidism (group 2, n = 15), and subjects without thyroid disorders (group 3, n = 19). Plasma lipids, glucose homeostasis markers, as well as plasma levels of uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine, and fibrinogen were determined before and after 12 weeks of fenofibrate therapy. Despite similar plasma lipid levels, mixed dyslipidemic patients with untreated hypothyroidism had decreased insulin sensitivity, as well as higher circulating levels of uric acid, hsCRP, homocysteine, and fibrinogen in comparison with the other groups. The effect of fenofibrate on plasma lipids and, with the exception of homocysteine, on circulating levels of all investigated risk factors was stronger in patients from groups 2 and 3 than in patients from group 1. The obtained results indicate that the effect of fenofibrate on plasma lipids and circulating levels of cardiovascular risk factors is partially related to thyroid function. They also suggest that to improve the strength of fibrate action in dyslipidemic patients with subclinical hypothyroidism, they should be administered together with L-thyroxine. © 2014 John Wiley & Sons Ltd.

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 effects of experimentally induced hyperthyroidism on the diving physiology of harbor seals (Phoca vitulina)

PubMed Central

Weingartner, Gundula M.; Thornton, Sheila J.; Andrews, Russel D.; Enstipp, Manfred R.; Barts, Agnieszka D.; Hochachka, Peter W.

2012-01-01

Many phocid seals are expert divers that remain submerged longer than expected based on estimates of oxygen storage and utilization. This discrepancy is most likely due to an overestimation of diving metabolic rate. During diving, a selective redistribution of blood flow occurs, which may result in reduced metabolism in the hypoperfused tissues and a possible decline in whole-body metabolism to below the resting level (hypometabolism). Thyroid hormones are crucial in regulation of energy metabolism in vertebrates and therefore their control might be an important part of achieving a hypometabolic state during diving. To investigate the effect of thyroid hormones on diving physiology of phocid seals, we measured oxygen consumption, heart rate, and post-dive lactate concentrations in five harbor seals (Phoca vitulina) conducting 5 min dives on command, in both euthyroid and experimentally induced hyperthyroid states. Oxygen consumption during diving was significantly reduced (by 25%) in both euthyroid and hyperthyroid states, confirming that metabolic rate during diving falls below resting levels. Hyperthyroidism increased oxygen consumption (by 7–8%) when resting in water and during diving, compared with the euthyroid state, illustrating the marked effect of thyroid hormones on metabolic rate. Consequently, post-dive lactate concentrations were significantly increased in the hyperthyroid state, suggesting that the greater oxygen consumption rates forced seals to make increased use of anaerobic metabolic pathways. During diving, hyperthyroid seals also exhibited a more profound decline in heart rate than seals in the euthyroid state, indicating that these seals were pushed toward their aerobic limit and required a more pronounced cardiovascular response. Our results demonstrate the powerful role of thyroid hormones in metabolic regulation and support the hypothesis that thyroid hormones play a role in modulating the at-sea metabolism of phocid seals. PMID:23060807

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

Medical comorbidity in polycystic ovary syndrome with special focus on cardiometabolic, autoimmune, hepatic and cancer diseases: an updated review.

PubMed

Glintborg, Dorte; Andersen, Marianne

2017-12-01

Polycystic ovary syndrome (PCOS) is defined by hyperandrogenism, irregular menses and polycystic ovaries when other causes are excluded. The possible implication of increased morbidity in PCOS for screening and follow-up is uncertain and is reviewed in this article. The increased risk of type 2 diabetes and cardiovascular disease in PCOS is closely associated with BMI. Women with PCOS should be screened for the elements of the metabolic syndrome upon diagnosis. Measurement of HbA1c and the lipid accumulation product could be important tools to differentiate women with high metabolic risk. The immune function in PCOS is impaired with increased secretion of autoantibodies and increased risk of type 1 diabetes, asthma and thyroid disease. The occurrence of thyroid disease could be modified by BMI and D-vitamin status. Screening for diabetes and thyroid disease is part of routine evaluation for endocrine diseases at baseline in PCOS, whereas the necessity of prospective screening for thyroid disease awaits future studies. Especially obese women with PCOS are at an increased risk of nonalcoholic fatty liver disease, gall bladder disease and endometrial cancer. Recent data support that screening and follow-up in patients with PCOS should be stratified according to BMI.

[Clinical case of acute renal failure revealing an autoimmune hypothyroidism].

PubMed

Montasser, Dina Ibrahim; Hassani, Mohamed; Zajjari, Yassir; Bahadi, Abdelali; Alayoud, Ahmed; Hamzi, Amine; Hassani, Kawtar; Moujoud, Omar; Asseraji, Mohamed; Kadiri, Moncif; Aatif, Taoufik; El Kabbaj, Driss; Benyahia, Mohamed; Allam, Mustapha; Akhmouch, Ismail; Oualim, Zouhir

2010-04-01

Although the clinic picture is often indicative of muscle manifestations in patients with hypothyroidism, signs and symptoms of this condition are variable from simple elevation of serum muscle enzymes with myalgia, muscle weakness, cramps to rhabdomyolysis with acute renal failure which remains a rare event. Thyroid hormones affect the function of almost every body organ, and thyroid dysfunction produces a wide range of metabolic disturbances. Hypothyroidism is associated with significant effects on the kidney which the pathophysiology seems to be multifactorial, but the exact mechanisms remain poorly understood. Hypothyroidism as a cause of renal impairment is usually overlooked, leading to unnecessary diagnostic procedures. The main objective of our observation is to report a case of acute renal failure revealing an autoimmune hypothyroidism in which thyroid hormone substitution led to a significant improvement in muscular, thyroid and renal disorders. Copyright 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Extracellular ATP is Differentially Metabolized on Papillary Thyroid Carcinoma Cells Surface in Comparison to Normal Cells.

PubMed

Bertoni, Ana Paula Santin; de Campos, Rafael Paschoal; Tsao, Marisa; Braganhol, Elizandra; Furlanetto, Tania Weber; Wink, Márcia Rosângela

2018-02-17

The incidence of differentiated thyroid cancer has been increasing. Nevertheless, its molecular mechanisms are not well understood. In recent years, extracellular nucleotides and nucleosides have emerged as important modulators of tumor microenvironment. Extracellular ATP is mainly hydrolyzed by NTPDase1/CD39 and NTPDase2/CD39L1, generating AMP, which is hydrolyzed by ecto-5'-nucleotidase (CD73) to adenosine, a possible promoter of tumor growth and metastasis. There are no studies evaluating the expression and functionality of these ectonucleotidases on normal or tumor-derived thyroid cells. Thus, we investigated the ability of thyroid cancer cells to hydrolyze extracellular ATP generating adenosine, and the expression of ecto-enzymes, as compared to normal cells. We found that normal thyroid derived cells presented a higher ability to hydrolyze ATP and higher mRNA levels for ENTDP1-2, when compared to papillary thyroid carcinoma (PTC) derived cells, which had a higher ability to hydrolyze AMP and expressed CD73 mRNA and protein at higher levels. In addition, adenosine induced an increase in proliferation and migration in PTC derived cells, whose effect was blocked by APCP, a non-hydrolysable ADP analogue, which is an inhibitor of CD73. Taken together, these results showed that thyroid follicular cells have a functional purinergic signaling. The higher expression of CD73 in PTC derived cells might favor the accumulation of extracellular adenosine in the tumor microenvironment, which could promote tumor progression. Therefore, as already shown for other tumors, the purinergic signaling should be considered a potential target for thyroid cancer management and treatment.

Effect of Short-Term Thyroxine Administration on Energy Metabolism and Mitochondrial Efficiency in Humans

PubMed Central

Johannsen, Darcy L.; Galgani, Jose E.; Johannsen, Neil M.; Zhang, Zhengyu; Covington, Jeffrey D.; Ravussin, Eric

2012-01-01

The physiologic effects of triiodothyronine (T3) on metabolic rate are well-documented; however, the effects of thyroxine (T4) are less clear despite its wide-spread use to treat thyroid-related disorders and other non-thyroidal conditions. Here, we investigated the effects of acute (3-day) T4 supplementation on energy expenditure at rest and during incremental exercise. Furthermore, we used a combination of in situ and in vitro approaches to measure skeletal muscle metabolism before and after T4 treatment. Ten healthy, euthyroid males were given 200 µg T4 (levothyroxine) per day for 3 days. Energy expenditure was measured at rest and during exercise by indirect calorimetry, and skeletal muscle mitochondrial function was assessed by in situ ATP flux (31P MRS) and in vitro respiratory control ratio (RCR, state 3/state 4 rate of oxygen uptake using a Clark-type electrode) before and after acute T4 treatment. Thyroxine had a subtle effect on resting metabolic rate, increasing it by 4% (p = 0.059) without a change in resting ATP demand (i.e., ATP flux) of the vastus lateralis. Exercise efficiency did not change with T4 treatment. The maximal capacity to produce ATP (state 3 respiration) and the coupled state of the mitochondria (RCR) were reduced by approximately 30% with T4 (p = 0.057 and p = 0.04, respectively). Together, the results suggest that T4, although less metabolically active than T3, reduces skeletal muscle efficiency and modestly increases resting metabolism even after short-term supplementation. Our findings may be clinically relevant given the expanding application of T4 to treat non-thyroidal conditions such as obesity and weight loss. PMID:22844412

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.

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.

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.

Prevalence of thyroid dysfunction in untreated cancer patients: a cross-sectional study.

PubMed

Dişel, Umut; Beşen, Ayberk; Karadeniz, Cemile; Mertsoylu, Hüseyin; Sezer, Ahmet; Köse, Fatih; TanerSümbül, Ahmet; Gürkut, Ozlem; Muallaoğlu, Sadik; Abali, Hüseyin; Ozyilkan, Ozgür

2012-12-01

The relationship between thyroid disease and cancer (and cancer therapies) has been under investigation for years. Factors that increase the risk for thyroid disease include iodine deficiency, autoimmune disorders, old age, and pregnancy. The screening policy for thyroid disease in the healthy population is not precisely defined, and the frequency of thyroid dysfunction in untreated cancer patients has not been investigated in any great detail. This study was designed to compare the prevalence of thyroid dysfunction in 457 untreated cancer patients at the time of initial diagnosis to that of 373 age- and sex-matched subjects who were healthy and cancer-free (control group). Thyroid dysfunction was found in 29.5 % (135/457) of the cancer patients, while only 15.4 % (56/373) of the control group had thyroid dysfunction (p = 0.0001). The most prevalent abnormality was euthyroid sick syndrome (14.0 %, 64/457). Overt and subclinical hyperthyroidism and overt hypothyroidism were observed more frequently in cancer patients than the control group, and these differences were all statistically significant. Thyroid dysfunction was more frequent in patients with poor performance scores and those over the age of 50 years. These data indicate that alterations in thyroid hormone metabolism are twice as common in patients with untreated cancer than in control subjects. Those alterations may lead to delayed diagnosis, suboptimal treatment, and a poorer prognosis. In all, this study suggests that screening with thyroid function tests is strongly recommended in all newly diagnosed cancer patients.

Thyroid Hormone Regulation of Metabolism

PubMed Central

Mullur, Rashmi; Liu, Yan-Yun

2014-01-01

Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

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.

Effects of long-term intraperitoneal injection of thyrotropin-releasing hormone (TRH) on aging- and obesity-related changes in body weight, lipid metabolism, and thyroid functions.

PubMed

Pierpaoli, Walter; Lesnikov, Vladimir A

2011-02-01

Adult adipose mice, high fat diet-fed (HFD) mice, anterior hypothalamus-lesioned obese mice and genetically obese mice, were injected daily with thyrotropin releasing hormone (TRH). The treatment provoked a mobilization of triglycerides in the peripheral blood, a decrease of leptin and a loss of body weight. The weight loss did not depend on TSH-mediated stimulation of thyroid hormone secretion with consequent metabolic hyperthyroidism. The levels of blood cholesterol were not affected or even suppressed. Even at a very high dosage TRH did not affect the obesity of genetically obese mice. The ubiquitous tripeptide TRH may thus constitute a key element in the hormone-controlled regulation of body weight and fat stores in the adult and aging body.

Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

PubMed Central

Rapoport, Basil

2013-01-01

Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.” Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction. Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo. Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves' disease. These changes involve differences in TSAb versus TBAb concentrations, affinities and/or potencies in individual patients. Thus, anti-thyroid drugs or suppression/hemodilution in pregnancy reduce initially low TSAb levels even further, leading to TBAb dominance. In contrast, TSAb emergence after LT4 administration may be sufficient to counteract TBAb inhibition. The occurrence of “switching” emphasizes the need for careful patient monitoring and management. Finally, whole genome screening of relatively rare “switch” patients and appropriate Graves' and Hashimoto's controls could provide unexpected and valuable information regarding the basis for thyroid autoimmunity. PMID:23025526

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.

Metabolic changes associated with papillary thyroid carcinoma: A nuclear magnetic resonance-based metabolomics study.

PubMed

Li, Yanyun; Chen, Minjian; Liu, Cuiping; Xia, Yankai; Xu, Bo; Hu, Yanhui; Chen, Ting; Shen, Meiping; Tang, Wei

2018-05-01

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer. Nuclear magnetic resonance (NMR)‑based metabolomic technique is the gold standard in metabolite structural elucidation, and can provide different coverage of information compared with other metabolomic techniques. Here, we firstly conducted NMR based metabolomics study regarding detailed metabolic changes especially metabolic pathway changes related to PTC pathogenesis. 1H NMR-based metabolomic technique was adopted in conju-nction with multivariate analysis to analyze matched tumor and normal thyroid tissues obtained from 16 patients. The results were further annotated with Kyoto Encyclopedia of Genes and Genomes (KEGG), and Human Metabolome Database, and then were analyzed using modules of pathway analysis and enrichment analysis of MetaboAnalyst 3.0. Based on the analytical techniques, we established the models of principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS‑DA) which could discriminate PTC from normal thyroid tissue, and found 15 robust differentiated metabolites from two OPLS-DA models. We identified 8 KEGG pathways and 3 pathways of small molecular pathway database which were significantly related to PTC by using pathway analysis and enrichment analysis, respectively, through which we identified metabolisms related to PTC including branched chain amino acid metabolism (leucine and valine), other amino acid metabolism (glycine and taurine), glycolysis (lactate), tricarboxylic acid cycle (citrate), choline metabolism (choline, ethanolamine and glycerolphosphocholine) and lipid metabolism (very-low‑density lipoprotein and low-density lipoprotein). In conclusion, the PTC was characterized with increased glycolysis and inhibited tricarboxylic acid cycle, increased oncogenic amino acids as well as abnormal choline and lipid metabolism. The findings in this study provide new insights into detailed metabolic changes of PTC, and hold great potential in the treatment of PTC.

Multiple metals predict prolactin and thyrotropin (TSH) levels in men

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

Meeker, John D., E-mail: meekerj@umich.edu; Rossano, Mary G.; Protas, Bridget

2009-10-15

Exposure to a number of metals can affect neuroendocrine and thyroid signaling, which can result in adverse effects on development, behavior, metabolism, reproduction, and other functions. The present study assessed the relationship between metal concentrations in blood and serum prolactin (PRL) and thyrotropin (TSH) levels, markers of dopaminergic, and thyroid function, respectively, among men participating in a study of environmental influences on male reproductive health. Blood samples from 219 men were analyzed for concentrations of 11 metals and serum levels of PRL and TSH. In multiple linear regression models adjusted for age, BMI and smoking, PRL was inversely associated withmore » arsenic, cadmium, copper, lead, manganese, molybdenum, and zinc, but positively associated with chromium. Several of these associations (Cd, Pb, Mo) are consistent with limited studies in humans or animals, and a number of the relationships (Cr, Cu, Pb, Mo) remained when additionally considering multiple metals in the model. Lead and copper were associated with non-monotonic decrease in TSH, while arsenic was associated with a dose-dependent increase in TSH. For arsenic these findings were consistent with recent experimental studies where arsenic inhibited enzymes involved in thyroid hormone synthesis and signaling. More research is needed for a better understanding of the role of metals in neuroendocrine and thyroid function and related health implications.« less

Bone disease in thyrotoxicosis.

PubMed

Reddy, P Amaresh; Harinarayan, C V; Sachan, Alok; Suresh, V; Rajagopal, G

2012-03-01

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis.

Effects of Chronic Exposure to an Environmentally Relevant Mixture of Brominated Flame Retardants on the Reproductive and Thyroid System in Adult Male Rats

PubMed Central

Ernest, Sheila R.; Wade, Michael G.; Lalancette, Claudia; Ma, Yi-Qian; Berger, Robert G.; Robaire, Bernard; Hales, Barbara F.

2012-01-01

Brominated flame retardants (BFRs) are incorporated into a wide variety of consumer products, are readily released into home and work environments, and are present in house dust. Studies using animal models have revealed that exposure to polybrominated diphenyl ethers (PBDEs) may impair adult male reproductive function and thyroid hormone physiology. Such studies have generally characterized the outcome of acute or chronic exposure to a single BFR technical mixture or congener but not the impact of environmentally relevant BFR mixtures. We tested whether exposure to the BFRs found in house dust would have an adverse impact on the adult male rat reproductive system and thyroid function. Adult male Sprague Dawley rats were exposed to a complex BFR mixture composed of three commercial brominated diphenyl ethers (52.1% DE-71, 0.4% DE-79, and 44.2% decaBDE-209) and hexabromocyclododecane (3.3%), formulated to mimic the relative congener levels in house dust. BFRs were delivered in the diet at target doses of 0, 0.02, 0.2, 2, or 20 mg/kg/day for 70 days. Compared with controls, males exposed to the highest dose of BFRs displayed a significant increase in the weights of the kidneys and liver, which was accompanied by induction of CYP1A and CYP2B P450 hepatic drug–metabolizing enzymes. BFR exposure did not affect reproductive organ weights, serum testosterone levels, testicular function, or sperm DNA integrity. The highest dose caused thyroid toxicity as indicated by decreased serum thyroxine (T4) and hypertrophy of the thyroid gland epithelium. At lower doses, the thickness of the thyroid gland epithelium was reduced, but no changes in hormone levels (T4 and thyroid-stimulating hormone) were observed. Thus, exposure to BFRs affected liver and thyroid physiology but not male reproductive parameters. PMID:22387749

Flavonoid Rutin Increases Thyroid Iodide Uptake in Rats

PubMed Central

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

2013-01-01

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

METABOLISM OF PBDES IN FATHEAD MINNOWS (PIMEPHALES PROMELAS) AND EFFECTS ON THYROID REGULATION

EPA Science Inventory

PBDE effects on fish and other wildlife continue to be poorly understood, and this research will contribute to filling this data gap. It will increase our understanding of PBDE metabolic pathways and mechanisms of thyroid dysfunction in fish exposed to this important class of ...

METABOLISM OF BROMINATED FLAME RETARDANTS IN HUMAN ASTROCYTES AND EFFECTS ON THYROID HORMONE HOMEOSTASIS

EPA Science Inventory

In this proposed study, hydroxylated PBDEs and brominated phenols likely will be formed in astrocytes as a result of cytochrome p450-mediated metabolism. Previous studies have shown that polychlorinated biphenyls (PCBs) affect the regulation of thyroid hormones at the bloo...

[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.

[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.

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.

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-stimulated increases in PGC-1α and UCP2 promote life history-specific endocrine changes and maintain a lipid-based metabolism

PubMed Central

Soñanez-Organis, José G.; Godoy-Lugo, José Arquimides; Horin, Lillian J.; Crocker, Daniel E.; Ortiz, Rudy M.

2017-01-01

Thyroid hormones (THs) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating THs that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity, suggesting that in mammals naturally adapted to prolonged fasting, THs are necessary to support metabolism. However, the functional relevance of this physiological paradox has remained largely unexplored, especially as it relates to the regulation of lipids. To address the hypothesis that TSH-mediated increase in THs contributes to lipid metabolism, we infused early and late-fasted pups with TSH and measured several key genes in adipose and muscle, and plasma hormones associated with regulation of lipid metabolism. TSH infusion increased the mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) more than 6.5-fold at 60 min in muscle, and expression of uncoupling protein 2 (UCP2) more than 27-fold during the early fast at 60 min, in adipose. Additionally, during the late fast period, the protein content of adipose CD36 increased 1.1-fold, and plasma nonesterified fatty acid (NEFA) concentrations increased 25% at 120 min, with NEFA levels returning to baseline after 24 h. We show that the TSH-induced increases in THs in fasting pups are functional and likely contribute to the maintenance of a lipid-based metabolism. PMID:27903512

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.

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...

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.

The Role of Thyroid Hormones as Inductors of Oxidative Stress and Neurodegeneration

PubMed Central

Villanueva, I.; Alva-Sánchez, C.; Pacheco-Rosado, J.

2013-01-01

Reactive oxygen species (ROS) are oxidizing agents amply implicated in tissue damage. ROS production is inevitably linked to ATP synthesis in most cells, and the rate of production is related to the rate of cell respiration. Multiple antioxidant mechanisms limit ROS dispersion and interaction with cell components, but, when the balance between ROS production and scavenging is lost, oxidative damage develops. Many traits of aging are related to oxidative damage by ROS, including neurodegenerative diseases. Thyroid hormones (THs) are a major factor controlling metabolic and respiratory rates in virtually all cell types in mammals. The general metabolic effect of THs is a relative acceleration of the basal metabolism that includes an increase of the rate of both catabolic and anabolic reactions. THs are related to oxidative stress not only by their stimulation of metabolism but also by their effects on antioxidant mechanisms. Thyroid dysfunction increases with age, so changes in THs levels in the elderly could be a factor affecting the development of neurodegenerative diseases. However, the relationship is not always clear. In this review, we analyze the participation of thyroid hormones on ROS production and oxidative stress, and the way the changes in thyroid status in aging are involved in neurodegenerative diseases. PMID:24386502

Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study.

PubMed

van den Berg, Eline H; van Tienhoven-Wind, Lynnda J N; Amini, Marzyeh; Schreuder, Tim C M A; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P F

2017-02-01

Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects. The study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5-4.0mU/L, free thyroxine (FT4) 11-19.5pmol/L and free triiodothyronine (FT3) 4.4-6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A P<0.01 was considered significant. FLI≥60 was found in 4274 (21.1%) of 20,289 individuals (62.1% male, median age 46years) with increased prevalence of MetS (P<0.0001). In age- and sex-adjusted analysis FLI≥60 was independently associated with a higher FT3 (OR 1.34, 95% CI 1.29-1.39, per SD increment, P<0.0001) and a lower FT4 (OR 0.73, 95% CI 0.70-0.75, P<0.0001) but not by TSH. The strongest association was found for the FT3/FT4 ratio (OR 1.44, 95% CI 1.39-1.49, P<0.0001). These associations remained similar after additional adjustment for the presence of MetS. In subjects with enlarged waist circumference, TSH and FT4 were lower while FT3 was higher, resulting in an increased FT3/FT4 ratio (P<0.0001). Euthyroid subjects with suspected NAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Values of iodine metabolism biomarkers in assessing the iodine nutrition status in surgically treated patients with thyroid disease.

PubMed

Han, Jian-hua; Wu, Lian; Yu, Song-lin; Fang, Hui-ling; Kamg, Wei-ming; Cheng, Xin-qi; Lu, Jie; Yu, Jian-chun; Qiu, Ling

2015-04-01

To assess the clinical application value of iodine metabolism biomarkers in assessing iodine nutrition status in surgically treated patients with thyroid disease. Blood,morning urine and 24-hour urine samples were collected in 31 healthy volunteers and in 30 surgically treated patients with thyroid disease before and after surgery. Iodine concentration was analyzed by inductively coupled plasma mass spectrometry. The iodine metabolism biomarkers including serum iodine (SI), morning urine iodine(UI), morning urine iodine/urine creatinine ratio (UI/UCr), 24-hour urine iodine (24 h UI), and 24-hour urine iodine excretion (24 h UIE) were evaluated in these two groups. In addition, the validation coincidence rate of iodine metabolism biomarkers in healthy volunteers to different reference ranges including World Health Organization, Mayo Clinic, and Quest Diagnostics were calculated. The UI/UCr ratio of pre-operative thyroid disease patients was significantly lower than that of healthy volunteers (P<0.05), while the other biomarkers showed no significant differences (all P>0.05) between these two groups. The SI, UI ,and 24 h UI in postoperative thyroid disease patients were significantly higher than those of the pre-operative patients (all P<0.05). Though the medians of all biomarkers in healthy volunteers were within the reference ranges,only the validation coincidence rates of SI, UI, and UI/UCr in the 41-70-year populations were over than 90% according to Mayo Clinic; furthermore, the area under the receiver operating characteristic curve about UI/UCr ratio (0.737) was the biggest within the iodine metabolism biomarkers. The UI/UCr ratio may be used for iodine nutrition evaluation in surgically treated patients with thyroid disease.

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.

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

PubMed

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

1997-01-01

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

Bone disease in thyrotoxicosis

PubMed Central

Reddy, P. Amaresh; Harinarayan, C. V.; Sachan, Alok; Suresh, V.; Rajagopal, G.

2012-01-01

Thyrotoxicosis, a clinical syndrome characterized by manifestations of excess thyroid hormone, is one of the commonly-recognised conditions of the thyroid gland. Thyrotoxicosis causes acceleration of bone remodelling and though it is one of the known risk factors for osteoporosis, the metabolic effects of thyroxine on bone are not well discussed. Studies show that thyroid hormones have effects on bone, both in vitro and in vivo. Treatment of thyrotoxicosis leads to reversal of bone loss and metabolic alterations, and decreases the fracture risk. There are limited studies in India as to whether these changes are fully reversible. In this review we discuss about the effects of thyrotoxicosis (endogenous and exogenous) on bone and mineral metabolism, effects of subclinical thyrotoxicosis on bone and mineral metabolism and effects of various forms of treatment in improving the bone mineral density in thyrotoxicosis. PMID:22561612

Thyroid Hormones and Changes in Body Weight and Metabolic Parameters in Response to Weight-Loss Diets: The POUNDS LOST Trial

PubMed Central

Liu, Gang; Liang, Liming; Bray, George A.; Qi, Lu; Hu, Frank B.; Rood, Jennifer; Sacks, Frank M.; Sun, Qi

2017-01-01

Background The role of thyroid hormones in diet-induced weight loss and subsequent weight regain is largely unknown. Objectives To examine the associations between thyroid hormones and changes in body weight and resting metabolic rate (RMR) in a diet-induced weight-loss setting. Subjects/Methods Data analysis was conducted among 569 overweight and obese participants aged 30–70 years with normal thyroid function participating in the 2-year 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. Results 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 6–24 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 ± standard error 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). Conclusions 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. PMID:28138133

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

PubMed Central

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

2017-01-01

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

Tiratricol-induced periodic paralysis: a review of nutraceuticals affecting thyroid function.

PubMed

Cohen-Lehman, Janna; Charitou, Marina M; Klein, Irwin

2011-01-01

To review the potential adverse effects of thyroid hormone-based nutraceuticals and describe a case of thyrotoxic periodic paralysis (TPP) after abuse of a dietary supplement containing 3,5,3'-triiodothyroacetic acid (tiratricol). We review the literature on potential dangers and therapeutic misadventures of thyroid hormone-based nutraceuticals and present the clinical, laboratory, and radiologic data of a bodybuilder in whom hypokalemic TPP developed after use of "Triax Metabolic Accelerator". A 23-year-old white man developed lower extremity paralysis, diaphoresis, and palpitations in the setting of low serum potassium levels. Laboratory results showed suppressed thyroid-stimulating hormone, low levels of free and total thyroxine, low total triiodothyronine level, and very low 24-hour radioiodine uptake. The patient ultimately admitted to taking a supplement containing tiratricol for approximately 2 months, and hypokalemic TPP was diagnosed. He was treated with potassium supplementation and a β-adrenergic blocking agent, which completely resolved his symptoms. Results of thyroid function tests normalized or approached normal 1 week after hospitalization, and future use of dietary supplements was strongly discouraged. Despite 2 warnings by the US Food and Drug Administration, products containing tiratricol are still available for sale on the Internet. This report illustrates both an unusual adverse effect of a nutraceutical containing tiratricol and the importance of educating our patients about the risks versus benefits of using these widely available but loosely regulated products.

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

PubMed

Pavelka, S

2014-01-01

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

Update on 3-iodothyronamine and its neurological and metabolic actions.

PubMed

Zucchi, Riccardo; Accorroni, Alice; Chiellini, Grazia

2014-01-01

3-iodothyronamine (T1AM) is an endogenous amine, that has been detected in many rodent tissues, and in human blood. It has been hypothesized to derive from thyroid hormone metabolism, but this hypothesis still requires validation. T1AM is not a ligand for nuclear thyroid hormone receptors, but stimulates with nanomolar affinity trace amine-associated receptor 1 (TAAR1), a G protein-coupled membrane receptor. With a lower affinity it interacts with alpha2A adrenergic receptors. Additional targets are represented by apolipoprotein B100, mitochondrial ATP synthase, and membrane monoamine transporters, but the functional relevance of these interactions is still uncertain. Among the effects reported after administration of exogenous T1AM to experimental animals, metabolic and neurological responses deserve special attention, because they were obtained at low dosages, which increased endogenous tissue concentration by about one order of magnitude. Systemic T1AM administration favored fatty acid over glucose catabolism, increased ketogenesis and increased blood glucose. Similar responses were elicited by intracerebral infusion, which inhibited insulin secretion and stimulated glucagon secretion. However, T1AM administration increased ketogenesis and gluconeogenesis also in hepatic cell lines and in perfused liver preparations, providing evidence for a peripheral action, as well. In the central nervous system, T1AM behaved as a neuromodulator, affecting adrenergic and/or histaminergic neurons. Intracerebral T1AM administration favored learning and memory, modulated sleep and feeding, and decreased the pain threshold. In conclusion T1AM should be considered as a component of thyroid hormone signaling and might play a significant physiological and/or pathophysiological role. T1AM analogs have already been synthetized and their therapeutical potential is currently under investigation. 3-iodothyronamine (T1AM) is a biogenic amine whose structure is closely related to that of thyroid hormone (3,5,3'-triiodothyronine, or T3). The differences with T3 are the absence of the carboxylate group and the substitution of iodine with hydrogen in 5 and 3' positions (Figure 1). In this paper we will review the evidence supporting the hypothesis that T1AM is a chemical messenger, namely that it is an endogenous substance able to interact with specific receptors producing significant functional effects. Special emphasis will be placed on neurological and metabolic effects, which are likely to have physiological and pathophysiological importance.

Soy protein diet alters expression of hepatic genes regulating fatty acid and thyroid hormone metabolism in the male rat

USDA-ARS?s Scientific Manuscript database

We determined effects of soy protein (SPI) and the isoflavone genistein (GEN) on mRNA expression of key lipid metabolism and thyroid hormone system genes in young adult, male Sprague-Dawley rats. SPI-fed rats had less retroperitoneal fat and less hepato-steatosis than casein (CAS, control protein)-...

THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

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

Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki

Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Functionmore » was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.« less

Symptom rating scale for assessing hyperthyroidism.

PubMed

Klein, I; Trzepacz, P T; Roberts, M; Levey, G S

1988-02-01

A hyperthyroid symptom scale (HSS) was designed and administered to ten subjects with untreated Graves' disease. All subjects had clinical and chemical evidence of hyperthyroidism and reproducible HSS scores of 20 or more points. During sequential treatments with propranolol hydrochloride (phase 2) followed by propylthiouracil (phase 3) there was a significant decline in the HSS scores at each phase. Accompanying the decrease in HSS scores was a decrease in heart rate, but there was no change in thyroid function test results at phase 2 and a decrease in heart rate, thyroid function test results, and goiter size at phase 3. This new scale includes ten categories of symptoms, it is sensitive to changes in both the adrenergic and metabolic components of hyperthyroidism, and it is useful in the clinical assessment and management of patients with thyrotoxicosis.

Selenoproteins in human body: focus on thyroid pathophysiology.

PubMed

Valea, Ana; Georgescu, Carmen Emanuela

2018-06-05

Selenium (Se) has a multilevel, complex and dynamic effect on the human body as a major component of selenocysteine, incorporated into selenoproteins, which include the selenocysteine-containing enzymes iodothyronine deiodinases. At the thyroid level, these proteins play an essential role in antioxidant protection and hormone metabolism. This is a narrative review based on PubMed/Medline database research regarding thyroid physiology and conditions with Se and Se-protein interferences. In humans, Se-dependent enzyme functions are best expressed through optimal Se intake, although there is gap in our knowledge concerning the precise mechanisms underlying the interrelation. There is a good level of evidence linking low serum Se to autoimmune thyroid diseases and, to a lesser extent, differentiated thyroid cancer. However, when it comes to routine supplementation, the results are heterogeneous, except in the case of mild Graves' orbitopathy. Autoimmune hypothyroidism is associated with a state of higher oxidative stress, but not all studies found an improvement of thyroid function after Se was introduced as antioxidant support. Meanwhile, no routine supplementation is recommended. Low Se intake is correlated with an increased risk of developing antithyroid antibodies, its supplementation decreasing their titres; there is also a potential reduction in levothyroxine replacement dose required for hypothyroidism and/or the possibility that it prevents progression of subclinical hypothyroidism, although not all studies agree. In thyroid-associated orbitopathy, euthyroidism is more rapidly achieved if the micronutrient is added to traditional drugs, while controls appear to benefit from the microelement only if they are deficient; thus, a basal assay of Se appears advisable to better select patients who need substitution. Clearly, further Se status biomarkers are required. Future introduction of individual supplementation algorithms based on baseline micronutrient levels, underlying or at-risk clinical conditions, and perhaps selenoprotein gene polymorphisms is envisaged.

Thyroid hormone and cerebellar development.

PubMed

Anderson, Grant W

2008-01-01

Thyroid hormone (TH) plays a key role in mammalian brain development. The developing brain is sensitive to both TH deficiency and excess. Brain development in the absence of TH results in motor skill deficiencies and reduced intellectual development. These functional abnormalities can be attributed to maldevelopment of specific cell types and regions of the brain including the cerebellum. TH functions at the molecular level by regulating gene transcription. Therefore, understanding how TH regulates cerebellar development requires identification of TH-regulated gene targets and the cells expressing these genes. Additionally, the process of TH-dependent regulation of gene expression is tightly controlled by mechanisms including regulation of TH transport, TH metabolism, toxicologic inhibition of TH signaling, and control of the nuclear TH response apparatus. This review will describe the functional, cellular, and molecular effects of TH deficit in the developing cerebellum and emphasize the most recent findings regarding TH action in this important brain region.

[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.

Hyperthyroidism causes mechanical insufficiency of myocardium with possibly increased SR Ca2+-ATPase activity.

PubMed

Takeuchi, Koh; Minakawa, M; Otaki, M; Odagiri, S; Itoh, K; Murakami, A; Yaku, H; Kitamura, N

2003-12-01

Hyperthyroidism is known to affect multiple organ functions, and thyroid hormone has been known to improve myocardial function in a failing heart. The purpose of this study is to elucidate the functional and metabolic effects of thyroid hormone on myocardium in a rat model exposed to long-term excess thyroid hormone, particularly focusing on the SR Ca(2+)-ATPase (SERCA2) function. 3,5,3'-Triiodo-L-thyronine (T3), or the vehicle, was subcutaneously given for 4 weeks (T3 and control [C] group). Bolus I.V. Thapsigargin (TG) was used to test the SERCA2 function (C-TG and T3-TG) in Langendorff perfused heart. Myocardial functions such as LV-developed pressure (LVDP; mmHg), +/- dP/dt (mmHg/s), tau (ms), and oxygen consumption (MVO(2); ml/min/g wt) were measured. SERCA2 and GLUT4 protein level were also evaluated by Western immunoblotting. Left ventricle to body weight (LV/BW) ratio was significantly higher in the T3 group. Both negative dP/dt and tau were significantly decreased by TG. It is interesting that the decrement of negative dP/dt and tau attained by TG was significantly larger in the hyperthyroid group (T3-TG) than in a normal heart (C-TG). SERCA2 and GLUT4 protein levels were not significantly different between control and the T3 group. We conclude that prolonged exposure to thyroid hormone causes hypertrophy of the myocardium and an augmentation of the SR Ca(2+) ATPase activity. Care must be taken in hyperthyroid heart during the ischemia-reperfusion process where the SRECA2 function is inhibited.

Targeting glutaminase-mediated glutamine dependence in papillary thyroid cancer.

PubMed

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

2018-06-25

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

Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study

PubMed Central

Ruiz-Núñez, Begoña; Tarasse, Rabab; Vogelaar, Emar F.; Janneke Dijck-Brouwer, D. A.; Muskiet, Frits A. J.

2018-01-01

Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21–69 years, 21 males) and 99 age- and sex-matched controls (19–65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation. Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (rT3) (13.3%). FT3 below the reference range, consistent with the “low T3 syndrome,” was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% confidence interval = 1.00–6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and WBC. We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels. The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of “non-thyroidal illness syndrome” and “low T3 syndrome” experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with, e.g., T3 and iodide supplements might be indicated. PMID:29615976

Free T4, Free T3, and Reverse T3 in Critically Ill, Thermally Injured Patients

DTIC Science & Technology

1980-09-01

with myxedema suggest that the pituitary was either suppressed by steroids or coma , that is, T, concentrations in a range of 0.25 mcg per other factors...tyrosine in patients with altered thyroid function. J. C(i. of tyrosine in thyrotoxicosis and myxedema . Metabolism, 20: Endocrinol., 24: 691, 1964. .384-391

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

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.

Thyroid hormone concentrations, disease, physical function, and mortality in elderly men.

PubMed

van den Beld, Annewieke W; Visser, Theo J; Feelders, Richard A; Grobbee, Diederick E; Lamberts, Steven W J

2005-12-01

Physiological changes in thyroid hormone concentrations might be related to changes in the overall physical function in the elderly. We determined to what extent thyroid hormone concentrations are related to physical function and mortality in elderly men. A longitudinal population study (the Zoetermeer study) was conducted. Mortality was registered in the subsequent 4 yr. Four hundred three independently and ambulatory living men (aged 73-94 yr) participated. The study examined the association between serum thyroid hormones and parameters of physical function as well as the association with mortality. TSH, free T4 (FT4) total T4, T3, rT3, and T4-binding globulin were measured. Physical function was estimated by the number of problems in activities of daily living, a measure of physical performance score (PPS), leg extensor strength and grip strength, bone density, and body composition. Serum rT3 increased significantly with age and the presence of disease. Sixty-three men met the biochemical criteria for the low T3 syndrome (decreased serum T3 and increased serum rT3). This was associated with a lower PPS, independent of disease. Furthermore, higher serum FT4 (within the normal range of healthy adults) and rT3 (above the normal range of healthy adults) were related with a lower grip strength and PPS, independent of age and disease. Isolated low T3 was associated with a better PPS and a higher lean body mass. Low FT4 was related to a decreased risk of 4-yr mortality. In a population of independently living elderly men, higher FT4 and rT3 concentrations are associated with a lower physical function. High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state. Low serum FT4 is associated with a better 4-yr survival; this may reflect an adaptive mechanism to prevent excessive catabolism.

Experimental models of developmental hypothyroidism.

PubMed

Argumedo, G S; Sanz, C R; Olguín, H J

2012-02-01

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

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

PubMed Central

Molehin, Deborah

2016-01-01

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

Phosphorous magnetic resonance spectroscopy-based skeletal muscle bioenergetic studies in subclinical hypothyroidism.

PubMed

Rana, P; Sripathy, G; Varshney, A; Kumar, P; Devi, M Memita; Marwaha, R K; Tripathi, R P; Khushu, S

2012-02-01

Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients. In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction. Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery. We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients. 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

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...

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

PubMed

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

2016-07-01

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

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

PubMed

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

2014-06-01

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

Thyroid transcriptome analysis reveals different adaptive responses to cold environmental conditions between two chicken breeds

PubMed Central

Yang, Xukai; Wang, Dehe; Zhu, Feng; Yang, Ning; Hou, Zhuocheng; Ning, Zhonghua

2018-01-01

Selection for cold tolerance in chickens is important for improving production performance and animal welfare. The identification of chicken breeds with higher cold tolerance and production performance will help to target candidates for the selection. The thyroid gland plays important roles in thermal adaptation, and its function is influenced by breed differences and transcriptional plasticity, both of which remain largely unknown in the chicken thyroid transcriptome. In this study, we subjected Bashang Long-tail (BS) and Rhode Island Red (RIR) chickens to either cold or warm environments for 21 weeks and investigated egg production performance, body weight changes, serum thyroid hormone concentrations, and thyroid gland transcriptome profiles. RIR chickens had higher egg production than BS chickens under warm conditions, but BS chickens produced more eggs than RIRs under cold conditions. Furthermore, BS chickens showed stable body weight gain under cold conditions while RIRs did not. These results suggested that BS breed is a preferable candidate for cold-tolerance selection and that the cold adaptability of RIRs should be improved in the future. BS chickens had higher serum thyroid hormone concentrations than RIRs under both environments. RNA-Seq generated 344.3 million paired-end reads from 16 sequencing libraries, and about 90% of the processed reads were concordantly mapped to the chicken reference genome. Differential expression analysis identified 46–1,211 genes in the respective comparisons. With regard to breed differences in the thyroid transcriptome, BS chickens showed higher cell replication and development, and immune response-related activity, while RIR chickens showed higher carbohydrate and protein metabolism activity. The cold environment reduced breed differences in the thyroid transcriptome compared with the warm environment. Transcriptional plasticity analysis revealed different adaptive responses in BS and RIR chickens to cope with the cold, and showed higher responsiveness in BS compared with RIR chickens, suggesting greater adaptability of the thyroid in BS chickens. Moreover, 10,053 differential splicing events were revealed among the groups, with RNA splicing and processing, gene expression, transport, and metabolism being the main affected biological processes, identifying a valuable alternative splicing repertoire for the chicken thyroid. A short isoform of TPO (encoding thyroid peroxidase) containing multiple open reading frames was generated in both breeds by skipping exons 4 and 5 in the cold environment. These findings provide novel clues for future studies of the molecular mechanisms underlying cold adaptation and/or acclimation in chickens. PMID:29320582

Thyroid transcriptome analysis reveals different adaptive responses to cold environmental conditions between two chicken breeds.

PubMed

Xie, Shanshan; Yang, Xukai; Wang, Dehe; Zhu, Feng; Yang, Ning; Hou, Zhuocheng; Ning, Zhonghua

2018-01-01

Selection for cold tolerance in chickens is important for improving production performance and animal welfare. The identification of chicken breeds with higher cold tolerance and production performance will help to target candidates for the selection. The thyroid gland plays important roles in thermal adaptation, and its function is influenced by breed differences and transcriptional plasticity, both of which remain largely unknown in the chicken thyroid transcriptome. In this study, we subjected Bashang Long-tail (BS) and Rhode Island Red (RIR) chickens to either cold or warm environments for 21 weeks and investigated egg production performance, body weight changes, serum thyroid hormone concentrations, and thyroid gland transcriptome profiles. RIR chickens had higher egg production than BS chickens under warm conditions, but BS chickens produced more eggs than RIRs under cold conditions. Furthermore, BS chickens showed stable body weight gain under cold conditions while RIRs did not. These results suggested that BS breed is a preferable candidate for cold-tolerance selection and that the cold adaptability of RIRs should be improved in the future. BS chickens had higher serum thyroid hormone concentrations than RIRs under both environments. RNA-Seq generated 344.3 million paired-end reads from 16 sequencing libraries, and about 90% of the processed reads were concordantly mapped to the chicken reference genome. Differential expression analysis identified 46-1,211 genes in the respective comparisons. With regard to breed differences in the thyroid transcriptome, BS chickens showed higher cell replication and development, and immune response-related activity, while RIR chickens showed higher carbohydrate and protein metabolism activity. The cold environment reduced breed differences in the thyroid transcriptome compared with the warm environment. Transcriptional plasticity analysis revealed different adaptive responses in BS and RIR chickens to cope with the cold, and showed higher responsiveness in BS compared with RIR chickens, suggesting greater adaptability of the thyroid in BS chickens. Moreover, 10,053 differential splicing events were revealed among the groups, with RNA splicing and processing, gene expression, transport, and metabolism being the main affected biological processes, identifying a valuable alternative splicing repertoire for the chicken thyroid. A short isoform of TPO (encoding thyroid peroxidase) containing multiple open reading frames was generated in both breeds by skipping exons 4 and 5 in the cold environment. These findings provide novel clues for future studies of the molecular mechanisms underlying cold adaptation and/or acclimation in chickens.

Both thyroid hormone levels and resting metabolic rate decrease in African striped mice when food availability decreases.

PubMed

Rimbach, Rebecca; Pillay, Neville; Schradin, Carsten

2017-03-01

In response to variation in food availability and ambient temperature ( T a ), many animals show seasonal adaptations in their physiology. Laboratory studies showed that thyroid hormones are involved in the regulation of metabolism, and their regulatory function is especially important when the energy balance of an individual is compromised. However, little is known about the relationship between thyroid hormones and metabolism in free-living animals and animals inhabiting seasonal environments. Here, we studied seasonal changes in triiodothyronine (T 3 ) levels, resting metabolic rate (RMR) and two physiological markers of energy balance (blood glucose and ketone bodies) in 61 free-living African striped mice ( Rhabdomys pumilio ) that live in an semi-arid environment with food shortage during the dry season. We predicted a positive relationship between T 3 levels and RMR. Further, we predicted higher T 3 levels, blood glucose levels and RMR, but lower ketone body concentrations, during the moist season when food availability is high compared with summer when food availability is low. RMR and T 3 levels were negatively related in the moist season but not in the dry season. Both RMR and T 3 levels were higher in the moist than in the dry season, and T 3 levels increased with increasing food availability. In the dry season, blood glucose levels were lower but ketone body concentrations were higher, indicating a change in substrate use. Seasonal adjustments in RMR and T 3 levels permit a reduction of energy expenditure when food is scarce, and reflect an adaptive response to reduced food availability in the dry season. © 2017. Published by The Company of Biologists Ltd.

Perchlorate in Water Supplies: Sources, Exposures, and Health Effects

PubMed Central

Steinmaus, Craig M.

2016-01-01

Perchlorate exposure occurs from ingestion of natural or manmade perchlorate in food or water. Perchlorate is used in a variety of industrial products including missile fuel, fireworks, and fertilizers, and industrial contamination of drinking water supplies has occurred in a number of areas. Perchlorate blocks iodide uptake into the thyroid, and decreases the production of thyroid hormone, a critical hormone for metabolism, neurodevelopment, and other physiologic functions. Occupational and clinical dosing studies have not identified clear adverse effects, but may be limited by small sample sizes, short study durations, and the inclusion of mostly healthy adults. Expanding evidence suggests that young children, pregnant women, fetuses, and people co-exposed to similarly acting agents may be especially susceptible to perchlorate. Given the ubiquitous nature of perchlorate exposure, and the importance of thyroid hormone for brain development, studying the impact of perchlorate on human health could have far-reaching public health implications. PMID:27026358

Thyroid hormone-induced oxidative stress.

PubMed

Venditti, P; Di Meo, S

2006-02-01

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

Thyroid hormone fluctuations indicate a thermoregulatory function in both a tropical (Alouatta palliata) and seasonally cold-habitat (Macaca fuscata) primate.

PubMed

Thompson, Cynthia L; Powell, Brianna L; Williams, Susan H; Hanya, Goro; Glander, Kenneth E; Vinyard, Christopher J

2017-11-01

Thyroid hormones boost animals' basal metabolic rate and represent an important thermoregulatory pathway for mammals that face cold temperatures. Whereas the cold thermal pressures experienced by primates in seasonal habitats at high latitudes and elevations are often apparent, tropical habitats also display distinct wet and dry seasons with modest changes in thermal environment. We assessed seasonal and temperature-related changes in thyroid hormone levels for two primate species in disparate thermal environments, tropical mantled howlers (Alouatta palliata), and seasonally cold-habitat Japanese macaques (Macaca fuscata). We collected urine and feces from animals and used ELISA to quantify levels of the thyroid hormone triiodothyronine (fT 3 ). For both species, fT 3 levels were significantly higher during the cooler season (wet/winter), consistent with a thermoregulatory role. Likewise, both species displayed greater temperature deficits (i.e., the degree to which animals warm their body temperature relative to ambient) during the cooler season, indicating greater thermoregulatory pressures during this time. Independently of season, Japanese macaques displayed increasing fT 3 levels with decreasing recently experienced maximum temperatures, but no relationship between fT 3 and recently experienced minimum temperatures. Howlers increased fT 3 levels as recently experienced minimum temperatures decreased, although demonstrated the opposite relationship with maximum temperatures. This may reflect natural thermal variation in howlers' habitat: wet seasons had cooler minimum and mean temperatures than the dry season, but similar maximum temperatures. Overall, our findings support the hypothesis that both tropical howlers and seasonally cold-habitat Japanese macaques utilize thyroid hormones as a mechanism to boost metabolism in response to thermoregulatory pressures. This implies that cool thermal pressures faced by tropical primates are sufficient to invoke an energetically costly and relatively longer-term thermoregulatory pathway. The well-established relationship between thyroid hormones and energetics suggests that the seasonal hormonal changes we observed could influence many commonly studied behaviors including food choice, range use, and activity patterns. © 2017 Wiley Periodicals, Inc.

Mutant HABP2 Causes Non-Medullary Thyroid Cancer | Center for Cancer Research

Cancer.gov

The thyroid is a butterfly-shaped gland that lies at the base of the throat in front of the windpipe. A member of the endocrine system, the thyroid secretes hormones to regulate heart rate, blood pressure, temperature, and metabolism. Cancer of the thyroid is the most common endocrine cancer and the eighth most common cancer in the U.S. An estimated 63,450 Americans will be

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

PubMed

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

2016-11-01

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

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

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.

Environmental heat stress modulates thyroid status and its response to repeated endotoxin (LPS) challenge in steers

USDA-ARS?s Scientific Manuscript database

Thyroid hormones are important in the adaptation to heat stress, allowing the adjustment of metabolic rates in favor of decreased energy utilization and heat production. Thyroid status is compromised in a variety of acute and chronic infections and toxin-mediated disease states. Our objective was to...

Direct calorimetry of free-moving eels with manipulated thyroid status

NASA Astrophysics Data System (ADS)

van Ginneken, Vincent; Ballieux, Bart; Antonissen, Erik; van der Linden, Rob; Gluvers, Ab; van den Thillart, Guido

2007-02-01

In birds and mammals, the thyroid gland secretes the iodothyronine hormones of which tetraiodothyronine (T4) is less active than triiodothyronine (T3). The action of T3 and T4 is calorigenic and is involved in the control of metabolic rate. Across all vertebrates, thyroid hormones also play a major role in differentiation, development and growth. Although the fish thyroidal system has been researched extensively, its role in thermogenesis is unclear. In this study, we measured overall heat production to an accuracy of 0.1 mW by direct calorimetry in a free-moving European eel ( Anguilla anguilla L.) with different thyroid status. Hyperthyroidism was induced by injection of T3 and T4, and hypothyroidism was induced with phenylthiourea. The results show for the first time at the organismal level, using direct calorimetry, that neither overall heat production nor overall oxygen consumption in eels is affected by hyperthyroidism. Therefore, we conclude that the thermogenic metabolism-stimulating effect of thyroid hormones (TH) is not present with a cold-blooded fish species like the European eel. This supports the concept that TH does not stimulate thermogenesis in poikilothermic species.

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.

Mutant HABP2 Causes Non-Medullary Thyroid Cancer | Center for Cancer Research

Cancer.gov

The thyroid is a butterfly-shaped gland that lies at the base of the throat in front of the windpipe. A member of the endocrine system, the thyroid secretes hormones to regulate heart rate, blood pressure, temperature, and metabolism. Cancer of the thyroid is the most common endocrine cancer and the eighth most common cancer in the U.S. An estimated 63,450 Americans will be diagnosed with thyroid cancer this year. The vast majority is of follicular cell origin, and the remaining cancer originates from parafollicular cells, so called medullary thyroid cancer.

[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.

Estrogen and Thyroid Hormone Receptor Activation by Medicinal Plants from Bahia, Brazil

PubMed Central

da Silva, Magnus Régios Dias; Costa, Silvia Lima; Velozo, Eudes da Silva

2018-01-01

Background: A number of medicinal plants are traditionally used for metabolic disorders in Bahia state, Brazil. The aim of this study was to evaluate the estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts prepared from 20 plants. Methods: Species were extracted and assayed for receptor activation through both ER and TR gene-reporter assays, using 17β-estradiol and triiodothyronine (T3), respectively, as the positive controls. Results: Cajanus cajan (Fabaceae), Abarema cochliacarpus (Fabaceae), and Borreria verticillata (Rubiaceae) were able to activate ER as much as the positive control (17β-estradiol). These three plant species were also assayed for TR activation. At the concentration of 50 µg/mL, C. cajans exerted the highest positive modulation on TR, causing an activation of 59.9%, while B. verticillata and A. cochliacarpus caused 30.8% and 23.3%, respectively. Conclusions: Our results contribute towards the validation of the traditional use of C. cajans, B. verticillata, and A. cochliacarpus in the treatment of metabolic disorders related to ER and TR functions. The gene-reporter assay was proven effective in screening crude plant extracts for ER/TR activation, endorsing this methodology as an important tool for future bioprospection studies focused on identifying novel starting molecules for the development of estrogen and thyroid agonists. PMID:29342924

Focus on nutrition: the role of iodine in nutrition and metabolism.

PubMed

Zicker, Steve; Schoenherr, Bill

2012-10-01

Iodine, which forms part of thyroid hormone, is essential for sustaining life in vertebrate animals. An absolute iodine requirement is difficult to determine because of adaptive responses to varying iodine intake. Excess or deficient iodine intake may result in altered thyroid metabolism. The magnitude and direction of the response to changes in dietary intake may also depend on previous iodine intake. Therefore, an understanding of the distribution, absorption, and metabolic fate of iodine is integral to the investigation of the role of iodine in disease states.

Does selenium supplementation affect thyroid function? Results from a randomized, controlled, double-blinded trial in a Danish population.

PubMed

Winther, Kristian Hillert; Bonnema, Steen Joop; Cold, Frederik; Debrabant, Birgit; Nybo, Mads; Cold, Søren; Hegedüs, Laszlo

2015-06-01

Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake. The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomized, double-blinded, placebo-controlled trial. A total of 491 males and females aged 60-74 years were randomized to 100 μg (n=124), 200 μg (n=122), or 300 μg (n=119) selenium-enriched yeast or matching yeast-based placebo tablets (n=126). A total of 361 participants, equally distributed across treatment groups, completed the 5-year intervention period. Plasma samples were analyzed for selenium and serum samples for TSH, free triiodothyronine (FT3), and free thyroxine (FT4) at baseline, and after 6 months, and 5 years of supplementation. Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P<0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/l (P=0.010) and 0.11 pmol/l (P=0.015), respectively, per 100 μg/day increase, with insignificant differences between 6 months and 5 years. No significant effects were found for FT3 and FT3:FT4 ratio. In euthyroid subjects, selenium supplementation minutely and dose-dependently affects thyroid function, when compared with placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved. © 2015 European Society of Endocrinology.

Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease.

PubMed

Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi

2016-01-01

3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.

Metabolic rate and thyroid activity of hens in relation to the state of feathering.

PubMed

Pietras, M

1981-01-01

Heat production, rectal temperature and thyroid activity were determined in NH X Lg hens that were 40 and 80% defeathered. Within individual groups there was a significant increase in heat production only in hens that were 80% defeathered. In comparison with the control group, defeathered chickens had higher metabolic rates during each examined period. During the third week of the experiment there was a temporary drop in the rectal temperature of the experimental birds. After nine weeks chicken with the greatest degree of defeathering had the highest thyroid weight and the highest levels of thyroxin in the blood plasma.

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

[Application of iodine metabolism analysis methods in thyroid diseases].

PubMed

Han, Jian-hua; Qiu, Ling

2013-08-01

The main physiological role of iodine in the body is to synthesize thyroid hormone. Both iodine deficiency and iodine excess can lead to severe thyroid diseases. While its role in thyroid diseases has increasingly been recognized, few relevant platforms and techniques for iodine detection have been available in China. This paper summarizes the advantages and disadvantages of currently iodine detection methods including direct titration, arsenic cerium catalytic spectrophotometry, chromatography with pulsed amperometry, colorimetry based on automatic biochemistry, inductively coupled plasma mass spectrometry, so as to optimize the iodine nutrition for patients with thyroid diseases.

Pendred syndrome.

PubMed

Wémeau, Jean-Louis; Kopp, Peter

2017-03-01

Pendred syndrome is an autosomal recessive disorder that is classically defined by the combination of sensorineural deafness/hearing impairment, goiter, and an abnormal organification of iodide with or without hypothyroidism. The hallmark of the syndrome is the impaired hearing, which is associated with inner ear malformations such as an enlarged vestibular aqueduct (EVA). The thyroid phenotype is variable and may be modified by the nutritional iodine intake. Pendred syndrome is caused by biallelic mutations in the SLC26A4/PDS gene, which encodes the multifunctional anion exchanger pendrin. Pendrin has affinity for chloride, iodide, and bicarbonate, among other anions. In the inner ear, pendrin functions as a chloride/bicarbonate exchanger that is essential for maintaining the composition and the potential of the endolymph. In the thyroid, pendrin is expressed at the apical membrane of thyroid cells facing the follicular lumen. Functional studies have demonstrated that pendrin can mediate iodide efflux in heterologous cells. This, together with the thyroid phenotype observed in humans (goiter, impaired iodine organification) suggests that pendrin could be involved in iodide efflux into the lumen, one of the steps required for thyroid hormone synthesis. Iodide efflux can, however, also occur in the absence of pendrin suggesting that other exchangers or channels are involved. It has been suggested that Anoctamin 1 (ANO1/TMEM16A), a calcium-activated anion channel, which is also expressed at the apical membrane of thyrocytes, could participate in mediating apical efflux. In the kidney, pendrin is involved in bicarbonate secretion and chloride reabsorption. While there is no renal phenotype under basal conditions, severe metabolic alkalosis has been reported in Pendred syndrome patients exposed to an increased alkali load. This review provides an overview on the clinical spectrum of Pendred syndrome, the functional data on pendrin with a focus on its potential role in the thyroid, as well as the controversy surrounding the relative physiological roles of pendrin and anoctamin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects.

PubMed

Roef, Greet L; Rietzschel, Ernst R; Van Daele, Caroline M; Taes, Youri E; De Buyzere, Marc L; Gillebert, Thierry C; Kaufman, Jean-Marc

2014-02-01

We have previously shown that in healthy young men, a less favorable body composition is associated with higher free triiodothyronine (fT3) levels within the euthyroid range. Besides, a higher free-triiodothyronine-to-free-thyroxin (fT3-to-fT4) ratio has been related to a less favorable metabolic phenotype and more placental growth in pregnant women. In the present study, we therefore investigated whether serum thyrotropin (TSH), thyroid hormone levels, and the fT3-to-fT4 ratio are associated with metabolic and adiposity-related cardiovascular risk markers in a healthy population of middle-aged euthyroid men and women. Thyroid parameters were measured in 2524 generally healthy subjects from the Asklepios Study (35-55 years, mean age 46 years). Analyses were restricted to 2315 subjects (1138 women and 1177 men), not using thyroid medication, not having anti-TPO levels above clinical cutoff values or TSH levels outside the reference range (0.27-4.2 mU/L). Twenty-seven percent of the women and 47.5% of the men were overweight, while 13% of women and 17% of men were obese. Twenty percent of the subjects were active smokers. Serum thyroid function parameters were determined by electrochemiluminescence. fT3 and the fT3-to-fT4 ratio were positively related to body mass index (BMI), waist circumference, and components of metabolic syndrome, that is, triglycerides, systolic and diastolic blood pressure, and fasting plasma glucose, and negatively with HDL-cholesterol levels, whereas fT4 was negatively associated with BMI, waist circumference, and triglycerides (p<0.001). TSH related positively with total cholesterol levels (p<0.01), triglycerides, and systolic and diastolic blood pressure (p<0.001). The fT3-to-fT4 ratio was further positively associated with the adiposity-related inflammation markers interleukin-6 and high-sensitivity C-reactive protein and to pulse wave velocity. All associations were adjusted for sex, age, height, and smoking, and most associations persisted after additional adjustment for weight or waist circumference. In healthy euthyroid middle-aged men and women, higher fT3 levels, lower fT4 levels, and thus a higher fT3-to-fT4 ratio are consistently associated with various markers of unfavorable metabolic profile and cardiovascular risk.

Effects of pre- and postnatal polychlorinated biphenyl exposure on metabolic rate and thyroid hormones of white-footed mice

USGS Publications Warehouse

French, J.B.; Voltura, M.B.; Tomasi, T.E.

2001-01-01

Energy budgets have proven to be a valuable tool for predicting life history from physiological data in terrestrial vertebrates, yet these concepts have not been applied to the physiological effects of contaminants. Contaminants might affect energy budgets by imposing an additional metabolic cost or by reducing the overall amount of energy taken in; either process will reduce the energy available for production (i.e., growth or reproduction). This study examined whole animal energetic effects of polychlorinated biphenyl (PCB) exposure in white-footed mice (Peromyscus leucopus). Exposure to PCBs is known to reduce concentrations of plasma thyroid hormones, and thyroid hormones exert strong control over the rate of energy metabolism in mammals. Peromyscus leucopus that were proven breeders were fed PCBs in their food at 0, 10, and 25 ppm. Through lactation, offspring were exposed to PCB from conception and were maintained on the maternal diet to adulthood. No effects were seen on energy metabolism (O-2 consumption, measured in adulthood) or on growth, but there were large dose-dependent decreases in thyroid hormone concentrations, particularly T-4. The apparent disparity in our data between unchanged metabolic rates and 50% reductions in T-4 concentrations can be rationalized by noting that free T-3 (the fraction not bound to plasma protein) in treated mice was not significantly different from controls and that metabolism is most strongly influenced by free T-3. Overall, this study did not demonstrate any energetic consequences of PCB exposure in P. leucopus at dietary concentrations up to 25 ppm.

Metabolic effects of liothyronine therapy in hypothyroidism: a randomized, double-blind, crossover trial of liothyronine versus levothyroxine.

PubMed

Celi, Francesco S; Zemskova, Marina; Linderman, Joyce D; Smith, Sheila; Drinkard, Bart; Sachdev, Vandana; Skarulis, Monica C; Kozlosky, Merel; Csako, Gyorgy; Costello, Rene; Pucino, Frank

2011-11-01

Levothyroxine (L-T(4)) therapy is based on the assumption that the conversion of T(4) into T(3) provides adequate amounts of active hormone at target tissues. However, in rodents, L-T(4) alone does not restore a euthyroid state in all tissues. Previous combination L-T(4)/liothyronine (L-T(3)) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action. Our objective was to evaluate the efficacy of thyroid hormone replacement with L-T(4) or L-T(3) at doses producing equivalent normalization of TSH. Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center. L-T(3) or L-T(4) were administered thrice daily to achieve a target TSH from 0.5-1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH. Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated. No difference was observed in TSH between L-T(3) and L-T(4) treatments. L-T(3) resulted in significant weight loss [L-T(4), 70.6 ± 12.5, vs. L-T(3), 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity. The substitution of L-T(3) for L-T(4) at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity.

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.

Altered fructosamine and lipid fractions in subclinical hypothyroidism.

PubMed

Udupa, Sridevi V; Manjrekar, Poornima A; Udupa, Vinit A; Vivian, D'Souza

2013-01-01

Thyroid function disorders lead to changes in the lipoprotein metabolism. To study the lipid and the glycaemic abnormalities in the subclinical hypothyroidism cases and to compare the same with the euthyroid, overt hypothyroid and the hyperthyroid subjects. Four groups, euthyroid (Group-I), hypothyroid (Group-II), subclinical hypothyroid (Group-III) and hyperthyroid (Group-IV), which consisted of 30 subjects each, of either sex, who were aged 25-55 years, underwent Fasting Plasma Glucose (FPG), fructosamine, lipid profile and total T3, T4 and TSH estimations. The subjects who were on lipid lowering or thyroid disorder drugs and known diabetics were excluded from the study. In Group-III, all the lipid fractions were comparable to those of Group-II and they were significantly deranged, as compared to those of Group-I. The fructosamine levels were significantly higher in Group-II and Group-III (p<0.05), but the subclinical hypothyroid pool had statistically lower levels than the hypothyroid pool (376.63±54.73, 587.80±65.10). In the Group-IV patients, the LDL-C levels were significantly higher as compared to those in the euthyroid pool. The fructosamine levels were significantly lower in comparison with both the euthyroid and the hypothyroid pools (both in Groups-II and III). The FPG levels were higher in all the classes of the thyroid abnormalities (subclinical hypothyroidnot significant) but within the reference range of 70-100mg/dl. Since the lipid derangement in subclinical hypothyroidism is on par with that in overt hypothyrodism, the subclinical hypothyroid cases also need to be treated similarly. The fructosamine values which are largely in excess of the FPG values, indicate a higher propensity to glycation and a decreased turnover of the proteins in the hypothyroid and the subclinical hypothyroid pools. Vice versa is true of the hyperthyroid pool. Fructosamine can be included in the thyroid work up of the patients to assess the metabolic function and the subsequent response after the initiation of the therapy.

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.

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

PubMed Central

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

2012-01-01

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

Sex-specific phenotypes of hyperthyroidism and hypothyroidism in mice.

PubMed

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

2016-01-01

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

EXPERIMENTAL THYROIDISM

PubMed Central

Cunningham, R. H.

1898-01-01

From the results of the various experiments already detailed I feel justified in drawing the following conclusions: (1) Absolutely fresh thyroid gland is not poisonous, in the usual sense of the term, when absorbed through the alimentary canal. (2) The symptoms of induced thyroidism are manifestations of an intoxication resulting from the ingestion of decomposed thyroid material, a conclusion that agrees in part with the previously related observations of Lanz. (3) The so-called experimental thyroidism is not specific for the thyroid only, for the ingestion of many substances derived from animal tissues other than the thyroid gland may produce an intoxication strikingly similar in every respect to that of experimental thyroidism. (4) Most, if not all, animal tissues yield substances which, if injected in large quantities directly into the circulation or beneath the skin, will produce an intoxication often very similar to that produced by injections of various substances derived from the fresh thyroid tissue. (5) The effects resulting from the intravascular or subcutaneous injections of aqueous extracts, decoctions and the concentrated extractives of the thyroid tissue, of the thymus, of muscle, etc., are by no means necessarily indicative of the function and the action of the hypothetical internal secretions of the same tissues during life. (6) The utilization of the fact that ingestion of decomposed thyroid material produces on certain occasions an intoxication with certain symptoms similar to some of those of G-raves' disease is not justifiable for the furtherance of the theory that the symptoms of exophthalmic goitre result from an over-production of the thyroid secretion. (7) Our results lead us to conclude with Drechsel that the fresh thyroid tissue yields at least probably two substances that are capable of palliating the symptoms of the acute cachexia in totally thyroidless dogs. (8) The thymus tissue also yields one and probably two substances that are as equally capable as the thyroid extractives of palliating the acute cachexia in totally thyroidless dogs. (9) Neither of the above substances is an enzyme, nor does either contain iodine. (10) Neither the feeding of minced raw thyroid glands, nor the injection of aqueous thyroid extracts, decoctions, and concentrated solutions of the extracted palliative thyroid principles is capable of keeping totally thyroidless young dogs alive longer than a few weeks (possibly three weeks). Still less capable are the thyroid preparations containing decomposition products. (11) The presence of one, or usually several, small accessory thyroid bodies, which gradually hypertrophy and wholly or partially assume the functions of the excised thyroid lobes, accounts for the occasionally long survival of thyroidectomized, thyroid-fed, young dogs. (12) Totally thyroidless young dogs are so quickly overwhelmed by the cachexia, and the intervals between the thyroidectomy and the onset of the severe dyspnœic attacks and subsequent deaths differ so slightly, no matter which of the usual varieties of fresh food are employed, that kinds of fresh food cannot be unquestionably affirmed to influence the onset of the cachexia in any especially definite manner. Animal foods, in which constituents poisonous to rabbits have developed, probably slightly hasten the onset of the severer symptoms, and the vaunted remarkably modifying influence of a diet of ordinary milk, such as Breisacher observed, does not exist in the case of the totally thyroidless dog. (13) Monkeys whose general metabolism is disturbed in consequence of the removal of a greater portion of the thyroid gland, evidently become more susceptible to those constituents of meat that are poisonous to rabbits, and sufficient clinical evidence exists for concluding that probably a like susceptibility to animal foods containing such constituents also exists in men when the function of the thyroid gland is sufficiently disturbed. (14) And, finally, as regards the thyroid factor in the pathology of exophthalmic goitre, I agree with Gley that the majority of the symptoms in many patients with that disease can apparently, from an experimental standpoint, be as plausibly explained by the hypothesis of partially deficient thyroid activity as by the hypothesis of augmentation of thyroid function. PMID:19866869

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.

Thyroid Hormones Reduce Incubation Period without Developmental or Metabolic Costs in Murray River Short-Necked Turtles (Emydura macquarii).

PubMed

McGlashan, Jessica K; Thompson, Michael B; Van Dyke, James U; Spencer, Ricky-John

Metabolic processes are affected by both temperature and thyroid hormones in ectothermic vertebrates. Temperature is the major determinant of incubation length in oviparous vertebrates, but turtles can also alter developmental rate independent of temperature. Temperature gradients within natural nests cause different developmental rates of turtle embryos within nests. Despite temperature-induced reductions in developmental rate, cooler-incubated neonates often hatch synchronously with warmer siblings via metabolic compensation. The physiological mechanisms underlying metabolic compensation are unknown, but thyroid hormones may play a critical role. We applied excess triiodothyronine (T 3 ) to developing eggs of Murray River short-necked turtle (Emydura macquarii)-a species that exhibits metabolic compensation and synchronous hatching-to determine whether T 3 influences developmental rate and whether changes to incubation period incur metabolic costs. We measured heart rate, oxygen consumption and incubation period of eggs, and morphology and performance of hatchlings. Embryos that were exposed to T 3 pipped up to 3.5 d earlier than untreated controls, despite no change in total metabolic expenditure, and there were no treatment differences in hatchling morphology. Hatchlings treated with T 3 demonstrated similar righting ability to hatchlings from the control groups. Exposure to T 3 shortens incubation length by accelerating embryonic development but without statistically increasing embryonic metabolism. Thus, T 3 is a mechanism that cooler-incubated reptiles could use to accelerate their development to allow synchronous hatching with their warmer clutch mates but at little or no metabolic cost. Thus, metabolic compensation for synchronous hatching may not be metabolically expensive if T 3 is the underlying mechanism.

Prevalence of thyroid dysfunction and autoimmunity in pregnant women with gestational diabetes and diabetes type 1.

PubMed

Velkoska Nakova, V; Krstevska, B; Dimitrovski, Ch; Simeonova, S; Hadzi-Lega, M; Serafimoski, V

2010-01-01

The aim of the present study was to determine the prevalence of abnormal thyroid function and antithyroid antibodies during pregnancy in women with diabetes type 1 and gestational diabetes mellitus (GDM). The study group included 83 pregnant women who attended the Outpatient Department of the Endocrinology, Diabetes and Metabolic Disorders Clinic in the period from 05.2009 to 11.2009. The one hundred-g. oral glucose tolerance test (OGTT) was conducted on the pregnant women except for women with diabetes type 1. Thyroid functions were evaluated in all the pregnant women. After routine screening for GDM, thirty of the pregnant women were healthy and GDM was diagnosed in forty of them. The rest, thirteen women, had diabetes type 1. The women who developed GDM showed a mean free thyroxin concentration (fT4) significantly lower than that observed in the healthy pregnant women and women with diabetes type 1. Among the pregnant women with GDM, 10 women or 25% had fT4 concentrations below the lower cut-off with normal thyroid-stimulating hormone concentrations (TSH). A statistically significant difference was found in the prevalence of antithyroid antibodies (anti-TPO) between the (30%) women with diabetes type 1 and (10%) healthy pregnant women (p<0.05). In the women positive for anti-TPO, TSH was significantly higher (p<0.05). The significantly higher prevalence of hypothyroxinemia in GDM pregnancies and anti-TPO titres in pregnancies with diabetes type 1, than in healthy pregnant women warrants routine screening for thyroid abnormalities in these groups of pregnant women.

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

PubMed

Maldjian, P D; Chen, T

2016-11-01

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

Thyroid, cortisol and growth hormone levels in adult Nigerians with metabolic syndrome.

PubMed

Udenze, Ifeoma Christiana; Olowoselu, Olusola Festus; Egbuagha, Ephraim Uchenna; Oshodi, Temitope Adewunmi

2017-01-01

The similarities in presentation of cortisol excess, growth hormone deficiency, hypothyroidism and metabolic syndrome suggest that subtle abnormalities of these endocrine hormones may play a causal role in the development of metabolic syndrome. The aim of this study is to determine the levels of cortisol, thyroid and growth hormones in adult Nigerians with metabolic syndrome and determine the relationship between levels of these hormones and components of the syndrome. This was a case control study conducted at the Lagos University Teaching Hospital, Lagos, Nigeria. Participants were fifty adult men and women with the metabolic syndrome, and fifty, age and sex matched males and females without the metabolic syndrome. Metabolic syndrome was defined based on the NCEP-ATPIII criteria. Written Informed consent was obtained from the participants. Socio demographic and clinical data were collected using a structured questionnaire. Venous blood was collected after an over-night fast. The Ethics committee of the Lagos University Teaching Hospital, Lagos, Nigeria, approved the study protocol. Comparison of continuous variables was done using the Student's t test. Correlation analysis was employed to determine the associations between variables. Statistical significance was set at P<0.05. Triiodotyronine (T3) was significantly decreased (p<0.001) and thyroxine (T4 ) significantly increased ( p<0.001) in metabolic syndrome compared to healthy controls. T3 correlated positively and significantly with waist circumference (p=0.004), glucose (p= 0.002), total cholesterol ( p=0.001) and LDL- cholesterol ( p<0.001 ) and negatively with body mass index ( p<0.001 )and triglyceride ( p=0.026). T4 had a negative significant correlation with waist circumference (p=0.004). Cortisol and growth hormone levels were similar in metabolic syndrome and controls. Cortisol however had a positive significant correlation with waist/hip ratio (p<0.001) while growth hormone correlated positively with HDL ( p=0.023)and negatively with diastolic blood pressure (p=0.049). Thyroid hormones T3 and T4 were associated with metabolic syndrome. The thyroid hormones, cortisol and growth hormones correlated with components of the syndrome. A therapeutic role may exit for these hormones in the management of metabolic syndrome and related disorders.

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

PubMed

Itoh, Mitsuyasu

2012-11-01

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

Circadian, endocrine, and metabolic effects of prolonged bedrest: Two 56-day bedrest studies

NASA Technical Reports Server (NTRS)

Vernikos-Danellis, J.; Winget, C. M.; Leach, C. S.; Rambaut, P. C.

1974-01-01

Two bedrest studies of 56 days each have been conducted to evaluate the effects of prolonged bedrest on circadian synchrony and endocrine and metabolic function. Measurements included the pituitary-adrenal, thyroid, parathyroid, insulin-glucose-growth hormones, catecholamine excretion, body temperature, and heart rate. The results indicated that a rigorous regimen of exercise did not prevent the endocrine and metabolic effects of prolonged bedrest. Changes in circadian, endocrine, and metabolic functions in bedrest appear to be due to changes in hydrostatic pressure and lack of postural cues rather than to inactivity, confinement, or the bleeding schedule. Prolonged bedrest, particularly beyond 24 days, resulted in rhythm desynchronization in spite of well regulated light/dark cycles, temperature, humidity, activity, and meal times and meal composition and in increased lability of all endocrine parameter measured. It also resulted in an apparent insensitivity of the glucose response to insulin, of cortisol secretion to ACTH, and of growth hormone secretion to hypoglycemia.

Exercise effect with the wheelchair aerobic fitness trainer on conditioning and metabolic function in disabled persons: a pilot study.

PubMed

Midha, M; Schmitt, J K; Sclater, M

1999-03-01

To determine the effect of exercise with the wheelchair aerobic fitness trainer (WAFT) on anthropometric indices, conditioning, and endocrine and metabolic parameters in persons with lower extremity disability. Exercise sessions with the WAFT lasted 20 to 30 minutes for two to three sessions. Tertiary-care Veterans Administration medical center. Twelve subjects (3 with quadriplegia, 7 with paraplegia, 1 with cerebrovascular accident, 1 with bilateral above-knee amputation). Anthropometric indices (heart rate, blood pressure, weight, oxygen utilization, body mass index, upper arm and abdominal circumference, arm power) and endocrine and metabolic parameters (fasting serum glucose, lipids, and thyroid function) were determined before and after 10 weeks of exercise with the WAFT. All patients noted improved feelings of well-being after training. Mean resting heart rate, upper arm fat area, and fasting serum cholesterol level decreased significantly. Peak oxygen consumption, midarm circumference, and free thyroxine index increased significantly with training. WAFT improves quality of life, conditioning, and endocrine-metabolic parameters in disabled persons.

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

PubMed

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

2016-03-01

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

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

PubMed Central

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

2015-01-01

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

Exogenous thyroid hormones regulate the activity of citrate synthase and cytochrome c oxidase in warm- but not cold-acclimated lake whitefish (Coregonus clupeaformis)

USGS Publications Warehouse

Zak, Megan A.; Regish, Amy M.; McCormick, Stephen; Manzon, Richard G.

2017-01-01

Thermal acclimation is known to elicit metabolic adjustments in ectotherms, but the cellular mechanisms and endocrine control of these shifts have not been fully elucidated. Here we examined the relationship between thermal acclimation, thyroid hormones and oxidative metabolism in juvenile lake whitefish. Impacts of thermal acclimation above (19 °C) or below (8 °C) the thermal optimum (13 °C) and exposure to exogenous thyroid hormone (60 µg T4/g body weight) were assessed by quantifying citrate synthase and cytochrome c oxidase activities in liver, red muscle, white muscle and heart. Warm acclimation decreased citrate synthase activity in liver and elevated both citrate synthase and cytochrome c oxidase activities in red muscle. In contrast, induction of hyperthyroidism in warm-acclimated fish stimulated a significant increase in liver citrate synthase and heart cytochrome c oxidase activities, and a decrease in the activity of both enzymes in red muscle. No change in citrate synthase or cytochrome c oxidase activities was observed following cold acclimation in either the presence or absence of exogenous thyroid hormones. Collectively, our results indicate that thyroid hormones influence the activity of oxidative enzymes more strongly in warm-acclimated than in cold-acclimated lake whitefish, and they may play a role in mediating metabolic adjustments observed during thermal acclimation.

Exogenous thyroid hormones regulate the activity of citrate synthase and cytochrome c oxidase in warm- but not cold-acclimated lake whitefish (Coregonus clupeaformis).

PubMed

Zak, Megan A; Regish, Amy M; McCormick, Stephen D; Manzon, Richard G

2017-06-01

Thermal acclimation is known to elicit metabolic adjustments in ectotherms, but the cellular mechanisms and endocrine control of these shifts have not been fully elucidated. Here we examined the relationship between thermal acclimation, thyroid hormones and oxidative metabolism in juvenile lake whitefish. Impacts of thermal acclimation above (19°C) or below (8°C) the thermal optimum (13°C) and exposure to exogenous thyroid hormone (60µg T 4 /g body weight) were assessed by quantifying citrate synthase and cytochrome c oxidase activities in liver, red muscle, white muscle and heart. Warm acclimation decreased citrate synthase activity in liver and elevated both citrate synthase and cytochrome c oxidase activities in red muscle. In contrast, induction of hyperthyroidism in warm-acclimated fish stimulated a significant increase in liver citrate synthase and heart cytochrome c oxidase activities, and a decrease in the activity of both enzymes in red muscle. No change in citrate synthase or cytochrome c oxidase activities was observed following cold acclimation in either the presence or absence of exogenous thyroid hormones. Collectively, our results indicate that thyroid hormones influence the activity of oxidative enzymes more strongly in warm-acclimated than in cold-acclimated lake whitefish, and they may play a role in mediating metabolic adjustments observed during thermal acclimation. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of Thyroid Hormones and Functional Characterization of Thyroid Hormone Receptor in the Pacific Oyster Crassostrea gigas Provide Insight into Evolution of the Thyroid Hormone System

PubMed Central

Huang, Wen; Xu, Fei; Qu, Tao; Zhang, Rui; Li, Li; Que, Huayong; Zhang, Guofan

2015-01-01

Thyroid hormones (THs) play important roles in development, metamorphosis, and metabolism in vertebrates. During the past century, TH functions were regarded as a synapomorphy of vertebrates. More recently, accumulating evidence has gradually convinced us that TH functions also occur in invertebrate chordates. To date, however, TH-related studies in non-chordate invertebrates have been limited. In this study, THs were qualitatively detected by two reliable methods (HPLC and LC/MS) in a well-studied molluscan species, the Pacific oyster Crassostrea gigas. Quantitative measurement of THs during the development of C. gigas showed high TH contents during embryogenesis and that oyster embryos may synthesize THs endogenously. As a first step in elucidating the TH signaling cascade, an ortholog of vertebrate TH receptor (TR), the most critical gene mediating TH effects, was cloned in C. gigas. The sequence of CgTR has conserved DNA-binding and ligand-binding domains that normally characterize these receptors. Experimental results demonstrated that CgTR can repress gene expression through binding to promoters of target genes and can interact with oyster retinoid X receptor. Moreover, CgTR mRNA expression was activated by T4 and the transcriptional activity of CgTR promoter was repressed by unliganded CgTR protein. An atypical thyroid hormone response element (CgDR5) was found in the promoter of CgTR, which was verified by electrophoretic mobility shift assay (EMSA). These results indicated that some of the CgTR function is conserved. However, the EMSA assay showed that DNA binding specificity of CgTR was different from that of the vertebrate TR and experiments with two dual-luciferase reporter systems indicated that l-thyroxine, 3,3′,5-triiodothyronine, and triiodothyroacetic acid failed to activate the transcriptional activity of CgTR. This is the first study to functionally characterize TR in mollusks. The presence of THs and the functions of CgTR in mollusks contribute to better understanding of the evolution of the TH system. PMID:26710071

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

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

2011-01-01

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

Metabolic and thyroidal response in air-breathing perch (Anabas testudineus) to water-borne kerosene.

PubMed

Peter, Valsa S; Joshua, Elizabeth K; Wendelaar Bonga, Sjoerd E; Peter, M C Subhash

2007-01-01

To address the physiological compensatory adaptations in air-breathing fish to a toxicant, we studied the metabolite pattern, serum and liver enzymes and thyroidal response in a tropical air-breathing perch, Anabas testudineus (kept at 30 degrees C in a 12-h L:D cycle) after exposing the fish for 48h to the water-soluble fraction of kerosene. The concentrations of serum glucose (P <0.05), triglycerides (P <0.01) and liver total protein (P <0.05) were significantly increased in kerosene-exposed fish. The serum urea level, however, remained unaffected. A significant (P <0.05) increase in liver RNA occurred without changing the liver DNA concentration. Kerosene exposure decreased the level of aspartate aminotransferase activities in serum (P <0.001) and liver (P <0.05) but it increased (P <0.05) the liver alanine aminotransferase activity without changing its activity in serum. The levels of serum (P <0.01) and liver (P <0.001) lactate dehydrogenase activity were declined and the serum (P <0.05) and liver (P <0.05) alkaline phosphatase activity levels were elevated in kerosene-treated fish. The nominated levels (3.33-6.66ml/L) of kerosene significantly (P <0.01) elevated the thyroxine (T(4)) titre, and reduced (P <0.05) the triiodothyronine (T(3)) titre. The fish pretreated with either T(3) or T(4) and exposed to kerosene had a metabolic and thyroidal response that differed from that in control fish treated with kerosene: no rise in serum glucose was observed, nor in triglycerides, total protein and RNA in the liver, whereas declined levels of T(4) and T(3) were observed. The upregulation of the thyroid along with the marked metabolite changes point to a positive involvement of thyroid in energy metabolism during kerosene exposure. This is consistent with the hypothesis that the fish thyroid responds to the action of petroleum products and influences the metabolic homeostasis of this air-breathing fish.

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.

Metabolic and Clinical Consequences of Hyperthyroidism on Bone Density

PubMed Central

Gorka, Jagoda; Taylor-Gjevre, Regina M.

2013-01-01

In 1891, Von Recklinghausen first established the association between the development of osteoporosis in the presence of overt hyperthyroidism. Subsequent reports have demonstrated that BMD loss is common in frank hyperthyroidism, and, to a lesser extent, in subclinical presentations. With the introduction of antithyroid medication in the 1940s to control biochemical hyperthyroidism, the accompanying bone disease became less clinically apparent as hyperthyroidism was more successfully treated medically. Consequently, the impact of the above normal thyroid hormones in the pathogenesis of osteoporosis may be presently underrecognized due to the widespread effective treatments. This review aims to present the current knowledge of the consequences of hyperthyroidism on bone metabolism. The vast number of recent papers touching on this topic highlights the recognized impact of this common medical condition on bone health. Our focus in this review was to search for answers to the following questions. What is the mechanisms of action of thyroid hormones on bone metabolism? What are the clinical consequences of hyperthyroidism on BMD and fracture risk? What differences are there between men and women with thyroid disease and how does menopause change the clinical outcomes? Lastly, we report how different treatments for hyperthyroidism benefit thyroid hormone-induced osteoporosis. PMID:23970897

Interactive effects of ambient acidity and salinity on thyroid function during acidic and post-acidic acclimation of air-breathing fish (Anabas testudineus Bloch).

PubMed

Peter, M C Subhash; Rejitha, V

2011-11-01

The interactive effects of ambient acidity and salinity on thyroid function are less understood in fish particularly in air-breathing fish. We, therefore, examined the thyroid function particularly the osmotic and metabolic competences of freshwater (FW) and salinity-adapted (SA; 20 ppt) air-breathing fish (Anabas testudineus) during acidic and post-acidic acclimation, i.e., during the exposure of fish to either acidified water (pH 4.2 and 5.2) for 48 h or clean water for 96 h after pre-exposure. A substantial rise in plasma T(4) occurred after acidic exposure of both FW and SA fish. Similarly, increased plasma T(3) and T(4) were found in FW fish kept for post-acidic acclimation and these suggest an involvement of THs in short-term acidic and post-acidic acclimation. Water acidification produced significant hyperglycaemia and hyperuremia in FW fish but not in SA fish. The SA fish when kept for post-acclimation, however, produced a significant hypouremia. In both FW and SA fish, gill Na(+), K(+)-ATPase activity decreased but kidney Na(+), K(+)-ATPase activity increased upon acidic acclimation. During post-acidic acclimation, gill Na(+), K(+)-ATPase activity of the FW fish showed a rise while decreasing its activity in the SA fish. Similarly, post-acidic acclimation reduced the Na(+), K(+)-ATPase activity of intestine but elevated its activity in the liver of SA fish. A higher tolerance of the SA fish to water acidification was evident in these fish as they showed tight plasma and tissue mineral status due to the ability of this fish to counteract the ion loss. In contrast, FW fish showed more sensitivity to water acidification as they loose more ions in that medium. The positive correlations of plasma THs with many tested metabolic and hydromineral indices of both FW and SA fish and also with water pH further confirm the involvement of THs in acidic and post-acidic acclimation in these fish. We conclude that thyroid function of this fish is more sensitive to environmental acidity than ambient salinity and salinity interference nullifies the toxic effect of water acidification. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical review: kinase inhibitors: adverse effects related to the endocrine system.

PubMed

Lodish, Maya B

2013-04-01

The use of kinase inhibitors (KIs) in the treatment of cancer has become increasingly common, and practitioners must be familiar with endocrine-related side effects associated with these agents. This review provides an update to the clinician regarding the management of potential endocrinological effects of KIs. PubMed was employed to identify relevant manuscripts. A review of the literature was conducted, and data were summarized and incorporated. KIs, including small molecule KIs and monoclonal antibodies directed against kinases, have emerged over the past decade as an important class of anticancer agents. KIs specifically interfere with signaling pathways that are dysregulated in certain types of cancers and also target common mechanisms of growth, invasion, metastasis, and angiogenesis. Currently, at least 20 KIs are approved as cancer therapeutics. However, KIs may affect a broad spectrum of targets and may have additional, unidentified mechanisms of action at the cellular level due to overlap between signaling pathways in the tumor cell and endocrine system. Recent reports in the literature have identified side effects associated with KIs, including alterations in thyroid function, bone metabolism, linear growth, gonadal function, fetal development, adrenal function, and glucose metabolism. Clinicians need to monitor the thyroid functions of patients on KIs. In addition, bone density and vitamin D status should be assessed. Special care should be taken to follow linear growth and development in children taking these agents. Clinicians should counsel patients appropriately on the potential adverse effects of KIs on fetal development.

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

Complications of thyroid and parathyroid surgery.

PubMed

Fewins, John; Simpson, C Blake; Miller, Frank R

2003-02-01

Today most complications of thyroid and parathyroid surgery are related to either metabolic derangements or injury to the recurrent laryngeal nerves. Other complications include superior laryngeal nerve injury, infection, airway compromise, and bleeding. Although the principal goal of thyroid and parathyroid surgery is the prevention of these complications, prompt recognition and intervention will minimize morbidity and provide the patient with the best chance of a satisfactory outcome.

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.

Relation with HOMA-IR and thyroid hormones in obese Turkish women with metabolic syndrome.

PubMed

Topsakal, S; Yerlikaya, E; Akin, F; Kaptanoglu, B; Erürker, T

2012-03-01

The aim of this study was to investigate the relationship between insulin resistance and thyroid function in obese pre- and postmenopausal women with or without metabolic syndrome (MetS). 141 obese women were divided into two groups, HOMA-IR<2.7 and HOMA-IR>2.7, to evaluate relation with HOMA-IR and fatness, hormone and blood parameters. They were then divided into four groups as pre- and postmenopausal with or without MetS. Various fatness, hormone and blood parameters were examined. Statistically significant difference was found in weight, body mass index (BMI), waist circumference, fat%, fasting insulin, TSH, FT3, FT4, FSH, Anti-microsomal antibody (ANTIM) and triglycerides levels in HOMA-IR<2.7 and HOMA-IR>2.7 obese Turkish women. This study showed that age, weight, BMI, waist circumference, fat%, fasting insulin, FT3, ANTIM, FSH, LH, total cholesterol, triglycerides, HDL, HOMA-IR, systolic and diastolic blood pressure levels were related in preand post menopausal status in obese women with or without MetS. Obesity may influence the levels of thyroid hormones and increases the risk of MetS in women. Postmenopausal status with MetS is associated with an increased TSH, FT3 and FT4 levels and HOMA-IR in obese women. Strong relation was observed with MetS and TSH and FT3 levels.

Nuclear Transcription Factors in the Mitochondria: A New Paradigm in Fine-Tuning Mitochondrial Metabolism.

PubMed

Sepuri, Naresh Babu V; Tammineni, Prasad; Mohammed, Fareed; Paripati, Arunkumar

2017-01-01

Noncanonical functions of several nuclear transcription factors in the mitochondria have been gaining exceptional traction over the years. These transcription factors include nuclear hormone receptors like estrogen, glucocorticoid, and thyroid hormone receptors: p53, IRF3, STAT3, STAT5, CREB, NF-kB, and MEF-2D. Mitochondria-localized nuclear transcription factors regulate mitochondrial processes like apoptosis, respiration and mitochondrial transcription albeit being nuclear in origin and having nuclear functions. Hence, the cell permits these multi-stationed transcription factors to orchestrate and fine-tune cellular metabolism at various levels of operation. Despite their ubiquitous distribution in different subcompartments of mitochondria, their targeting mechanism is poorly understood. Here, we review the current status of mitochondria-localized transcription factors and discuss the possible targeting mechanism besides the functional interplay between these factors.

Thyroid Hormone Receptor Antagonists: From Environmental Pollution to Novel Small Molecules.

PubMed

Mackenzie, Louise S

2018-01-01

Thyroid hormone receptors (TRs) are nuclear receptors which control transcription, and thereby have effects in all cells within the body. TRs are an important regulator in many basic physiological processes including development, growth, metabolism, and cardiac function. The hyperthyroid condition results from an over production of thyroid hormones resulting in a continual stimulation of thyroid receptors which is detrimental for the patient. Therapies for hyperthyroidism are available, but there is a need for new small molecules that act as TR antagonists to treat hyperthyroidism. Many compounds exhibit TR antagonism and are considered detrimental to health. Some drugs in the clinic (most importantly, amiodarone) and environmental pollution exhibit TR antagonist properties and thus have the potential to induce hypothyroidism in some people. This chapter provides an overview of novel small molecules that have been specifically designed or screened for their TR antagonist activity as novel treatments for hyperthyroidism. While novel compounds have been identified, to date none have been developed sufficiently to enter clinical trials. Furthermore, a discussion on other sources of TR antagonists is discussed in terms of side effects of current drugs in the clinic as well as environmental pollution. © 2018 Elsevier Inc. All rights reserved.

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 ...

Effects of a Model Inducer, Phenobarbital, on Thyroid Hormone Glucuronidation in Rat Hepatocytes

EPA Science Inventory

In vivo, hepatic enzyme inducers such as phenobarbital (PB) decrease circulating thyroid hormone (TH) concentrations. This decrease in circulating TH occurs in part through extrathyroidal mechanisms. Specifically, through the induction of hepatic xenobiotic metabolizing enzymes...

Iodine concentration calculated by dual-energy computed tomography (DECT) as a functional parameter to evaluate thyroid metabolism in patients with hyperthyroidism.

PubMed

Binh, Duong Duc; Nakajima, Takahito; Otake, Hidenori; Higuchi, Tetsuya; Tsushima, Yoshito

2017-07-19

Thyroid function in patients with Grave's disease is usually evaluated by thyroid scintigraphy with radioactive iodine. Recently, dual-energy computed tomography (DECT) with two different energy X-rays can calculate iodine concentrations and can be applied for iodine measurements in thyroid glands. This study aimed to assess the potential use of DECT for the functional assessment of the thyroid gland. Thirteen patients with Grave's disease treated at our hospital from May to September 2015 were included in this retrospective study. Before treatments, all subjects had undergone both iodine scintigraphy [three and 24 h after oral administration of 123 I (20 μCi)] and non-enhanced DECT. The region of interests (ROIs) were placed in both lobes of the thyroid glands, and CT values (HU: Hounsfield unit) and iodine concentrations (mg/mL) calculated from DECT images were measured. The correlation between CT values and iodine concentrations from DECT in the thyroid gland was evaluated and then the iodine concentrations were compared with radioactive iodine uptake ratios by thyroid scintigraphy. Mean (±SD) 123 I uptake increased from 46.3 (±22.2) % (range, 11.1-80.1) at 3 h, to 66.5 (±15.2) % (range, 40.0-86.1) at 24 h (p < 0.01). CT values ranged from 34.5 to 98.7 HU [mean: 67.8 (±18.6)], while the iodine concentrations calculated with DECT ranged from 0.0 to 1.3 mg/mL [mean: 0.5 (±0.4)]. A moderate positive correlation between CT values and the calculated iodine concentrations in the thyroid gland was seen (R = 0.429, p < 0.05). A significant negative correlation between 123 I uptake at 3 h and iodine concentration by DECT were seen (R = -0.680, p < 0.05), although no correlation was observed between 123 I uptake at 3 h and CT values (p = 0.087). No correlation was observed between 123 I uptake at 24 h and CT values (p = 0.153) or that between 123 I uptake at 24 h and iodine concentration by DECT (p = 0.073). The negative correlation of 123 I uptake at 3 h with iodine concentration evaluated by DECT was better than that observed with simple CT value. DECT may have a potential role in the evaluation of iodine turnover in hyperthyroid patients.

Associations between metabolic syndrome, serum thyrotropin, and thyroid antibodies status in postmenopausal women, and the role of interleukin-6.

PubMed

Siemińska, Lucyna; Wojciechowska, Celina; Walczak, Krzysztof; Borowski, Artur; Marek, Bogdan; Nowak, Mariusz; Kajdaniuk, Dariusz; Foltyn, Wanda; Kos-Kudła, Beata

2015-01-01

The prevalence of metabolic syndrome increases after menopause; however, the role of concomitant subclinical hypothyroidism has not been completely elucidated. The aim of the study was to identify associations between thyrotropin, immune status, inflammation, and metabolic syndrome in postmenopausal women. The specific goals were: to assess thyrotropin (TSH) and interleukin-6 (IL-6) concentrations in the serum of subclinical hypothyroid postmenopausal women with and without metabolic syndrome and compare them with euthyroid controls; to test whether immune status is related to metabolic syndrome in postmenopausal women and determine the role of IL-6; to examine the relationships between TSH and different features of metabolic syndrome: insulin resistance, waist circumferences, waist-to-hip ratio (WHR), BMI, metabolic parameters (triglycerides, total cholesterol and high-density lipoprotein cholesterol), and inflammatory cytokines (IL-6). Three hundred and seventy-two postmenopausal women were included in the study: 114 women had subclinical hypothyroidism (10.0 uIU/mL > TSH ≥ 4.5 uIU/mL, normal fT4), and 258 women were in euthyreosis (TSH 0.35-4.5 uIU/mL, normal fT4); both groups were matched by age. Anthropometric measurements were conducted (BMI, waist circumference, WHR) and blood pressure was measured. In all subjects the following were assessed in serum: lipid profile, glucose, insulin, TSH, fT4, thyroid antibodies (T-Abs) - TPO-Abs, TG-Abs, and IL-6 concentrations. The prevalence of metabolic syndrome was 49.12% in subclinical hypothyroid women and 46.89% in euthyroid women. However, the proportion of subjects with one or two abnormalities was significantly higher in the subclinical hypothyroid group (45.61%) than in the euthyroid group (32.17%). When we compared subclinical hypothyroid women with and without metabolic syndrome, subjects with metabolic syndrome had higher BMI, abdominal circumferences, WHR, and HOMA-I. They presented higher systolic and diastolic blood pressure. Serum concentrations of cholesterol, triglycerides, fasting glucose, IL-6, TSH, T-Abs were also higher and serum cHDL was lower. There were no significant differences in fT4 concentrations. A similar comparison was made for euthyroid women with and without metabolic syndrome. Higher BMI, waist circumference, WHR, HOMA-I, and systolic blood pressure were observed in subjects with metabolic syndrome. Serum concentrations of TSH, triglycerides, glucose, and IL-6 were also higher, but the concentration of cHDL was significantly lower. There were no significant differences in fT4, T-Abs, cholesterol levels, and diastolic pressure. When we compared euthyroid women T-Abs (+) and T-Abs (-), the prevalence of metabolic syndrome was similar (48.68% vs. 46.15%). There were no differences in BMI, waist circumference, WHR, lipid profile, glucose, and HOMA-I, fT4. However, thyroid autoimmunity was associated with elevated TSH and IL-6 levels. When we analysed subclinical hypothyroid women with and without thyroid autoimmunity, there were no significant differences in glucose and lipid profile. However, Hashimoto`s subjects were more obese, had higher waist circumference, WHR, HOMA-I, and higher prevalence of metabolic syndrome. Serum concentrations of TSH and IL-6 were also higher and fT4 was lower. Among all of the women, serum TSH concentration was significantly correlated with BMI, waist circumference, WHR, systolic blood pressure, cholesterol, triglycerides, and TPO-Abs. When the variables of subjects with upper quartile of TSH were compared with lower quartile of TSH, we found significantly higher BMI, waist circumference, WHR, increased concentration of IL-6, cholesterol, triglycerides, and T-Abs, and concentrations of cHDL and fT4 were lower. OR for metabolic syndrome in subjects with upper quartile TSH vs. lower quartile was 1.35 (95% confidence interval [CI] 1.10-1.60). Our study confirms that metabolic syndrome in both euthyroid and subclinical hypothyroid women is connected with obesity, visceral fat accumulation, and higher TSH and IL-6 concentrations. Immune thyroiditis is associated with higher TSH and IL-6 levels. Obese subclinical hypothyroid women with Hashimoto`s thyroditis have a higher prevalence of metabolic syndrome when compared with subclinical hypothyroid women without thyroid autoimmunity. It is possible that in the crosstalking between subclinical hypothyroidism and metabolic syndrome, enhanced proinflammatory cytokine release in the course of immunological thyroiditis plays a role.

Calcitonin control of calcium metabolism during weightlessness

NASA Technical Reports Server (NTRS)

Soliman, Karam F. A.

1993-01-01

The main objective of this proposal is to elucidate calcitonin role in calcium homeostasis during weightlessness. In this investigation our objectives are to study: the effect of weightlessness on thyroid and serum calcitonin, the effect of weightlessness on the circadian variation of calcitonin in serum and the thyroid gland, the role of light as zeitgeber for calcitonin circadian rhythm, the circadian pattern of thyroid sensitivity to release calcitonin in response to calcium load, and the role of serotonin and norepinephrine in the control of calcitonin release. The main objective of this research/proposal is to establish the role of calcitonin in calcium metabolism during weightlessness condition. Understanding the mechanism of these abnormalities will help in developing therapeutic means to counter calcium imbalance in spaceflights.

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

PubMed

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

2016-10-01

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

Prevalence of subclinical hypothyroidism in obese children or adolescents and association between thyroid hormone and the components of metabolic syndrome.

PubMed

Jin, Hye Young

2018-05-16

Subclinical hypothyroidism is defined as elevated thyroid-stimulating hormone (TSH) levels with the normal concentrations of thyroxine (T4) or free thyroxine (fT4), and its clinical significance is unclear. The purpose of this study is to investigate the prevalence of subclinical hypothyroidism in children and adolescents and determine the relationship between lipid profiles, insulin resistance and thyroid hormones. A retrospective, cross-sectional study was performed using data from a subset of the KNHANES VI. The subjects whose ages were in the range of 10-19 years were enrolled when their thyroid function tests were available (n = 1104), and their laboratory and anthropometric data were analysed. Subclinical hypothyroidism was more commonly identified in the obese group (27 of 111) compared to the other groups (127 of 993) (24.3 vs. 12.8%, P = 0.002). Total cholesterol and triglyceride levels were higher in a group with subclinical hypothyroidism. Body mass index (BMI) was positively correlated with serum concentrations of the TSH and negatively correlated with serum concentrations of fT4 after adjusting for age. The concentrations of total cholesterol and triglyceride were positively correlated with the TSH concentrations following adjustment for age and BMI standard deviation scores. The fT4 concentrations were negatively linked with total cholesterol after adjusting for age and BMI standard deviation scores. No significant correlation was found between insulin resistance index and TSH and fT4. Subclinical hypothyroidism was common in the obese group, and the concentrations of TSH were linked with the lipid profile. Subclinical hypothyroidism in obese children or adolescents should be closely monitored while also evaluating metabolic risk factors. © 2018 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

Ultrasonographic assessment of the thyroid gland structure in inflammatory bowel disease patients.

PubMed

Neubauer, Katarzyna; Woźniak-Stolarska, Barbara

2012-01-01

The etiopathogenesis of inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is still not fully elucidated and seems to be multifactorial. It has been suggested that genetic, immunological and environmental factors participate in IBD development. IBD extraintestinal manifestations include rheumatic, metabolic, dermatologic, ophthalmologic, hepatobiliary, pancreatic, urologic, pulmonary, neurological, hematological and thromboembolic complications. Thyroid gland diseases have not been confirmed as extraintestinal manifestations of IBD. However, it is known that some thyroid diseases share an immunological background with IBD, and that dysfunction of the thyroid gland may induce gastrointestinal symptoms. Ultrasound examination is the gold standard for evaluation of thyroid gland morphology. This study was designed to assess the prevalence of abnormalities in the structure of the thyroid gland in IBD patients and to compare it to the control group. The study group consisted of 199 consecutive IBD patients (80 CD patients and 119 UC patients) hospitalized at the Department of Gastroenterology and Hepatology of Wroclaw Medical University (Poland). The control group consisted of 42 healthy volunteers and patients with functional gastrointestinal disorders. The most common finding in the ultrasound examination in IBD patients were tumors. Tumors, which were smaller than or equal to 10 mm were present in 11.5% of IBD patients; and tumors larger than 10 mm were present in 13.1%. These results show that small tumors (less than 10 mm in diameter) of the thyroid gland are more frequent among patients with CD and UC compared to the control group (p = 0.0001 and p = 0.001, respectively). Additionally, enlargement of the thyroid gland occurs more often in UC patients compared to the control group (p = 0.003). There was no difference in the frequency of thyroid abnormalities between UC and CD patients. In patients with inflammatory bowel diseases focal lesions relating to tumors of the thyroid gland are more common than in the control group. In patients with ulcerative colitis enlargement of the thyroid gland is more frequent than in the control group. Initial assessments of IBD patients should include ultrasound examinations of the thyroid gland.

Photoacoustic spectroscopic differences between normal and malignant thyroid tissues

NASA Astrophysics Data System (ADS)

Li, Li; Xie, Wengming; Li, Hui

2012-12-01

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

Positron emission tomography as an aid in the diagnosis and follow-up of Riedel's thyroiditis.

PubMed

Kotilainen, Pirkko; Airas, Laura; Kojo, Tiina; Kurki, Timo; Kataja, Kaisa; Minn, Heikki; Nuutila, Pirjo

2004-06-01

We describe the usage of positron emission tomography (PET) as an aid in the initial diagnosis and follow-up of Riedel's thyroiditis. A 41-year-old patient was admitted for an enlarged and tender thyroid gland in association with severe systemic symptoms of inflammation. Imaging with fluorine-18 fluorodeoxyglucose (FDG) and PET demonstrated an intensive uptake of FDG in both lobes of the thyroid gland as an indication of severe inflammation. The diagnosis of Riedel's thyroiditis was confirmed by the histological findings of biopsy specimens taken during a palliative thyroid resection. The inflammatory symptoms and local pain dramatically disappeared after commencement of high-dose corticosteroid therapy. A follow-up PET scan after 2 weeks of corticosteroid treatment showed a 60% decrease in the uptake of FDG in the thyroid. This indicates that FDG metabolic activity can also be used to assess a patient's response to therapy in Riedel's thyroiditis.

The Lipid Parameters and Lipoprotein(a) Excess in Hashimoto Thyroiditis.

PubMed

Yetkin, D O; Dogantekin, B

2015-01-01

Objective. The risk of atherosclerotic heart disease is increased in autoimmune thyroiditis, although the reason is not clear. Lipoprotein(a) (Lp(a)) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. The aim of this study is to investigate the relationship between Lp(a) levels and thyroid hormones in Hashimoto patients. Method. 154 premenopausal female Hashimoto patients (48 patients with overthypothyroid (OH), 50 patients with subclinical hypothyroid (SH), and 56 patients with euthyroid Hashimoto to (EH)) were enrolled in this study. The control group consists of 50 age matched volunteers. In every group, thyroid function tests and lipid parameters with Lp(a) were measured. Lp(a) excess was defined as Lp(a) > 30 mg/dL. Results. Total-C, LDL-C, TG, and Lp(a) levels were increased in Hashimoto group. Total-C, LDL-C, and TG levels were higher in SH group than in the control group. Total-C and LDL-C levels were also higher in EH group compared to controls. Lp(a) levels were similar in SH and EH groups with controls. However, excess Lp(a) was more common in subclinical hypothyroid and euthyroid Hashimoto group than in the control group. Conclusion. The Total-C and LDL-C levels and excess Lp(a) were higher even in euthyroid Hashimoto patients. Thyroid autoimmunity may have some effect on Lp(a) and lipid metabolism.

The Lipid Parameters and Lipoprotein(a) Excess in Hashimoto Thyroiditis

PubMed Central

Yetkin, D. O.; Dogantekin, B.

2015-01-01

Objective. The risk of atherosclerotic heart disease is increased in autoimmune thyroiditis, although the reason is not clear. Lipoprotein(a) (Lp(a)) excess has been identified as a powerful predictor of premature atherosclerotic vascular diseases. The aim of this study is to investigate the relationship between Lp(a) levels and thyroid hormones in Hashimoto patients. Method. 154 premenopausal female Hashimoto patients (48 patients with overthypothyroid (OH), 50 patients with subclinical hypothyroid (SH), and 56 patients with euthyroid Hashimoto to (EH)) were enrolled in this study. The control group consists of 50 age matched volunteers. In every group, thyroid function tests and lipid parameters with Lp(a) were measured. Lp(a) excess was defined as Lp(a) > 30 mg/dL. Results. Total-C, LDL-C, TG, and Lp(a) levels were increased in Hashimoto group. Total-C, LDL-C, and TG levels were higher in SH group than in the control group. Total-C and LDL-C levels were also higher in EH group compared to controls. Lp(a) levels were similar in SH and EH groups with controls. However, excess Lp(a) was more common in subclinical hypothyroid and euthyroid Hashimoto group than in the control group. Conclusion. The Total-C and LDL-C levels and excess Lp(a) were higher even in euthyroid Hashimoto patients. Thyroid autoimmunity may have some effect on Lp(a) and lipid metabolism. PMID:26064115

Progressive Ischemic Stroke due to Thyroid Storm-Associated Cerebral Venous Thrombosis

PubMed Central

Tanabe, Natsumi; Hiraoka, Eiji; Hoshino, Masataka; Deshpande, Gautam A.; Sawada, Kana; Norisue, Yasuhiro; Tsukuda, Jumpei; Suzuki, Toshihiko

2017-01-01

Patient: Female, 49 Final Diagnosis: Cerebral venous thrombosis Symptoms: Altered mental state • weakness in limbs Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Cerebral venous thrombosis (CVT) is a rare but fatal complication of hyperthyroidism that is induced by the hypercoagulable state of thyrotoxicosis. Although it is frequently difficult to diagnose CVT promptly, it is important to consider it in the differential diagnosis when a hyperthyroid patient presents with atypical neurologic symptoms. Care Report: A 49-year-old Japanese female with unremarkable medical history came in with thyroid storm and multiple progressive ischemic stroke identified at another hospital. Treatment for thyroid storm with beta-blocker, glucocorticoid, and potassium iodide-iodine was started and MR venography was performed on hospital day 3 for further evaluation of her progressive ischemic stroke. The MRI showed CVT, and anticoagulation therapy, in addition to the anti-thyroid agents, was initiated. The patient’s thyroid function was successfully stabilized by hospital day 10 and further progression of CVT was prevented. Conclusions: Physicians should consider CVT when a patient presents with atypical course of stroke or with atypical MRI findings such as high intensity area in apparent diffusion coefficient (ADC) mapping. Not only is an early diagnosis and initiation of anticoagulation important, but identifying and treating the underlying disease is essential to avoid the progression of CVT. PMID:28228636

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

PubMed Central

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

2016-01-01

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

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

PubMed Central

Portulano, Carla; Paroder-Belenitsky, Monika

2014-01-01

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

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

PubMed

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

2017-06-09

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

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

PubMed

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

2004-03-30

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

An Adolescent Boy with Comorbid Anorexia Nervosa and Hashimoto Thyroiditis.

PubMed

Pehlivantürk Kızılkan, Melis; Kanbur, Nuray; Akgül, Sinem; Alikaşifoğlu, Ayfer

2016-03-05

Low triiodothyronine syndrome is a physiological adaptation encountered in anorexia nervosa (AN) and generally improves with sufficient weight gain. However, when a primary thyroid pathology accompanies AN, both the evaluation of thyroid hormone levels and the management of the co-morbid disease become more challenging. Hashimoto thyroiditis could complicate the management of AN by causing hyper- or hypothyroidism. AN could also negatively affect the treatment of Hashimoto thyroiditis by altering body weight and metabolic rate, as well as by causing drug non-compliance. We present the case of a 15-year-old boy with comorbid AN restrictive sub-type and Hashimoto thyroiditis. In this case report, we aimed to draw attention to the challenges that could be encountered in the diagnosis, treatment, and follow-up of patients with AN when accompanied by Hashimoto thyroiditis.

An Adolescent Boy with Comorbid Anorexia Nervosa and Hashimoto Thyroiditis

PubMed Central

Pehlivantürk Kızılkan, Melis; Kanbur, Nuray; Akgül, Sinem; Alikaşifoğlu, Ayfer

2016-01-01

Low triiodothyronine syndrome is a physiological adaptation encountered in anorexia nervosa (AN) and generally improves with sufficient weight gain. However, when a primary thyroid pathology accompanies AN, both the evaluation of thyroid hormone levels and the management of the co-morbid disease become more challenging. Hashimoto thyroiditis could complicate the management of AN by causing hyper- or hypothyroidism. AN could also negatively affect the treatment of Hashimoto thyroiditis by altering body weight and metabolic rate, as well as by causing drug non-compliance. We present the case of a 15-year-old boy with comorbid AN restrictive sub-type and Hashimoto thyroiditis. In this case report, we aimed to draw attention to the challenges that could be encountered in the diagnosis, treatment, and follow-up of patients with AN when accompanied by Hashimoto thyroiditis. PMID:26757948

Acute and emergency care for thyrotoxicosis and thyroid storm.

PubMed

Idrose, Alzamani Mohammad

2015-07-01

Thyroid hormones affect all organ systems and, in excess, can cause increased metabolic rate, heart rate, ventricle contractility, and gastrointestinal motility as well as muscle and central nervous system excitability. Thyroid storm is the extreme manifestation of thyrotoxicosis with an estimated incidence of 0.20 per 100,000 per year among hospitalized patients in Japan. The mortality of thyroid storm without treatment ranges from 80% to 100%; but with treatment, the mortality rate is between 10% and 50%. The diagnostic strategy for thyroid storm may take into consideration Burch-Wartofsky scoring or Akamizu's diagnostic criteria. Multiple treatment aims need to be addressed in managing thyroid storm effectively. This paper puts together all aspects to be considered for the management of hyperthyroidism and thyroid storm during the acute and emergency phase as well as consideration of special populations.

Acute and emergency care for thyrotoxicosis and thyroid storm

PubMed Central

2015-01-01

Thyroid hormones affect all organ systems and, in excess, can cause increased metabolic rate, heart rate, ventricle contractility, and gastrointestinal motility as well as muscle and central nervous system excitability. Thyroid storm is the extreme manifestation of thyrotoxicosis with an estimated incidence of 0.20 per 100,000 per year among hospitalized patients in Japan. The mortality of thyroid storm without treatment ranges from 80% to 100%; but with treatment, the mortality rate is between 10% and 50%. The diagnostic strategy for thyroid storm may take into consideration Burch–Wartofsky scoring or Akamizu's diagnostic criteria. Multiple treatment aims need to be addressed in managing thyroid storm effectively. This paper puts together all aspects to be considered for the management of hyperthyroidism and thyroid storm during the acute and emergency phase as well as consideration of special populations. PMID:29123713

[Influence of replacement growth hormone therapy (hGH) on pituitary-thyroid and pituitary-adrenal systems in prepubertal children with GH deficiency].

PubMed

Vyshnevs'ka, O A; Bol'shova, O V

2013-06-01

Today, the most pathogenic therapy of GH deficiency is hGH replacement therapy. Replacement hGH therapy a highly effective method of growth correction in children with GH deficiency, but further investigations are necessary for timely detection of disturbances of other organs and systems. The authors reported that hGH therapy supressed thyroid and adrenal functions. Besides, most patients with GH deficiency have multiple defficiency of pituitary hormones (both TSH and ACTH), so hGH therapy can enhances hypothyroidism and hypoadrenalism. In the Department of Pediatric Endocrinology of the Institute of Endocrinology and Metabolism a great experience was accumulated in the treatment of GH deficiency children and in the study of the efficacy and safety of this treatment.

Thyroid hormones and cognitive functioning in healthy, euthyroid women: a correlational study.

PubMed

Grigorova, Miglena; Sherwin, Barbara B

2012-04-01

Thyroid hormones (THs) play a critical role in differentiation, growth, and metabolism of animal and human organ systems, including the brain. Although associations between normal levels of THs and cognitive functions in healthy elderly individuals have been reported, the findings are inconsistent, possibly due to differences in study designs. Because thyroid disease occurs more frequently in women, the goal of the present study was to examine the relationship between levels of THs and performance on neuropsychological tests in 122 healthy, euthyroid women whose mean age was 51 years. Higher levels of free T3 were positively associated with longer completion times (slower performance) on Trail Making Test - Part A (p = 0.006) and Part B (p = 0.032) and on the Tower of London test (p = 0.002). Higher levels of thyroglobulin antibodies (TgAb) were positively correlated with more errors on the Trail Making Test Part B (p = 0.000), on the Word Fluency test (p = 0.023), and on the Design Fluency test (p = 0.045). No significant correlations between TH levels and scores on mood, verbal memory, or working memory measures were observed. The findings point to a possible link between THs and cognitive processes that are mediated primarily by frontal cortex, areas associated with executive function tasks, and suggest that elevations in levels of free T3 and TgAB within the normal range may negatively influence executive functions. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

Marginal iodide deficiency and thyroid function: dose-response analysis for quantitative pharmacokinetic modeling.

PubMed

Gilbert, M E; McLanahan, E D; Hedge, J; Crofton, K M; Fisher, J W; Valentín-Blasini, L; Blount, B C

2011-04-28

Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25, or 0 μg/kg I to the base diet (~25 μg I/kg chow) to produce 5 nominal I levels, ranging from excess (basal+added I, Treatment 1: 1000 μg I/kg chow) to deficient (Treatment 5: 25 μg I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation. Published by Elsevier Ireland Ltd.

Hyperthyroidism After Allogeneic Hematopoietic Stem Cell Transplantation: A Report of Four Cases

PubMed Central

Sağ, Erdal; Gönç, Nazlı; Alikaşifoğlu, Ayfer; Kuşkonmaz, Barış; Uçkan, Duygu; Özön, Alev; Kandemir, Nurgün

2015-01-01

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for many hematological disorders, primary immunodeficiencies, and metabolic disorders. Thyroid dysfunction is one of the frequently seen complications of HSCT. However, hyperthyroidism due to Graves’ disease, autoimmune thyroiditis, and thyrotoxicosis are rare. Herein, we report a series of 4 patients who were euthyroid before HSCT but developed hyperthyroidism (3 of them developed autoimmune thyroid disease) after transplantation. PMID:26777050

Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance

PubMed Central

Alvarez-Crespo, Mayte; Csikasz, Robert I.; Martínez-Sánchez, Noelia; Diéguez, Carlos; Cannon, Barbara; Nedergaard, Jan; López, Miguel

2016-01-01

Objective Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Methods Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. Results We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). Conclusions We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. PMID:27069867

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

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

PubMed

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

2018-03-01

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

Orchidectomy of middle-aged rats decreases liver deiodinase 1 and pituitary deiodinase 2 activity.

PubMed

Sosic-Jurjevic, Branka; Filipovic, Branko; Renko, Kostja; Ajdzanovic, Vladimir; Manojlovic-Stojanoski, Milica; Milosevic, Verica; Köhrle, Josef

2012-11-01

Endogenous androgens are involved in regulation of thyroid function and metabolism of thyroid hormones. As serum testosterone level progressively declines with age, this regulation may change. We tested how androgen deprivation, achieved by orchidectomy, affects thyroid homeostasis in middle-aged rats. Fifteen-month-old Wistar rats were orchidectomized (Orx) or sham-operated under ketamine anesthesia (15 mg/kg body weight). Five weeks after the surgery, animals were decapitated. Thyroids were used for histomorphometric and ultrastructural examinations and together with livers and pituitaries for real-time quantitative PCR and deiodinase (DIO) activity measurements. Serum testosterone, TSH, l-thyroxine (T(4)), and cholesterol (Chol) levels were determined. As expected, middle-aged control rats had lower (P<0.05) testosterone and T(4) compared with 3-month-old males. In the Orx middle-aged group, we detected diminished serum testosterone (P<0.05), no change in TSH and T(4) levels, and higher Chol level (P<0.05), in comparison with age-matched controls. Histomorphometric analysis of thyroid tissue revealed decreased relative volume densities of follicles and colloid (P<0.05). Relevant gene expressions and DIO1 enzyme activity were not changed in the thyroids of Orx rats. Liver Dio1 gene expression and DIO1 activity were decreased (P<0.05) in comparison with the control values. Pituitary levels of TSHβ, Dio1, and Dio2 mRNAs did not change, while DIO2 activity decreased (P<0.05). In conclusion, orchidectomy of middle-aged rats affected thyroid structure with no effect on serum T(4) and TSH. However, decreased liver DIO1 and pituitary DIO2 enzyme activities indicate compensatory-adaptive changes in local T(3) production.

Circulating levels of irisin is elevated in hypothyroidism, a case-control study.

PubMed

Ateş, İhsan; Altay, Mustafa; Topçuoğlu, Canan; Yılmaz, Fatma Meriç

2016-04-01

Objective Our objective in this study was to determine the relationship between irisin hormone, which has a similar effect with thyroid hormones on adipose tissue and the metabolism, and the thyroid functions and the obesity secondary to thyroid disease. Subjects and methods Seventy-four patients were included in the study, of the patients, 37 were newly diagnosed with Hashimoto's thyroiditis related hypothyroidism but not started on a treatment yet, and the remaining 37 were healthy volunteers without a known disease. Serum thyroid stimulating hormone (TSH), free thyroxin (fT4), anti-thyroglobulin and anti-thyroid peroxidase were measured and thyroid ultrasonography was performed in both groups. Serum irisin levels were measured using the commercially available ELISA kit. The hypothyroidism group had higher levels of irisin compared to the control group (2.77 ng/mL vs. 2.15 ng/mL respectively; p = 0.017). Results The hypothyroidism group had higher median levels of irisin in the obese patients than those in the control group (3.10 ng/mL vs. 2.10 ng/mL respectively; p = 0.013). Irisin level was negatively correlated with age in the whole population and patients with hypothyroidism (r = -0.255, p = 0.028; r = -0.346, p = 0.036 respectively). Irisin level was positively correlated with TSH (r = 0.247, p = 0.034) but negatively correlated with the fT4 (r = -0.316, p = 0.006) in the whole population. Obesity, fT4 and irisin levels were identified to be independent predictors in the diagnosis of hypothyroidism in the multivariable logistic regression analysis. Conclusion To the best of our knowledge, this study is the first in literature to identify that obesity, irisin level and fT4 level are independent risk factors for hypothyroidism.

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

PubMed

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

2016-03-22

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

TAS2R bitter taste receptors regulate thyroid function

PubMed Central

Clark, Adam A.; Dotson, Cedrick D.; Elson, Amanda E. T.; Voigt, Anja; Boehm, Ulrich; Meyerhof, Wolfgang; Steinle, Nanette I.; Munger, Steven D.

2015-01-01

Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca2+ increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca2+ release in Nthy-Ori 3-1 cells, but not basal Ca2+ levels, in a dose-dependent manner. Ca2+ responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo- or hyperthyroidism.—Clark, A. A., Dotson, C. D., Elson, A. E. T., Voigt, A., Boehm, U., Meyerhof, W., Steinle, N. I., Munger, S. D. TAS2R bitter taste receptors regulate thyroid function. PMID:25342133

A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic serum parameters: II. Effects upon thyroid function, gastrin, STH, and glucose tolerance.

PubMed

Kuhl, H; Gahn, G; Romberg, G; Althoff, P H; Taubert, H D

1985-07-01

The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon thyroid function and some other biochemical serum parameters was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle. There was a significant increase (13%) in basal glucose level during treatment with both OC, but no change in glucose tolerance. Both the EE/NG and FE/DG preparation elevated serum T4 (40%), FT4 (15-22%), T3 (17-28%), and TBG (20%) significant, whereby the effect was more pronounced during the second treatment period after washing-out. The effective thyroxine ratio (ETR) was slightly (4%) but significantly increased. Contrary to this, the levels of FT3, reverse T3 (rT3), TSH, and gastrin were not altered. STH showed great individual fluctuations, but was significantly elevated by 50% during treatment with both OC. There was no effect of endogenous estradiol upon thyroid or other parameter, even though it was raised considerably in some women under OC. Although the increase in T4 and T3 is probably due to a rise in estrogen-induced TBG production, the data seem to indicate that there is a slight but effective stimulation of thyroid function during treatment with low-dose OC.

Thyroid hormones: Possible roles in epilepsy pathology.

PubMed

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

2015-09-01

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

Metabolic Effects of Liothyronine Therapy in Hypothyroidism: A Randomized, Double-Blind, Crossover Trial of Liothyronine Versus Levothyroxine

PubMed Central

Zemskova, Marina; Linderman, Joyce D.; Smith, Sheila; Drinkard, Bart; Sachdev, Vandana; Skarulis, Monica C.; Kozlosky, Merel; Csako, Gyorgy; Costello, Rene; Pucino, Frank

2011-01-01

Context: Levothyroxine (l-T4) therapy is based on the assumption that the conversion of T4 into T3 provides adequate amounts of active hormone at target tissues. However, in rodents, l-T4 alone does not restore a euthyroid state in all tissues. Previous combination l-T4/liothyronine (l-T3) therapy trials focused on quality-of-life endpoints, and limited information is available on the effects on other measures of thyroid hormone action. Objective: Our objective was to evaluate the efficacy of thyroid hormone replacement with l-T4 or l-T3 at doses producing equivalent normalization of TSH. Participants, Design, and Setting: Fourteen hypothyroid patients participated in this randomized, double-blind, crossover intervention at the National Institutes of Health Clinical Center. Interventions: l-T3 or l-T4 were administered thrice daily to achieve a target TSH from 0.5–1.5 mU/liter. Volunteers were studied as inpatients after 6 wk on a stable dose and at the target TSH. Main Outcome Measures: Serum thyroid hormones, lipid parameters, and indices of glucose metabolism were evaluated. Results: No difference was observed in TSH between l-T3 and l-T4 treatments. l-T3 resulted in significant weight loss [l-T4, 70.6 ± 12.5, vs. l-T3, 68.5 ± 11.9 kg (P = 0.009)] and in a 10.9 ± 10.0% decrease in total cholesterol (P = 0.002), 13.3 ± 12.1% decrease in low-density lipoprotein-cholesterol (P = 0.002), and an 18.3 ± 28.6% decrease in apolipoprotein B (P = 0.018). No significant differences were observed in high-density lipoprotein-cholesterol, heart rate, blood pressure, exercise tolerance, or insulin sensitivity. Conclusions: The substitution of l-T3 for l-T4 at equivalent doses (relative to the pituitary) reduced body weight and resulted in greater thyroid hormone action on the lipid metabolism, without detected differences in cardiovascular function or insulin sensitivity. PMID:21865366

Atherosclerosis affecting vision: therapy.

PubMed

Eggers, H

1966-05-01

The visual consequences and the pathogenesis and therapy of atherosclerosis are discussed. Atherosclerosis apparently is the result of hepatic failure to produce a stable suspension of cholesterol esters in the plasma. In some instances this represents an inherent metabolic defect. Usually it represents improper diet, namely, the excessive intake of saturated fatty acids and the inadequate intake of polyunsaturated fatty acids. Excessive ingestion of carbohydrates, insufficient physical exercise and reduced thyroid function are contributing causes. The final common denominators leading to tissue injury and destruction are vascular insufficiency and hypoxia. Hypertension is a separate disease, often concurrent with atherosclerosis. In diabetes, also a separate disease, atherosclerosis is one of the sequelae. Therapy primarily consists of the reduction or elimination of meat and milk fats from the diet, and the inclusion or increase of marine fats and vegetable oils. Simultaneously, carbohydrate intake is restricted. Adequate thyroid function, a normal hemoglobin level, and sufficient physical exercise are important. A supplementary intake of vitamins B6 and E, and of lipotropic substances is recommended.

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

NASA Astrophysics Data System (ADS)

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

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

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.

Altered Fructosamine and Lipid Fractions in Subclinical Hypothyroidism

PubMed Central

Udupa, Sridevi V.; Manjrekar, Poornima A.; Udupa, Vinit A.; Vivian, D’Souza

2013-01-01

Background: Thyroid function disorders lead to changes in the lipoprotein metabolism. Objectives: To study the lipid and the glycaemic abnormalities in the subclinical hypothyroidism cases and to compare the same with the euthyroid, overt hypothyroid and the hyperthyroid subjects. Methodology: Four groups, euthyroid (Group-I), hypothyroid (Group-II), subclinical hypothyroid (Group-III) and hyperthyroid (Group-IV), which consisted of 30 subjects each, of either sex, who were aged 25-55 years, underwent Fasting Plasma Glucose (FPG), fructosamine, lipid profile and total T3, T4 and TSH estimations. The subjects who were on lipid lowering or thyroid disorder drugs and known diabetics were excluded from the study. Results: In Group-III, all the lipid fractions were comparable to those of Group-II and they were significantly deranged, as compared to those of Group-I. The fructosamine levels were significantly higher in Group-II and Group-III (p<0.05), but the subclinical hypothyroid pool had statistically lower levels than the hypothyroid pool (376.63±54.73, 587.80±65.10). In the Group-IV patients, the LDL-C levels were significantly higher as compared to those in the euthyroid pool. The fructosamine levels were significantly lower in comparison with both the euthyroid and the hypothyroid pools (both in Groups-II and III). The FPG levels were higher in all the classes of the thyroid abnormalities (subclinical hypothyroidnot significant) but within the reference range of 70-100mg/dl. Conclusion: Since the lipid derangement in subclinical hypothyroidism is on par with that in overt hypothyrodism, the subclinical hypothyroid cases also need to be treated similarly. The fructosamine values which are largely in excess of the FPG values, indicate a higher propensity to glycation and a decreased turnover of the proteins in the hypothyroid and the subclinical hypothyroid pools. Vice versa is true of the hyperthyroid pool. Fructosamine can be included in the thyroid work up of the patients to assess the metabolic function and the subsequent response after the initiation of the therapy. PMID:23449765

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.

Endocrine profiles and neuropsychologic correlates of functional hypothalamic amenorrhea in adolescents.

PubMed

Bomba, Monica; Gambera, Alessandro; Bonini, Luisa; Peroni, Maria; Neri, Francesca; Scagliola, Pasquale; Nacinovich, Renata

2007-04-01

To determine trigger factors and neuropsychologic correlates of functional hypothalamic amenorrhea (FHA) in adolescence and to evaluate the correlations with the endocrine-metabolic profile. Cross-sectional comparison of adolescents with FHA and eumenorrheic controls Academic medical institution Twenty adolescent girls with FHA (aged <18 years) and 20 normal cycling girls All subjects underwent endocrine-gynecologic (hormone) and neuropsychiatric (tests and interview) investigations. A separate semistructured interview was also used to investigate parents. Gonadotropins, leptin, prolactin, androgens, estrogens, cortisol, carrier proteins (SHBG, insulin-like growth factor-binding protein 1), and metabolic parameters (insulin, insulin-like growth factor 1, thyroid hormones) were assayed in FHA and control subjects. All girls were evaluated using a test for depression, a test for disordered eating, and a psychodynamic semistructured interview. Adolescents with FHA showed a particular susceptibility to common life events, restrictive disordered eating, depressive traits, and psychosomatic disorders. The endocrine-metabolic profile was strictly correlated to the severity of the psychopathology. Functional hypothalamic amenorrhea in adolescence is due to a particular neuropsychologic vulnerability to stress, probably related to familial relationship styles, expressed by a proportional endocrine impairment.

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.

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

PubMed

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

2005-12-01

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

Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms*

PubMed Central

Wang, Yong; Yu, Xing; Zhao, Qun-zi; Zheng, Shu; Qing, Wen-jie; Miao, Chun-di; Sanjay, Jaiswal

2016-01-01

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trβ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis. PMID:27381728

Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms.

PubMed

Wang, Yong; Yu, Xing; Zhao, Qun-Zi; Zheng, Shu; Qing, Wen-Jie; Miao, Chun-di; Sanjay, Jaiswal

2016-07-01

We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trβ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis.

Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake.

PubMed

Carreras, M C; Peralta, J G; Converso, D P; Finocchietto, P V; Rebagliati, I; Zaninovich, A A; Poderoso, J J

2001-12-01

Changes in O(2) uptake at different thyroid status have been explained on the basis of the modulation of mitochondrial enzymes and membrane biophysical properties. Regarding the nitric oxide (NO) effects, we tested whether liver mitochondrial nitric oxide synthase (mtNOS) participates in the modulation of O(2) uptake in thyroid disorders. Wistar rats were inoculated with 400 microCi (131)I (hypothyroid group), 20 microg thyroxine (T(4))/100 g body wt administered daily for 2 wk (hyperthyroid group) or vehicle (control). Basal metabolic rate, mitochondrial function, and mtNOS activity were analyzed. Systemic and liver mitochondrial O(2) uptake and cytochrome oxidase activity were lower in hypothyroid rats with respect to controls; mitochondrial parameters were further decreased by L-arginine (-42 and -34%, P < 0.05), consistent with 5- to 10-fold increases in matrix NO concentration. Accordingly, mtNOS expression (75%) and activity (260%) were selectively increased in hypothyroidism and reverted by hormone replacement without changes in other nitric oxide isoforms. Moreover, mtNOS activity correlated with serum 3,5,3'-triiodothyronine (T(3)) and O(2) uptake. Increased mtNOS activity was also observed in skeletal muscle mitochondria from hypothyroid rats. Therefore, we suggest that modulation of mtNOS is a substantial part of thyroid effects on mitochondrial O(2) uptake.

Thyroid Hormone Role and Economy in the Developing Testis.

PubMed

Hernandez, Arturo

2018-01-01

Thyroid hormones (TH) exhibit pleiotropic regulatory effects on growth, development, and metabolism, and it is becoming increasingly apparent that the developing testis is an important target for them. Testicular development is highly dependent on TH status. Both hypo- and hyperthyroidism affect testis size and the proliferation and differentiation of Sertoli, Leydig, and germ cells, with consequences for steroidogenesis, spermatogenesis, and male fertility. These observations suggest that an appropriate content of TH and by implication TH action in the testis, whether the result of systemic hormonal levels or regulatory mechanisms at the local level, is critical for normal testicular and reproductive function. The available evidence indicates the presence in the developing testis of a number of transporters, deiodinases and receptors that could play a role in the timely delivery of TH action on testicular cells. These include the thyroid hormone receptor alpha (THRA), the MCT8 transporter, the TH-activating deiodinase DIO2, and the TH-inactivating deiodinase DIO3, all of which appear to modulate testicular TH economy and testis outcomes. © 2018 Elsevier Inc. All rights reserved.

Plasmatic endothelin-1 levels in hyperthyroid patients before and after antithyroid therapy.

PubMed

Cesareo, R; Tarabuso, A; Di Benedetto, M; Lacerna, F; Reda, G

2000-03-01

The Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial cells in many vascular diseases probably as a response to vessel damage. In hyperthyroidism as in other endocrinological diseases elevated ET-1 plasma levels have been found. The effect of antithyroid therapy on ET-1 plasmatic levels was evaluated by measuring ET-1 plasma levels before and 2 and 6 months after treatment with methimazole in 14 patients affected by hyperthyroidism. The hyperthyroid patients had significantly higher ET-1 levels than the controls (18.85 +/- 5.7 vs 10.9 +/- 2.1 pg/ml), while after treatment no difference was found. The ET-1 plasma levels of hyperthyroid patients correlated closely with the raised thyroid metabolic activity independently of its cause. It is possible that the increased ET-1 levels in hyperthyroid patients are the expression of blood vessel damage caused by high thyroid hormone levels. Moreover the results of this study could suggest that, in future, ET-1 plasmatic levels might be considered as a functional thyroid index in hyperthyroid diseases.

Metabolic effects of the iodothyronine functional analogue TRC150094 on the liver and skeletal muscle of high-fat diet fed overweight rats: an integrated proteomic study.

PubMed

Silvestri, Elena; Glinni, Daniela; Cioffi, Federica; Moreno, Maria; Lombardi, Assunta; de Lange, Pieter; Senese, Rosalba; Ceccarelli, Michele; Salzano, Anna Maria; Scaloni, Andrea; Lanni, Antonia; Goglia, Fernando

2012-07-06

A novel functional iodothyronine analogue, TRC150094, which has a much lower potency toward thyroid hormone receptor (α1/β1) activation than triiodothyronine, has been shown to be effective at reducing adiposity in rats simultaneously receiving a high-fat diet (HFD). Here, by combining metabolic, functional and proteomic analysis, we studied how the hepatic and skeletal muscle phenotypes might respond to TRC150094 treatment in HFD-fed overweight rats. Drug treatment increased both the liver and skeletal muscle mitochondrial oxidative capacities without altering mitochondrial efficiency. Coherently, in terms of individual respiratory in-gel activity, blue-native analysis revealed an increased activity of complex V in the liver and of complexes II and V in tibialis muscle in TCR150094-treated animals. Subsequently, the identification of differentially expressed proteins and the analysis of their interrelations gave an integrated view of the phenotypic/metabolic adaptations occurring in the liver and muscle proteomes during drug treatment. TRC150094 significantly altered the expression of several proteins involved in key liver metabolic pathways, including amino acid and nitrogen metabolism, and fructose and mannose metabolism. The canonical pathways most strongly influenced by TRC150094 in tibialis muscle included glycolysis and gluconeogenesis, amino acid, fructose and mannose metabolism, and cell signaling. The phenotypic/metabolic influence of TRC150094 on the liver and skeletal muscle of HFD-fed overweight rats suggests the potential clinical application of this iodothyronine analogue in ameliorating metabolic risk parameters altered by diet regimens.

Function of the Alpha6 in Breast Carcinoma

DTIC Science & Technology

1999-10-01

Miao , J., S. Araki, K. Kaji, and H . Hayashi. 1997. Integrin P34 is involved in apoptotic signal transduction in endothelial cells. Biochem. and Biophys...cadherin expression in neoplasatic verus normal thyroid tissue. J. Natl. Cancer Inst. 88:442-449. 6. Shaw, L. M., I. Rabinovitz, H . H .-F. Wang, A. Toker, and...Integrin and cAMP Metabolism Kathleen L. O’Connor, Bao-Kim Nguyen and Arthur M. Mercurio Department of Medicine, Beth Israel Deaconess Medical Center and

Ambient salinity modifies the action of triiodothyronine in the air-breathing fish Anabas testudineus Bloch: effects on mitochondria-rich cell distribution, osmotic and metabolic regulations.

PubMed

Peter, M C Subhash; Leji, J; Peter, Valsa S

2011-04-01

The hydromineral and metabolic actions of thyroid hormone on osmotic acclimation in fish is less understood. We, therefore, studied the short-term action of triiodothyronine (T(3)), the potent thyroid hormone, on the distribution and the function of gill mitochondria-rich (MR) cells and on the whole body hydromineral and metabolic regulations of air-breathing fish (Anabas testudineus) adapted to either freshwater (FW) or acclimated to seawater (SA; 30 g L(-1)). As expected, 24 h T(3) injection (100 ng g(-1)) elevated (P<0.05) plasma T(3) but classically reduced (P<0.05) plasma T(4). The higher Na(+), K(+)-ATPase immunoreactivity and the varied distribution pattern of MR cells in the gills of T(3)-treated FW and SA fish, suggest an action of T(3) on gill MR cell migration, though the density of these cells remained unchanged after T(3) treatment. The ouabain-sensitive Na(+), K(+)-ATPase activity, a measure of hydromineral competence, showed increases (P<0.05) in the gills of both FW and SA fish after T(3) administration, but inhibited (P<0.05) in the kidney of the FW fish and not in the SA fish. Exogenous T(3) reduced glucose (P<0.05) and urea (P<0.05) in the plasma of FW fish, whereas these metabolites were elevated (P<0.05) in the SA fish, suggesting a modulatory effect of ambient salinity on the T(3)-driven metabolic actions. Our data identify gill MR cell as a target for T(3) action as it promotes the spatial distribution and the osmotic function of these cells in both fresh water and in seawater. The results besides confirming the metabolic and osmotic actions of T(3) in fish support the hypothesis that the differential actions of T(3) may be due to the direct influence of ambient salinity, a major environmental determinant that alters the osmotic and metabolic strategies of fish. Copyright © 2011 Elsevier Inc. All rights reserved.

SPORADIC GOITROUS CRETINISM

PubMed Central

Mosier, H. David

1959-01-01

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

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.

Variants and pitfalls on radioiodine scans in pediatric patients with differentiated thyroid carcinoma.

PubMed

Mostafa, Mohamed; Vali, Reza; Chan, Jeffrey; Omarkhail, Yusuaf; Shammas, Amer

2016-10-01

Potentially false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma can mimic functioning thyroid tissue and functioning thyroid carcinomatous tissue. Such false-positive findings comprise variants and pitfalls that can vary slightly in children as compared with adults. To determine the patterns and frequency of these potential false-positive findings on radioiodine scans in children with differentiated thyroid carcinoma. We reviewed a total of 223 radioiodine scans from 53 pediatric patients (mean age 13.3 years, 37 girls) with differentiated thyroid carcinoma. Focal or regional activity that likely did not represent functioning thyroid tissue or functioning thyroid carcinomatous tissue were categorized as variants or pitfalls. The final diagnosis was confirmed by reviewing the concurrent and follow-up clinical data, correlative ultrasonography, CT scanning, serum thyroglobulin and antithyroglobulin antibody levels. We calculated the frequency of these variants and pitfalls from diagnostic and post-therapy radioiodine scans. The most common variant on the radioiodine scans was the thymic activity (24/223, 10.8%) followed by the cardiac activity (8/223, 3.6%). Salivary contamination and star artifact, caused by prominent thyroid remnant, were the most important observed pitfalls. Variants and pitfalls that mimic functioning thyroid tissue or functioning thyroid carcinomatous tissue on radioiodine scan in children with differentiated thyroid carcinoma are not infrequent, but they decrease in frequency on successive radioiodine scans. Potential false-positive findings can be minimized with proper knowledge of the common variants and pitfalls in children and correlation with clinical, laboratory and imaging data.

Differentiated thyroid carcinoma with functional autonomy.

PubMed

Yaturu, Subhashini; Fowler, Marjorie R

2002-01-01

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

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.

Increased waist circumference is independently associated with hypothyroidism in Mexican Americans: replicative evidence from two large, population-based studies

PubMed Central

2014-01-01

Background Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans. Methods We conducted association testing for 18 MS traits in two large studies on Mexican Americans – the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007–10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007–10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) – a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007–10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions. Results TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007–10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007–10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age. Conclusions WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies. PMID:24913450

Increased waist circumference is independently associated with hypothyroidism in Mexican Americans: replicative evidence from two large, population-based studies.

PubMed

Mamtani, Manju; Kulkarni, Hemant; Dyer, Thomas D; Almasy, Laura; Mahaney, Michael C; Duggirala, Ravindranath; Comuzzie, Anthony G; Samollow, Paul B; Blangero, John; Curran, Joanne E

2014-06-10

Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans. We conducted association testing for 18 MS traits in two large studies on Mexican Americans - the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007-10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007-10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) - a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007-10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions. TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007-10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007-10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age. WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies.

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.

Evaluation of thyroid tissue by Raman spectroscopy

NASA Astrophysics Data System (ADS)

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

2010-02-01

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

Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function.

PubMed

Díez, Juan J; Hernanz, Angel; Medina, Sonia; Bayón, Carmen; Iglesias, Pedro

2002-10-01

Tumour necrosis factor-alpha (TNF-alpha) is a cytokine with numerous immunological and metabolic activities. Receptors for TNF-alpha have been demonstrated in thyroid follicular cells and TNF-alpha and its receptors have been implicated in the cytotoxic mechanisms that characterize the thyroid destruction in autoimmune thyroid disease. In patients with Graves' disease, serum levels of TNF-alpha have been reported to be elevated and administration of TNF-alpha to humans has been shown to induce hormonal alterations resembling those seen in the nonthyroidal illness syndrome. To evaluate serum concentrations of TNF-alpha and the soluble receptor for TNF-alpha (sTNFR-I) in a group of patients with thyroid dysfunction before and after normalization of thyroid function with appropriate therapy. We studied 20 patients with hypothyroidism (18 women and 2 men, mean age +/- SD, 48.8 +/- 16.1 years) and 20 patients with hyperthyroidism (14 women and 6 men, age 44.6 +/- 15.9 years). Patients were assessed at the time of diagnosis and again after normalization of thyroid function tests with appropriate therapy. A group of 20 healthy subjects (15 women and 5 men, age 44.9 +/- 15.1 years) were also studied as a control group. All subjects were ambulatory and were studied as outpatients during visits to the endocrinology clinic. Serum concentrations of free T4 (FT4), total T3, TSH, TNF-alpha and sTNFR-I were measured in all subjects. TNF-alpha and sTNFR-I were measured using a quantitative enzyme immunoassay. In patients with hypothyroidism serum concentrations of TNF-alpha (3.17 +/- 1.18 pg/ml) and sTNFR-I (1273 +/- 364 pg/ml) were significantly higher than those found in controls (2.42 +/- 0.76 pg/ml, P < 0.05, and 971 +/- 235 pg/ml, P < 0.01, respectively). Normalization of thyroid function with l-thyroxine therapy did not significantly modify TNF-alpha or sTNFR-I levels. There were no differences in pre- and post-therapy values of TNF-alpha and sTNFR-I in patients with autoimmune (n = 14) or nonautoimmune (n = 6) hypothyroidism. Before therapy, patients with hyperthyroidism showed elevated serum concentrations of TNF-alpha (3.36 +/- 1.21 pg/ml; P < 0.01) and sTNFR-I (2274 +/- 579 pg/ml; P < 0.001) in relation to the control group. Treatment of hyperthyroidism was accompanied by a normalization of TNF-alpha levels (2.46 +/- 0.89 pg/ml; P < 0.001) and by a significant decrease in sTNFR-I concentrations (1369 +/- 475 pg/ml; P < 0.001). Post-therapy levels of TNF-alpha and sTNFR-I showed a significant correlation with loss of weight (r = 0.674, P < 0.01, and r = 0.629, P < 0.01, respectively) in hypothyroid patients. No correlation between these parameters was found in the group of patients with hyperthyroidism. In summary, these results confirm the relevance of activation of the TNF-alpha system in patients with thyroid dysfunction, as high plasma concentrations of TNF-alpha and sTNFR-I have been demonstrated in patients with hypothyroidism or hyperthyroidism. Treatment of hyperthyroidism is accompanied by a significant reduction in the previously elevated concentrations of both TNF-alpha and sTNFR-I. However, these changes are not seen when normalizing thyroid function in patients with hypothyroidism.

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

PubMed

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

2012-04-01

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

Positive association of free triiodothyronine with pancreatic β-cell function in people with prediabetes.

PubMed

Oda, T; Taneichi, H; Takahashi, K; Togashi, H; Hangai, M; Nakagawa, R; Ono, M; Matsui, M; Sasai, T; Nagasawa, K; Honma, H; Kajiwara, T; Takahashi, Y; Takebe, N; Ishigaki, Y; Satoh, J

2015-02-01

To analyse the effects of thyroid hormones on β-cell function and glucose metabolism in people with prediabetes who are euthyroid. A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of β-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic β-cell function. In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic β-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of β-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

Thyroid and parathyroid imaging

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

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

1986-01-01

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

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.

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...

Developmental Profile and effects of perinatal PBDE exposure in Hepatic Phase I, II, III and deiodinase I gene expression involved in thyroid hormone metabolism in male rat pups

EPA Science Inventory

Previous studies demonstrated that perinatal exposure to PBDEs, a major class of brominated flame retardants, may affect thyroid hormone (TH) concentrations by inducing hepatic uridinediphosphate-glucoronosyltransferases (UGTs). This study further examines effects of the commerc...

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

PubMed

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

2017-11-01

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

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

PubMed

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

2016-01-01

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

International spinal cord injury endocrine and metabolic extended data set.

PubMed

Bauman, W A; Wecht, J M; Biering-Sørensen, F

2017-05-01

The objective of this study was to develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Extended Data Set (ISCIEMEDS) within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of endocrine and metabolic findings in the SCI population. This study was conducted in an international setting. The ISCIEMEDS was developed by a working group. The initial ISCIEMEDS was revised based on suggestions from members of the International SCI Data Sets Committee, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations, societies and individual reviewers. The data set was posted for two months on ISCoS and ASIA websites for comments. Variable names were standardized, and a suggested database structure for the ISCIEMEDS was provided by the Common Data Elements (CDEs) project at the National Institute on Neurological Disorders and Stroke (NINDS) of the US National Institute of Health (NIH), and are available at https://commondataelements.ninds.nih.gov/SCI.aspx#tab=Data_Standards. The final ISCIEMEDS contains questions on the endocrine and metabolic conditions related to SCI. Because the information may be collected at any time, the date of data collection is important to determine the time after SCI. ISCIEMEDS includes information on carbohydrate metabolism (6 variables), calcium and bone metabolism (12 variables), thyroid function (9 variables), adrenal function (2 variables), gonadal function (7 variables), pituitary function (6 variables), sympathetic nervous system function (1 variable) and renin-aldosterone axis function (2 variables). The complete instructions for data collection and the data sheet itself are freely available on the website of ISCoS (http://www.iscos.org.uk/international-sci-data-sets).

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.

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.

MicroRNAs in thyroid development, function and tumorigenesis.

PubMed

Fuziwara, Cesar Seigi; Kimura, Edna Teruko

2017-11-15

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

[Obesity and hypothyroidism: myth or reality?].

PubMed

Portmann, Luc; Giusti, Vittorio

2007-04-04

While obesity has been historically considered a criteria to establish the diagnosis of hypothyroidism, the association between them is seldom encountered in patients. Nowadays the main metabolic criteria is the gain of weight in the presence of other symptoms of hypothyroidism. The large differences between the thermogenesis of hypothyroid and hyperthyroid patients underline the complex relationship of thyroid hormones and metabolic pathways. The treatment of a subclinical hypothyroidism has almost no influence on the body weight, whereas in more severe dysfunctions a weight loss is expected, usually less than 10% of body weight. Thereafter severe obesity may not be secondary to a thyroid failure.

Evaluation of the relationship between subclinical hypothyroidism and metabolic syndrome components among workers.

PubMed

Cheserek, Maureen Jepkorir; Wu, Guirong; Shen, Liye; Shi, Yonghui; Le, Guowei

2014-04-01

Both hyperthyroidism and overt hypothyroidism are associated with increased prevalence of metabolic syndrome and its components, while data on subclinical hypothyroidism is currently limited especially in working populations. The aim of this study was to examine the association between subclinical hypothyroidism and metabolic syndrome components in workers; and to evaluate whether there are differences by sex and occupation. A total of 1150 university employees (male - 792, female - 358) aged 30-60 years who came for an annual medical check-up were studied. Anthropometric measurements were taken, and blood pressure, fasting plasma glucose (FPG), lipid profiles, thyroid stimulating hormone (TSH), free thyroxin (FT4) and free triiodothyronine (FT3) levels were measured. After adjustment for age and body mass index (BMI), TSH was positively associated with increased triglyceride (TG) levels (β = 0.108, p = 0.020) and FPG (β = 0.130, p = 0.006) in subclinical hypothyroid male workers. However, TSH was not associated (p > 0.05) with any component of metabolic syndrome (MS) in the euthyroid group. In females, TSH was not correlated with MS components in both euthyroid and subclinical hypothyroid groups. Furthermore, comparison by occupation showed higher TSH in subclinical hypothyroid male workers employed in administration (5.23 ± 0.52 mU/l) than those working as academics (5.12 ± 0.52 mU/l), which resulted in elevated systolic and diastolic blood pressure, FPG, total cholesterol, TG and high density lipoprotein cholesterol. In females, BMI, systolic and diastolic blood pressure, TG and FPG were significantly (p < 0.05) higher in subclinical hypothyroid administrators than those in academics. Subclinical hypothyroidism was associated with metabolic syndrome components in male workers and not in females. Administration workers showed increased metabolic risks compared to academics. The findings suggest that the assessment of thyroid function in individuals with metabolic syndrome in the workplace may be favorable especially among men.

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.

Psychiatric and physical comorbidities and their impact on the course of bipolar disorder: A prospective, naturalistic 4-year follow-up study.

PubMed

Amann, Benedikt L; Radua, Joaquim; Wunsch, Christian; König, Barbara; Simhandl, Christian

2017-05-01

The aim of the present study was to increase the available evidence on how physical and psychiatric comorbidities influence the long-term outcome in bipolar I and II disorder. We examined the prevalence of comorbid physical (metabolic, cardiovascular, thyroid, and neurological) diseases and psychiatric (neurotic, stress-related, somatoform, and personality) disorders and their impact on the risk of relapse in bipolar disorder. A total of 284 consecutively admitted patients with ICD-10 bipolar I (n=161) and II (n=123) disorder were followed up naturalistically over a period of 4 years. Globally, 22.0% patients had metabolic, 18.8% cardiovascular, 18.8% thyroid, and 7.6% neurological diseases; 15.5% had neurotic, stress-related, and somatoform disorders; 12.0% had personality disorders; and 52.9% had nicotine dependence. We did not find any effect of comorbid metabolic, cardiovascular or neurological diseases or psychiatric disorders on the relapse risk. However, the presence of thyroid diseases, and especially hypothyroidism, was associated with an increased risk of manic relapse in bipolar disorder I (thyroid disease: hazard ratio [HR]=2.7; P=.003; hypothyroidism: HR=3.7;, P<.001). Among patients with hypothyroidism, higher blood levels of baseline thyroid-stimulating hormone (bTSH) were also associated with an increased risk of manic relapse (HR=1.07 per milli-international units per liter; P=.011), whereas blood levels of free triiodothyronine (fT 3 ) or free thyroxine (fT 4 ) were not found to have an influence. Our data underline the negative long-term impact of thyroid diseases, and especially hypothyroidism with high blood levels of bTSH, on bipolar disorder with more manic episodes, and the importance of its detection and treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Improved endothelial function and lipid profile compensate for impaired hemostatic and inflammatory status in iatrogenic chronic subclinical hyperthyroidism of thyroid cancer patients on L-t4 therapy.

PubMed

Gazdag, A; Nagy, E V; Burman, K D; Paragh, G; Jenei, Z

2010-06-01

We aimed to compare the changes of endothelial function and haemostatic, inflammatory and metabolic parameters of short-term iatrogenic hypothyroidism to the characteristics of subclinical hyperthyroidism in patients with differentiated thyroid cancer. Twenty four women (mean age 42.4+/-8.1 years) had undergone total thyroidectomy and radioiodine ablation in treatment for differentiated thyroid cancer. We measured serum thyroglobulin, thyroid function, plasma levels of lipid parameters, homocystine, C-reactive protein, fibrinogen, von Willebrandt factor activity (vWF), nitric oxide, as well as flow-mediated vasodilatation (FMD) and nitroglycerin-mediated vasodilatation of the brachial artery during iatrogenic hypothyroidism (TSH 89.82+/-29.36 mU/L) and again in the same patients during subclinical hyperthyroidism secondary to exogenous levothyroxine administration (TSH 0.24+/-0.11 mU/L). In hypothyroidism, FMD was markedly lower than in subclinical hyperthyroidism (6.79+/-4.44 vs. 14.37+/-8.33%, p<0.005). Total cholesterol (7.34+/-1.23 vs. 4.75+/-1.14 mmol/L, p<0.001), LDL-cholesterol (4.55+/-1.10 vs. 2.70+/-0.89 mmol/L, p<0.005) and homocystine (12.95+/-4.49 vs. 9.62+/-2.29 micromol/L, p<0.005) were significantly higher in hypothyroidism. There was no difference in nitroglycerin-mediated vasodilatation, blood pressure, serum triglyceride and HDL-cholesterol levels according to thyroid function. Fibrinogen (3.23+/-0.50 vs. 4.01+/-0.84 g/L, p<0.005), vWF (90.09+/-25.92 vs.130.63+/-29.97%, p<0.001), C-reactive protein (4.39+/-5.16 vs. 5.55+/-5.15 mg/L, p<0.001) and plasma nitric oxide (24.56+/-6.71 vs. 32.34+/-7.0 micromol/L, <0.005) values were significantly lower in hypothyroidism. FMD correlated in a positive manner with fibrinogen, vWF and nitrogen oxide. Chronic subclinical hyperthyroidism was associated with improved endothelial function and lipid profile, while haemostatic and inflammatory parameters were impaired. The two opposite mechanisms may well compensate for each other at the level of the vessel wall. (c) J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart, New York.

Erythrocyte metabolism in hyperthyroidism: a microcalorimetric study on changes in the Embden-Meyerhof and the hexose monophosphate pathways.

PubMed

Monti, M; Hedner, P; Ikomi-Kumm, J; Valdemarsson, S

1987-05-01

Erythrocyte metabolism was studied in vitro by microcalorimetry in 10 hyperthyroid subjects before and after treatment. By inhibiting the enzyme enolase in the Embden-Meyerhof pathway with sodium fluoride (NaF) we have recorded the anaerobic and aerobic contributions in erythrocyte thermogenesis. The decrease in heat production rate in samples with NaF corresponds to the anaerobic contribution, whereas the values from samples with NaF reflect aerobic processes. Before treatment, total heat production rate was 120 +/- 2 mW/l erythrocytes which was higher than the post-treatment value of 99 +/- 2 (P less than 0.001) as well as the value for 14 euthyroid subjects, 108 +/- 2 mW/l (P less than 0.001). The NaF inhibitable rate was 73 +/- 2 before and 63 +/- 1 mW/l after therapy (P less than 0.01). These values correspond to 61 +/- 1 and 64 +/- 1% (n.s.) of the total heat production rate, and were similar to that of 61 +/- 2% for the controls. Heat production rates in the presence of NaF were 47 +/- 1 before and 36 +/- 1 mW/l after therapy (P less than 0.001), representing 39 +/- 1 and 36 +/- 1% of total values, respectively. The present results show that overall metabolism is increased in erythrocytes from hyperthyroid subjects before treatment and returns to normal after normalization of the thyroid function. Moreover, by using microcalorimetry we found that the metabolic activity along the Embden-Meyerhof anaerobic pathway as well as along the hexose monophosphate aerobic pathway in erythrocytes is stimulated by thyroid hormones.

Brown Adipose Tissue Function Is Enhanced in Long-Lived, Male Ames Dwarf Mice

PubMed Central

McFadden, Samuel; Fang, Yimin; Huber, Joshua A.; Zhang, Chi; Sun, Liou Y.; Bartke, Andrzej

2016-01-01

Ames dwarf mice (Prop1df/df) are long-lived due to a loss of function mutation, resulting in deficiency of GH, TSH, and prolactin. Along with a marked extension of longevity, Ames dwarf mice have improved energy metabolism as measured by an increase in their oxygen consumption and heat production, as well as a decrease in their respiratory quotient. Along with alterations in energy metabolism, Ames dwarf mice have a lower core body temperature. Moreover, Ames dwarf mice have functionally altered epididymal white adipose tissue (WAT) that improves, rather than impairs, their insulin sensitivity due to a shift from pro- to anti-inflammatory cytokine secretion. Given the unique phenotype of Ames dwarf epididymal WAT, their improved energy metabolism, and lower core body temperature, we hypothesized that Ames dwarf brown adipose tissue (BAT) may function differently from that of their normal littermates. Here we use histology and RT-PCR to demonstrate that Ames dwarf mice have enhanced BAT function. We also use interscapular BAT removal to demonstrate that BAT is necessary for Ames dwarf energy metabolism and thermogenesis, whereas it is less important for their normal littermates. Furthermore, we show that Ames dwarf mice are able to compensate for loss of interscapular BAT by using their WAT depots as an energy source. These findings demonstrate enhanced BAT function in animals with GH and thyroid hormone deficiencies, chronic reduction of body temperature, and remarkably extended longevity. PMID:27740871

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

PubMed

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

2016-12-01

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

The impact of thyroid diseases on bone metabolism and fracture risk.

PubMed

Amashukeli, M; Giorgadze, E; Tsagareli, M; Nozadze, N; Jeiranashvili, N

2010-01-01

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. One of the leading causes of secondary osteoporosis are thyroid diseases; this fact carries special importance for Georgia because of thyroid disease prevalence in Georgian population. In the present article we discuss the mechanisms, by which thyroid hormones and thyroid stimulating hormone (TSH) act on bone. We also present the data of meta-analysis of large studies, which demonstrate the complex relationship between the thyroid diseases and bone mineral density as well as the fracture risk; namely by overt and subclinical thyrotoxicosis, hypothyroidism and the treatment with the suppressive doses of levothyroxine. Beside that, we review the related data and the possible reasons, why different treatment regimens of Grave's disease: conservative, operative and radioiodine are related to different fracture risks. Finally, we discuss briefly the practical aspects of the treatment of secondary osteoporosis, related with thyroid diseases.

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

NASA Astrophysics Data System (ADS)

Weng, Sheng

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

The international spinal cord injury endocrine and metabolic function basic data set.

PubMed

Bauman, W A; Biering-Sørensen, F; Krassioukov, A

2011-10-01

To develop the International Spinal Cord Injury (SCI) Endocrine and Metabolic Function Basic Data Set within the framework of the International SCI Data Sets that would facilitate consistent collection and reporting of basic endocrine and metabolic findings in the SCI population. International. The International SCI Endocrine and Metabolic Function Data Set was developed by a working group. The initial data set document was revised on the basis of suggestions from members of the Executive Committee of the International SCI Standards and Data Sets, the International Spinal Cord Society (ISCoS) Executive and Scientific Committees, American Spinal Injury Association (ASIA) Board, other interested organizations and societies, and individual reviewers. In addition, the data set was posted for 2 months on ISCoS and ASIA websites for comments. The final International SCI Endocrine and Metabolic Function Data Set contains questions on the endocrine and metabolic conditions diagnosed before and after spinal cord lesion. If available, information collected before injury is to be obtained only once, whereas information after injury may be collected at any time. These data include information on diabetes mellitus, lipid disorders, osteoporosis, thyroid disease, adrenal disease, gonadal disease and pituitary disease. The question of gonadal status includes stage of sexual development and that for females also includes menopausal status. Data will be collected for body mass index and for the fasting serum lipid profile. The complete instructions for data collection and the data sheet itself are freely available on the websites of ISCoS (http://www.iscos.org.uk) and ASIA (http://www.asia-spinalinjury.org).

Cytomorphological Spectrum of Thyroiditis: A Review of 110 Cases

PubMed Central

Nair, Rahul; Gambhir, Anushree; Kaur, Supreet; Pandey, Aditi; Shetty, Abhinav; Naragude, Piyusha

2018-01-01

Introduction Different types of thyroiditis may share some parallel clinical and biochemical features. Timely intervention can significantly reduce morbidity and mortality. Aim Aim of this study is to find the frequency of various thyroiditis, study the cytomorphological features and correlate with clinical findings including radiological findings, thyroid function test, and anti-thyroid peroxidase antibodies (Anti-TPO antibodies). Materials and Methods The study included consecutive 110 cases of thyroiditis. Detailed cytomorphological features were studied and correlated with ultrasonography findings, thyroid function test, anti-thyroid peroxidase antibodies (anti-TPO) and histopathological features where thyroidectomy specimens were received for histopathological examination. Results The majority were Hashimoto's thyroiditis (n = 100) and females (n = 103). Other forms of thyroiditis were Hashimoto's thyroiditis with colloid goiter (n = 5), De Quervain's thyroiditis (n = 3), and one case each of postpartum thyroiditis and Hashimoto's thyroiditis with associated malignancy. The majority of patients were in the age group of 21–40 (n = 70) and the majority (n = 73) had diffuse enlargement of thyroid. The majority of patients were hypothyroid (n = 52). The serum anti-TPO antibodies were elevated in 47 patients out of 71 patients. In the 48 patients who underwent ultrasonography, 38 were diagnosed as having thyroiditis. The most consistent cytomorphological features seen in fine-needle aspiration smears of Hashimoto's thyroiditis were increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. Conclusion The diagnostic cytological features in Hashimoto's thyroiditis are increased background lymphocytes, lymphocytic infiltration of thyroid follicular cell clusters, and Hurthle cells. FNAC remains the “Gold Standard” for diagnosing Hashimoto's thyroiditis. Clinical history, thyroid function, and biochemical parameters are the key for diagnosis of other forms of thyroiditis. PMID:29686830

Follicle stimulating hormone, its novel association with sex hormone binding globulin in men and postmenopausal women.

PubMed

Wang, Ningjian; Zhang, Kun; Han, Bing; Li, Qin; Chen, Yi; Zhu, Chunfang; Chen, Yingchao; Xia, Fangzhen; Zhai, Hualing; Jiang, Boren; Shen, Zhoujun; Lu, Yingli

2017-06-01

Follicle stimulating hormone plays direct roles in a variety of nongonadal tissues and sex hormone binding globulin is becoming the convergence of the crosstalk among metabolic diseases. However, no studies have explored the association between follicle stimulating hormone and sex hormone binding globulin. We aimed to study this association among men and women. SPECT-China is a population-based study conducted since 2014. This study included 4206 men and 2842 postmenopausal women. Collected serum was assayed for gonadotropins, sex hormone binding globulin, sex hormones etc. Regression analyses were performed to assess the relationship between sex hormone binding globulin and follicle stimulating hormone and other variables including metabolic factors, thyroid function and sex hormones. Treatment with follicle stimulating hormone at different concentrations of 0, 5, 50 and 100 IU/L for 24 h was performed in HepG2 cells. In Spearman correlation, sex hormone binding globulin was significantly correlated with FSH, triglycerides, thyroxins, body mass index and blood pressure in men and postmenopausal women (all P < 0.05). In regression analyses, follicle stimulating hormone was a significant predictor of sex hormone binding globulin in men and postmenopausal women (P < 0.05), independent of above variables. Follicle stimulating hormone induced sex hormone binding globulin expression in a dose-dependent fashion in HepG2 cells. Serum follicle stimulating hormone levels were positively associated with circulating sex hormone binding globulin levels in men and postmenopausal women. This association is independent of age, insulin resistance, hepatic function, lipid profile, thyroid function, adiposity, blood pressure, and endogenous sex hormones.

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers

PubMed Central

Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-01-01

The presence of 137Cesium (137Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l−1) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (–11%) levels, but only for the rats exposed to 137Cs intake in adulthood. Large changes in 17β-estradiol (–69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. PMID:27466399

Thyroid function and the risk of dementia: The Rotterdam Study.

PubMed

Chaker, Layal; Wolters, Frank J; Bos, Daniel; Korevaar, Tim I M; Hofman, Albert; van der Lugt, Aad; Koudstaal, Peter J; Franco, Oscar H; Dehghan, Abbas; Vernooij, Meike W; Peeters, Robin P; Ikram, M Arfan

2016-10-18

To study the role of thyroid function in dementia, cognitive function, and subclinical vascular brain disease with MRI. Analyses were performed within the Rotterdam Study (baseline 1997), a prospective, population-based cohort. We evaluated the association of thyroid-stimulating hormone (TSH) and free thyroxine with incident dementia using Cox models adjusted for age, sex, cardiovascular risk factors, and education. Absolute risks were calculated accounting for death as a competing risk factor. Associations of thyroid function with cognitive test scores and subclinical vascular brain disease (white matter lesions, lacunes, and microbleeds) were assessed with linear or logistic regression. Additionally, we stratified by sex and restricted analyses to normal thyroid function. We included 9,446 participants with a mean age of 65 years. During follow-up (mean 8.0 years), 601 participants had developed dementia. Higher TSH was associated with lower dementia risk in both the full and normal ranges of thyroid function (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.83-0.98; and HR 0.76, 95% CI 0.64-0.91, respectively). This association was independent of cardiovascular risk factors. Dementia risk was higher in individuals with higher free thyroxine (HR 1.04, 95% CI 1.01-1.07). Absolute 10-year dementia risk decreased from 15% to 10% with higher TSH in older women. Higher TSH was associated with better global cognitive scores (p = 0.021). Thyroid function was not related to subclinical vascular brain disease as indicated by MRI. High and high-normal thyroid function is associated with increased dementia risk. Thyroid function is not related to vascular brain disease as assessed by MRI, suggesting a role for thyroid hormone in nonvascular pathways leading to dementia. © 2016 American Academy of Neurology.

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

PubMed

Lazarus, John H

2005-01-01

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

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.

Assessment of renal function and electrolytes in patients with thyroid dysfunction in Addis Ababa, Ethiopia: a cross sectional study.

PubMed

Abebe, Nardos; Kebede, Tedla; Wolde, Mistire

2016-01-01

Studies demonstrated that abnormal thyroid functions may result in decreased or increased kidney size, kidney weight, and affect renal functions. In this regard, studies on the association of abnormal thyroid functions and renal function tests are scarcely found in Ethiopia. To assess renal function and electrolytes in patients with thyroid dysfunction, in Addis Ababa, Ethiopia. Cross sectional study was conducted from March 21/2015-May 27/2015 at Arsho Advanced Medical Laboratory. During the study period, 71 patients with thyroid dysfunction were eligible, and socio demographic data collected by structured questionnaire. Then blood sample was collected for thyroid function tests, renal function and blood electrolyte analysis. The collected data was analyzed by SPSS version 20. ANOVA and binary logistic regression were employed to evaluate the mean deference and associations of thyroid hormone with renal function and electrolyte balances. Among the renal function tests, serum uric acid, and creatinine mean values were significantly decreased in hyperthyroid patients; whereas, eGFR mean value was significantly increased in hyperthyroid study patients (P<0.05). Meanwhile, from the electrolyte measurements made, only the mean serum sodium value was significantly increased in hyperthyroid study participants. Binary logistic regression analysis on the association of thyroid dysfunction with electrolyte balance and renal function tests indicated that serum sodium, creatinine, eGFR values and hyperthyroidism have a statistical significant association at AOR 95% CI of 0.141(0.033-0.593, P=0.008); 16.236(3.481-75.739, P=0.001), and 13.797(3.261-58.67, P=0.001) respectively. The current study reveals, thyroid abnormalities may lead to renal function alterations and also may disturb electrolyte balance. Knowledge of this significant association has worthwhile value for clinicians, to manage their patients' optimally.

Environmental heat stress modulates thyroid status and its response to repeated endotoxin challenge in steers

USDA-ARS?s Scientific Manuscript database

While the Holstein breed has been recognized as particularly sensitive to heat stress (HS), few data address the compounded dairy industry issue of responses to disease vectors in the face of HS. Thyroid hormones are important in the adaptation to HS, allowing the adjustment of metabolic rates in f...

ALTERATIONS IN mRNA GENE EXPRESSION ASSOCIATED WITH CHOLESTEROL METABOLISM, CELL CYCLE, AND OXIDATIVE STRESS INDUCED BY TRIAZOLE CONTAINING CONAZOLES IN RAT LIVER

EPA Science Inventory

Conazoles are fungicides used as pharmaceuticals and in agriculture. Triadimefon was hepatotoxic and induced follicular cell adenomas in the thyroid gland. In contrast,propiconazole and myclobutanil were hepatotoxic but had no effect on the thyroid gland. It was proposed that tri...

Thyroiditis

MedlinePlus

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

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

PubMed

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

2010-10-01

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

Thyroid storm complicated by bicytopenia and disseminated intravascular coagulation.

PubMed

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

2014-07-24

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

Natural History of Thyroid Function in Adults with Down Syndrome--10-Year Follow-Up Study

ERIC Educational Resources Information Center

Prasher, V.; Gomez, G.

2007-01-01

Background: The natural history of thyroid function in adults with Down syndrome (DS) is unknown. Method: This study investigated annual thyroid function tests in 200 adults with DS over a 10-year period. Results: Transient and persistent thyroid dysfunction was common. The 5- and 10-year incidence of definite hypothyroidism was 0.9%-1.64% and…

Hybrid SPECT-CT and PET-CT imaging of differentiated thyroid carcinoma.

PubMed

Wong, K K; Zarzhevsky, N; Cahill, J M; Frey, K A; Avram, A M

2009-10-01

Hybrid imaging modalities such as radioiodine single photon emission CT with integrated CT ((131)I SPECT-CT) and 2-(fluorine-18)-fluoro-2-deoxy-D-glucose positron emission tomography with integrated CT (FDG PET-CT) allow the rapid and efficient fusion of functional and anatomic images, and provide diagnostic information that may influence management decisions in patients with differentiated thyroid carcinoma (DTC). Diagnostic localisation and therapy of these tumours are dependent upon their capacity to concentrate radioiodine ((131)I) via uptake through the sodium-iodide symporter and retention within the tumour. The prognosis for most patients with DTC is favourable, although controversy exists regarding the role of post-operative (131)I therapy in patients at low-risk for disease. Accurate identification of functional thyroid tissue (benign or malignant) using diagnostic (131)I planar scintigraphy complemented by SPECT-CT imaging enables the completion of post-operative staging and patient risk stratification prior to (131)I therapy administration. In patients with non-iodine-avid tumours (negative (131)I scan but elevated thyroglobulin indicative of persistent or recurrent disease), FDG PET-CT is used to identify tumours with enhanced glucose metabolism and to localise the source of thyroglobulin production. The CT component of this hybrid technology provides anatomic localisation of activity and allows CT-based attenuation correction of PET images. Images from 15 patients illustrate the applications of (131)I SPECT-CT and FDG PET-CT.

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.

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

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.

HYPOTHYROIDISM - A SPECIAL COMORBIDITY FACTOR IN PATIENTS WITH OSTEOARTHROSIS: CLINICAL, PATHOPHYSIOLOGICAL AND PROGNOSTIC ASPECTS.

PubMed

Voloshyna, L; Doholich, О; Sithinska, I

2017-11-01

Objective - to study the features of the functional and morphological condition of the thyroid gland (TG) in patients with osteoarthrosis (OA), the incidence and forms of hypothyroidism and their effects on clinical manifestations, metabolic disorders and the results of the treatment of OA and comorbid processes. A complex examination involved 312 patients with OA aged 37-76 years. Methods used: anthropometric, clinical, ultrasonographic, biochemical, radioimmunological (levels of TSH, free thyroxine, antibodies to thyroid peroxidase). It has been established that with increasing age in patients OA phenomena are progressing, there is an increase in comorbid diseases, especially of the cardiovascular system with atherosclerotic genesis, they become more severe. Against this background, clinical hypothyroidism was found in 4.44% and subclinical one in 13.78%. Stratification of the clinical form of hypothyroidism contributed to the deterioration of the course and outcome of the treatment of OA and comorbid diseases. Both forms of hypothyroidism intensified the degrees of metabolic disorders in the blood, reduced the glomerular filtration rate, especially the clinical form. Manifestations of hypothyroidism were observed in patients with OA with its significant systemic manifestations, high comorbidity rate, in individuals aged over 50, especially 60 years, mainly in women (83,72%). In patients with OA aged over 50 years with a high comorbidity rate, it is advisable to conduct an ultrasound examination of the thyroid gland, to measure the levels of TSH, free thyroxine in order to diagnose hypothyroidism early and to treat it timely as one of the ways to improve the overall outcomes of the treatment of such patients.

Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development.

PubMed

Kero, Jukka; Ahmed, Kashan; Wettschureck, Nina; Tunaru, Sorin; Wintermantel, Tim; Greiner, Erich; Schütz, Günther; Offermanns, Stefan

2007-09-01

The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.

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

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

PubMed

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

2018-03-04

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

Effects of long-term temperature acclimation on thyroid hormone deiodinase function, plasma thyroid hormone levels, growth, and reproductive status of male Atlantic cod, Gadus morhua.

PubMed

Cyr, D G; Idler, D R; Audet, C; McLeese, J M; Eales, J G

1998-01-01

The recent collapse of the Northwestern Atlantic cod fisheries has coincided with a cooling of water temperatures. During this time the condition factor of cod has been poor. The objective of the present study was to determine the effects of long-term temperature acclimation on growth reproduction and thyroid function in laboratory held Atlantic cod (Gadus morhua). One of the key parameters used to assess thyroid function is the peripheral metabolism of L-thyroxine (T4) by microsomal deiodinase enzymes. Deiodinase function has not been described for gadid fish. T4 outer-ring deiodinating activity (apparent K(m) 1-2 nM) was confined primarily to liver. Its properties resembled those for hepatic T4ORD activity of other teleosts and the mammalian type II deiodinase. The T4ORD activity of cod liver exceeded that of salmonids and could explain the high plasma T3 levels (10-18 ng/ml), which were 2-5 times greater than T4 levels. T4 and T3 inner-ring deiodination was confined mainly to brain. In order to determine the effects of long-term temperature acclimation on cod, somatic growth, reproduction, and thyroidal status were assessed monthly in 400-900-g satiation-fed male Atlantic cod captured in June from the St. Lawrence Estuary and then acclimated from August to the following June under a natural photoperiod at 2-4 degrees C (LT) or 6-10 degrees C (HT). Reproductive status was determined from the gonadosomatic index (GSI), plasma testosterone (T) and 11-ketotestosterone (11-KT) levels, and the appearance of milt; thyroidal status was determined from plasma T4 and 3,5,3'-triiodo-L-thyronine (T3) levels and hepatic T4ORD activity to produce biologically active T3. Testis maturation (high levels of 1 and 11-KT, and milt release) occurred in April and May and was uninfluenced by acclimation temperature. LT cod grew more slowly than HT cod. Differences in body weight were particularly evident from December to February. In conclusion, (i) cod possess outer- and inner-ring deiodinase activities, predominating respectively in liver and brain, and with properties resembling those of other teleosts, (ii) T4ORD activity of liver is unusually high and may account for the high plasma T3 levels in this species, (iii) T4ORD activity tends to increase during periods of increased somatic growth, and (iv) chronic acclimation of male cod to 2-4 degrees C, as opposed to 6-10 degrees C, decreases somatic growth but does alter circulating levels of thyroid hormones and androgens and it does not change the time of sexual maturation.

Red palm oil supplementation does not increase blood glucose or serum lipids levels in Wistar rats with different thyroid status.

PubMed

Rauchová, H; Vokurková, M; Pavelka, S; Vaněčková, I; Tribulová, N; Soukup, T

2018-05-04

Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status. We induced hypothyroidism and hyperthyroidism in rats by oral administration of either methimazole or mixture of thyroid hormones. Different thyroid status (EU - euthyroid, HY - hypothyroid and HT - hyperthyroid) was characterized by different serum thyroid hormones levels (total and free thyroxine and triiodothyronine), changes in the activity of a marker enzyme of thyroid status - liver mitochondrial glycerol-3-phosphate dehydrogenase, and altered absolute and relative heart weights. Fasting blood glucose levels were higher in HT rats in comparison with EU and HY rats, but the changes caused by RPO supplementation were not significant. The achievement of the HY status significantly increased serum levels of total cholesterol, as well as with high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol: 2.43+/-0.15, 1.48+/-0.09, 0.89+/-0.08 mmol/l, compared to EU: 1.14+/-0.06, 0.77+/-0.06, 0.34+/-0.05 mmol/l and HT: 1.01+/-0.06, 0.69+/-0.04, 0.20+/-0.03 mmol/l, respectively. RPO supplementation did not increase significantly levels of blood lipids but tended to increase glutathione levels in the liver. In conclusion, RPO supplementation did not induce the presumed deterioration of glucose and lipid metabolism in rats with three well-characterized alterations in thyroid status.

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

PubMed

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

2015-11-01

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

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

PubMed Central

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

2015-01-01

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

[CYP7A1 gene polymorphism and the characteristics of dyslipidemias in patients with nonalcoholic fatty liver disease concurrent with hypothyroidism].

PubMed

Zhaldak, D A; Melekhovets, O K; Orlovskyi, V F

To investigate the association of the polymorphic variants -204A > C (rs 3808607) in the CYP7A1 gene with the development of dyslipidemias in healthy individuals, in patients with non-alcoholic fatty liver disease (NAFLD) and in those with NAFLD concurrent with hypothyroidism. DNA samples and lipidograms were examined in 180 patients, including 60 healthy individuals (Group 1), 60 patients with hypothyroidism concurrent with NAFLD (Group 2), and 60 patients with NAFLD (Group 3). All the patients underwent ultrasound examination of the thyroid gland and abdominal cavity organs; FibroMax scores were calculated. All the study groups most frequently showed a homozygous AA genotype (86.6% of cases in Group 1, 80% in Group 2, and 83.3% in Group 3). The development of NAFLD in CC genotype carriers is characterized by the most pronounced changes in lipid metabolism (atherogenic index (AI), 7.32 in Group 3) compared to the genotypes AA (AI, 4.56 in Group 2 and 1.73 in Group 1) and CC (AI, 6.43 in Group 2 and 2.52 in Group 1) in functional insufficiency of thyroid hormones and relative normal conditions. The analysis of the relationship of polymorphic variants CYP7A1 rs 38088607 to lipid metabolic disturbances in the study groups showed that the significantly higher levels of atherogenic cholesterol fractions were determined in the CC genotype compared to AA genotype carriers and they did not depend on the presence of NAFLD and hypothyroidism. The findings make it possible to consider the AA homozygous genotype of variant mutation CYP7A1 rs 38088607 as protective against dyslipidemia. However, in functional insufficiency of thyroid hormones, the level of triglycerides is significantly higher in both genotypes, which suggests that hypothyroidism plays an essential role in the development of dyslipidemia and NAFLD.

Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status

PubMed Central

Hasselgren, Per-Olof; Glasgow, Allison; Doyle, Ashley N.; Lee, Alice J.; Fox, Peter; Gautam, Shiva; Hennessey, James V.; Kolodny, Gerald M.

2017-01-01

Background: In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes, and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insights regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase. Methods: The study subjects underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scanning after cold exposure to measure BAT mass and activity while undergoing treatment for differentiated thyroid cancer, first while hypothyroid following TH withdrawal at the time of the radioactive iodine treatment and then three to six months after starting TH suppressive treatment when they were iatrogenically thyrotoxic. Thermogenic and metabolic parameters were measured in both phases. Results: All study subjects had detectable BAT under cold stimulation in both the hypothyroid and thyrotoxic state. The majority but not all (4/6) subjects showed an increase in detectable BAT volume and activity under cold stimulation between the hypothyroid and thyrotoxic phase (total BAT volume: 72.0 ± 21.0 vs. 87.7 ± 16.5 mL, p = 0.25; total BAT activity 158.1 ± 72.8 vs. 189.0 ± 55.5 SUV*g/mL, p = 0.34). Importantly, circulating triiodothyronine was a stronger predictor of energy expenditure changes compared with cold-induced BAT activity. Conclusions: Iatrogenic hypothyroidism lasting two to four weeks does not prevent cold-induced BAT activation, while the use of TH to induce thyrotoxicosis does not consistently increase cold-induced BAT activity. It remains to be determined which physiological factors besides TH play a role in regulating BAT function. PMID:27750020

Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status.

PubMed

Gavrila, Alina; Hasselgren, Per-Olof; Glasgow, Allison; Doyle, Ashley N; Lee, Alice J; Fox, Peter; Gautam, Shiva; Hennessey, James V; Kolodny, Gerald M; Cypess, Aaron M

2017-01-01

In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes, and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insights regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase. The study subjects underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scanning after cold exposure to measure BAT mass and activity while undergoing treatment for differentiated thyroid cancer, first while hypothyroid following TH withdrawal at the time of the radioactive iodine treatment and then three to six months after starting TH suppressive treatment when they were iatrogenically thyrotoxic. Thermogenic and metabolic parameters were measured in both phases. All study subjects had detectable BAT under cold stimulation in both the hypothyroid and thyrotoxic state. The majority but not all (4/6) subjects showed an increase in detectable BAT volume and activity under cold stimulation between the hypothyroid and thyrotoxic phase (total BAT volume: 72.0 ± 21.0 vs. 87.7 ± 16.5 mL, p = 0.25; total BAT activity 158.1 ± 72.8 vs. 189.0 ± 55.5 SUV*g/mL, p = 0.34). Importantly, circulating triiodothyronine was a stronger predictor of energy expenditure changes compared with cold-induced BAT activity. Iatrogenic hypothyroidism lasting two to four weeks does not prevent cold-induced BAT activation, while the use of TH to induce thyrotoxicosis does not consistently increase cold-induced BAT activity. It remains to be determined which physiological factors besides TH play a role in regulating BAT function.

Transient hyperthyroidism of hyperemesis gravidarum.

PubMed

Tan, Jackie Y L; Loh, Keh Chuan; Yeo, George S H; Chee, Yam Cheng

2002-06-01

To characterise the clinical, biochemical and thyroid antibody profile in women with transient hyperthyroidism of hyperemesis gravidarum. Prospective observational study. Hospital inpatient gynaecological ward. Women admitted with hyperemesis gravidarum and found to have hyperthyroidism. Fifty-three women were admitted with hyperemesis gravidarum and were found to have hyperthyroidism. Each woman was examined for clinical signs of thyroid disease and underwent investigations including urea, creatinine, electrolytes, liver function test, thyroid antibody profile and serial thyroid function test until normalisation. Gestation at which thyroid function normalised, clinical and thyroid antibody profile and pregnancy outcome (birthweight, gestation at delivery and Apgar score at 5 minutes). Full data were available for 44 women. Free T4 levels normalised by 15 weeks of gestation in the 39 women with transient hyperthyroidism while TSH remained suppressed until 19 weeks of gestation. None of these women were clinically hyperthyroid. Thyroid antibodies were not found in most of them. Median birthweight in the infants of mothers who experienced weight loss of > 5% of their pre-pregnancy weight was lower compared with those of women who did not (P = 0.093). Five women were diagnosed with Graves' disease based on clinical features and thyroid antibody profile. In transient hyperthyroidism of hyperemesis gravidarum, thyroid function normalises by the middle of the second trimester without anti-thyroid treatment. Clinically overt hyperthyroidism and thyroid antibodies are usually absent. Apart from a non-significant trend towards lower birthweights in the infants of mothers who experienced significant weight loss, pregnancy outcome was generally good. Routine assessment of thyroid function is unnecessary for women with hyperemesis gravidarum in the absence of any clinical features of hyperthyroidism.

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

PubMed

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

2018-01-25

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

Role of Cholestyramine in Refractory Hyperthyroidism: A Case Report and Literature Review

PubMed Central

Alswat, Khaled A.

2015-01-01

Patient: Female, 52 Final Diagnosis: Refractory iodine induced hyperthyroidism Symptoms: Neck swelling • shortness of breath Medication: Cholestyramine Clinical Procedure: Total thyroidectomy Specialty: Endocrinology and Metabolic Objective: Unusual clinical course Background: Hyperthyroidism is a common disease that usually responds to the conventional therapy of anti-thyroidal medications (methimazole or PTU) and beta-blocker. Refractory hyperthyroidism is a rare condition in which hyperthyroidism fails to respond to the above therapy. Cholestyramine has been shown to decrease thyroid hormone level when added to the ongoing anti-thyroidal medications. Case Report: A 52-year-old woman with past medical history of enlarging goiter presented with obstructive symptoms of worsening shortness of breath and snoring. Admission thyroid function test showed mild hyperthyroidism (suppressed TSH, slightly high FT4, and high normal FT3) that worsened after she received a CT scan with contrast and failed to respond to a 3-week course of high-dose dexamethasone, high-dose carbimazole, and up-titrated propranolol. Five days after cholestyramine was added, her FT4 decreased by 30% and normalized after 12 days. The patient underwent total thyroidectomy as definitive treatment for the hyperthyroidism and for the obstructive symptoms. Conclusions: Cholestyramine is an effective additional treatment for hyperthyroidism and may be an effective treatment for refractory iodine-induced hyperthyroidism. The possibility of self-remission (natural course) is less likely given the dramatic and rapid response to cholestyramine. PMID:26207323

Tributyltin disrupts feeding and energy metabolism in the goldfish (Carassius auratus).

PubMed

Zhang, Jiliang; Sun, Ping; Yang, Fan; Kong, Tao; Zhang, Ruichen

2016-06-01

Tributyltin (TBT) can induce obesogen response. However, little is known about the adverse effects of TBT on food intake and energy metabolism. The present study was designed to investigate the effects of TBT, at environmental concentrations of 2.44 and 24.4 ng/L (1 and 10 ng/L as Sn), on feeding and energy metabolism in goldfish (Carassius auratus). After exposure for 54 d, TBT increased the weight gain and food intake in fish. The patterns of brain neuropeptide genes expression were in line with potential orexigenic effects, with increased expression of neuropeptide Y and apelin, and decreased expression of pro-opiomelanocortin, ghrelin, cocaine and amphetamine-regulated transcript, and corticotropin-releasing factor. Interestingly, the energy metabolism indicators (oxygen consumption, ammonia exertion and swimming activity) and the serum thyroid hormones were all significantly increased at the 2.44 ng/L TBT group in fish. However, no changes of energy metabolism indicators or a decrease of thyroid hormones was found at the 24.4 ng/L TBT group, which indicated a complex disrupting effect on metabolism of TBT. In short, TBT can alter feeding and energy metabolism in fish, which might promote the obesogenic responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Endocrine manifestations related to inherited metabolic diseases in adults

PubMed Central

2012-01-01

Most inborn errors of metabolism (IEM) are recessive, genetically transmitted diseases and are classified into 3 main groups according to their mechanisms: cellular intoxication, energy deficiency, and defects of complex molecules. They can be associated with endocrine manifestations, which may be complications from a previously diagnosed IEM of childhood onset. More rarely, endocrinopathies can signal an IEM in adulthood, which should be suspected when an endocrine disorder is associated with multisystemic involvement (neurological, muscular, hepatic features, etc.). IEM can affect all glands, but diabetes mellitus, thyroid dysfunction and hypogonadism are the most frequent disorders. A single IEM can present with multiple endocrine dysfunctions, especially those involving energy deficiency (respiratory chain defects), and metal (hemochromatosis) and storage disorders (cystinosis). Non-autoimmune diabetes mellitus, thyroid dysfunction and/or goiter and sometimes hypoparathyroidism should steer the diagnosis towards a respiratory chain defect. Hypogonadotropic hypogonadism is frequent in haemochromatosis (often associated with diabetes), whereas primary hypogonadism is reported in Alström disease and cystinosis (both associated with diabetes, the latter also with thyroid dysfunction) and galactosemia. Hypogonadism is also frequent in X-linked adrenoleukodystrophy (with adrenal failure), congenital disorders of glycosylation, and Fabry and glycogen storage diseases (along with thyroid dysfunction in the first 3 and diabetes in the last). This is a new and growing field and is not yet very well recognized in adulthood despite its consequences on growth, bone metabolism and fertility. For this reason, physicians managing adult patients should be aware of these diagnoses. PMID:22284844

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

PubMed

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

2018-04-04

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

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

PubMed

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

1999-08-01

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

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.

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

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

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

1962-09-10

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

Oxidative muscular injury and its relevance to hyperthyroidism.

PubMed

Asayama, K; Kato, K

1990-01-01

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

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

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

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

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

An Overview of Selenium Uptake, Metabolism, and Toxicity in Plants

PubMed Central

Gupta, Meetu; Gupta, Shikha

2017-01-01

Selenium (Se) is an essential micronutrient for humans and animals, but lead to toxicity when taken in excessive amounts. Plants are the main source of dietary Se, but essentiality of Se for plants is still controversial. However, Se at low doses protects the plants from variety of abiotic stresses such as cold, drought, desiccation, and metal stress. In animals, Se acts as an antioxidant and helps in reproduction, immune responses, thyroid hormone metabolism. Selenium is chemically similar to sulfur, hence taken up inside the plants via sulfur transporters present inside root plasma membrane, metabolized via sulfur assimilatory pathway, and volatilized into atmosphere. Selenium induced oxidative stress, distorted protein structure and function, are the main causes of Se toxicity in plants at high doses. Plants can play vital role in overcoming Se deficiency and Se toxicity in different regions of the world, hence, detailed mechanism of Se metabolism inside the plants is necessary for designing effective Se phytoremediation and biofortification strategies. PMID:28123395

Update on the Management of Thyroid Disease during Pregnancy.

PubMed

Yim, Chang Hoon

2016-09-01

Thyroid dysfunction during pregnancy can result in serious complications for both the mother and infant; however, these complications can be prevented by optimal treatment of maternal overt thyroid dysfunction. Although several studies have demonstrated that maternal subclinical hypothyroidism is associated with obstetric complications and neurocognitive impairments in offspring, there is limited evidence that levothyroxine treatment can improve these complications. Therefore, most professional societies do not recommend universal screening for thyroid dysfunction during pregnancy, and instead recommend a case-finding approach in which only high-risk women are tested. However, recent studies have estimated that targeted thyroid function testing misses approximately 30% to 55% of hypothyroidism cases in pregnant women, and some associations and researchers have recommended universal screening of pregnant women to facilitate the early detection and treatment of overt hypothyroidism. This review summarizes recent data on thyroid function test changes, thyroid functional disorder management, and thyroid screening during pregnancy.

Pulmonary complications of endocrine and metabolic disorders.

PubMed

Milla, Carlos E; Zirbes, Jacquelyn

2012-03-01

There are many important respiratory manifestations of endocrine and metabolic diseases in children. Acute and chronic pulmonary infections are the most common respiratory abnormalities in patients with diabetes mellitus, although cardiogenic and non-cardiogenic pulmonary oedema are also possible. Pseudohypoaldosteronism type 1 may be indistinguishable from cystic fibrosis (CF) unless serum aldosterone, plasma renin activity, and urinary electrolytes are measured and mutation analysis rules out CF. Hypo- and hyperthyroidism may alter lung function and affect the central respiratory drive. The thyroid hormone plays an essential role in lung development, surfactant synthesis, and lung defence. Complications of hypoparathyroidism are largely due to hypocalcaemia. Laryngospasm can lead to stridor and airway obstruction. Ovarian tumours, benign or malignant, may present with unilateral or bilateral pleural effusions. Metabolic storage disorders, primarily as a consequence of lysosomal dysfunction from enzymatic deficiencies, constitute a diverse group of rare conditions that can have profound effects on the respiratory system. Copyright © 2011 Elsevier Ltd. All rights reserved.

Post-treatment cognitive dysfunction in women treated with thyroidectomy for papillary thyroid carcinoma.

PubMed

Jung, Mi Sook; Visovatti, Moira

2017-03-01

The purpose of the study is to assess cognitive function in papillary thyroid cancer, one type of differentiated thyroid cancer, and to identify factors associated with cognitive dysfunction. Korean women treated with papillary thyroid cancer post thyroidectomy (n = 90) and healthy women similar in age and educational level (n = 90) performed attention and working memory tests and completed self-report questionnaires on cognitive complaints, psychological distress, symptom distress, and cultural characteristics. Comparative and multivariable regression analyses were performed to determine differences in cognitive function and possible predictors of neurocognitive performance and cognitive complaints. Thyroid cancer survivors performed and perceived their function to be significantly worse on tests of attention and working memory compared to individuals without thyroid cancer. Regression analyses found that having thyroid cancer, older age, and lower educational level were associated with worse neurocognitive performance, while greater fatigue, more sleep problems, and higher levels of childrearing burden but not having thyroid cancer were associated with lower perceived effectiveness in cognitive functioning. Findings suggest that women receiving thyroid hormone replacement therapy after thyroidectomy for papillary thyroid cancer are at risk for attention and working memory problems. Coexisting symptoms and culture-related women's burden affected perceived cognitive dysfunction. Health care providers should assess for cognitive problems in women with thyroid cancer and intervene to reduce distress and improve quality of life.

High Body Mass Index Is an Indicator of Maternal Hypothyroidism, Hypothyroxinemia, and Thyroid-Peroxidase Antibody Positivity during Early Pregnancy

PubMed Central

Han, Cheng; Li, Chenyan; Mao, Jinyuan; Wang, Weiwei; Xie, Xiaochen; Zhou, Weiwei; Li, Chenyang; Xu, Bin; Bi, Lihua; Meng, Tao; Du, Jianling; Zhang, Shaowei; Gao, Zhengnan; Zhang, Xiaomei; Yang, Liu; Fan, Chenling; Teng, Weiping; Shan, Zhongyan

2015-01-01

Background. Maternal thyroid dysfunction in early pregnancy may increase the risk of adverse pregnancy complications and neurocognitive deficiencies in the developing fetus. Currently, some researchers demonstrated that body mass index (BMI) is associated with thyroid function in nonpregnant population. Hence, the American Thyroid Association recommended screening thyroid function in obese pregnant women; however, the evidence for this is weak. For this purpose, our study investigated the relationship between high BMI and thyroid functions during early pregnancy in Liaoning province, an iodine-sufficient region of China. Methods. Serum thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroid-peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) concentration, urinary iodine concentration (UIC), and BMI were determined in 6303 pregnant women. Results. BMI ≥ 25 kg/m2 may act as an indicator of hypothyroxinemia and TPOAb positivity and BMI ≥ 30 kg/m2 was associated with increases in the odds of hypothyroidism, hypothyroxinemia, and TPOAb positivity. The prevalence of isolated hypothyroxinemia increased among pregnant women with BMI > 24 kg/m2. Conclusions. High BMI during early pregnancy may be an indicator of maternal thyroid dysfunction; for Asian women whose BMI > 24 kg/m2 and who are within 8 weeks of pregnancy, thyroid functions should be assessed especially. PMID:26273610

Quantitative single-photon emission computed tomography/computed tomography for technetium pertechnetate thyroid uptake measurement

PubMed Central

Lee, Hyunjong; Kim, Ji Hyun; Kang, Yeon-koo; Moon, Jae Hoon; So, Young; Lee, Won Woo

2016-01-01

Abstract Objectives: Technetium pertechnetate (99mTcO4) is a radioactive tracer used to assess thyroid function by thyroid uptake system (TUS). However, the TUS often fails to deliver accurate measurements of the percent of thyroid uptake (%thyroid uptake) of 99mTcO4. Here, we investigated the usefulness of quantitative single-photon emission computed tomography/computed tomography (SPECT/CT) after injection of 99mTcO4 in detecting thyroid function abnormalities. Materials and methods: We retrospectively reviewed data from 50 patients (male:female = 15:35; age, 46.2 ± 16.3 years; 17 Graves disease, 13 thyroiditis, and 20 euthyroid). All patients underwent 99mTcO4 quantitative SPECT/CT (185 MBq = 5 mCi), which yielded %thyroid uptake and standardized uptake value (SUV). Twenty-one (10 Graves disease and 11 thyroiditis) of the 50 patients also underwent conventional %thyroid uptake measurements using a TUS. Results: Quantitative SPECT/CT parameters (%thyroid uptake, SUVmean, and SUVmax) were the highest in Graves disease, second highest in euthyroid, and lowest in thyroiditis (P < 0.0001, Kruskal–Wallis test). TUS significantly overestimated the %thyroid uptake compared with SPECT/CT (P < 0.0001, paired t test) because other 99mTcO4 sources in addition to thyroid, such as salivary glands and saliva, contributed to the %thyroid uptake result by TUS, whereas %thyroid uptake, SUVmean and SUVmax from the SPECT/CT were associated with the functional status of thyroid. Conclusions: Quantitative SPECT/CT is more accurate than conventional TUS for measuring 99mTcO4 %thyroid uptake. Quantitative measurements using SPECT/CT may facilitate more accurate assessment of thyroid tracer uptake. PMID:27399139

Clinical trials of the prototype Rutherford Appleton Laboratory MWPC positron camera at the Royal Marsden Hospital

NASA Astrophysics Data System (ADS)

Flower, M. A.; Ott, R. J.; Webb, S.; Leach, M. O.; Marsden, P. K.; Clack, R.; Khan, O.; Batty, V.; McCready, V. R.; Bateman, J. E.

1988-06-01

Two clinical trials of the prototype RAL multiwire proportional chamber (MWPC) positron camera were carried out prior to the development of a clinical system with large-area detectors. During the first clinical trial, the patient studies included skeletal imaging using 18F, imaging of brain glucose metabolism using 18F FDG, bone marrow imaging using 52Fe citrate and thyroid imaging with Na 124I. Longitudinal tomograms were produced from the limited-angle data acquisition from the static detectors. During the second clinical trial, transaxial, coronal and sagittal images were produced from the multiview data acquisition. A more detailed thyroid study was performed in which the volume of the functioning thyroid tissue was obtained from the 3D PET image and this volume was used in estimating the radiation dose achieved during radioiodine therapy of patients with thyrotoxicosis. Despite the small field of view of the prototype camera, and the use of smaller than usual amounts of activity administered, the PET images were in most cases comparable with, and in a few cases visually better than, the equivalent planar view using a state-of-the-art gamma camera with a large field of view and routine radiopharmaceuticals.

Common variants in the G protein beta3 subunit gene and thyroid disorders in a formerly iodine-deficient population.

PubMed

Völzke, Henry; Bornhorst, Alexa; Rimmbach, Christian; Petersenn, Holger; Geissler, Ingrid; Nauck, Matthias; Wallaschofski, Henri; Kroemer, Heyo K; Rosskopf, Dieter

2009-10-01

Heterotrimeric G proteins are key mediators of signals from membrane receptors-including the thyroid-stimulating hormone (TSH) receptor-to cellular effectors. Gain-of-function mutations in the TSH receptor and the Galpha(S) subunit occur frequently in hyperfunctioning thyroid nodules and differentiated thyroid carcinomas, whereby the T allele of a common polymorphism (825C>T, rs5443) in the G protein beta3 subunit gene (GNB3) is associated with increased G protein-mediated signal transduction and a complex phenotype. The aim of this study was to investigate whether this common polymorphism affects key parameters of thyroid function and morphology and influences the pathogenesis of thyroid diseases in the general population. The population-based cross-sectional Study of Health in Pomerania is a general health survey with focus on thyroid diseases in northeast Germany, a formerly iodine-deficient area. Data from 3428 subjects (1800 men and 1628 women) were analyzed for an association of the GNB3 genotype with TSH, free triiodothyronine and thyroxine levels, urine iodine and thiocyanate excretion, and thyroid ultrasound morphology including thyroid volume, presence of goiter, and thyroid nodules. There was no association between GNB3 genotype status and the functional or morphological thyroid parameters investigated, neither in crude analyses nor upon multivariable analyses including known confounders of thyroid disorders. Based on the data from this large population-based survey, we conclude that the GNB3 825C>T polymorphism does not affect key parameters of thyroid function and morphology in the general population of a formerly iodine-deficient area.

Sorafenib induced thyroiditis in two patients with hepatocellular carcinoma.

PubMed

van Doorn, Leni; Eskens, Ferry A L M; Visser, Theo J; van der Lugt, Aad; Mathijssen, Ron H J; Peeters, Robin P

2011-02-01

Sorafenib is a multi-targeted tyrosine kinase inhibitor licensed for the treatment of hepatocellular carcinoma and renal cell carcinoma. Thyroid function test abnormalities have been reported for different tyrosine kinase inhibitors, but only limited data on thyroid function test abnormalities related to sorafenib are available, demonstrating the occurrence of hypothyroidism in patients treated with sorafenib. We describe two patients who developed temporary hyperthyroidism during the course of sorafenib treatment, which was followed by overt and subclinical hypothyroidism, respectively. Thyroid ultrasonography showed an atrophic thyroid gland in patient 1 , and signs of thyroiditis in patient 2 . Detailed reassessment of thyroid volumes on routinely performed computerized tomography scans showed a gradual decrease in thyroid volume during sorafenib treatment in one patient, suggesting progressive thyroid destruction. This case report describes in detail and for the first time two cases of sorafenib-induced thyroiditis. We assume that this sorafenib-induced destructive thyroiditis is an important cause of sorafenib-induced hypothyroidism.

Laparoscopic gastric bypass in patients on thyroid replacement therapy for subnormal thyroid function - prevalence and short-term outcome.

PubMed

Szomstein, Samuel; Avital, Shmuel; Brasesco, Oscar; Mehran, Amir; Cabral, Jose M; Rosenthal, Raul

2004-01-01

Hypothyroidism is associated with increased body weight. Weight gain may occur despite normal levels of serum thyroid stimulating hormone (TSH) and thyroxine (T4) achieved by replacement therapy. We evaluated the prevalence of patients on thyroid replacement for subnormal thyroid function who were operated on for morbid obesity and monitored their postoperative weight loss pattern. Data was identified from a prospectively accrued database of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) or laparoscopic adjustable gastric banding (LAGB) for morbid obesity from February 2000 to November 2001. All patients with subnormal thyroid function, diagnosed by past thyroid function tests and treated by an endocrinologist, who were on thyroid replacement therapy, were identified; 5 of these were matched for age, gender, preoperative body mass index (BMI) and surgical procedure (LRYGBP) to 5 non-hypothyroid patients. Weight loss at 3 and 9 months after surgery was compared between the 2 groups. 192 patients underwent LRYGBP (n=155) or LAGB (n=37). Of the 21 patients (10.9%) on thyroid replacement identified, 14 were primary, 4 were postablative, and 3 were post-surgical; 17 underwent LRYGBP. All patients had normal preoperative serum levels of TSH and T4. Comparison of the 2 matched groups of patients revealed no difference in weight loss at 3 and 9 months after surgery (P=1.0). The prevalence of euthyroid patients on thyroid replacement for subnormal thyroid function who undergo surgical intervention for morbid obesity is high. Short-term weight loss in these patients is comparable to normal thyroid patients. Longer follow-up may be necessary to demonstrate the weight loss pattern in this group.

Taurine ameliorated thyroid function in rats co-administered with chlorpyrifos and lead.

PubMed

Akande, Motunrayo Ganiyat; Shittu, Muftau; Uchendu, Chidiebere; Yaqub, Lukuman Surakat

2016-12-01

Chlorpyrifos is a widely used organophosphate insecticide for domestic, agricultural and industrial purposes. Lead is a toxic heavy metal and it is used for domestic and industrial purposes. Taurine is a semi essential amino acid with bioprotective properties. The aim of this study was to investigate the effects of taurine on thyroid function in Wistar rats co-administered with chlorpyrifos and lead. The rats were divided into 5 groups of 10 rats each. The first two groups were administered with distilled water and soya oil (1 ml/kg) respectively. The other groups received taurine (50 mg/kg), chlorpyrifos + lead [chlorpyrifos (4.25 mg/kg, 1/20 median lethal dose] and lead (233.25 mg/kg, 1/20 median lethal dose) and taurine + chlorpyrifos + lead respectively. The treatments were administered once daily by oral gavage for 16 weeks. The rats were euthanized after the completion of the study and the thyroid function and thyroid histoarchitecture were evaluated. The results revealed that co-administration of chlorpyrifos and lead to the rats induced perturbations in thyroid function and this was manifested by reductions in the concentrations of triiodothyronine and thyroxine, increased thyroid stimulating hormone concentration and degeneration of the follicular epithelia of the thyroid gland. Taurine alleviated the perturbations in thyroid function and improved thyroid gland histoarchitecture. The beneficial effects of taurine may be attributed to its ability to protect the body from toxicity and oxidative stress. Taurine may be useful for prophylaxis against disruptions in thyroid function in animals that are exposed to environmental chlorpyrifos and lead.

Alternate pathways of thyroid hormone metabolism.

PubMed

Wu, Sing-Yung; Green, William L; Huang, Wen-Sheng; Hays, Marguerite T; Chopra, Inder J

2005-08-01

The major thyroid hormone (TH) secreted by the thyroid gland is thyroxine (T(4)). Triiodothyronine (T(3)), formed chiefly by deiodination of T(4), is the active hormone at the nuclear receptor, and it is generally accepted that deiodination is the major pathway regulating T(3) bioavailability in mammalian tissues. The alternate pathways, sulfation and glucuronidation of the phenolic hydroxyl group of iodothyronines, the oxidative deamination and decarboxylation of the alanine side chain to form iodothyroacetic acids, and ether link cleavage provide additional mechanisms for regulating the supply of active hormone. Sulfation may play a general role in regulation of iodothyronine metabolism, since sulfation of T(4) and T(3) markedly accelerates deiodination to the inactive metabolites, reverse triiodothyronine (rT(3)) and T(2). Sulfoconjugation is prominent during intrauterine development, particularly in the precocial species in the last trimester including humans and sheep, where it may serve both to regulate the supply of T(3), via sulfation followed by deiodination, and to facilitate maternal-fetal exchange of sulfated iodothyronines (e.g., 3,3'-diiodothyronine sulfate [T(2)S]). The resulting low serum T(3) may be important for normal fetal development in the late gestation. The possibility that T(2)S or its derivative, transferred from the fetus and appearing in maternal serum or urine, can serve as a marker of fetal thyroid function is being studied. Glucuronidation of TH often precedes biliary-fecal excretion of hormone. In rats, stimulation of glucuronidation by various drugs and toxins may lead to lower T(4) and T(3) levels, provocation of thyrotropin (TSH) secretion, and goiter. In man, drug induced stimulation of glucuronidation is limited to T(4), and does not usually compromise normal thyroid function. However, in hypothyroid subjects, higher doses of TH may be required to maintain euthyroidism when these drugs are given. In addition, glucuronidates and sulfated iodothyronines can be hydrolyzed to their precursors in gastrointestinal tract and various tissues. Thus, these conjugates can serve as a reservoir for biologically active iodothyronines (e.g., T(4), T(3), or T(2)). The acetic acid derivatives of T(4), tetrac and triac, are minor products in normal thyroid physiology. However, triac has a different pattern of receptor affinity than T(3), binding preferentially to the beta receptor. This makes it useful in the treatment of the syndrome of resistance to thyroid hormone action, where the typical mutation affects only the beta receptor. Thus, adequate binding to certain mutated beta receptors can be achieved without excessive stimulation of alpha receptors, which predominate in the heart. Ether link cleavage of TH is also a minor pathway in normal subjects. However, this pathway may become important during infections, when augmented TH breakdown by ether-link cleavage (ELC) may assist in bactericidal activity. There is a recent claim that decarboxylated derivates of thyronines, that is, monoiodothyronamine (T(1)am) and thyronamine (T(0)am), may be biologically important and have actions different from those of TH. Further information on these interesting derivatives is awaited.

Serum microRNA miR-206 is decreased in hyperthyroidism and mediates thyroid hormone regulation of lipid metabolism in HepG2 human hepatoblastoma cells.

PubMed

Zheng, Yingjuan; Zhao, Chao; Zhang, Naijian; Kang, Wenqin; Lu, Rongrong; Wu, Huadong; Geng, Yingxue; Zhao, Yaping; Xu, Xiaoyan

2018-04-01

The actions of thyroid hormone (TH) on lipid metabolism in the liver are associated with a number of genes involved in lipogenesis and lipid metabolism; however, the underlying mechanisms through which TH impacts on lipid metabolism remain to be elucidated. The present study aimed to investigate the effects of hyperthyroidism on the serum levels of the microRNA (miR) miR‑206 and the role of miR‑206 on TH‑regulated lipid metabolism in liver cells. Serum was obtained from 12 patients diagnosed with hyperthyroidism and 10 healthy control subjects. Human hepatoblastoma (HepG2) cells were used to study the effects of triiodothyronine (T3) and miR‑206 on lipid metabolism. Expression of miR‑206 in serum and cells was determined by reverse transcription‑quantitative polymerase chain reaction analysis. Lipid accumulation in HepG2 cells was assessed with Oil Red O staining. Suppression or overexpression of miR‑206 was performed via transfection with a miR‑206 mimic or miR‑206 inhibitor. Serum miR‑206 was significantly decreased in patients with hyperthyroidism compared with euthyroid controls. Treatment of HepG2 cells with T3 led to reduced total cholesterol (TC) and triglyceride (TG) content, accompanied by reduced miR‑206 expression. Inhibition of endogenous miR‑206 expression decreased intracellular TG and TC content in HepG2 cells. By contrast, overexpression of miR‑206 in HepG2 partially prevented the reduction in TG content induced by treatment with T3. In conclusion, serum miR‑206 expression is reduced in patients with hyperthyroidism. In addition, miR‑206 is involved in T3‑mediated regulation of lipid metabolism in HepG2 cells, indicating a role for miR‑206 in thyroid hormone‑induced disorders of lipid metabolism in the liver.

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

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

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

1987-05-01

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

Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates.

PubMed

Holzer, Guillaume; Morishita, Yoshiaki; Fini, Jean-Baptiste; Lorin, Thibault; Gillet, Benjamin; Hughes, Sandrine; Tohmé, Marie; Deléage, Gilbert; Demeneix, Barbara; Arvan, Peter; Laudet, Vincent

2016-08-05

Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology, and behavior) but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Danio rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish, and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function, are well conserved despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Morbidity study of extruder personnel with potential exposure to brominated dioxins and furans. II. Results of clinical laboratory studies.

PubMed

Ott, M G; Zober, A

1996-12-01

To test whether dioxins affect liver and thyroid function, lipid metabolism and glucose or immunological variables, in workers exposed to brominated dioxins and furans. 34 male production employees (29 were extruder operators) and eight technical support personnel were studied, all of whom were potentially exposed to polybrominated dibenzo-p-dioxins (PBDDs) and furans (PBDFs) during production of resins containing polybrominated diphenyl ethers (PBDEs). Controls were from a similar resin producing plant that did not use PBDEs. Blood samples were analysed for tetra, penta, and hexabrominated congeners, but 2,3,7,8-TBDD was the only exposure measure used in the regression analyses. Seven liver function indicators, five measures of blood lipids and glucose, four haematology and blood coagulation measures, and three measures of thyroid function were examined. None of the variables was statistically related to concentration of 2,3,7,8-TBDD in the regression analyses. Cigarette smoking was related to several outcomes at the 0.05 level: aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase (GLDH), erythrocyte sedimentation rate, and white blood cell count. Body mass index was also related to alanine aminotransferase, gamma-glutamyltranspeptidase, cholinesterase, GLDH, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, and glucose concentrations. No definitive associations between liver, blood lipid, thyroid, or immunological variables and exposure to brominated dioxins or blood lipid concentration of 2,3,7,8-TBDD were found. The study population was small and hence the findings must be interpreted with caution. Nevertheless, these results provide a base for interpreting the results of clinical studies in similarly exposed populations.

Hypothyroidism in utero stimulates pancreatic beta cell proliferation and hyperinsulinaemia in the ovine fetus during late gestation.

PubMed

Harris, Shelley E; De Blasio, Miles J; Davis, Melissa A; Kelly, Amy C; Davenport, Hailey M; Wooding, F B Peter; Blache, Dominique; Meredith, David; Anderson, Miranda; Fowden, Abigail L; Limesand, Sean W; Forhead, Alison J

2017-06-01

Thyroid hormones are important regulators of growth and maturation before birth, although the extent to which their actions are mediated by insulin and the development of pancreatic beta cell mass is unknown. Hypothyroidism in fetal sheep induced by removal of the thyroid gland caused asymmetric organ growth, increased pancreatic beta cell mass and proliferation, and was associated with increased circulating concentrations of insulin and leptin. In isolated fetal sheep islets studied in vitro, thyroid hormones inhibited beta cell proliferation in a dose-dependent manner, while high concentrations of insulin and leptin stimulated proliferation. The developing pancreatic beta cell is therefore sensitive to thyroid hormone, insulin and leptin before birth, with possible consequences for pancreatic function in fetal and later life. The findings of this study highlight the importance of thyroid hormones during pregnancy for normal development of the fetal pancreas. Development of pancreatic beta cell mass before birth is essential for normal growth of the fetus and for long-term control of carbohydrate metabolism in postnatal life. Thyroid hormones are also important regulators of fetal growth, and the present study tested the hypotheses that thyroid hormones promote beta cell proliferation in the fetal ovine pancreatic islets, and that growth retardation in hypothyroid fetal sheep is associated with reductions in pancreatic beta cell mass and circulating insulin concentration in utero. Organ growth and pancreatic islet cell proliferation and mass were examined in sheep fetuses following removal of the thyroid gland in utero. The effects of triiodothyronine (T 3 ), insulin and leptin on beta cell proliferation rates were determined in isolated fetal ovine pancreatic islets in vitro. Hypothyroidism in the sheep fetus resulted in an asymmetric pattern of organ growth, pancreatic beta cell hyperplasia, and elevated plasma insulin and leptin concentrations. In pancreatic islets isolated from intact fetal sheep, beta cell proliferation in vitro was reduced by T 3 in a dose-dependent manner and increased by insulin at high concentrations only. Leptin induced a bimodal response whereby beta cell proliferation was suppressed at the lowest, and increased at the highest, concentrations. Therefore, proliferation of beta cells isolated from the ovine fetal pancreas is sensitive to physiological concentrations of T 3 , insulin and leptin. Alterations in these hormones may be responsible for the increased beta cell proliferation and mass observed in the hypothyroid sheep fetus and may have consequences for pancreatic function in later life. © 2017 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.

Need of tetraiodothyronine supplemental therapy in pregnant women

NASA Astrophysics Data System (ADS)

Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

2013-10-01

Thyroid hormones are essential for fetal development. Normal thyroid function in pregnant women adjusts by itself in cases of pregnancy, phenomenon that is deficient in cases of previous maternal thyroid disease. The study group was represented by 120 females, with reproductive age, with known thyroid disease, that had a up to delivery pregnancy. Thyroid ultrasound parameters and functional parameters were follow-up during the 9-month of gestation. The study proposes a mathematical model of predicting the need and the amount of tetraiodothyronine treatment in pregnant women with prevalent thyroid disease.

Diagnostic and functional structure of a high-resolution thyroid nodule clinic.

PubMed

Fernández-García, José Carlos; Mancha-Doblas, Isabel; Ortega-Jiménez, María Victoria; Ruiz-Escalante, José Francisco; Castells-Fusté, Ignasi; Tofé-Povedano, Santiago; Argüelles-Jiménez, Iñaki; Tinahones, Francisco José

2014-01-01

Appearance of a thyroid nodule has become a daily occurrence in clinical practice. Adequate thyroid nodule assessment requires several diagnostic tests and multiple medical appointments, which results in a substantial delay in diagnosis. Implementation of a high-resolution thyroid nodule clinic largely avoids these drawbacks by condensing in a single appointment all tests required for adequate evaluation of thyroid nodule. This paper reviews the diagnostic and functional structure of a high-resolution thyroid nodule clinic. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

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

PubMed

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

2017-11-01

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

Neurotoxicity of Thyroid Disrupting Contaminants

EPA Science Inventory

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

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

PubMed

Mansourian, Azad Reza

2010-08-15

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

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

Radioiodine: the classic theranostic agent.

PubMed

Silberstein, Edward B

2012-05-01

Radioiodine has the distinction of being the first theranostic agent in our armamentarium. Millennia were required to discover that the agent in orally administered seaweed and its extracts, which had been shown to cure neck swelling due to thyromegaly, was iodine, first demonstrated to be a new element in 1813. Treatment of goiter with iodine began at once, but its prophylactic value to prevent a common form of goiter took another century. After Enrico Fermi produced the first radioiodine, (128)I, in 1934, active experimentation in the United States and France delineated the crucial role of iodine in thyroid metabolism and disease. (130)I and (131)I were first employed to treat thyrotoxicosis by 1941, and thyroid cancer in 1943. After World War II, (131)I became widely available at a reasonable price for diagnostic testing and therapy. The rectilinear scanner of Cassen and Curtis (Science 1949;110:94-95), and a dedicated gamma camera invented by Anger (Nature 1952;170:200-201), finally permitted the diagnostic imaging of thyroid disease, with (131)I again the radioisotope of choice, although there were short-lived attempts to employ (125)I and (132)I for this purpose. (123)I was first produced in 1949 but did not become widely available until about 1982, 10 years after a production technique eliminated high-energy (124)I contamination. I continues to be the radioiodine of choice for the diagnosis of benign thyroid disease, whereas (123)I and (131)I are employed in the staging and detection of functioning thyroid cancer. (124)I, a positron emitter, can produce excellent anatomically correlated images employing positron emission tomography/computed tomography equipment and has the potential to enhance heretofore imperfect dosimetric studies in determining the appropriate administered activity to ablate/treat thyroid cancer. Issues of acceptable measuring error in thyroid cancer dosimetry and the role in (131)I therapy of tumor heterogeneity, tumor hypoxia, and kinetics must be overcome, and long-term outcome studies following (131)I given based on this new dosimetry must be completed before the nuclear medicine community will be able to predictably cure our thyroid cancer patients with this technology. Copyright © 2012 Elsevier Inc. All rights reserved.

Biochemical Testing of the Thyroid: TSH is the Best and, Oftentimes, Only Test Needed - A Review for Primary Care.

PubMed

Sheehan, Michael T

2016-06-01

Disorders of thyroid function are common, and screening, diagnosis, and management are often performed by primary care providers. While management of significant biochemical abnormalities is reasonably straight forward, laboratory tests only slightly outside, or even within, the normal range are becoming more difficult to appropriately manage. A large part of this increasing difficulty in appropriate management is caused by patients requesting, and even demanding, certain tests or treatments that may not be indicated. Symptoms of thyroid dysfunction are non-specific and extremely prevalent in the general population. This, along with a growing body of information available to patients via the lay press and internet suggesting that traditional thyroid function testing is not reliable, has fostered some degree of patient mistrust. Increasingly, when a physician informs a patient that their thyroid is not the cause of their symptoms, the patient is dissatisfied and even angry. This review aims to clarify the interpretation of normal and mild abnormalities of thyroid function tests by describing pituitary-thyroid physiology and through an in depth review of, arguably, the three most important biochemical tests of thyroid function: TSH, free T4, and anti-TPO antibodies. It is important for primary care providers to have an understanding of the shortcomings and proper interpretation of these tests to be better able to discuss thyroid function with their patients. © 2016 Marshfield Clinic.

Advances in assessment, diagnosis, and treatment of hyperthyroidism in children.

PubMed

Amer, Kim Siarkowski

2005-04-01

The thyroid gland is responsible for regulating multiple complex metabolic processes that affect most organs. Physical growth and cognitive development are dependent on proper levels of thyroid hormone. This article will review common challenges in the diagnosis of hyperthyroidism in children, the approaches to treatment, and the nursing interventions guided toward child and family responses to thyroid disease. A comparison of signs and symptoms of hypothyroidism and hyperthyroidism is also included. The nursing interventions addressed in the article integrate the biological, psychological, social, and environmental stresses and adaptations necessary to cope with hyperthyroid disease.

Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab

PubMed Central

Jansen, Yanina; Schreuer, Max; Everaert, Hendrik; Velkeniers, Brigitte; Neyns, Bart; Bravenboer, Bert

2016-01-01

Context: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. Objective: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. Design and Setting: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. 18Fluorodeoxyglucose uptake on positron emission tomography/computed tomography (18FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. Patients: Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. Main Outcome Measures: Patient characteristics, thyroid function (TSH, free T4), thyroid autoantibodies, and 18FDG-PET/CT. Results: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased 18FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. Conclusions: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates. PMID:27571185

SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals

PubMed Central

Akieda-Asai, Sayaka; Zaima, Nobuhiro; Ikegami, Koji; Kahyo, Tomoaki; Yao, Ikuko; Hatanaka, Takahiro; Iemura, Shun-ichiro; Sugiyama, Rika; Yokozeki, Takeaki; Eishi, Yoshinobu; Koike, Morio; Ikeda, Kyoji; Chiba, Takuya; Yamaza, Haruyoshi; Shimokawa, Isao; Song, Si-Young; Matsuno, Akira; Mizutani, Akiko; Sawabe, Motoji; Chao, Moses V.; Tanaka, Masashi; Kanaho, Yasunori; Natsume, Tohru; Sugimura, Haruhiko; Date, Yukari; McBurney, Michael W.; Guarente, Leonard; Setou, Mitsutoshi

2010-01-01

Background SIRT1, a NAD-dependent deacetylase, has diverse roles in a variety of organs such as regulation of endocrine function and metabolism. However, it remains to be addressed how it regulates hormone release there. Methodology/Principal Findings Here, we report that SIRT1 is abundantly expressed in pituitary thyrotropes and regulates thyroid hormone secretion. Manipulation of SIRT1 level revealed that SIRT1 positively regulated the exocytosis of TSH-containing granules. Using LC/MS-based interactomics, phosphatidylinositol-4-phosphate 5-kinase (PIP5K)γ was identified as a SIRT1 binding partner and deacetylation substrate. SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kγ and enhanced PIP5Kγ enzyme activity. SIRT1-mediated TSH secretion was abolished by PIP5Kγ knockdown. SIRT1 knockdown decreased the levels of deacetylated PIP5Kγ, PI(4,5)P2, and reduced the secretion of TSH from pituitary cells. These results were also observed in SIRT1-knockout mice. Conclusions/Significance Our findings indicated that the control of TSH release by the SIRT1-PIP5Kγ pathway is important for regulating the metabolism of the whole body. PMID:20668706

Role of Nuclear Medicine in the Diagnosis of Benign Thyroid Diseases.

PubMed

Garberoglio, Sara; Testori, Ornella

2016-01-01

A deep understanding of thyroid pathophysiology is the basis for diagnosing and treating benign thyroid diseases with radioactive materials, known as radiopharmaceuticals, which are introduced into the body by injection or orally. After the radiotracer administration, the patient becomes the emitting source, and several devices have been studied to detect and capture these emissions (gamma or beta-negative) and transform them into photons, parametric images, numbers and molecular information. Thyroid scintigraphy is the only technique that allows the assessment of thyroid regional function and, therefore, the detection of areas of autonomously functioning thyroid nodules. Scintigraphy visualizes the distribution of active thyroid tissue and displays the differential accumulation of radionuclides in the investigated cells, thus providing a functional map. Moreover, this technique is a fundamental tool in the clinical and surgical management of thyroid diseases, including: single thyroid nodules with a suppressed thyroid-stimulating hormone level, for which fine-needle aspiration biopsy (FNAB) is used to identify hot nodules; multinodular goiters, especially larger ones, to identify cold or indeterminate areas requiring FNAB and hot areas that do not need cytologic evaluation, and to evaluate mediastinal extension; the diagnosis of ectopic thyroid tissue; subclinical hyperthyroidism to identify occult hyperfunctioning tissue; follicular lesions to identify a functioning cellular adenoma that could be benign, although such nodules are mostly cold on scintigraphy; to distinguish low-uptake from high-uptake thyrotoxicosis, and to determine eligibility for radioiodine therapy. © 2016 S. Karger AG, Basel.

Skin findings in autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls.

PubMed

Takir, Mümtaz; Özlü, Emin; Köstek, Osman; Türkoğlu, Zafer; Mutlu, Hasan Hüseyin; Uzunçakmak, Tuğba Kevser; Akdeniz, Necmettin; Karadağ, Ayşe Serap

2017-06-12

Thyroid disorders are associated with a wide variety of skin disorders that respond to treatment of hormone imbalance in most cases and thus are of vital importance to dermatologists. This study aimed to evaluate skin findings associated with autoimmune and nonautoimmune thyroid disease with respect to thyroid functional status and healthy controls. A total of 300 consecutive patients with either autoimmune (n = 173) or nonautoimmune (n = 127) thyroid disease and 100 healthy control subjects were included in this cross-sectional study. Data on patient demographics, thyroid function tests, and skin findings were recorded for patient and control groups. Compared to control subjects, patients had higher proportions in populations with alopecia (P < 0.001), nail thinning (P = 0.02), brittle nails (P = 0.001), pruritus (P < 0.001), diffuse hyperhidrosis (P = 0.01), flushing (P = 0.001), and xerosis (P < 0.001). Onycholysis (P = 0.02), yellow skin (P = 0.04), periorbital edema (P = 0.03), psoriasis (P = 0.001), and palmoplantar hyperkeratosis (P = 0.007) were significantly more common in patients with autoimmune than nonautoimmune thyroid disease. A significantly higher percentage of patients with autoimmune rather than nonautoimmune thyroid disease had overall skin findings (P = 0.03) among the hyperthyroid patients.Conclusions: Our findings indicate that the presence of skin findings in a majority of thyroid patients significantly differs for certain cutaneous manifestations with respect to controls, autoimmune etiology, and thyroid functional status.

Upregulation of uncoupling proteins by oral administration of capsiate, a nonpungent capsaicin analog.

PubMed

Masuda, Yoriko; Haramizu, Satoshi; Oki, Kasumi; Ohnuki, Koichiro; Watanabe, Tatsuo; Yazawa, Susumu; Kawada, Teruo; Hashizume, Shu-ichi; Fushiki, Tohru

2003-12-01

Capsiate is a nonpungent capsaicin analog, a recently identified principle of the nonpungent red pepper cultivar CH-19 Sweet. In the present study, we report that 2-wk treatment of capsiate increased metabolic rate and promoted fat oxidation at rest, suggesting that capsiate may prevent obesity. To explain these effects, at least in part, we examined uncoupling proteins (UCPs) and thyroid hormones. UCPs and thyroid hormones play important roles in energy expenditure, the maintenance of body weight, and thermoregulation. Two-week treatment of capsiate increased the levels of UCP1 protein and mRNA in brown adipose tissue and UCP2 mRNA in white adipose tissue. This dose of capsiate did not change serum triiodothyronine or thyroxine levels. A single dose of capsiate temporarily raised both UCP1 mRNA in brown adipose tissue and UCP3 mRNA in skeletal muscle. These results suggest that UCP1 and UCP2 may contribute to the promotion of energy metabolism by capsiate, but that thyroid hormones do not.

Physiological serum 25-hydroxyvitamin D concentrations are associated with improved thyroid function-observations from a community-based program.

PubMed

Mirhosseini, Naghmeh; Brunel, Ludovic; Muscogiuri, Giovanna; Kimball, Samantha

2017-12-01

Vitamin D deficiency has been associated with an increased risk of hypothyroidism and autoimmune thyroid disease. Our aim was to investigate the influence of vitamin D supplementation on thyroid function and anti-thyroid antibody levels. We constructed a database that included 11,017 participants in a health and wellness program that provided vitamin D supplementation to target physiological serum 25-hydroxyvitmain D [25(OH)D] concentrations (>100 nmol/L). Participant measures were compared between entry to the program (baseline) and follow-up (12 ± 3 months later) using an intent-to-treat analysis. Further, a nested case-control design was utilized to examine differences in thyroid function over 1 year in hypothyroid individuals and euthyroid controls. More than 72% of participants achieved serum 25(OH)D concentrations >100 nmol/L at follow-up, with 20% above 125 nmol/L. Hypothyroidism was detected in 2% (23% including subclinical hypothyroidism) of participants at baseline and 0.4% (or 6% with subclinical) at follow-up. Serum 25(OH)D concentrations ≥125 nmol/L were associated with a 30% reduced risk of hypothyroidism and a 32% reduced risk of elevated anti-thyroid antibodies. Hypothyroid cases were found to have higher mean serum 25(OH)D concentrations at follow-up, which was a significant positive predictor of improved thyroid function. The results of the current study suggest that optimal thyroid function might require serum 25(OH)D concentrations above 125 nmol/L. Vitamin D supplementation may offer a safe and economical approach to improve thyroid function and may provide protection from developing thyroid disease.

Endogenous subclinical thyroid disorders, physical and cognitive function, depression, and mortality in older individuals.

PubMed

de Jongh, Renate T; Lips, Paul; van Schoor, Natasja M; Rijs, Kelly J; Deeg, Dorly J H; Comijs, Hannie C; Kramer, Mark H H; Vandenbroucke, Jan P; Dekkers, Olaf M

2011-10-01

To what extent endogenous subclinical thyroid disorders contribute to impaired physical and cognitive function, depression, and mortality in older individuals remains a matter of debate. A population-based, prospective cohort of the Longitudinal Aging Study Amsterdam. TSH and, if necessary, thyroxine and triiodothyronine levels were measured in individuals aged 65 years or older. Participants were classified according to clinical categories of thyroid function. Participants with overt thyroid disease or use of thyroid medication were excluded, leaving 1219 participants for analyses. Outcome measures were physical and cognitive function, depressive symptoms (cross-sectional), and mortality (longitudinal) Sixty-four (5.3%) individuals had subclinical hypothyroidism and 34 (2.8%) individuals had subclinical hyperthyroidism. Compared with euthyroidism (n=1121), subclinical hypo-, and hyper-thyroidism were not significantly associated with impairment of physical or cognitive function, or depression. On the contrary, participants with subclinical hypothyroidism did less often report more than one activity limitation (odds ratio 0.44, 95% confidence interval (CI) 0.22-0.86). After a median follow-up of 10.7 years, 601 participants were deceased. Subclinical hypo- and hyper-thyroidism were not associated with increased overall mortality risk (hazard ratio 0.89, 95% CI 0.59-1.35 and 0.69, 95% CI 0.40-1.20 respectively). This study does not support disadvantageous effects of subclinical thyroid disorders on physical or cognitive function, depression, or mortality in an older population.

Chronic exposure of adult, postnatal and in utero rat models to low-dose 137Cesium: impact on circulating biomarkers.

PubMed

Manens, Line; Grison, Stéphane; Bertho, Jean-Marc; Lestaevel, Philippe; Guéguen, Yann; Benderitter, Marc; Aigueperse, Jocelyne; Souidi, Maâmar

2016-11-01

The presence of 137 Cesium ( 137 Cs) in the environment after nuclear accidents at Chernobyl and more recently Fukushima Daiichi raises many health issues for the surrounding populations chronically exposed through the food chain. To mimic different exposure situations, we set up a male rat model of exposure by chronic ingestion of a 137 Cs concentration likely to be ingested daily by residents of contaminated areas (6500 Bq.l -1 ) and tested contaminations lasting 9 months for adult, neonatal and fetal rats. We tested plasma and serum biochemistry to identify disturbances in general indicators (lipids, proteins, carbohydrates and electrolytes) and in biomarkers of thyroid, heart, brain, bone, kidney, liver and testis functions. Analysis of the general indicators showed increased levels of cholesterol (+26%), HDL cholesterol (+31%), phospholipids B (+15%) and phosphorus (+100%) in the postnatal group only. Thyroid, heart, brain, bone and kidney functions showed no blood changes in any model. The liver function evaluation showed changes in total bilirubin (+67%) and alkaline phosphatase (-11%) levels, but only for the rats exposed to 137 Cs intake in adulthood. Large changes in 17β-estradiol (-69%) and corticosterone (+36%) levels affected steroidogenesis, but only in the adult model. This study showed that response profiles differed according to age at exposure: lipid metabolism was most radiosensitive in the postnatal model, and steroid hormone metabolism was most radiosensitive in rats exposed in adulthood. There was no evidence of deleterious effects suggesting a potential impact on fertility or procreation. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Energetics, adaptation, and adaptability.

PubMed

Ulijaszek, Stanley J

1996-01-01

Energy capture and conversion are fundamental to human existence, and over the past three decades biological anthropologists have used a number of approaches which incorporate energetics measures in studies of human population biology. Human groups can vary enormously in their energy expenditure. This review considers evidence for genetic adaptation and presents models for physiological adaptability to reduced physiological energy availability and/or negative energy balance. In industrialized populations, different aspects of energy expenditure have been shown to have a genetic component, including basal metabolic rate, habitual physical activity level, mechanical efficiency of work performance, and thermic effect of food. Metabolic adaptation to low energy intakes has been demonstrated in populations in both developing and industrialized nations. Thyroid hormone-related effects on energy metabolic responses to low physiological energy availability are unified in a model, linking energetic adaptability in physical activity and maintenance metabolism. Negative energy balance has been shown to be associated with reduced reproductive function in women experiencing seasonal environments in some developing countries. Existing models relating negative energy balance to menstrual or ovulatory function are largely descriptive, and do not propose any physiological mechanisms for this phenomenon. A model is proposed whereby reduced physiological energy availability could influence ovulatory function via low serum levels of the amino acid aspartate and reduced sympathetic nervous system activity. © 1996 Wiley-Liss, Inc. Copyright © 1996 Wiley-Liss, Inc.

Effects of hyperthyroidism, hypothyroidism, and thyroid autoimmunity on female sexual function.

PubMed

Oppo, A; Franceschi, E; Atzeni, F; Taberlet, A; Mariotti, S

2011-06-01

Thyroid hormones affect male and female sexual functions, but data in hypo- and hyperthyroid women are scanty. To investigate sexual function in hypo- and hyperthyroid women before and immediately after restoration of euthyroidism and in women with euthyroid Hashimoto's thyroiditis (HT). Fifty-six women with thyroid diseases (age 19-50 yr; 22 with hyperthyroidism, 17 with hypothyroidism, and 17 with euthyroid HT) and 30 age-matched healthy women. Hypoactive sexual desire, disorders of sexual arousal, vaginal lubrication, orgasm, satisfaction, and sexual pain (SPD) were assessed by Female Sexual Function Index. Serum TSH, free T4 (FT4) and thyroid autoantibodies (anti-thyroglobulin, anti-thyroperoxidase, and TSH-receptor antibodies) were assessed at the diagnosis; FT4 and TSH were repeated after treatment to confirm normalization of thyroid function. All sexual domains scores were significantly reduced (p ranging <0.0001-<0.05) in both hypo- and hyperthyroid women. Correction of hypothyroidism was associated to normalization of desire, satisfaction, and pain, while arousal and orgasm remained unchanged. In hyperthyroid women therapy normalized sexual desire, arousal/lubrication, satisfaction, and pain, while orgasm remained significantly impaired. Interestingly, euthyroid HT women displayed a significant decrease in sexual desire (p<0.0005), with no changes in the other sexual domains. Both hypo- and hyperthyroidism markedly impair female sexual function. A rapid improvement is observed with the restoration of euthyroidism, although a longer period of time may be needed for full normalization. Preliminary data suggest that thyroid autoimmunity may selectively impair sexual desire, independently from thyroid function.

Thyroid nodule

MedlinePlus

... has grown Another possible treatment is an ethanol (alcohol) injection into the nodule to shrink ... Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, ...

The microRNA-processing enzyme Dicer is essential for thyroid function.

PubMed

Frezzetti, Daniela; Reale, Carla; Calì, Gaetano; Nitsch, Lucio; Fagman, Henrik; Nilsson, Ola; Scarfò, Marzia; De Vita, Gabriella; Di Lauro, Roberto

2011-01-01

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.

Effects of electromagnetic radiation exposure on bone mineral density, thyroid, and oxidative stress index in electrical workers

PubMed Central

Kunt, Halil; Şentürk, İhsan; Gönül, Yücel; Korkmaz, Mehmet; Ahsen, Ahmet; Hazman, Ömer; Bal, Ahmet; Genç, Abdurrahman; Songur, Ahmet

2016-01-01

Background In the literature, some articles report that the incidence of numerous diseases increases among the individuals who live around high-voltage electric transmission lines (HVETL) or are exposed vocationally. However, it was not investigated whether HVETL affect bone metabolism, oxidative stress, and the prevalence of thyroid nodule. Methods Dual-energy X-ray absorptiometry (DEXA) bone density measurements, serum free triiodothyronine (FT3), free thyroxine (FT4), RANK, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), phosphor, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were analyzed to investigate this effect. Results Bone mineral density levels of L1–L4 vertebrae and femur were observed significantly lower in the electrical workers. ALP, phosphor, RANK, RANKL, TOS, OSI, and anteroposterior diameter of the left thyroid lobe levels were significantly higher, and OPG, TAS, and FT4 levels were detected significantly lower in the study group when compared with the control group. Conclusion Consequently, it was observed that the balance between construction and destruction in the bone metabolism of the electrical workers who were employed in HVETL replaced toward destruction and led to a decrease in OPG levels and an increase in RANK and RANKL levels. In line with the previous studies, long-term exposure to an electromagnetic field causes disorders in many organs and systems. Thus, it is considered that long-term exposure to an electromagnetic field affects bone and thyroid metabolism and also increases OSI by increasing the TOS and decreasing the antioxidant status. PMID:26929645

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

Marine-Lenhart syndrome with papillary thyroid carcinoma.

PubMed

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

2015-04-01

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

12-month efficacy of a single radiofrequency ablation on autonomously functioning thyroid nodules.

PubMed

Bernardi, Stella; Stacul, Fulvio; Michelli, Andrea; Giudici, Fabiola; Zuolo, Giulia; de Manzini, Nicolò; Dobrinja, Chiara; Zanconati, Fabrizio; Fabris, Bruno

2017-09-01

Radiofrequency ablation has been advocated as an alternative to radioiodine and/or surgery for the treatment of autonomously functioning benign thyroid nodules. However, only a few studies have measured radiofrequency ablation efficacy on autonomously functioning benign thyroid nodules. The aim of this work was to evaluate the 12-month efficacy of a single session of radiofrequency ablation (performed with the moving shot technique) on solitary autonomously functioning benign thyroid nodules. Thirty patients with a single, benign autonomously functioning benign thyroid nodules, who were either unwilling or ineligible to undergo surgery and radioiodine, were treated with radiofrequency ablation between April 2012 and May 2015. All the patients underwent a single radiofrequency ablation, performed with the 18-gauge needle and the moving shot technique. Clinical, laboratory, and ultrasound evaluations were scheduled at baseline, and after 1, 3, 6, and 12 months from the procedure. A single radiofrequency ablation reduced thyroid nodule volume by 51, 63, 69, and 75 % after 1, 3, 6, and 12 months, respectively. This was associated with a significant improvement of local cervical discomfort and cosmetic score. As for thyroid function, 33 % of the patients went into remission after 3 months, 43 % after 6 months, and 50 % after 12 months from the procedure. This study demonstrates that a single radiofrequency ablation allowed us to withdraw anti-thyroid medication in 50 % of the patients, who remained euthyroid afterwards. This study shows that a single radiofrequency ablation was effective in 50 % of patients with autonomously functioning benign thyroid nodules. Patients responded gradually to the treatment. It is possible that longer follow-up studies might show greater response rates.

Low thyroid function is not associated with an accelerated deterioration in renal function.

PubMed

Meuwese, Christiaan L; van Diepen, Merel; Cappola, Anne R; Sarnak, Mark J; Shlipak, Michael G; Bauer, Douglas C; Fried, Linda P; Iacoviello, Massimo; Vaes, Bert; Degryse, Jean; Khaw, Kay-Tee; Luben, Robert N; Åsvold, Bjørn O; Bjøro, Trine; Vatten, Lars J; de Craen, Anton J M; Trompet, Stella; Iervasi, Giorgio; Molinaro, Sabrina; Ceresini, Graziano; Ferrucci, Luigi; Dullaart, Robin P F; Bakker, Stephan J L; Jukema, J Wouter; Kearney, Patricia M; Stott, David J; Peeters, Robin P; Franco, Oscar H; Völzke, Henry; Walsh, John P; Bremner, Alexandra; Sgarbi, José A; Maciel, Rui M B; Imaizumi, Misa; Ohishi, Waka; Dekker, Friedo W; Rodondi, Nicolas; Gussekloo, Jacobijn; den Elzen, Wendy P J

2018-04-18

Chronic kidney disease (CKD) is frequently accompanied by thyroid hormone dysfunction. It is currently unclear whether these alterations are the cause or consequence of CKD. This study aimed at studying the effect of thyroid hormone alterations on renal function in cross-sectional and longitudinal analyses in individuals from all adult age groups. Individual participant data (IPD) from 16 independent cohorts having measured thyroid stimulating hormone, free thyroxine levels and creatinine levels were included. Thyroid hormone status was defined using clinical cut-off values. Estimated glomerular filtration rates (eGFR) were calculated by means of the four-variable Modification of Diet in Renal Disease (MDRD) formula. For this IPD meta-analysis, eGFR at baseline and eGFR change during follow-up were computed by fitting linear regression models and linear mixed models in each cohort separately. Effect estimates were pooled using random effects models. A total of 72 856 individuals from 16 different cohorts were included. At baseline, individuals with overt hypothyroidism (n = 704) and subclinical hypothyroidism (n = 3356) had a average (95% confidence interval) -4.07 (-6.37 to -1.78) and -2.40 (-3.78 to -1.02) mL/min/1.73 m2 lower eGFR as compared with euthyroid subjects (n = 66 542). In (subclinical) hyperthyroid subjects (n = 2254), average eGFR was 3.01 (1.50-4.52) mL/min/1.73 m2 higher. During 329 713 patient years of follow-up, eGFR did not decline more rapidly in individuals with low thyroid function compared with individuals with normal thyroid function. Low thyroid function is not associated with a deterioration of renal function. The cross-sectional association may be explained by renal dysfunction causing thyroid hormone alterations.

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

PubMed

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

2013-07-01

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

Serum Levels of Follistatin Are Positively Associated With Serum-Free Thyroxine Levels in Patients With Hyperthyroidism or Euthyroidism

PubMed Central

Tseng, Fen-Yu; Chen, Yen-Ting; Chi, Yu-Chao; Chen, Pei-Lung; Yang, Wei-Shiung

2016-01-01

Abstract Follistatin is a glycoprotein with various biologic functions that plays a role in adipocyte differentiation, muscle stimulation, anti-inflammation, and energy homeostasis. Thyroid hormones influence energy expenditure, glucose, and lipid metabolism. The association between serum follistatin level and thyroid function statuses has seldom been evaluated. The objectives of this study were to compare serum follistatin concentrations in different thyroid function statuses and to evaluate the associations between serum follistatin and free thyroxine (fT4) levels. In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid individuals (EU group) were recruited. The patients of HY group were treated with antithyroid regimens as clinically indicated, whereas no medication was given to EU group. The demographic and anthropometric characteristics, biochemical data, serum levels of follistatin, and thyroid function of both groups at baseline and at the 6th month were compared. Data of all patients were pooled for the analysis of the associations between the levels of follistatin and fT4. At baseline, the HY group had significantly higher serum follistatin levels than the EU group (median [Q1, Q3]: 1.81 [1.33, 2.78] vs 1.13 [0.39, 1.45] ng/mL, P < 0.001). When treated with antithyroid regimens, the follistatin serum levels in HY group decreased to 1.54 [1.00, 1.88] ng/mL at the 6th month. In all patients, the serum levels of follistatin were positively associated with fT4 levels at baseline (β = 0.54, P = 0.005) and at the 6th month (β = 0.59, P < 0.001). The association between follistatin and fT4 levels remained significant in the stepwise multivariate regression analysis, both initially and at the 6th month. In comparison to the EU group, patients with hyperthyroidism had higher serum follistatin levels, which decreased after receiving antithyroid treatment. In addition, the serum follistatin concentrations were positively associated with serum fT4 levels in patients with hyperthyroidism or euthyroidism. PMID:26844494

The Brazilian consensus for the clinical approach and treatment of subclinical hypothyroidism in adults: recommendations of the thyroid Department of the Brazilian Society of Endocrinology and Metabolism.

PubMed

Sgarbi, Jose A; Teixeira, Patrícia F S; Maciel, Lea M Z; Mazeto, Glaucia M F S; Vaisman, Mario; Montenegro Junior, Renan M; Ward, Laura S

2013-04-01

Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in Brazil, especially among women and the elderly. Although an increasing number of studies have related SCH to an increased risk of coronary artery disease and mortality, there have been no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these risks, and the treatment remains controversial. This consensus, sponsored by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed by Brazilian experts with extensive clinical experience with thyroid diseases, presents these recommendations based on evidence for the clinical management of SCH patients in Brazil. After structuring the clinical questions, the search for evidence in the literature was initially performed in the MedLine-PubMed database and later in the Embase and SciELO - Lilacs databases. The strength of evidence was evaluated according to the Oxford classification system and established based on the experimental design used, considering the best available evidence for each question and the Brazilian experience. The topics covered included SCH definition and diagnosis, natural history, clinical significance, treatment and pregnancy, and the consensus issued 29 recommendations for the clinical management of adult patients with SCH. Treatment with levothyroxine was recommended for all patients with persistent SCH with serum TSH values > 10 mU/L and for certain patient subgroups.

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

PubMed

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

2012-06-01

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

The Brazilian consensus for the diagnosis and treatment of hyperthyroidism: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism.

PubMed

Maia, Ana Luiza; Scheffel, Rafael S; Meyer, Erika Laurini Souza; Mazeto, Glaucia M F S; Carvalho, Gisah Amaral de; Graf, Hans; Vaisman, Mario; Maciel, Lea M Z; Ramos, Helton E; Tincani, Alfio José; Andrada, Nathalia Carvalho de; Ward, Laura S

2013-04-01

Hyperthyroidism is characterized by increased synthesis and release of thyroid hormones by the thyroid gland. Thyrotoxicosis refers to the clinical syndrome resulting from excessive circulating thyroid hormones, secondary to hyperthyroidism or due to other causes. This article describes evidence-based guidelines for the clinical management of thyrotoxicosis. This consensus, developed by Brazilian experts and sponsored by the Department of Thyroid Brazilian Society of Endocrinology and Metabolism, aims to address the management, diagnosis and treatment of patients with thyrotoxicosis, according to the most recent evidence from the literature and appropriate for the clinical reality of Brazil. After structuring clinical questions, search for evidence was made available in the literature, initially in the database MedLine, PubMed and Embase databases and subsequently in SciELO - Lilacs. The strength of evidence was evaluated by Oxford classification system was established from the study design used, considering the best available evidence for each question. We have defined 13 questions about the initial clinical approach for the diagnosis and treatment that resulted in 53 recommendations, including the etiology, treatment with antithyroid drugs, radioactive iodine and surgery. We also addressed hyperthyroidism in children, teenagers or pregnant patients, and management of hyperthyroidism in patients with Graves' ophthalmopathy and various other causes of thyrotoxicosis. The clinical diagnosis of hyperthyroidism usually offers no difficulty and should be made with measurements of serum TSH and thyroid hormones. The treatment can be performed with antithyroid drugs, surgery or administration of radioactive iodine according to the etiology of thyrotoxicosis, local availability of methods and preferences of the attending physician and patient.

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.

Short-chain chlorinated paraffins (SCCPs) induced thyroid disruption by enhancement of hepatic thyroid hormone influx and degradation in male Sprague Dawley rats.

PubMed

Gong, Yufeng; Zhang, Haijun; Geng, Ningbo; Xing, Liguo; Fan, Jingfeng; Luo, Yun; Song, Xiaoyao; Ren, Xiaoqian; Wang, Feidi; Chen, Jiping

2018-06-01

Short-chain chlorinated paraffins (SCCPs) are known to disturb thyroid hormone (TH) homeostasis in rodents. However, the mechanism remains to be fully characterized. In this study, male Sprague Dawley rats received SCCPs (0, 1, 10, or 100mg/kg/day) via gavage once a day for consecutive 28days. Plasma and hepatic TH concentrations, thyrocyte structure, as well as thyroid and hepatic mRNA and protein levels of genes associated with TH homeostasis were examined. Moreover, we performed molecular docking to predict interactions between constitutive androstane receptor (CAR), a key regulator in xenobiotic-induced TH metabolism, with different SCCP molecules. Exposure to SCCPs significantly decreased the circulating free thyroxine (T 4 ) and triiodothyronine (T 3 ) levels, but increased thyroid-stimulating hormone (TSH) levels by a feedback mechanism. Decreased hepatic T 4 and increased hepatic T 3 levels were also seen after 100mg/kg/day SCCPs exposure. SCCPs didn't show any significant effects on the expression of thyroid TH synthesis genes or thyrocyte structure. However, stimulation effects were observed for mRNA and protein levels of hepatic uridine diphosphoglucuronosyl transferase (UGT) 1A1 and organic anion transporter 2, suggesting an accelerated TH metabolism in rat liver. The increased cytochrome P450 2B1 but not 1A1 mRNA and protein levels indicated that the CAR signaling was activated by SCCPs exposure. According to docking analysis, SCCPs form hydrophobic interactions with CAR and the binding affinity shows dependency on chlorine content. Overall, our data showed that CAR implicated enhancement of hepatic TH influx and degradation could be the main cause for SCCPs induced TH deficiency in male rats. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2010-09-01

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

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

PubMed Central

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

2010-01-01

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

Factors associated with serum thyroglobulin levels in a population living in Belarus

PubMed Central

Cahoon, Elizabeth K; Rozhko, Alexander; Hatch, Maureen; Polyanskaya, Olga; Ostroumova, Evgenia; Tang, Min; Nadirov, Eldar; Yauseyenka, Vasilina; Savasteeva, Irina; McConnell, Robert J; Pfeiffer, Ruth M; Brenner, Alina V

2013-01-01

SUMMARY Objective Serum thyroglobulin (Tg) has been associated with a number of thyroid disorders and has been proposed as an indicator of iodine deficiency in a population. However, few studies have addressed the epidemiology of Tg in a population-based setting or in the context of exposure to radioactive iodine-131 (I-131). Our objective was to evaluate baseline levels of Tg in relation to socio-demographic characteristics, iodine status, and thyroid function for individuals exposed to I-131. Design A population-based cohort assembled in Belarus following the Chornobyl accident provided demographic factors, clinical data, and physiological measurements. Participants Our analytic sample included 10,344 subjects of whom 7,890 had no thyroid disease and 2,454 had evidence of structural or functional thyroid abnormality. Measurements Standardized assays were used to measure serum Tg, urinary iodine, TSH, and antibodies to Tg and thyroid peroxidase. Ultrasound was used to assess the presence of nodules and estimate thyroid volume. Results In the fully adjusted model, percent change in Tg was significantly increased among females, smokers, and subjects of older age and Tg increased with decreasing urinary iodine concentration, increasing serum TSH and increasing thyroid volume (p-values for trend < 0.0001), and presence of thyroid nodules (p < 0.05). We found a complex interaction between region of residence, rural/urban living, presence/absence of thyroid abnormalities, and serum Tg (p < 0.0001). Conclusions In residents of Belarus, serum Tg is significantly related to presence of thyroid abnormalities as well as indicators of thyroid function and iodine deficiency and, therefore, could be used to characterize the iodine status and thyroid function of individuals in the context of epidemiological study. PMID:23190420

Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

PubMed Central

2010-01-01

Context Hyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear. Objective Prospective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause. Design We have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine. Results The study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003). Conclusion The results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones. PMID:20807449

Genomic evidence of reactive oxygen species elevation in papillary thyroid carcinoma with Hashimoto thyroiditis.

PubMed

Yi, Jin Wook; Park, Ji Yeon; Sung, Ji-Youn; Kwak, Sang Hyuk; Yu, Jihan; Chang, Ji Hyun; Kim, Jo-Heon; Ha, Sang Yun; Paik, Eun Kyung; Lee, Woo Seung; Kim, Su-Jin; Lee, Kyu Eun; Kim, Ju Han

2015-01-01

Elevated levels of reactive oxygen species (ROS) have been proposed as a risk factor for the development of papillary thyroid carcinoma (PTC) in patients with Hashimoto thyroiditis (HT). However, it has yet to be proven that the total levels of ROS are sufficiently increased to contribute to carcinogenesis. We hypothesized that if the ROS levels were increased in HT, ROS-related genes would also be differently expressed in PTC with HT. To find differentially expressed genes (DEGs) we analyzed data from the Cancer Genomic Atlas, gene expression data from RNA sequencing: 33 from normal thyroid tissue, 232 from PTC without HT, and 60 from PTC with HT. We prepared 402 ROS-related genes from three gene sets by genomic database searching. We also analyzed a public microarray data to validate our results. Thirty-three ROS related genes were up-regulated in PTC with HT, whereas there were only nine genes in PTC without HT (Chi-square p-value < 0.001). Mean log2 fold changes of up-regulated genes was 0.562 in HT group and 0.252 in PTC without HT group (t-test p-value = 0.001). In microarray data analysis, 12 of 32 ROS-related genes showed the same differential expression pattern with statistical significance. In gene ontology analysis, up-regulated ROS-related genes were related with ROS metabolism and apoptosis. Immune function-related and carcinogenesis-related gene sets were enriched only in HT group in Gene Set Enrichment Analysis. Our results suggested that ROS levels may be increased in PTC with HT. Increased levels of ROS may contribute to PTC development in patients with HT.

Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature.

PubMed

Elston, Marianne S; Sehgal, Shekhar; Du Toit, Stephen; Yarndley, Tania; Conaglen, John V

2016-09-01

Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 μg per day. Low-moderate dose biotin is a common component of multivitamin preparations, and high-dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. A tertiary endocrine service in Hamilton, New Zealand. The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

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

PubMed

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

2017-09-01

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

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.

Tris(2-butoxyethyl)phosphate and triethyl phosphate alter embryonic development, hepatic mRNA expression, thyroid hormone levels, and circulating bile acid concentrations in chicken embryos

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

Egloff, Caroline; Crump, Doug, E-mail: doug.crump@ec.gc.ca; Porter, Emily

The organophosphate flame retardants tris(2-butoxyethyl) phosphate (TBOEP) and triethyl phosphate (TEP) are used in a wide range of applications to suppress or delay the ignition and spread of fire. Both compounds have been detected in the environment and TBOEP was recently measured in free-living avian species. In this study, TBOEP and TEP were injected into the air cell of chicken embryos at concentrations ranging from 0 to 45,400 ng/g and 0 to 241,500 ng/g egg, respectively. Pipping success, development, hepatic mRNA expression of 9 target genes, thyroid hormone levels, and circulating bile acid concentrations were determined. Exposure to the highestmore » doses of TBOEP and TEP resulted in negligible detection of the parent compounds in embryonic contents at pipping indicating their complete metabolic degradation. TBOEP exposure had limited effects on chicken embryos, with the exception of hepatic CYP3A37 mRNA induction. TEP exposure decreased pipping success to 68%, altered growth, increased liver somatic index (LSI) and plasma bile acids, and modulated genes associated with xenobiotic and lipid metabolism and the thyroid hormone pathway. Plasma thyroxine levels were decreased at all TEP doses, including an environmentally-relevant concentration (8 ng/g), and gallbladder hypotrophy was evident at ≥ 43,200 ng/g. Tarsus length and circulating thyroxine concentration emerged as potential phenotypic anchors for the modulation of transthyretin mRNA. The increase in plasma bile acids and LSI, gallbladder hypotrophy, and discoloration of liver tissue represented potential phenotypic outcomes associated with modulation of hepatic genes involved with xenobiotic and lipid metabolism. - Highlights: • TBOEP is not embryolethal to chicken embryos. • TEP affected embryonic viability, morphometric endpoints, and thyroid hormone levels. • TEP altered mRNA levels of xenobiotic and lipid metabolism genes. • TEP increased plasma bile acids and caused gallbladder hypotrophy. • TEP elicited more adverse molecular and phenotypic effects than TBOEP.« less

SULPHUR-CONTAINING AMINO ACIDS METABOLISM IN EXPERIMENTAL HYPER- AND HYPOTHYROIDISM IN RATS.

PubMed

Nechiporuk, V; Zaichko, N; Korda, М; Melnyk, A; Koloshko, O

2017-10-01

Hyper- and hypothyroidism are some of the most common endocrinopathies that cause many metabolic disorders including amino acids metabolism. However, a specific molecular mechanism of thyroid hormones influence on sulphur-containing amino acids metabolism has not been established. The aim of our research was to investigate experimentally the influence of thyroid gland functional state on the main enzymatic systems of sulphur-containing amino acids metabolism in liver and kidneys, the content of homocysteine, cysteine and H2S in blood. The rats were administered with L-thyroxine and mercazolil to simulate the states of hyper- and hypothyroidism, which were confirmed by the content of fT3, fT4 and TSH in the blood. In liver and kidneys of the animals with hypothyroidism we observed the decrease in the activity of enzymes of remethylation cycle of S-adenosylmethioninsyntase, S-adenosylhomocysteinhyhdrolase, betaine-homocysteine methyltransferase. Suppression of transsulfuration transformation of homocysteine to cysteine in hypothyroidism was mainly due to the inhibition of cystathionine synthase activity of cystathionine-β-synthase, wherein cystathionase activity of cystathionine-γ-lyase was not changed. In animals with hypothyroidism we also noticed the inhibition of cysteine desulfunation reactions: the activity of enzymes of cystathionine-β-synthase, cystathionine-γ-lyase and cysteine aminotransferase significantly decreased in liver and kidneys. Experimental hyperthyroidism was accompanied by increase in activity of remethylation cycle enzymes, increase in cystationine synthase activity of cystathionine-β-synthase in liver and activity of these enzymes in kidneys. The simulation of hyperthyroidism led to the decrease of homocysteine concentration, and of hypothyroidism - to the increase of homocysteine and cysteine concentrations and reduced H2S content in blood of the animals. Thus, the significant risk factors for the development of atherosclerosis, endothelial dysfunction and hypercoagulation in hypothyroid conditions may be the disorders in the processes of remethylation, transsulfuration, and desulfuration of sulphur-containing amino acids in organs.

Submandibular ectopic thyroid with normally located thyroid gland.

PubMed

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

2014-01-01

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

Increased incidence of thyroid dysfunction and autoimmunity in patients with vernal keratoconjunctivitis.

PubMed

Stagi, Stefano; Pucci, Neri; Di Grande, Laura; de Libero, Cinzia; Caputo, Roberto; Pantano, Stefano; Mattei, Ivan; Mori, Francesca; de Martino, Maurizio; Novembre, Elio

2014-01-01

Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; P<0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; P<0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, P<0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity.

Increased Incidence of Thyroid Dysfunction and Autoimmunity in Patients with Vernal Keratoconjunctivitis

PubMed Central

Stagi, Stefano; Pucci, Neri; Di Grande, Laura; de Libero, Cinzia; Caputo, Roberto; Pantano, Stefano; Mattei, Ivan; Mori, Francesca; de Martino, Maurizio; Novembre, Elio

2014-01-01

Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; P<0.05). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; P<0.05) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; P = NS). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, P<0.05). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity. PMID:25140177

An unusual case of hypopituitarism and transient thyrotoxicosis following asymptomatic pituitary apoplexy.

PubMed

Yoshida, Masanori; Murakami, Miho; Ueda, Harumi; Miyata, Misaki; Takahashi, Norio; Oiso, Yutaka

2014-01-01

Although pituitary function is often impaired in pituitary apoplexy, the development of thyrotoxicosis is rare. We describe an unusual case of hypopituitarism due to pituitary apoplexy coexisting with transient hyperthyroidism. A 74-year-old woman presented with severe fatigue, palpitation, appetite loss, hypotension, and hyponatremia. Endocrine studies showed hyperthyroidism and anterior pituitary hormone deficiencies. A magnetic resonance imaging suggested recent-onset pituitary apoplexy in a pituitary tumor, although the patient had no apoplectic symptoms such as headache and visual disturbance. Thyrotoxicosis and adrenal insufficiency worsened her general condition. Glucocorticoid supplementation improved her clinical symptoms and hyponatremia. Serum anti-thyrotropin receptor and thyroid-stimulating antibody titers were negative, and her thyroid function was spontaneously normalized without antithyroid medication, suggesting painless thyroiditis. Thereafter, her thyroid function decreased because of central hypothyroidism and 75 µg of levothyroxine was needed to maintain thyroid function at the euthyroid stage. The pituitary mass was surgically removed and an old hematoma was detected in the specimen. Considering that painless thyroiditis develops as a result of an autoimmune process, an immune rebound mechanism due to adrenal insufficiency probably caused painless thyroiditis. Although the most common type of thyroid disorder in pituitary apoplexy is central hypothyroidism, thyrotoxicosis caused by painless thyroiditis should be considered even if the patient has pituitary deficiencies. Because thyrotoxicosis with adrenal insufficiency poses a high risk for a life-threatening adrenal crisis, prompt diagnosis and treatment are critical.

Comparison of metabolic ratios of urinary estrogens between benign and malignant thyroid tumors in postmenopausal women

PubMed Central

2013-01-01

Background Estrogen metabolism may be associated with the pathophysiological development of papillary thyroid carcinoma (PTC). Methods To evaluate the differential estrogen metabolism between benign and malignant PTCs, estrogen profiling by gas chromatography–mass spectrometry was applied to urine samples from postmenopausal patients with 9 benign tumors and 18 malignant stage I and III/IV PTCs. Results The urinary concentration of 2-methoxyestradiol was significantly lower in the stage I malignant patients (3.5-fold; P < 0.025) than in the benign group. The metabolic ratios of 16α-OH-estrone/estrone and estriol/estradiol, which are responsible for 16α-hydroxylase activity, were increased more than 2.5-fold in the advanced-stage malignant PTC (P < 0.02 each). The more than 6.2-fold decrease in the urinary 2-/16α-hydroxylase ratio in stage III/IV malignant PTC was consistent with the ratio in postmenopausal patients with endocrine gland cancers. In addition, reductive 17β-hydroxysteroid dehydrogenase (17β-HSD; estradiol/estrone or estriol/16α-OH-estrone) was present at significantly higher levels in subjects with stage III/IV malignant PTCs than in benign subjects (>3.5-fold difference; P < 0.002). In particular, the estriol/16α-OH-estrone ratio differentiated between the benign and early-stage malignant patients (P < 0.01). Conclusions Increased 16α-hydroxylation and/or a decreased 2-/16α-ratio, as well increased reductive 17β-HSD, with regard to estrogen metabolism could provide potential biomarkers. The devised profiles could be useful for differentiating malignant thyroid carcinomas from benign adenomas in postmenopausal women. PMID:24156385

Responsiveness to thyroid hormone and to ambient temperature underlies differences between brown adipose tissue and skeletal muscle thermogenesis in a mouse model of diet-induced obesity.

PubMed

Ueta, Cintia B; Olivares, Emerson L; Bianco, Antonio C

2011-09-01

Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism.

Responsiveness to Thyroid Hormone and to Ambient Temperature Underlies Differences Between Brown Adipose Tissue and Skeletal Muscle Thermogenesis in a Mouse Model of Diet-Induced Obesity

PubMed Central

Ueta, Cintia B.; Olivares, Emerson L.

2011-01-01

Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism. PMID:21771890

Glomerular filtration rate is associated with free triiodothyronine in euthyroid subjects: Comparison between various equations to estimate renal function and creatinine clearance.

PubMed

Anderson, Josephine L C; Gruppen, Eke G; van Tienhoven-Wind, Lynnda; Eisenga, Michele F; de Vries, Hanne; Gansevoort, Ron T; Bakker, Stephan J L; Dullaart, Robin P F

2018-02-01

Effects of variations in thyroid function within the euthyroid range on renal function are unclear. Cystatin C-based equations to estimate glomerular filtration rate (GFR) are currently advocated for mortality and renal risk prediction. However, the applicability of cystatin C-based equations is discouraged in patients with overt thyroid dysfunction, since serum cystatin C and creatinine levels are oppositely affected by thyroid dysfunction. Here, we compared relationships of thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) with various measures of kidney function in euthyroid subjects. Relationships of eGFR, based on creatinine (eGFRcrea), cystatin C (eGFRcysC), creatinine+cystatin C combined (eGFRcrea-cysC) and creatinine clearance (CrCl) with TSH, FT4 and FT3 were determined in 2180 euthyroid subjects (TSH, FT4 and FT3 all within the reference range; anti-thyroid peroxidase autoantibodies negative) who did not use thyroid hormones, anti-thyroid drugs, amiodarone or lithium carbonate. In multivariable models including TSH, FT3 and FT4 together, eGFRcrea, eGFRcysC and eGFRcrea-cysC and CrCl were all positively related to FT3 (P≤0.001), translating into a 2.61 to 2.83mL/min/1.73m 2 increase in eGFR measures and a 3.92mL/min increase in CrCl per 1pmol/L increment in FT3. These relationships with FT3 remained taking account of relevant covariates. In euthyroid subjects renal function is associated with thyroid function status, especially by serum FT3, irrespective of the eGFR equation applied. In the euthyroid state, cystatin C-based eGFR equations are appropriate to assess the relationship of renal function with variation in thyroid function status. Copyright © 2017 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

MRI-based three-dimensional thermal physiological characterization of thyroid gland of human body.

PubMed

Jin, Chao; He, Zhi Zhu; Yang, Yang; Liu, Jing

2014-01-01

This article is dedicated to present a MRI (magnetic resonance imaging) based three-dimensional finite element modeling on the thermal manifestations relating to the pathophysiology of thyroid gland. An efficient approach for identifying the metabolic dysfunctions of thyroid has also been demonstrated through tracking the localized non-uniform thermal distribution or enhanced dynamic imaging. The temperature features over the skin surface and thyroid domain have been characterized using the numerical simulation and experimental measurement which will help better interpret the thermal physiological mechanisms of the thyroid under steady-state or water-cooling condition. Further, parametric simulations on the hypermetabolism symptoms of hyperthyroidism and thermal effects within thyroid domain caused by varying breathing airflow in the trachea and blood-flow in artery and vein were performed. It was disclosed that among all the parameters, the airflow volume has the largest effect on the total heat flux of thyroid surface. However, thermal contributions caused by varying the breathing frequency and blood-flow velocity are negligibly small. The present study suggests a generalized way for simulating the close to reality physiological behavior or process of human thyroid, which is of significance for disease diagnosis and treatment planning. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

Quantitative thyroid scintigraphy in greyhounds suspected of primary hypothyroidism.

PubMed

Pinilla, Manuel; Shiel, Robert E; Brennan, Sheila F; McAllister, Hester; Mooney, Carmel T

2009-01-01

The existence of hypothyroidism in greyhounds remains controversial and its investigation is complicated by the low circulating thyroid hormone concentrations typically found in healthy dogs of this breed. Quantitative measurement of thyroidal technetium-99m pertechnetate ((99m)TcO4-) uptake is known to be useful in assessing thyroid function in other breeds. The aim of this study was to evaluate thyroid scintigraphy as a method of assessing thyroid function in greyhounds suspected of primary hypothyroidism. Twenty greyhounds (eight females, 12 males) were studied. Thirteen had bald thigh syndrome and seven poor performance and low total T4. Total T4 concentrations were decreased in 18 (90%), and free T4 in two (10%) dogs. All canine thyroid stimulating hormone concentrations were within the reference interval. Thyroidal (99m)TcO4- uptake values (mean +/- SD, 0.76 +/- 0.26%) were within the reference limits published for euthyroid dogs (0.39-1.86%) making hypothyroidism highly unlikely. There were no significant differences (P < 0.05) when comparing data between dogs with bald thigh syndrome (13 dogs) and the remaining dogs (seven dogs). Seventeen (85%) dogs had higher uptake in the left thyroid gland than in the right that might reflect an anatomic feature of the greyhound breed. Calculation of percent thyroidal uptake of (99m)TcO4- is more accurate than thyroid: salivary gland ratios because of high variability in salivary gland uptake. Percent thyroidal uptake of (99m)TcO4- should be used when assessing thyroid function scintigraphically in the greyhound breed.

Thyroid autoimmunity and function among Ugandan children and adolescents with type-1 diabetes mellitus.

PubMed

Muhame, Rugambwa Michael; Mworozi, Edison Arwanire; McAssey, Karen; Lubega, Irene

2014-01-01

Up to 30% of type-1 diabetes mellitus (T1DM) patients have co-existent thyroid autoimmunity with up to 50% of them having associated thyroid dysfunction. Routine screening for thyroid autoimmunity and dysfunction is recommended in all T1DM patients. However, this was not currently practiced in Ugandan paediatric diabetes clinics. There was also paucity of data regarding thyroid autoimmunity and dysfunction in African children and adolescents with diabetes mellitus. The objective of this study was to quantify the magnitude of thyroid autoimmunity and dysfunction in Ugandan children with TIDM. This was a cross sectional descriptive study to determine the prevalence of thyroid autoantibodies and describe thyroid function among children and adolescents aged 1-19 years with diabetes mellitus attending the paediatric diabetes clinic at Mulago National Referral Hospital, Kampala, Uganda. Following enrollment, we obtained details of clinical history and performed physical examination. Blood (plasma) was assayed to determine levels of antibodies to thyroid peroxidase (antiTPO), free thyroxine (FT4) and thyrotropin (TSH). The prevalence of thyroid autoimmunity was 7.3% (5/69). All antiTPO positive subjects were post pubertal, aged between 13-17 years with females comprising 3/5 of the antiTPO positive subjects. All study subjects were clinically euthyroid; however, 7.3% (5/69) of the study subjects had subclinical hypothyroidism. These data strengthen the argument for routine screening of all diabetic children and adolescents for thyroid autoimmunity (particularly anti-TPO) as recommended by international guidelines. We also recommend evaluation of thyroid function in diabetic children and adolescents to minimize the risk of undiagnosed thyroid dysfunction.

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.

Morbidity study of extruder personnel with potential exposure to brominated dioxins and furans. II. Results of clinical laboratory studies.

PubMed Central

Ott, M G; Zober, A

1996-01-01

OBJECTIVE: To test whether dioxins affect liver and thyroid function, lipid metabolism and glucose or immunological variables, in workers exposed to brominated dioxins and furans. METHODS: 34 male production employees (29 were extruder operators) and eight technical support personnel were studied, all of whom were potentially exposed to polybrominated dibenzo-p-dioxins (PBDDs) and furans (PBDFs) during production of resins containing polybrominated diphenyl ethers (PBDEs). Controls were from a similar resin producing plant that did not use PBDEs. Blood samples were analysed for tetra, penta, and hexabrominated congeners, but 2,3,7,8-TBDD was the only exposure measure used in the regression analyses. Seven liver function indicators, five measures of blood lipids and glucose, four haematology and blood coagulation measures, and three measures of thyroid function were examined. RESULTS: None of the variables was statistically related to concentration of 2,3,7,8-TBDD in the regression analyses. Cigarette smoking was related to several outcomes at the 0.05 level: aspartate aminotransferase, alanine aminotransferase, glutamate dehydrogenase (GLDH), erythrocyte sedimentation rate, and white blood cell count. Body mass index was also related to alanine aminotransferase, gamma-glutamyltranspeptidase, cholinesterase, GLDH, cholesterol, triglycerides, high density lipoprotein, low density lipoprotein, and glucose concentrations. No definitive associations between liver, blood lipid, thyroid, or immunological variables and exposure to brominated dioxins or blood lipid concentration of 2,3,7,8-TBDD were found. CONCLUSIONS: The study population was small and hence the findings must be interpreted with caution. Nevertheless, these results provide a base for interpreting the results of clinical studies in similarly exposed populations. PMID:8994404

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

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

PubMed Central

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

2013-01-01

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

Transcriptome Network Analysis Reveals Aging-Related Mitochondrial and Proteasomal Dysfunction and Immune Activation in Human Thyroid

PubMed Central

Cho, Byuri Angela; Yoo, Seong-Keun; Song, Young Shin; Kim, Su-jin; Lee, Kyu Eun; Shong, Minho

2018-01-01

Background: Elucidating aging-related transcriptomic changes in human organs is necessary to understand the aging physiology and mechanisms, but little is known regarding the thyroid gland. We investigated aging-related transcriptomic alterations in the human thyroid gland and characterized the related molecular functions. Methods: Publicly available RNA sequencing data of 322 thyroid tissue samples from the Genotype-Tissue Expression project were analyzed. In addition, our own 64 RNA sequencing data of normal thyroid tissue samples were used as a validation set. To comprehensively evaluate the associations between aging and transcriptomic changes, we performed a weighted gene coexpression network analysis and pathway enrichment analysis. The thyroid differentiation score was then used for further analysis, defining the correlations between thyroid differentiation and aging. Results: The most significant aging-related transcriptomic change in thyroid was the downregulation of genes related to the mitochondrial and proteasomal functions (p = 3 × 10−6). Moreover, genes that are associated with immune processes were significantly upregulated with age (p = 3 × 10−4), and all of them overlapped with the upregulated genes in the thyroid glands affected by lymphocytic thyroiditis. Furthermore, these aging-related changes were not significantly different according to sex, but in terms of the thyroid differentiation, females were more susceptible to aging-related changes (p for trend = 0.03). Conclusions: Aging-related transcriptomic changes in the thyroid gland were associated with mitochondrial and proteasomal dysfunction, loss of differentiation, and activation of autoimmune processes. Our results provide clues to better understanding the age-related decline in thyroid function and higher susceptibility to autoimmune thyroid disease. PMID:29652618

A rare cause of hyperthyroidism: functioning thyroid metastases.

PubMed

Gardner, Daphne; Ho, Su Chin

2014-10-09

Hyperthyroidism is a common medical problem that is readily treated with antithyroid medications. However, attributing the correct aetiology of hyperthyroidism alters management and outcome. We present a case of a 66-year-old woman with a seemingly common problem of hyperthyroidism associated with a goitre, which was initially attributed to a toxic nodule. However, Tc-99m pertechnetate uptake scan and thyroid-stimulating hormone receptor antibody were negative, inconsistent with a toxic nodule or Grave's disease. Her thyroid function tests proved difficult to control over the next few months. She eventually proceeded to a total thyroidectomy and histology revealed follicular variant papillary thyroid carcinoma. She was started on levothyroxine postoperatively but developed severe hyperthyroidism, revealing the cause of hyperthyroidism to be autonomously functioning thyroid metastases. Although functioning thyroid metastases are very rare, they need to be considered among the differential diagnoses of hyperthyroidism, as there are nuances in management that could alter the eventual outcome. 2014 BMJ Publishing Group Ltd.

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

Inherited hypothyroidism.

PubMed

Jackson, I M

1976-03-01

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

Consequences of dysthyroidism on the digestive tract and viscera

PubMed Central

Daher, Ronald; Yazbeck, Thierry; Jaoude, Joe Bou; Abboud, Bassam

2009-01-01

Thyroid hormones define basal metabolism throughout the body, particularly in the intestine and viscera. Gastrointestinal manifestations of dysthyroidism are numerous and involve all portions of the tract. Thyroid hormone action on motility has been widely studied, but more complex pathophysiologic mechanisms have been indicated by some studies although these are not fully understood. Both thyroid hormone excess and deficiency can have similar digestive manifestations, such as diarrhea, although the mechanism is different in each situation. The liver is the most affected organ in both hypo- and hyperthyroidism. Specific digestive diseases may be associated with autoimmune thyroid processes, such as Hashimoto’s thyroiditis and Grave’s disease. Among them, celiac sprue and primary biliary cirrhosis are the most frequent although a clear common mechanism has never been proven. Overall, thyroid-related digestive manifestations were described decades ago but studies are still needed in order to confirm old concepts or elucidate undiscovered mechanisms. All practitioners must be aware of digestive symptoms due to dysthyroidism in order to avoid misdiagnosis of rare but potentially lethal situations. PMID:19533804

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

PubMed

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

2011-04-14

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

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

PubMed

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

2018-02-01

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

Effects of different extracts of curcumin on TPC1 papillary thyroid cancer cell line.

PubMed

Perna, Angelica; De Luca, Antonio; Adelfi, Laura; Pasquale, Tammaro; Varriale, Bruno; Esposito, Teresa

2018-02-15

The thyroid gland is one of the largest endocrine glands in the body. The vast majority of TCs (> 90%) originate from follicular cells and are defined as differentiated thyroid cancers (DTC) and the two histological subtypes are the papillary TC with its variants and the follicular TC. Curcumin possesses a wide variety of biological functions, and thanks to its properties, it has gained considerable attention due to its profound medicinal values (Prasad, Gupta, Tyagi, and Aggarwal, Biotechnol Adv 32:1053-1064, 2014). We have undertaken the present work in order to define the possible role of curcumin in modulating the genetic expression of cell markers and to understand the effectiveness of this nutraceutical in modulating the regression of cancer phenotype. As a template we used the TPC-1 cells treated with the different extracts of turmeric, and examined the levels of expression of different markers (proliferative, inflammatory, antioxidant, apoptotic). Treatment with the three different curcumin extracts displays anti-inflammatory, antioxidant properties and it is able to influence cell cycle with slightly different effects upon the extracts. Furthermore curcumin is able to influence cell metabolic activity vitality. In conclusion curcumin has the potential to be developed as a safe therapeutic but further studies are needed to verify its antitumor ability in vivo.

Preoperative thyroid function and weight loss after bariatric surgery.

PubMed

Neves, João Sérgio; Souteiro, Pedro; Oliveira, Sofia Castro; Pedro, Jorge; Magalhães, Daniela; Guerreiro, Vanessa; Costa, Maria Manuel; Bettencourt-Silva, Rita; Santos, Ana Cristina; Queirós, Joana; Varela, Ana; Freitas, Paula; Carvalho, Davide

2018-05-16

Thyroid function has an important role on body weight regulation. However, the impact of thyroid function on weight loss after bariatric surgery is still largely unknown. We evaluated the association between preoperative thyroid function and the excess weight loss 1 year after surgery, in 641 patients with morbid obesity who underwent bariatric surgery. Patients with a history of thyroid disease, treatment with thyroid hormone or antithyroid drugs and those with preoperative evaluation consistent with overt hypothyroidism or hyperthyroidism were excluded. The preoperative levels of TSH and FT4 were not associated with weight loss after bariatric surgery. The variation of FT3 within the reference range was also not associated with weight loss. In contrast, the subgroup with FT3 above the reference range (12.3% of patients) had a significantly higher excess weight loss than patients with normal FT3. This difference remained significant after adjustment for age, sex, BMI, type of surgery, TSH and FT4. In conclusion, we observed an association between high FT3 and a greater weight loss after bariatric surgery, highlighting a group of patients with an increased benefit from this intervention. Our results also suggest a novel hypothesis: the pharmacological modulation of thyroid function may be a potential therapeutic target in patients undergoing bariatric surgery.

Neuroendocrine recovery initiated by cognitive behavioral therapy in women with functional hypothalamic amenorrhea: a randomized, controlled trial.

PubMed

Michopoulos, Vasiliki; Mancini, Fulvia; Loucks, Tammy L; Berga, Sarah L

2013-06-01

To determine whether cognitive behavior therapy (CBT), which we had shown in a previous study to restore ovarian function in women with functional hypothalamic amenorrhea (FHA), could also ameliorate hypercortisolemia and improve other neuroendocrine and metabolic concomitants of in FHA. Randomized controlled trial. Clinical research center at an academic medical university. Seventeen women with FHA were randomized either to CBT or observation. CBT versus observation. Circulatory concentrations of cortisol, leptin, thyroid-stimulating hormone (TSH), total and free thyronine (T(3)), and total and free thyroxine (T(4)) before and immediately after completion of CBT or observation. (Each woman served as her own control.) Cognitive behavior therapy but not observation reduced cortisol levels in women with FHA. There were no changes in cortisol, leptin, TSH, T(3), or T(4) levels in women randomized to observation. Women treated with CBT showed increased levels of leptin and TSH, but their levels of T(3) and T(4) remained unchanged. In women with FHA, CBT ameliorated hypercortisolism and improved the neuroendocrine and metabolic concomitants of FHA while observation did not. We conclude that a cognitive, nonpharmacologic approach aimed at alleviating problematic attitudes not only can restore ovarian activity but also improve neuroendocrine and metabolic function in women with FHA. NCT01674426. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[Hormones and hair growth].

PubMed

Trüeb, R M

2010-06-01

With respect to the relationship between hormones and hair growth, the role of androgens for androgenetic alopecia (AGA) and hirsutism is best acknowledged. Accordingly, therapeutic strategies that intervene in androgen metabolism have been successfully developed for treatment of these conditions. Clinical observations of hair conditions involving hormones beyond the androgen horizon have determined their role in regulation of hair growth: estrogens, prolactin, thyroid hormone, cortisone, growth hormone (GH), and melatonin. Primary GH resistance is characterized by thin hair, while acromegaly may cause hypertrichosis. Hyperprolactinemia may cause hair loss and hirsutism. Partial synchronization of the hair cycle in anagen during late pregnancy points to an estrogen effect, while aromatase inhibitors cause hair loss. Hair loss in a causal relationship to thyroid disorders is well documented. In contrast to AGA, senescent alopecia affects the hair in a diffuse manner. The question arises, whether the hypothesis that a causal relationship exists between the age-related reduction of circulating hormones and organ function also applies to hair and the aging of hair.

Thyroid function during intermittent exposure to hypobaric hypoxia

NASA Astrophysics Data System (ADS)

Sawhney, R. C.; Malhotra, A. S.

1990-09-01

Circulatory levels of triiodothyronine (T3) and thyroxine (T4) and their kinetics were studied in rabbits exposed to intermittent hypobaric hypoxia (5200 m, 395 mm Hg, PO2 83 mm Hg) 6 h daily for 5 weeks in a decompression chamber maintained at room temperature of 22° 24° C. Kinetics of T3 and T4 were studied on days 21 and 28 of hypoxic exposure. The T3 and T4 values were found to be significantly lower on day 8 of exposure to hypoxia compared to the pre-exposure values. The decreased levels were maintained throughout the entire period of hypoxic stress. The metabolic clearance rate, production rate, distribution space and extrathyroidal T3 and T4 pools were significantly decreased in animals under hypoxic stress compared to the control animals. The decline in thyroid hormone levels and their production in rabbits under hypoxic stress indicate an adaptive phenomenon under conditions of low oxygen availability.

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

PubMed Central

Albi, Elisabetta; Perrella, Giuseppina; Lazzarini, Andrea; Cataldi, Samuela; Lazzarini, Remo; Floridi, Alessandro; Ambesi-Impiombato, Francesco Saverio; Curcio, Francesco

2014-01-01

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein. PMID:24979136

Overexpression of Interleukin-4 in the Thyroid of Transgenic Mice Upregulates the Expression of Duox1 and the Anion Transporter Pendrin

PubMed Central

Achouri, Younes; Hahn, Stephan; Many, Marie-Christine; Craps, Julie; Refetoff, Samuel; Liao, Xiao-Hui; Dumont, Jacques E.; Van Sande, Jacqueline; Corvilain, Bernard; Miot, Françoise; De Deken, Xavier

2016-01-01

Background: The dual oxidases (Duox) are involved in hydrogen peroxide generation, which is essential for thyroid hormone synthesis, and therefore they are markers of thyroid function. During inflammation, cytokines upregulate DUOX gene expression in the airway and the intestine, suggesting a role for these proteins in innate immunity. It was previously demonstrated that interleukin-4 (IL-4) upregulates DUOX gene expression in thyrocytes. Although the role of IL-4 in autoimmune thyroid diseases has been studied extensively, the effects of IL-4 on thyroid physiology remain largely unknown. Therefore, a new animal model was generated to study the impact of IL-4 on thyroid function. Methods: Transgenic (Thyr-IL-4) mice with thyroid-targeted expression of murine IL-4 were generated. Transgene expression was verified at the mRNA and protein level in thyroid tissues and primary cultures. The phenotype of the Thyr-IL-4 animals was characterized by measuring serum thyroxine (T4) and thyrotropin levels and performing thyroid morphometric analysis, immunohistochemistry, whole transcriptome sequencing, quantitative reverse transcription polymerase chain reaction, and ex vivo thyroid function assays. Results: Thyrocytes from two Thyr-IL-4 mouse lines (#30 and #52) expressed IL-4, which was secreted into the extracellular space. Although 10-month-old transgenic animals had T4 and thyrotropin serum levels in the normal range, they had altered thyroid follicular structure with enlarged follicles composed of elongated thyrocytes containing numerous endocytic vesicles. These follicles were positive for T4 staining the colloid, indicating their capacity to produce thyroid hormones. RNA profiling of Thyr-IL-4 thyroid samples revealed modulation of multiple genes involved in inflammation, while no major leukocyte infiltration could be detected. Upregulated expression of Duox1, Duoxa1, and the pendrin anion exchanger gene (Slc26a4) was detected. In contrast, the iodide symporter gene Slc5a5 was markedly downregulated resulting in impaired iodide uptake and reduced thyroid hormone levels in transgenic thyroid tissue. Hydrogen peroxide production was increased in Thyr-IL-4 thyroid tissue compared with wild-type animals, but no significant oxidative stress could be detected. Conclusions: This is the first study to show that ectopic expression of IL-4 in thyroid tissue upregulates Duox1/Duoxa1 and Slc26a4 expression in the thyroid. The present data demonstrate that IL-4 could affect thyroid morphology and function, mainly by downregulating Slc5a5 expression, while maintaining a normal euthyroid phenotype. PMID:27599561

Bioprinting of a functional vascularized mouse thyroid gland construct.

PubMed

Bulanova, Elena A; Koudan, Elizaveta V; Degosserie, Jonathan; Heymans, Charlotte; Pereira, Frederico DAS; Parfenov, Vladislav A; Sun, Yi; Wang, Qi; Akhmedova, Suraya A; Sviridova, Irina K; Sergeeva, Natalia S; Frank, Georgy A; Khesuani, Yusef D; Pierreux, Christophe E; Mironov, Vladimir A

2017-08-18

Bioprinting can be defined as additive biofabrication of three-dimensional (3D) tissues and organ constructs using tissue spheroids, capable of self-assembly, as building blocks. The thyroid gland, a relatively simple endocrine organ, is suitable for testing the proposed bioprinting technology. Here we report the bioprinting of a functional vascularized mouse thyroid gland construct from embryonic tissue spheroids as a proof of concept. Based on the self-assembly principle, we generated thyroid tissue starting from thyroid spheroids (TS) and allantoic spheroids (AS) as a source of thyrocytes and endothelial cells (EC), respectively. Inspired by mathematical modeling of spheroid fusion, we used an original 3D bioprinter to print TS in close association with AS within a collagen hydrogel. During the culture, closely placed embryonic tissue spheroids fused into a single integral construct, EC from AS invaded and vascularized TS, and epithelial cells from the TS progressively formed follicles. In this experimental setting, we observed formation of a capillary network around follicular cells, as observed during in utero thyroid development when thyroid epithelium controls the recruitment, invasion and expansion of EC around follicles. To prove that EC from AS are responsible for vascularization of the thyroid gland construct, we depleted endogenous EC from TS before bioprinting. EC from AS completely revascularized depleted thyroid tissue. The cultured bioprinted construct was functional as it could normalize blood thyroxine levels and body temperature after grafting under the kidney capsule of hypothyroid mice. Bioprinting of functional vascularized mouse thyroid gland construct represents a further advance in bioprinting technology, exploring the self-assembling properties of tissue spheroids.

Thyroid disrupting chemicals: Mechanisms and mixtures

EPA Science Inventory

Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

Environmental Issues in Thyroid Diseases.

PubMed

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

2017-01-01

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

Accidental finding of Hashimoto-like thyroiditis in male B.U.T. 6 turkeys at slaughter.

PubMed

Plesch, P; Schade, B; Breithaupt, A; Bellof, G; Kienzle, E

2014-10-01

In the context of a study on the tolerance of rapeseed meal in B.U.T. 6 turkeys, thyroid glands were histologically and immunohistochemically examined because of potential thyreostatic effects. In all groups including the controls with no rapeseed meal in their food, there was a high incidence of lymphocytic infiltration and thyroiditis (14% of thyroids with moderate to severe lymphocytic thyroiditis). Thirty per cent of mononuclear inflammatory cells were immunohistochemically identified as T cells. There were occasional accumulations of PAX-5 labelled cells, indicating germinal centre development. These lesions resemble Hashimoto's disease in humans. The effect on thyroid function is unknown. Mild hypothyreosis might enhance productivity but also explain dispositions towards diseases seen in context with thyroid dysfunction such as skin diseases (foot pad disease?) and cardiovascular problems. Further studies on thyroid function in these turkeys are needed. Journal of Animal Physiology and Animal Nutrition © 2013 Blackwell Verlag GmbH.

[The thyroid gland in emotional and pain stress].

PubMed

Akhmetov, I Z

1987-01-01

The reaction of wild rodent thyroid gland on emotional and painful stress appearing as a result of animal's catching has been studied. The thyroid activity has been shown to raise considerably during the primary stage of stress reaction. Later on the function of the gland normalizes in animals without trauma and in traumatized animals it becomes weaker. The complete normalization of the thyroid function in traumatized animals coincides with osteal regeneration according to time.

NF-κB Essential Modulator (NEMO) Is Critical for Thyroid Function.

PubMed

Reale, Carla; Iervolino, Anna; Scudiero, Ivan; Ferravante, Angela; D'Andrea, Luca Egildo; Mazzone, Pellegrino; Zotti, Tiziana; Leonardi, Antonio; Roberto, Luca; Zannini, Mariastella; de Cristofaro, Tiziana; Shanmugakonar, Muralitharan; Capasso, Giovambattista; Pasparakis, Manolis; Vito, Pasquale; Stilo, Romania

2016-03-11

The I-κB kinase (IKK) subunit NEMO/IKKγ (NEMO) is an adapter molecule that is critical for canonical activation of NF-κB, a pleiotropic transcription factor controlling immunity, differentiation, cell growth, tumorigenesis, and apoptosis. To explore the functional role of canonical NF-κB signaling in thyroid gland differentiation and function, we have generated a murine strain bearing a genetic deletion of the NEMO locus in thyroid. Here we show that thyrocyte-specific NEMO knock-out mice gradually develop hypothyroidism after birth, which leads to reduced body weight and shortened life span. Histological and molecular analysis indicate that absence of NEMO in thyrocytes results in a dramatic loss of the thyroid gland cellularity, associated with down-regulation of thyroid differentiation markers and ongoing apoptosis. Thus, NEMO-dependent signaling is essential for normal thyroid physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Exaggerated thyroid stimulating hormone secretion in children exposed to the Chernobyl nuclear reactor catastrophe.

PubMed

Boyarskaya, O Y; Kopilova, O V

2008-02-01

We present results of a long-term study of the morpho-functional state of the thyroid gland and of the functional capacities of the hypothalamic-hypophyseal system, as shown by thyrotropin releasing hormone stimulation, in different groups of children who suffered from the Chernobyl accident. It was shown that the thyroid gland of the children who were evacuated from the 30-km zone was damaged most severely due to the influence of radioactive iodine (131I). Living on radionuclide-polluted territories in conditions of iodine deficiency has been an additional contributory factor in the development of thyroid gland diseases. Latent functional deficiency of the hypothalamic-hypophyseal system can be one of the reasons leading to oncopathology of the thyroid gland.

Autoimmune thyroid disease in pregnancy: a review.

PubMed

Galofre, Juan C; Davies, Terry F

2009-11-01

The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%-15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T(4)) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L.

Autoimmune Thyroid Disease in Pregnancy: A Review

PubMed Central

Galofre, Juan C.

2009-01-01

Abstract The maternal physiological changes that occur in normal pregnancy induce complex endocrine and immune responses. During a normal pregnancy, thyroid gland volume may enlarge, and thyroid hormone production increases. Hence, the interpretation of thyroid function during gestation needs to be adjusted according to pregnancy-specific ranges. The elevated prevalence of gestation-related thyroid disorders (10%–15%) and the important repercussions for both mother and fetus reported in multiple studies throughout the world denote, in our opinion, the necessity for routine thyroid function screening both before and during pregnancy. Once thyroid dysfunction is suspected or confirmed, management of the thyroid disorder necessitates regular monitoring in order to ensure a successful outcome. The aim of treating hyperthyroidism in pregnancy with antithyroid drugs is to maintain serum thyroxine (T4) in the upper normal range of the assay used with the lowest possible dose of drug, whereas in hypothyroidism, the goal is to return serum thyroid-stimulating hormone (TSH) to the range between 0.5 and 2.5 mU/L. PMID:19951221

Ectopic Thyroid Tissue in Submandibular and Infrahyoid Region

PubMed Central

Mutlu, Vahit

2014-01-01

The thyroid is the first endocrine gland to form during embryogenesis. At this stage, incomplete or anomalous migration of thyroid tissue causes ectopic localization of the gland. Submandibular ectopic thyroid tissue with a coexisting normally located thyroid gland is extremely rare. In this case aimed to present the findings of the 65-years-old female patient who is bilateral subtotal thyroidectomy operation performed for multinodular goiter of 12 years ago. Case, painless mass in the right submandibular and infrahyoid region for 6 months was admitted to our clinic with complaints. Result of contrast-enhanced neck computed tomography, ultrasound-guided fine-needle aspiration biopsy and thyroid scintigraphy were found of functional residual thyroid tissue in the normal localization as well as 2×3 cm mass in the submandibular area and 1×2 cm mass lesion in the infrahyoid region. The patient referred to excisional biopsy. Normal thyroid follicules and no evidence of malignancy were found in specimen pathologically. Postoperative follow-up of thyroid function tests were normal. PMID:25610328

[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.

Autonomously hyperfunctioning cystic nodule harbouring thyroid carcinoma - Case report and literature review.

PubMed

Lima, Maria João; Soares, Virgínia; Koch, Pedro; Silva, Artur; Taveira-Gomes, António

2018-01-01

Hyperthyroidism is rarely associated with malignancy, but it cannot rule out thyroid cancer. Although there is published data describing this coexistence, thyroid carcinomas inside autonomously functioning nodules are uncommon. A 49-year-old woman presented with a cervical mass, unexplained weight loss and anxiousness, sweating and insomnia. On physical examination, she had a palpable left thyroid nodule. Thyroid function tests showed suppressed TSH (<0,1 uUI/mL), thyroxine 1,44 ng/dL (normal range 0,70-1,48) and triiodothyronine 4,33 pg/mL (normal range 1,71-3,71). Ultrasound imaging revealed a left lobe, 4 cm partial cystic nodule. 99mTC thyroid scintigraphy showed a hyperfunctioning nodule with suppression of the remainder parenchyma. Fine-needle aspiration cytology was nondiagnostic (cystic fluid). The patient was started on thiamazole 5 mg daily with subsequent normalization of thyroid function, but she developed cervical foreign body sensation and a left hemithyroidectomy was performed. Histology showed a 4 cm cystic nodule with a follicular variant papillary carcinoma and the patient underwent completion thyroidectomy, followed by radio-iodine ablation. Published literature showed an increased prevalence of autonomously functioning nodules, harbouring thyroid carcinomas in adults. Papillary carcinoma is the most frequently described but the follicular variant is rare. Although rare, thyroid cancer is not definitively excluded in hyperthyroid patients and it should always be considered as differential diagnosis. Copyright © 2018. Published by Elsevier Ltd.

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

PubMed

Lynshiang, D S; Gupta, B B

2000-07-01

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

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

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis.

PubMed

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young; Lee, Won Woo

2018-01-01

Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol ( p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake ( p = 0.004), SUVmean ( p < 0.001), SUVmax ( p = 0.002), and functional thyroid mass ( p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism ( p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 - 1.035). Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis

PubMed Central

Kim, Ji-Young; Kim, Ji Hyun; Moon, Jae Hoon; Kim, Kyoung Min; Oh, Tae Jung; Lee, Dong-Hwa; So, Young

2018-01-01

Objective Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. Materials and Methods Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. Results All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). Conclusion Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism. PMID:29713225

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.

Assessment of petroleum streams for thyroid toxicity.

PubMed

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

2016-07-08

The thyroid gland, and its associated endocrine hormones, is a growing area of interest in regulatory toxicology due to its important role in metabolism, growth and development. This report presents a review of the toxicology data on chemically complex petroleum streams for thyroid hormone effects. Toxicological summaries and studies from all available published and un-published sources were considered, drawing upon the European REACH regulatory submissions for 19 petroleum streams, with in depth review of 11 individual study reports and 31 published papers on related products or environmental settings. Findings relevant to thyroid pathology or thyroid hormone homeostasis were specifically sought, summarized, and discussed. A total of 349 studies of 28-days or longer duration were considered in the review, including data on mice, rats, rabbits, dogs, humans, and fish. The thyroid was almost invariably not a target organ in these studies. Three rodent studies did find thyroid effects; one on a jet fuel product (JP-8), and two studies on a heavy fuel oil product (F-179). The JP-8 product differs from other fuels due to the presence of additives, and the finding of reduced T4 levels in mice in the study occurred at a dose that is above that expected to occur in environmental settings (e.g. 2000mg/kg). The finding for F-179 involved thyroid inflammation at 10-55mg/kg that co-occurred with liver pathology in rats, indicating a possible secondary effect with questionable relevance to humans. In the few cases where findings did occur, the polycyclic aromatic hydrocarbon (PAH) content was higher than in related substances, and, in support of one possible adverse outcome pathway, one in-vitro study reported reduced thyroid peroxidase (TPO) activity with exposure to some PAH compounds (pyrene, benzo(k)fluoranthene, and benzo(e)pyrene). However, it could not be determined from the data available for this review, whether these specific PAH compounds were substantially higher in the JP-8 or F-179 products than in studies in which thyroid effects were not observed. Thus, a few products may carry a weak potential to affect the thyroid at high doses in rodents, possibly through secondary effects on the rodent liver or possibly through a pathway involving the inhibition of TPO by specific members of the PAH family. Human epidemiology evidence found weak and inconsistent effects on the thyroid but without identification of specific chemicals involved. Two studies in petroleum workers, which found a lower rate of morbidity and mortality overall, reported a statistically significant increase in thyroid cancer, but the small number of cases could not exclude confounding variables as possible explanations for the statistical findings. Overall, the available data indicates a low potential for thyroid hormone effects from exposure to petroleum streams, especially when the aromatic content is low. Because regulatory studies for most chemicals do not include detailed thyroid function or receptor studies, it remains possible that subclinical effects on this system may exist that were not detectable using conventional pathology or hormone measurements. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Thyroid function status and plasma lipids among cardiology patients in Georgia.

PubMed

Chapidze, G; Enquobahrie, D; Kapanadze, S; Dolidze, N; Soh, J; Williams, M

2007-01-01

Thyroid dysfunction as an important cardiovascular risk factor, is not well characterized among cardiology patients of Georgia. Further, a consensus has not been reached about the relationships between thyroid function markers and plasma lipids. We investigated these risk factors among 250 cardiology patients admitted to the Emergency Cardiology Center. A cross sectional study was conducted using in-person interviews, medical records, physical exams and laboratory studies. Thyroid stimulating hormone, free thyroxine 3, free thyroxine 4 and plasma lipids were measured using standardized assays. Overall, thyroid dysfunction was detected among 28.6% of the study population (19.5% males and 39.6% females). Overt hypo- and hyperthyroidism were present among 12.4% and 6.0% of patients, while, subclinical hypo- and hyperthyroidism were present among 2.8% and 6.4% of patients respectively. Both clinical and subclinical hypothyroidism were associated with elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) concentrations (p-values for trend <0.005). Further, TC and LDL-C were highly correlated with thyroid function markers (all p-values <0.000). Triglycerides and high-density lipoprotein cholesterol concentrations were not associated with thyroid function status. Hyperthyroidism was not associated with plasma lipid variation. thyroid dysfunction was prevalent among cardiology patients in Georgia. Hypothyroidism was associated with elevated TC and LDL-C concentrations. Future studies that examine the clinical relevance of observed differences in lipid profiles among this population are needed.

Thyroid cell lines in research on goitrogenesis.

PubMed

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

1991-12-01

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

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...

[Evaluation of salivary gland function in women with autoimmune thyroid diseases].

PubMed

Koczor-Rozmus, Aleksandra; Zwirska-Korczala, Krystyna; Sadlak-Nowicka, Jadwiga; Ilewicz, Leşzek; Mayer-Parka, Danuta; Wierucka-Młynarczyk, Beata

2003-01-01

The function of the salivary glands is regulated by nervous system which influences salivary circulation. Moreover the volume of secreted saliva depends on the humoral agents, including thyroid hormones. The aim of the study was to determine the quantity of the secreted mixed resting and stimulated saliva in women with autoimmune thyroid diseases (AITD) depending on the function of the thyroid gland (hyperthyroidism, hypothyroidism and euthyroidism). The association between thyroid antibody concentrations (TPO-Ab, Tg-Ab, TR-Ab) and volume of secreted saliva was also examined. Studies were performed in 106 women suffering from AITD and 15 healthy volunteers. In hyperthyroid women there was a decrease in volumes of resting (57.14%) and stimulated (89.29%) saliva. Similarly, a decrease in secretion of resting (75%) and stimulated (66.67%) saliva was shown in hypothyroid women. In euthyroid patients with AITD there was a partial normalisation of salivary glands function. The negative correlation between concentrations of TPO-Ab, Tg-Ab and the volume of resting and stimulated saliva was found. In conclusion, AITD may be associated with disturbances in salivary secretion which depends on thyroid hormones production. It can be suggested that autoimmunological processes within salivary glands may influence their function.

Propylthiouracil

MedlinePlus

... produces too much thyroid hormone, speeding the body's metabolism, and causing certain symptoms) in adults and children ... to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website ( ...

Morphological, diagnostic and surgical features of ectopic thyroid gland: a review of literature.

PubMed

Guerra, Germano; Cinelli, Mariapia; Mesolella, Massimo; Tafuri, Domenico; Rocca, Aldo; Amato, Bruno; Rengo, Sandro; Testa, Domenico

2014-01-01

Ectopic thyroid tissue remains a rare developmental abnormality involving defective or aberrant embryogenesis of the thyroid gland during its passage from the floor of the primitive foregut to its usual final position in pre-tracheal region of the neck. Its specific prevalence accounts about 1 case per 100.000-300.000 persons and one in 4.000-8.000 patients with thyroid disease show this condition. The cause of this defect is not fully known. Despite genetic factors have been associated with thyroid gland morphogenesis and differentiation, just recently some mutation has been associated with human thyroid ectopy. Lingual region in the most common site of thyroid ectopy but ectopic thyroid tissue were found in other head and neck locations. Nevertheless, aberrant ectopic thyroid tissue has been found in other places distant from the neck region. Ectopic tissue is affected by different pathological changes that occur in the normal eutopic thyroid. Patients may present insidiously or as an emergency. Diagnostic management of thyroid ectopy is performed by radionuclide thyroid imaging, ultrasonography, CT scan, MRI, biopsy and thyroid function tests. Asymptomatic euthyroid patients with ectopic thyroid do not usually require therapy but are kept under observation. For those with symptoms, treatment depends on size of the gland, nature of symptoms, thyroid function status and histological findings. Surgical excision is often required as treatment for this condition. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. 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.

[The myxoedema coma exists, we met it].

PubMed

Fritsch, N; Tran-Van, D; Dardare, E; Gentile, A; Deroudilhe, G; Fontaine, B

2007-09-01

The myxoedema coma corresponds to the ultimate evolution of a hypothyroidism and is characterized by a major deficit in thyroid hormones responsible for a collapse of the metabolism. The preventive and curative treatment is based on the administration of thyroid hormones, whose benefits are opposed to the cardiovascular risks related to an iatrogenic hyperthyroidism for patients often old with cardiopathy. We report the case of a 92-year-old patient with unbalanced hypothyroidism and chronic cardiac deficiency, who presented a myxoedema coma in the postoperative period of an urgent digestive surgery. This observation illustrates the difficulties in treating patients with unbalanced hypothyroidism following emergency surgery, in the absence of consensus on the type and the amounts of thyroid hormones substitution.

[Morphological changes in the thyroid gland of rats during various phases of the estral cycle].

PubMed

Pliner, L I; Ledovskaia, S M

1975-08-01

The functional state of the thyroid gland and the concentration of thyroid hormones in the peripheral blood were studied in 20 mature female albino rats during their estral cycle. Evaluation of the thyroid functional state was made according to data of histological, morphological (the diameter of folliculi, the height of the thyroid epithelium) and histochemical analysis (determination of NAD and NADP-dehydrogenase, succinatedehydrogenase, lactate dehydrogenase, peroxydase, acid and alkaline phosphatase) as well as biochemical determination of iodine bound with protein (IBP) in the blood plasma and investigation of the ratio of the parameters in question under conditions of the sex cycle. The cyclic changes of the morphological state of the thyroid gland attended by the phases of the estral cycle were revealed. The activation of the organ was observed in proestrus and estrus which was evidenced by high levels of activity of the enzymes under study, high concentration of IBP in the blood and increased height of thyreocytes. A decreased function of the thyroid parenchyma was observed at the period of metaestrus-diestrus.

THYROID DISRUPTING CHEMICALS: CHALLENGES IN ASSESSING NEUROTOXIC RISK FROM ENVIRONMENTAL MIXTURES.

EPA Science Inventory

Environmental contaminants are known to act as thyroid disrupting chemicals (TDCs). Broadly defined, TDCs are xenobiotics that alter the structure or function of the thyroid gland, alter regulatory enzymes associated with thyroid hormone (TH) homeostasis, or change circulating o...

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.

Encapsulation of Iron and Other Micronutrients for Food Fortification

NASA Astrophysics Data System (ADS)

Zimmermann, Michael B.; Windhab, Erich J.

Iodine, vitamin A and iron deficiencies are important global public health problems, particularly for preschool children and pregnant women in low-income countries (World Health Organization 2000). These deficiencies are mainly due to monotonous, poor-quality diets that do not meet nutrient requirements. In countries where existing food supplies and/or limited access fail to provide adequate levels of these nutrients in the diet, food fortification is a promising approach. Co-fortification of foods with iron, iodine and vitamin A may be advantageous due to beneficial interactions of these micronutrients in metabolism. Studies in animals and humans have shown that iron deficiency anemia (IDA) impairs thyroid metabolism (Zimmermann et al. 2000a, 2000b; Hess et al. 2002a, 2002b). Vitamin A deficiency may exacerbate anemia through impairment of iron metabolism (Semba and Bloem 2002). Vitamin A, together with iodine, may reduce thyroid hyperstimulation and risk for goiter (Zimmermann et al. 2007). These micronutrient interactions strongly argue for multiple micronutrient fortification. However, food fortification with iron is not straightforward.

Nuclear Receptors, Mitochondria, and Lipid Metabolism

PubMed Central

Alaynick, William A.

2009-01-01

Lipid metabolism is a continuum from emulsification and uptake of lipids in the intestine to cellular uptake and transport to compartments such as mitochondria. Whether fats are shuttled into lipid droplets in adipose tissue or oxidized in mitochondria and peroxisomes depends on metabolic substrate availability, energy balance and endocrine signaling of the organism. Several members of the nuclear hormone receptor superfamily are lipid-sensing factors that affect all aspects of lipid metabolism. The physiologic actions of glandular hormones (e.g. thyroid, mineralocorticoid and glucocorticoid), vitamins (e.g. vitamins A and D) and reproductive hormones (e.g. progesterone, estrogen and testosterone) and their cognate receptors are well established. The peroxisome proliferator activated receptors (PPARs) and Liver X receptors (LXRs), acting in concert with PPARγ Coactivator 1α (PGC-1α), have been shown to regulate insulin sensitivity and lipid handling. These receptors are the focus of intense pharmacologic studies to expand the armamentarium of small molecule ligands to treat diabetes and the metabolic syndrome (hypertension, insulin resistance, hyperglycemia, dyslipidemia, and obesity). Recently, additional partners of PGC-1α have moved to the forefront of metabolic research, the Estrogen-related Receptors (ERRs). Although no endogenous ligands for these receptors have been identified, phenotypic analyses of knockout mouse models demonstrate an important role for these molecules in substrate sensing and handling as well as mitochondrial function. PMID:18375192

The Association between Selenium and Other Micronutrients and Thyroid Cancer Incidence in the NIH-AARP Diet and Health Study

PubMed Central

O’Grady, Thomas J.; Kitahara, Cari M.; DiRienzo, A. Gregory; Gates, Margaret A.

2014-01-01

Background Selenium is an essential trace element that is important for thyroid hormone metabolism and has antioxidant properties which protect the thyroid gland from oxidative stress. The association of selenium, as well as intake of other micronutrients, with thyroid cancer is unclear. Methods We evaluated associations of dietary selenium, beta-carotene, calcium, vitamin D, vitamin C, vitamin E, folate, magnesium, and zinc intake with thyroid cancer risk in the National Institutes of Health – American Association of Retired Persons Diet and Health Study, a large prospective cohort of 566,398 men and women aged 50–71 years in 1995–1996. Multivariable-adjusted Cox proportional hazards regression was used to examine associations between dietary intake of micronutrients, assessed using a food frequency questionnaire, and thyroid cancer cases, ascertained by linkage to state cancer registries and the National Death Index. Results With the exception of vitamin C, which was associated with an increased risk of thyroid cancer (HRQ5 vs Q1, 1.34; 95% CI, 1.02–1.76; Ptrend, <0.01), we observed no evidence of an association between quintile of selenium (HRQ5 vs Q1, 1.23; 95% CI, 0.92–1.65; Ptrend, 0.26) or other micronutrient intake and thyroid cancer. Conclusion Our study does not suggest strong evidence for an association between dietary intake of selenium or other micronutrients and thyroid cancer risk. More studies are needed to clarify the role of selenium and other micronutrients in thyroid carcinogenesis. PMID:25329812

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

Thyroid Function Variations Within the Reference Range Do Not Affect Quality of Life, Mood, or Cognitive Function in Community-Dwelling Older Men.

PubMed

Samuels, Mary H; Kaimal, Rajani; Waring, Avantika; Fink, Howard A; Yaffe, Kristine; Hoffman, Andrew R; Orwoll, Eric; Bauer, Douglas

2016-09-01

Variations in thyroid function within the laboratory reference range have been associated with a number of clinical outcomes. However, quality of life, mood, and cognitive function have not been extensively studied, and it is not clear whether mild variations in thyroid function have major effects on these neurocognitive outcomes. Data were analyzed from the Osteoporotic Fractures in Men (MrOS) Study, a cohort of community-dwelling men aged 65 years and older in the United States. A total of 539 participants who were not taking thyroid medications and had age-adjusted TSH levels within the reference range underwent detailed testing of quality of life, mood, and cognitive function at baseline. The same quality of life, mood, and cognitive outcomes were measured again in 193 of the men after a mean follow-up of 6 years. Outcomes were analyzed using thyrotropin (TSH) and free thyroxine (FT4) levels as continuous independent variables, adjusting for relevant covariates. At baseline, there were no associations between TSH or FT4 levels and measures of quality of life, mood, or cognition in the 539 euthyroid men. Baseline thyroid function did not predict changes in these outcomes over a mean of 6 years in the 193 men in the longitudinal analysis. Variations in thyroid function within the age-adjusted laboratory reference range are not associated with variations in quality of life, mood, or cognitive function in community-dwelling older men.

Transient hypothyroidism in infants born to mothers with chronic thyroiditis--a nationwide study of twenty-three cases. The Transient Hypothyroidism Study Group.

PubMed

Matsuura, N; Konishi, J

1990-06-01

To define the difference in prognosis and the clinical features of transient neonatal hypothyroidism in infants born to mothers with chronic thyroiditis, we conducted a nationwide study of this condition. Sixteen mothers with chronic thyroiditis and twenty-three of their offspring with transient hypothyroidism were registered and reported in this paper. Five (group A) of twenty-two live infants showed physical, mental and/or psychomotor developmental delay (IQ below 80). No significant difference between TSH-binding inhibitor immunoglobulin (TBII) or thyroid-stimulation blocking antibody (TSBAb) activities in groups A and B (normal development) were noted. Moreover, there was no significant difference in thyroid function in the newborn period, ages at the start of thyroid medication or the dose and duration of treatment in the two groups. A striking difference observed between the two groups was the thyroid function of their mothers during pregnancy. In group A, four mothers were hypothyroid during pregnancy, and another mother discontinued thyroid medication in the last trimester and her baby was most delayed at the start thyroid medication. On the other hand, the mothers of only two of seventeen live cases in group B had mild hypothyroidism during pregnancy. There were two sets of siblings whose mother received inadequate treatment during the first pregnancy and adequate treatment during the second pregnancy. The psychomotor, physical and mental developmental delay were observed in their first babies. These findings suggested that maternal thyroid function during pregnancy might be an important factor in the prognosis of infants born to mothers with chronic thyroiditis.

Prevalence of thyroid disorders in North Indian Type 2 diabetic subjects: A cross sectional study.

PubMed

Ozair, Maaz; Noor, Saba; Raghav, Alok; Siddiqi, Sheelu Shafiq; Chugtai, Anjum Mirza; Ahmad, Jamal

2018-05-01

Type 2 diabetes mellitus (T2DM) is a major health burden worldwide with many patients encountering thyroid dysfunction later in their life. Various studies have found that diabetes and thyroid disorders mutually influence each other and both disorders tend to coexists. However, the prevalence of thyroid dysfunction and associated clinical variables in these patients has not been investigated. The study aimed at determining the incidence and prevalence of thyroid dysfunction in patients with T2DM in relation to age, sex, metabolic syndrome and other co-morbid conditions. In this cross-sectional study, 250 Type 2 DM patients were enrolled aged between 40 and 75 years. All the patients were evaluated for thyroid dysfunction by testing thyroid profile (T3, T4 and TSH. These subjects were also investigated for fasting blood sugar (FBS), post prandial glucose (PPG) glycosylated hemoglobin (HbA1c), serum cholesterol, serum triglycerides, high density lipoprotein (HDL), low density lipoprotein(LDL), very low density lipoprotein(VLDL), blood urea, serum creatinine and presence of other co-morbid conditions. The observations and interpretations were recorded and results obtained were statistically analyzed. A high prevalence of thyroid dysfunction (28%) was observed in type 2 diabetic patients with subclinical hypothyroidism (18.8%) as the commonest thyroid disorder. Thyroid dysfunction was more prevalent in females, with presence of dyslipidemia, retinopathy, poor glycemic state (HbA1c ≥7) and longer duration of diabetes as significant contributing factors associated. In addition to glycemic status, screening of thyroid disorder should be routinely done in type 2 diabetic subjects along with other comorbid conditions. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-10-01

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

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.